Patients seek healthy skin that conveys overall health and well-being. Cosmeceuticals claim to therapeutically affect the structure and function of the skin, and it is rational to hold them to scientific standards that substantiate efficacy claims.¹ Notably, it is increasingly important to consider nature-based products in helping patients and consumers to achieve healthier skin. Despite the availability of sophisticated efficacy testing, explanations of the underlying physiologic and pharmacologic principles of nature-based products lag behind those of conventional formulations. In many instances, simple form and function information cannot adequately support their desired use and expected benefits. In addition, cosmetic regulations do not even permit structure-function claims that are allowed for dietary supplements.

Physicians whose patients want recommendations for nature-based products often do not know where to turn for definitive product and use information. Unlike prescription medications or even beauty-from-within dietary supplement products, natural cosmetics and cosmeceuticals are barred from communicating scientific evidence and experience of use to form proper opinions for recommendations. Without the benefit of full product labeling, physicians are left to mine sparse, confusing, and often contradictory literature in an effort to self-educate. Here, we share our experiences with patients, our operating knowledge base, and our recommendations for investigation to improve the available information and ensure practicing physicians have the information they need to appropriately recommend nature-based products.

General Observations Pertaining to Patients and Nature-Based Products

Ethnic and cultural customs and traditions have accepted and employed nature-based products for skin health for millennia (eTables 1–3).^2-20 African and the derived Caribbean cultures frequently use shea butter, black soap, or coconut oil. East Asian ethnobotanical practices include the use of ginseng, green tea, almond, and angelica root in skin care. Indian culture employs Ayurvedic medicine principles that include herbal remedies comprised of ground chickpeas, rice, turmeric, neem, ashwagandha, moringa, and kutki. These cultural traditions continue into modern times, and patients regularly use these products. Modern social trends that focus on a healthy lifestyle also create demand for nature-based products for skin health. In our opinion, the current growing interest in nature-based products implies continued growth in their use as patients become more familiar and comfortable with them.

For beauty and skin health, a new trend has evolved in which the first source of advice is rarely a dermatologist. Social media, nonphysician influencers, and pseudoscience have created an authority previously reserved for dermatologists among patients and consumers. Bloggers and social media influencers, posting their individual real-world experiences, shape the perceptions of consumers and patients.^21,22 Nonphysician influencers leverage their celebrity to provide guidance and advice on beauty and cosmetic tips.²³ Much of the evidence supporting cosmetic and especially nature-based products for skin care and health often is believed to be less rigorous and of lower quality than that typically supporting physician recommendations.^24-26

Nature-Based Products in Skin Health and Dermatologic Conditions

Patients turn to nature-based products for skin care and health for many reasons. The simplest reason is that they grew up with such products and continue their use. Many patients find nature-based products themselves, have favorable experiences, and seek advice on their efficacy and safety for continued use. Patients also use these products as part of a holistic approach to health in which diet and exercise coincide with the idea of ministering to the whole self instead of preventing or treating an illness. These nature-based treatment options fit their natural lifestyles. Patients sometimes express concerns about synthetic products that lead them to seek out nature-based products. Chemicals and preservatives (eg, parabens, sunscreens, nanoparticles) may evoke concerns about negative health consequences, which can be a cause of great anxiety to patients.

Nature-based products, when recommended by physicians, can fulfill important roles. As healthier alternatives, they can address health concerns in the belief that plant-based ingredients may be more compatible with overall health than synthetic ingredients. This compatibility may have resulted from the human species coevolving with plant species containing therapeutic utility, leading to the development of specific receptors for many natural products, such as digoxin from foxglove (Digitalis purpurea), opioids from poppies (Papaver somniferum), and cannabinoids (Cannabis sativa and hybrids). Natural products can become alternatives to synthetic products or adjuncts to prescription medications. Often, inclusion of nature-based products into a treatment plan enables patients to feel that they are a more integral part of the care team treating their conditions. By virtue of physician recommendations, patients may have expectations on product efficacy being as robust as prescription products with the safety profile of plant-based products. Patients should be advised to accept a realistic view of the efficacy and tolerability profiles. In the end, patients consider physician recommendations based on the assumption that they are credible and derived from experience and knowledge.

Physician Perceptions of Nature-Based Products

Physicians recommend nature-based products based on several factors. Central to the recommendation is an understanding, through appropriate documentation, that the product will be reasonably efficacious. Critical to this point, physicians must understand what ingredients are in nature-based products, their concentrations or amounts, and why they are present. However, our experience with nature-based products suggests that many of these factors are not met. Limited or unclear information on the efficacy of nature-based products fails to satisfy a physician’s need for adequate information to support recommendations. Although natural ingredients are listed on product labels, their intended benefit and efficacy characteristics often are unclear or poorly stated, in some cases resulting from improper labeling and in other cases due to claim restrictions imposed on cosmetics. In addition, insufficient details on formulation, such as type and percentages of oils, antioxidants, and vitamins, hinder the physician’s ability to identify and explain mechanisms that bring benefit to the patient. Universal benchmarks do not exist for amounts or concentrations of ingredients that are required for a stated benefit.²⁷ Currently, no standards exist for assurances that product quality, control, and efficacy are consistently reproducible. For example, angel dusting is a practice that discloses that an active ingredient is present, yet these ingredients may be present in quantities that are insufficient to provide measurable benefit. Sourcing of ingredients also can be concerning, as they may not always meet manufacturer, physician, or patient expectations for characterization or efficacy.^28,29 Dry testing, which is when a manufacturer contracts a laboratory to certify their ingredients without performing assays, has been increasingly reported in lay and botanical literature over the last few years.³⁰

It is unknown if many nature-based products clinically exhibit their stated efficacy. Empirical evidence or well-conducted clinical studies on which to base recommendations of these products are limited. Individual natural ingredients, however, do have some supporting evidence of efficacy: shea butter moisturizes³¹; coconut oil exhibits anti-inflammatory properties^32,33; and vinegar, yogurt, and diluted tea tree oil exhibit antibacterial properties in postprocedure care and fungal infections, and as adjuvants to prescription antibiotics in atopic dermatitis, acne, and rosacea.^34-41 Honey also has been shown to improve wound healing and is even available as a medical device for wounds.^42,43 Although nature-based products are an interesting alternative to synthetic products, they require a fulsome understanding of characteristics and efficacy properties to support physician recommendations.

Physician Recommendations

Physicians must be educated to understand when and how to recommend nature-based products. Although we recommend increased product information to guide physicians, current laws, including the Federal Food, Drug, and Cosmetic Act and the Fair Packaging and Labeling Act, are satisfactory from a regulatory standpoint.⁴⁴ Here, we discuss the information physicians could use to support an informed recommendation of nature-based products.

A clear specific explanation of natural ingredient sources, their intended efficacy, and rigorous scientific clinical evidence supporting their use should be given. Manufacturers are needed to document and report the structure and function of natural ingredients, leading to a common understanding by practicing dermatologists.⁴⁵ For this reason, manufacturers must provide nonambiguous and standardized methods and measures to demonstrate the mechanism of ingredient efficacy and the limits of safety and tolerability.

We recommend that manufacturers provide standardized transparency into the composition of nature-based formulations, including amounts and concentrations of ingredients; geographic sources; parts of plants used; and if extracted, what agent(s) this standard is based on (eg, hypericin in Saint-John’s-wort or kavalactones in kava kava). Most natural products contain an aqueous phase and therefore will likely require preservatives such as synthetic parabens or alcohols to avoid degradation. Unnecessary ingredients, including fragrances, fillers, and support chemicals, should be absent since inert agents may exhibit biologic effects, obscuring the boundary between active and inert. A clear explanation of the origins of these nature-based ingredients and the concentration, purity, and activity assessment should be provided. In the context of an authoritative review with standardized measures, labels that provide the common name, plant name, part used, how it was obtained, concentrations and/or amounts, and standardized activity measures can be helpful to the recommending physician, who will then know the efficacy patients should expect from the ingredients. They also can assess the expected tolerability based on the concentrations and their own experience managing a particular disorder, tempered by the patient’s experiences with prior therapies. Transparent and standardized labeling describing the formulation, quantities of ingredients, and intended activity will help inform expectations of efficacy.

We recommend clear preclinical and clinical demonstrations of the efficacy and benefits that are claimed by nature-based formulations. Properly designed placebo- or active-controlled, blinded, randomized studies with standardized measures and end points are recommended to determine efficacy and safety. These demonstrations of efficacy can provide physicians with credible evidence on which to base their recommendations and guide the use of products for the patient’s best experience. Given sufficient involvement from manufacturers and publication of the information in peer-reviewed journals, the relative benefits for each nature-based product can be cataloged as a resource for physicians.

Conclusion

Patients turn to nature-based products for many reasons. They have high expectations but also harbor concerns as to the efficacy of these products for skin and health care. Physicians seek to recommend nature-based products for these patients but often find themselves disadvantaged by limited published evidence and insufficient labeling information on composition and efficacy, which should support recommendations for use. To remedy this situation, we suggest research to allow a clear explanation of the activity of natural ingredients, clear demonstrations of the efficacy of nature-based formulas using clinical standardized measures and end points, and clear education and disclosure of ingredients contained within nature-based products.



Acknowledgments—Burt’s Bees (Durham, North Carolina) provided funding for editorial support by Medical Dynamics, Inc (New York, New York).

Patients seek healthy skin that conveys overall health and well-being. Cosmeceuticals claim to therapeutically affect the structure and function of the skin, and it is rational to hold them to scientific standards that substantiate efficacy claims.¹ Notably, it is increasingly important to consider nature-based products in helping patients and consumers to achieve healthier skin. Despite the availability of sophisticated efficacy testing, explanations of the underlying physiologic and pharmacologic principles of nature-based products lag behind those of conventional formulations. In many instances, simple form and function information cannot adequately support their desired use and expected benefits. In addition, cosmetic regulations do not even permit structure-function claims that are allowed for dietary supplements.

Physicians whose patients want recommendations for nature-based products often do not know where to turn for definitive product and use information. Unlike prescription medications or even beauty-from-within dietary supplement products, natural cosmetics and cosmeceuticals are barred from communicating scientific evidence and experience of use to form proper opinions for recommendations. Without the benefit of full product labeling, physicians are left to mine sparse, confusing, and often contradictory literature in an effort to self-educate. Here, we share our experiences with patients, our operating knowledge base, and our recommendations for investigation to improve the available information and ensure practicing physicians have the information they need to appropriately recommend nature-based products.

General Observations Pertaining to Patients and Nature-Based Products

Ethnic and cultural customs and traditions have accepted and employed nature-based products for skin health for millennia (eTables 1–3).^2-20 African and the derived Caribbean cultures frequently use shea butter, black soap, or coconut oil. East Asian ethnobotanical practices include the use of ginseng, green tea, almond, and angelica root in skin care. Indian culture employs Ayurvedic medicine principles that include herbal remedies comprised of ground chickpeas, rice, turmeric, neem, ashwagandha, moringa, and kutki. These cultural traditions continue into modern times, and patients regularly use these products. Modern social trends that focus on a healthy lifestyle also create demand for nature-based products for skin health. In our opinion, the current growing interest in nature-based products implies continued growth in their use as patients become more familiar and comfortable with them.

For beauty and skin health, a new trend has evolved in which the first source of advice is rarely a dermatologist. Social media, nonphysician influencers, and pseudoscience have created an authority previously reserved for dermatologists among patients and consumers. Bloggers and social media influencers, posting their individual real-world experiences, shape the perceptions of consumers and patients.^21,22 Nonphysician influencers leverage their celebrity to provide guidance and advice on beauty and cosmetic tips.²³ Much of the evidence supporting cosmetic and especially nature-based products for skin care and health often is believed to be less rigorous and of lower quality than that typically supporting physician recommendations.^24-26

Nature-Based Products in Skin Health and Dermatologic Conditions

Patients turn to nature-based products for skin care and health for many reasons. The simplest reason is that they grew up with such products and continue their use. Many patients find nature-based products themselves, have favorable experiences, and seek advice on their efficacy and safety for continued use. Patients also use these products as part of a holistic approach to health in which diet and exercise coincide with the idea of ministering to the whole self instead of preventing or treating an illness. These nature-based treatment options fit their natural lifestyles. Patients sometimes express concerns about synthetic products that lead them to seek out nature-based products. Chemicals and preservatives (eg, parabens, sunscreens, nanoparticles) may evoke concerns about negative health consequences, which can be a cause of great anxiety to patients.

Nature-based products, when recommended by physicians, can fulfill important roles. As healthier alternatives, they can address health concerns in the belief that plant-based ingredients may be more compatible with overall health than synthetic ingredients. This compatibility may have resulted from the human species coevolving with plant species containing therapeutic utility, leading to the development of specific receptors for many natural products, such as digoxin from foxglove (Digitalis purpurea), opioids from poppies (Papaver somniferum), and cannabinoids (Cannabis sativa and hybrids). Natural products can become alternatives to synthetic products or adjuncts to prescription medications. Often, inclusion of nature-based products into a treatment plan enables patients to feel that they are a more integral part of the care team treating their conditions. By virtue of physician recommendations, patients may have expectations on product efficacy being as robust as prescription products with the safety profile of plant-based products. Patients should be advised to accept a realistic view of the efficacy and tolerability profiles. In the end, patients consider physician recommendations based on the assumption that they are credible and derived from experience and knowledge.

Physician Perceptions of Nature-Based Products

Physicians recommend nature-based products based on several factors. Central to the recommendation is an understanding, through appropriate documentation, that the product will be reasonably efficacious. Critical to this point, physicians must understand what ingredients are in nature-based products, their concentrations or amounts, and why they are present. However, our experience with nature-based products suggests that many of these factors are not met. Limited or unclear information on the efficacy of nature-based products fails to satisfy a physician’s need for adequate information to support recommendations. Although natural ingredients are listed on product labels, their intended benefit and efficacy characteristics often are unclear or poorly stated, in some cases resulting from improper labeling and in other cases due to claim restrictions imposed on cosmetics. In addition, insufficient details on formulation, such as type and percentages of oils, antioxidants, and vitamins, hinder the physician’s ability to identify and explain mechanisms that bring benefit to the patient. Universal benchmarks do not exist for amounts or concentrations of ingredients that are required for a stated benefit.²⁷ Currently, no standards exist for assurances that product quality, control, and efficacy are consistently reproducible. For example, angel dusting is a practice that discloses that an active ingredient is present, yet these ingredients may be present in quantities that are insufficient to provide measurable benefit. Sourcing of ingredients also can be concerning, as they may not always meet manufacturer, physician, or patient expectations for characterization or efficacy.^28,29 Dry testing, which is when a manufacturer contracts a laboratory to certify their ingredients without performing assays, has been increasingly reported in lay and botanical literature over the last few years.³⁰

It is unknown if many nature-based products clinically exhibit their stated efficacy. Empirical evidence or well-conducted clinical studies on which to base recommendations of these products are limited. Individual natural ingredients, however, do have some supporting evidence of efficacy: shea butter moisturizes³¹; coconut oil exhibits anti-inflammatory properties^32,33; and vinegar, yogurt, and diluted tea tree oil exhibit antibacterial properties in postprocedure care and fungal infections, and as adjuvants to prescription antibiotics in atopic dermatitis, acne, and rosacea.^34-41 Honey also has been shown to improve wound healing and is even available as a medical device for wounds.^42,43 Although nature-based products are an interesting alternative to synthetic products, they require a fulsome understanding of characteristics and efficacy properties to support physician recommendations.

Physician Recommendations

Physicians must be educated to understand when and how to recommend nature-based products. Although we recommend increased product information to guide physicians, current laws, including the Federal Food, Drug, and Cosmetic Act and the Fair Packaging and Labeling Act, are satisfactory from a regulatory standpoint.⁴⁴ Here, we discuss the information physicians could use to support an informed recommendation of nature-based products.

A clear specific explanation of natural ingredient sources, their intended efficacy, and rigorous scientific clinical evidence supporting their use should be given. Manufacturers are needed to document and report the structure and function of natural ingredients, leading to a common understanding by practicing dermatologists.⁴⁵ For this reason, manufacturers must provide nonambiguous and standardized methods and measures to demonstrate the mechanism of ingredient efficacy and the limits of safety and tolerability.

We recommend that manufacturers provide standardized transparency into the composition of nature-based formulations, including amounts and concentrations of ingredients; geographic sources; parts of plants used; and if extracted, what agent(s) this standard is based on (eg, hypericin in Saint-John’s-wort or kavalactones in kava kava). Most natural products contain an aqueous phase and therefore will likely require preservatives such as synthetic parabens or alcohols to avoid degradation. Unnecessary ingredients, including fragrances, fillers, and support chemicals, should be absent since inert agents may exhibit biologic effects, obscuring the boundary between active and inert. A clear explanation of the origins of these nature-based ingredients and the concentration, purity, and activity assessment should be provided. In the context of an authoritative review with standardized measures, labels that provide the common name, plant name, part used, how it was obtained, concentrations and/or amounts, and standardized activity measures can be helpful to the recommending physician, who will then know the efficacy patients should expect from the ingredients. They also can assess the expected tolerability based on the concentrations and their own experience managing a particular disorder, tempered by the patient’s experiences with prior therapies. Transparent and standardized labeling describing the formulation, quantities of ingredients, and intended activity will help inform expectations of efficacy.

We recommend clear preclinical and clinical demonstrations of the efficacy and benefits that are claimed by nature-based formulations. Properly designed placebo- or active-controlled, blinded, randomized studies with standardized measures and end points are recommended to determine efficacy and safety. These demonstrations of efficacy can provide physicians with credible evidence on which to base their recommendations and guide the use of products for the patient’s best experience. Given sufficient involvement from manufacturers and publication of the information in peer-reviewed journals, the relative benefits for each nature-based product can be cataloged as a resource for physicians.

Conclusion

Patients turn to nature-based products for many reasons. They have high expectations but also harbor concerns as to the efficacy of these products for skin and health care. Physicians seek to recommend nature-based products for these patients but often find themselves disadvantaged by limited published evidence and insufficient labeling information on composition and efficacy, which should support recommendations for use. To remedy this situation, we suggest research to allow a clear explanation of the activity of natural ingredients, clear demonstrations of the efficacy of nature-based formulas using clinical standardized measures and end points, and clear education and disclosure of ingredients contained within nature-based products.



Acknowledgments—Burt’s Bees (Durham, North Carolina) provided funding for editorial support by Medical Dynamics, Inc (New York, New York).

Patients seek healthy skin that conveys overall health and well-being. Cosmeceuticals claim to therapeutically affect the structure and function of the skin, and it is rational to hold them to scientific standards that substantiate efficacy claims.¹ Notably, it is increasingly important to consider nature-based products in helping patients and consumers to achieve healthier skin. Despite the availability of sophisticated efficacy testing, explanations of the underlying physiologic and pharmacologic principles of nature-based products lag behind those of conventional formulations. In many instances, simple form and function information cannot adequately support their desired use and expected benefits. In addition, cosmetic regulations do not even permit structure-function claims that are allowed for dietary supplements.

Physicians whose patients want recommendations for nature-based products often do not know where to turn for definitive product and use information. Unlike prescription medications or even beauty-from-within dietary supplement products, natural cosmetics and cosmeceuticals are barred from communicating scientific evidence and experience of use to form proper opinions for recommendations. Without the benefit of full product labeling, physicians are left to mine sparse, confusing, and often contradictory literature in an effort to self-educate. Here, we share our experiences with patients, our operating knowledge base, and our recommendations for investigation to improve the available information and ensure practicing physicians have the information they need to appropriately recommend nature-based products.

General Observations Pertaining to Patients and Nature-Based Products

Ethnic and cultural customs and traditions have accepted and employed nature-based products for skin health for millennia (eTables 1–3).^2-20 African and the derived Caribbean cultures frequently use shea butter, black soap, or coconut oil. East Asian ethnobotanical practices include the use of ginseng, green tea, almond, and angelica root in skin care. Indian culture employs Ayurvedic medicine principles that include herbal remedies comprised of ground chickpeas, rice, turmeric, neem, ashwagandha, moringa, and kutki. These cultural traditions continue into modern times, and patients regularly use these products. Modern social trends that focus on a healthy lifestyle also create demand for nature-based products for skin health. In our opinion, the current growing interest in nature-based products implies continued growth in their use as patients become more familiar and comfortable with them.

For beauty and skin health, a new trend has evolved in which the first source of advice is rarely a dermatologist. Social media, nonphysician influencers, and pseudoscience have created an authority previously reserved for dermatologists among patients and consumers. Bloggers and social media influencers, posting their individual real-world experiences, shape the perceptions of consumers and patients.^21,22 Nonphysician influencers leverage their celebrity to provide guidance and advice on beauty and cosmetic tips.²³ Much of the evidence supporting cosmetic and especially nature-based products for skin care and health often is believed to be less rigorous and of lower quality than that typically supporting physician recommendations.^24-26

Nature-Based Products in Skin Health and Dermatologic Conditions

Patients turn to nature-based products for skin care and health for many reasons. The simplest reason is that they grew up with such products and continue their use. Many patients find nature-based products themselves, have favorable experiences, and seek advice on their efficacy and safety for continued use. Patients also use these products as part of a holistic approach to health in which diet and exercise coincide with the idea of ministering to the whole self instead of preventing or treating an illness. These nature-based treatment options fit their natural lifestyles. Patients sometimes express concerns about synthetic products that lead them to seek out nature-based products. Chemicals and preservatives (eg, parabens, sunscreens, nanoparticles) may evoke concerns about negative health consequences, which can be a cause of great anxiety to patients.

Nature-based products, when recommended by physicians, can fulfill important roles. As healthier alternatives, they can address health concerns in the belief that plant-based ingredients may be more compatible with overall health than synthetic ingredients. This compatibility may have resulted from the human species coevolving with plant species containing therapeutic utility, leading to the development of specific receptors for many natural products, such as digoxin from foxglove (Digitalis purpurea), opioids from poppies (Papaver somniferum), and cannabinoids (Cannabis sativa and hybrids). Natural products can become alternatives to synthetic products or adjuncts to prescription medications. Often, inclusion of nature-based products into a treatment plan enables patients to feel that they are a more integral part of the care team treating their conditions. By virtue of physician recommendations, patients may have expectations on product efficacy being as robust as prescription products with the safety profile of plant-based products. Patients should be advised to accept a realistic view of the efficacy and tolerability profiles. In the end, patients consider physician recommendations based on the assumption that they are credible and derived from experience and knowledge.

Physician Perceptions of Nature-Based Products

Physicians recommend nature-based products based on several factors. Central to the recommendation is an understanding, through appropriate documentation, that the product will be reasonably efficacious. Critical to this point, physicians must understand what ingredients are in nature-based products, their concentrations or amounts, and why they are present. However, our experience with nature-based products suggests that many of these factors are not met. Limited or unclear information on the efficacy of nature-based products fails to satisfy a physician’s need for adequate information to support recommendations. Although natural ingredients are listed on product labels, their intended benefit and efficacy characteristics often are unclear or poorly stated, in some cases resulting from improper labeling and in other cases due to claim restrictions imposed on cosmetics. In addition, insufficient details on formulation, such as type and percentages of oils, antioxidants, and vitamins, hinder the physician’s ability to identify and explain mechanisms that bring benefit to the patient. Universal benchmarks do not exist for amounts or concentrations of ingredients that are required for a stated benefit.²⁷ Currently, no standards exist for assurances that product quality, control, and efficacy are consistently reproducible. For example, angel dusting is a practice that discloses that an active ingredient is present, yet these ingredients may be present in quantities that are insufficient to provide measurable benefit. Sourcing of ingredients also can be concerning, as they may not always meet manufacturer, physician, or patient expectations for characterization or efficacy.^28,29 Dry testing, which is when a manufacturer contracts a laboratory to certify their ingredients without performing assays, has been increasingly reported in lay and botanical literature over the last few years.³⁰

It is unknown if many nature-based products clinically exhibit their stated efficacy. Empirical evidence or well-conducted clinical studies on which to base recommendations of these products are limited. Individual natural ingredients, however, do have some supporting evidence of efficacy: shea butter moisturizes³¹; coconut oil exhibits anti-inflammatory properties^32,33; and vinegar, yogurt, and diluted tea tree oil exhibit antibacterial properties in postprocedure care and fungal infections, and as adjuvants to prescription antibiotics in atopic dermatitis, acne, and rosacea.^34-41 Honey also has been shown to improve wound healing and is even available as a medical device for wounds.^42,43 Although nature-based products are an interesting alternative to synthetic products, they require a fulsome understanding of characteristics and efficacy properties to support physician recommendations.

Physician Recommendations

Physicians must be educated to understand when and how to recommend nature-based products. Although we recommend increased product information to guide physicians, current laws, including the Federal Food, Drug, and Cosmetic Act and the Fair Packaging and Labeling Act, are satisfactory from a regulatory standpoint.⁴⁴ Here, we discuss the information physicians could use to support an informed recommendation of nature-based products.

A clear specific explanation of natural ingredient sources, their intended efficacy, and rigorous scientific clinical evidence supporting their use should be given. Manufacturers are needed to document and report the structure and function of natural ingredients, leading to a common understanding by practicing dermatologists.⁴⁵ For this reason, manufacturers must provide nonambiguous and standardized methods and measures to demonstrate the mechanism of ingredient efficacy and the limits of safety and tolerability.

We recommend that manufacturers provide standardized transparency into the composition of nature-based formulations, including amounts and concentrations of ingredients; geographic sources; parts of plants used; and if extracted, what agent(s) this standard is based on (eg, hypericin in Saint-John’s-wort or kavalactones in kava kava). Most natural products contain an aqueous phase and therefore will likely require preservatives such as synthetic parabens or alcohols to avoid degradation. Unnecessary ingredients, including fragrances, fillers, and support chemicals, should be absent since inert agents may exhibit biologic effects, obscuring the boundary between active and inert. A clear explanation of the origins of these nature-based ingredients and the concentration, purity, and activity assessment should be provided. In the context of an authoritative review with standardized measures, labels that provide the common name, plant name, part used, how it was obtained, concentrations and/or amounts, and standardized activity measures can be helpful to the recommending physician, who will then know the efficacy patients should expect from the ingredients. They also can assess the expected tolerability based on the concentrations and their own experience managing a particular disorder, tempered by the patient’s experiences with prior therapies. Transparent and standardized labeling describing the formulation, quantities of ingredients, and intended activity will help inform expectations of efficacy.

We recommend clear preclinical and clinical demonstrations of the efficacy and benefits that are claimed by nature-based formulations. Properly designed placebo- or active-controlled, blinded, randomized studies with standardized measures and end points are recommended to determine efficacy and safety. These demonstrations of efficacy can provide physicians with credible evidence on which to base their recommendations and guide the use of products for the patient’s best experience. Given sufficient involvement from manufacturers and publication of the information in peer-reviewed journals, the relative benefits for each nature-based product can be cataloged as a resource for physicians.

Conclusion

Patients turn to nature-based products for many reasons. They have high expectations but also harbor concerns as to the efficacy of these products for skin and health care. Physicians seek to recommend nature-based products for these patients but often find themselves disadvantaged by limited published evidence and insufficient labeling information on composition and efficacy, which should support recommendations for use. To remedy this situation, we suggest research to allow a clear explanation of the activity of natural ingredients, clear demonstrations of the efficacy of nature-based formulas using clinical standardized measures and end points, and clear education and disclosure of ingredients contained within nature-based products.



Acknowledgments—Burt’s Bees (Durham, North Carolina) provided funding for editorial support by Medical Dynamics, Inc (New York, New York).

Case Report

A 62-year-old woman presented with multiple large friable tumors of the abdominal panniculus. The patient also reported an unintentional 75-lb weight loss over the last 9 months as well as vaginal bleeding and fecal discharge from the vagina of 2 weeks’ duration. The patient had a surgical and medical history of a robotic-assisted hysterectomy and bilateral salpingo-oophorectomy performed 4 years prior to presentation. Final surgical pathology showed complex atypical endometrial hyperplasia with no adenocarcinoma identified.

Physical examination revealed multiple large, friable, exophytic tumors of the left side of the lower abdominal panniculus within close vicinity of the patient’s abdominal hysterectomy scars (Figure 1). The largest lesion measured approximately 6 cm in length. Laboratory values were elevated for carcinoembryonic antigen (5.9 ng/mL [reference range, <3.0 ng/mL]) and cancer antigen 125 (202 U/mL [reference range, <35 U/mL]). Computed tomography of the abdomen and pelvis revealed diffuse metastatic disease.

Comment

Incidence and Pathogenesis
Endometrial carcinoma is the most common gynecologic malignancy in the United States, but it rarely progresses to disseminated disease because of routine gynecologic examinations and the low threshold for surgical intervention. Cutaneous metastases represent one of the rarest presentations of disseminated disease, occurring in only 0.8% of those diagnosed with endometrial carcinoma.¹ Cutaneous metastases occur almost exclusively in women older than 50 years and typically appear several months to years after hysterectomy. Although the exact pathogenesis is unknown, it is theorized that small foci of malignant cells may be seeded during surgery, leading to visceral and cutaneous involvement.

Clinical Presentation
Lesions vary morphologically, most commonly presenting as nonspecific, painless, hemorrhagic nodules. Lesions typically present in areas of direct local extension; prior radiotherapy; or areas of initial surgery, as was the case with our patient.² Approximately 20 cases of umbilical involvement (Sister Mary Joseph nodule) have been reported in the literature. These cases are thought to occur from direct local spread of disease from the peritoneum.³ Hematogenous and lymphatic spread to distant sites such as the scalp and mandible also have been reported. More than 50% of patients will have underlying visceral metastatic disease at the time of diagnosis.³

Histopathologic Findings
Histopathology varies with the morphology of the underlying primary tumor, with endometrioid adenocarcinoma being the most common form associated with cutaneous metastasis, as was the case with our patient.⁴ Histology is characterized by dermal proliferation of atypical glandular epithelium with diffuse hemorrhage. Staining typically is positive for CK7 and negative for CK20 and CDX2.⁵ Histopathology and immunohistochemical staining are not specific for diagnosis and must be correlated with clinical history.

Management and Prognosis
Similar to cutaneous metastasis in other internal malignancies, prognosis is poor, as widespread dissemination of the underlying malignancy typically is present. Mean life expectancy is 4 to 12 months.⁶ Treatment is primarily palliative, as chemotherapy and radiotherapy are largely ineffective.

Conclusion

Our patient represents a dramatic form of cutaneous extension of a common disease. Dermatologists often are consulted because of the nonspecific nature of the lesions and must be conscious of this entity. As with other cutaneous metastases, a thorough medical and surgical history in conjunction with histopathology are necessary for an accurate diagnosis.

Case Report

A 62-year-old woman presented with multiple large friable tumors of the abdominal panniculus. The patient also reported an unintentional 75-lb weight loss over the last 9 months as well as vaginal bleeding and fecal discharge from the vagina of 2 weeks’ duration. The patient had a surgical and medical history of a robotic-assisted hysterectomy and bilateral salpingo-oophorectomy performed 4 years prior to presentation. Final surgical pathology showed complex atypical endometrial hyperplasia with no adenocarcinoma identified.

Physical examination revealed multiple large, friable, exophytic tumors of the left side of the lower abdominal panniculus within close vicinity of the patient’s abdominal hysterectomy scars (Figure 1). The largest lesion measured approximately 6 cm in length. Laboratory values were elevated for carcinoembryonic antigen (5.9 ng/mL [reference range, <3.0 ng/mL]) and cancer antigen 125 (202 U/mL [reference range, <35 U/mL]). Computed tomography of the abdomen and pelvis revealed diffuse metastatic disease.

Comment

Incidence and Pathogenesis
Endometrial carcinoma is the most common gynecologic malignancy in the United States, but it rarely progresses to disseminated disease because of routine gynecologic examinations and the low threshold for surgical intervention. Cutaneous metastases represent one of the rarest presentations of disseminated disease, occurring in only 0.8% of those diagnosed with endometrial carcinoma.¹ Cutaneous metastases occur almost exclusively in women older than 50 years and typically appear several months to years after hysterectomy. Although the exact pathogenesis is unknown, it is theorized that small foci of malignant cells may be seeded during surgery, leading to visceral and cutaneous involvement.

Clinical Presentation
Lesions vary morphologically, most commonly presenting as nonspecific, painless, hemorrhagic nodules. Lesions typically present in areas of direct local extension; prior radiotherapy; or areas of initial surgery, as was the case with our patient.² Approximately 20 cases of umbilical involvement (Sister Mary Joseph nodule) have been reported in the literature. These cases are thought to occur from direct local spread of disease from the peritoneum.³ Hematogenous and lymphatic spread to distant sites such as the scalp and mandible also have been reported. More than 50% of patients will have underlying visceral metastatic disease at the time of diagnosis.³

Histopathologic Findings
Histopathology varies with the morphology of the underlying primary tumor, with endometrioid adenocarcinoma being the most common form associated with cutaneous metastasis, as was the case with our patient.⁴ Histology is characterized by dermal proliferation of atypical glandular epithelium with diffuse hemorrhage. Staining typically is positive for CK7 and negative for CK20 and CDX2.⁵ Histopathology and immunohistochemical staining are not specific for diagnosis and must be correlated with clinical history.

Management and Prognosis
Similar to cutaneous metastasis in other internal malignancies, prognosis is poor, as widespread dissemination of the underlying malignancy typically is present. Mean life expectancy is 4 to 12 months.⁶ Treatment is primarily palliative, as chemotherapy and radiotherapy are largely ineffective.

Conclusion

Our patient represents a dramatic form of cutaneous extension of a common disease. Dermatologists often are consulted because of the nonspecific nature of the lesions and must be conscious of this entity. As with other cutaneous metastases, a thorough medical and surgical history in conjunction with histopathology are necessary for an accurate diagnosis.

Case Report

A 62-year-old woman presented with multiple large friable tumors of the abdominal panniculus. The patient also reported an unintentional 75-lb weight loss over the last 9 months as well as vaginal bleeding and fecal discharge from the vagina of 2 weeks’ duration. The patient had a surgical and medical history of a robotic-assisted hysterectomy and bilateral salpingo-oophorectomy performed 4 years prior to presentation. Final surgical pathology showed complex atypical endometrial hyperplasia with no adenocarcinoma identified.

Physical examination revealed multiple large, friable, exophytic tumors of the left side of the lower abdominal panniculus within close vicinity of the patient’s abdominal hysterectomy scars (Figure 1). The largest lesion measured approximately 6 cm in length. Laboratory values were elevated for carcinoembryonic antigen (5.9 ng/mL [reference range, <3.0 ng/mL]) and cancer antigen 125 (202 U/mL [reference range, <35 U/mL]). Computed tomography of the abdomen and pelvis revealed diffuse metastatic disease.

Comment

Incidence and Pathogenesis
Endometrial carcinoma is the most common gynecologic malignancy in the United States, but it rarely progresses to disseminated disease because of routine gynecologic examinations and the low threshold for surgical intervention. Cutaneous metastases represent one of the rarest presentations of disseminated disease, occurring in only 0.8% of those diagnosed with endometrial carcinoma.¹ Cutaneous metastases occur almost exclusively in women older than 50 years and typically appear several months to years after hysterectomy. Although the exact pathogenesis is unknown, it is theorized that small foci of malignant cells may be seeded during surgery, leading to visceral and cutaneous involvement.

Clinical Presentation
Lesions vary morphologically, most commonly presenting as nonspecific, painless, hemorrhagic nodules. Lesions typically present in areas of direct local extension; prior radiotherapy; or areas of initial surgery, as was the case with our patient.² Approximately 20 cases of umbilical involvement (Sister Mary Joseph nodule) have been reported in the literature. These cases are thought to occur from direct local spread of disease from the peritoneum.³ Hematogenous and lymphatic spread to distant sites such as the scalp and mandible also have been reported. More than 50% of patients will have underlying visceral metastatic disease at the time of diagnosis.³

Histopathologic Findings
Histopathology varies with the morphology of the underlying primary tumor, with endometrioid adenocarcinoma being the most common form associated with cutaneous metastasis, as was the case with our patient.⁴ Histology is characterized by dermal proliferation of atypical glandular epithelium with diffuse hemorrhage. Staining typically is positive for CK7 and negative for CK20 and CDX2.⁵ Histopathology and immunohistochemical staining are not specific for diagnosis and must be correlated with clinical history.

Management and Prognosis
Similar to cutaneous metastasis in other internal malignancies, prognosis is poor, as widespread dissemination of the underlying malignancy typically is present. Mean life expectancy is 4 to 12 months.⁶ Treatment is primarily palliative, as chemotherapy and radiotherapy are largely ineffective.

Conclusion

Our patient represents a dramatic form of cutaneous extension of a common disease. Dermatologists often are consulted because of the nonspecific nature of the lesions and must be conscious of this entity. As with other cutaneous metastases, a thorough medical and surgical history in conjunction with histopathology are necessary for an accurate diagnosis.

Patients frequently present to dermatologists with nail disorders as their chief concern. Alternatively, nail conditions may be encountered by the examining physician as an incidental finding that may be a clue to underlying systemic disease. Competence in the diagnosis and treatment of nail diseases can drastically improve patient quality of life and can be lifesaving,¹ but many dermatologists find management of nail diseases challenging.² Bridging this educational gap begins with dermatology resident and medical student education. In a collaboration with dermatology educators, the American Academy of Dermatology (AAD) prepared a free online core curriculum for medical students that covers the essential concepts of dermatology. We sought to determine the integration of nail education in the AAD Basic Dermatology Curriculum.

Methods

A cross-sectional study of the AAD Basic Dermatology Curriculum was conducted to determine nail disease content. The curriculum modules were downloaded in June 2018,³ and mentions of nails were recorded and evaluated for overall quantities and relevant content. References to nail procedures and diagnostic techniques including nail biopsies, fungal cultures, microscopy on nail scrapings, nail clippings, and nail-related cancers also were assessed in the analysis.

Results

Of 342 patients discussed in cases and quizzes, nails were mentioned for 19 patients (89 times total)(Table 1). Additionally, there were 2 mentions each of nail clippings and nail tumors, 0 mentions of nail biopsies, and 1 mention each of fungal cultures and microscopy on nail scrapings (Table 1). Of the 40 modules, nails were mentioned in 12 modules (Table 2) and 6 introductions to the modules (Table 1). There were no mentions of the terms nails, subungual, or onychomycosis in the learning objectives.³

Comment

Our study demonstrates a paucity of content relevant to nails in the AAD Basic Dermatology Curriculum. Medical students are missing an important opportunity to learn about diagnosis and management of nail conditions and may incorrectly conclude that nail expertise is not essential to becoming a competent board-certified dermatologist.

Particularly concerning is the exclusion of nail examinations in the skin exam module addressing full-body skin examinations (0 mentions in 31 slides). This curriculum may negatively influence medical students and may then follow at the resident level, with a study reporting that 50.3% (69/137) of residents examine nails only when the patient brings it to their attention.⁴

Most concerning was the inadequate coverage of nail unit melanoma in the melanoma module (1 mention in 53 slides). Furthermore, the ABCDE—asymmetry, border, color, diameter, and evolving—mnemonic for cutaneous melanoma was covered in 6 slides in this module, and the ABCDEF—family history added—mnemonic for nail unit melanoma was completely excluded. Not surprisingly, resident knowledge of melanonychia diagnosis is deficient, with a prior study demonstrating that 62% (88/142) of residents were not confident diagnosing and managing patients with melanonychia, and only 88% (125/142) of residents were aware of the nail melanoma mnemonic.⁴

Similarly, nail biopsy for melanonychia diagnosis was excluded from the curriculum, whereas skin biopsy was thoroughly discussed in the context of a cutaneous melanoma diagnosis. This deficient teaching may track to the dermatology resident curriculum, as a survey of third-year dermatology residents (N=240) showed that 58% performed 10 or fewer nail procedures, and one-third of residents felt incompetent in nail surgery.⁵

We acknowledge that the AAD Basic Dermatology Curriculum is simply an introduction to dermatology. However, given that dermatologists are among the major specialists who care for nail patients, we advocate for more content on nail diseases in this curriculum. Nails can easily be incorporated into existing modules, and a new module specifically dedicated to nail disease should be added. Moreover, we envision that our findings will positively reflect on competence in treating nail disease for dermatology residents.

Patients frequently present to dermatologists with nail disorders as their chief concern. Alternatively, nail conditions may be encountered by the examining physician as an incidental finding that may be a clue to underlying systemic disease. Competence in the diagnosis and treatment of nail diseases can drastically improve patient quality of life and can be lifesaving,¹ but many dermatologists find management of nail diseases challenging.² Bridging this educational gap begins with dermatology resident and medical student education. In a collaboration with dermatology educators, the American Academy of Dermatology (AAD) prepared a free online core curriculum for medical students that covers the essential concepts of dermatology. We sought to determine the integration of nail education in the AAD Basic Dermatology Curriculum.

Methods

A cross-sectional study of the AAD Basic Dermatology Curriculum was conducted to determine nail disease content. The curriculum modules were downloaded in June 2018,³ and mentions of nails were recorded and evaluated for overall quantities and relevant content. References to nail procedures and diagnostic techniques including nail biopsies, fungal cultures, microscopy on nail scrapings, nail clippings, and nail-related cancers also were assessed in the analysis.

Results

Of 342 patients discussed in cases and quizzes, nails were mentioned for 19 patients (89 times total)(Table 1). Additionally, there were 2 mentions each of nail clippings and nail tumors, 0 mentions of nail biopsies, and 1 mention each of fungal cultures and microscopy on nail scrapings (Table 1). Of the 40 modules, nails were mentioned in 12 modules (Table 2) and 6 introductions to the modules (Table 1). There were no mentions of the terms nails, subungual, or onychomycosis in the learning objectives.³

Comment

Our study demonstrates a paucity of content relevant to nails in the AAD Basic Dermatology Curriculum. Medical students are missing an important opportunity to learn about diagnosis and management of nail conditions and may incorrectly conclude that nail expertise is not essential to becoming a competent board-certified dermatologist.

Particularly concerning is the exclusion of nail examinations in the skin exam module addressing full-body skin examinations (0 mentions in 31 slides). This curriculum may negatively influence medical students and may then follow at the resident level, with a study reporting that 50.3% (69/137) of residents examine nails only when the patient brings it to their attention.⁴

Most concerning was the inadequate coverage of nail unit melanoma in the melanoma module (1 mention in 53 slides). Furthermore, the ABCDE—asymmetry, border, color, diameter, and evolving—mnemonic for cutaneous melanoma was covered in 6 slides in this module, and the ABCDEF—family history added—mnemonic for nail unit melanoma was completely excluded. Not surprisingly, resident knowledge of melanonychia diagnosis is deficient, with a prior study demonstrating that 62% (88/142) of residents were not confident diagnosing and managing patients with melanonychia, and only 88% (125/142) of residents were aware of the nail melanoma mnemonic.⁴

Similarly, nail biopsy for melanonychia diagnosis was excluded from the curriculum, whereas skin biopsy was thoroughly discussed in the context of a cutaneous melanoma diagnosis. This deficient teaching may track to the dermatology resident curriculum, as a survey of third-year dermatology residents (N=240) showed that 58% performed 10 or fewer nail procedures, and one-third of residents felt incompetent in nail surgery.⁵

We acknowledge that the AAD Basic Dermatology Curriculum is simply an introduction to dermatology. However, given that dermatologists are among the major specialists who care for nail patients, we advocate for more content on nail diseases in this curriculum. Nails can easily be incorporated into existing modules, and a new module specifically dedicated to nail disease should be added. Moreover, we envision that our findings will positively reflect on competence in treating nail disease for dermatology residents.

Patients frequently present to dermatologists with nail disorders as their chief concern. Alternatively, nail conditions may be encountered by the examining physician as an incidental finding that may be a clue to underlying systemic disease. Competence in the diagnosis and treatment of nail diseases can drastically improve patient quality of life and can be lifesaving,¹ but many dermatologists find management of nail diseases challenging.² Bridging this educational gap begins with dermatology resident and medical student education. In a collaboration with dermatology educators, the American Academy of Dermatology (AAD) prepared a free online core curriculum for medical students that covers the essential concepts of dermatology. We sought to determine the integration of nail education in the AAD Basic Dermatology Curriculum.

Methods

A cross-sectional study of the AAD Basic Dermatology Curriculum was conducted to determine nail disease content. The curriculum modules were downloaded in June 2018,³ and mentions of nails were recorded and evaluated for overall quantities and relevant content. References to nail procedures and diagnostic techniques including nail biopsies, fungal cultures, microscopy on nail scrapings, nail clippings, and nail-related cancers also were assessed in the analysis.

Results

Of 342 patients discussed in cases and quizzes, nails were mentioned for 19 patients (89 times total)(Table 1). Additionally, there were 2 mentions each of nail clippings and nail tumors, 0 mentions of nail biopsies, and 1 mention each of fungal cultures and microscopy on nail scrapings (Table 1). Of the 40 modules, nails were mentioned in 12 modules (Table 2) and 6 introductions to the modules (Table 1). There were no mentions of the terms nails, subungual, or onychomycosis in the learning objectives.³

Comment

Our study demonstrates a paucity of content relevant to nails in the AAD Basic Dermatology Curriculum. Medical students are missing an important opportunity to learn about diagnosis and management of nail conditions and may incorrectly conclude that nail expertise is not essential to becoming a competent board-certified dermatologist.

Particularly concerning is the exclusion of nail examinations in the skin exam module addressing full-body skin examinations (0 mentions in 31 slides). This curriculum may negatively influence medical students and may then follow at the resident level, with a study reporting that 50.3% (69/137) of residents examine nails only when the patient brings it to their attention.⁴

Most concerning was the inadequate coverage of nail unit melanoma in the melanoma module (1 mention in 53 slides). Furthermore, the ABCDE—asymmetry, border, color, diameter, and evolving—mnemonic for cutaneous melanoma was covered in 6 slides in this module, and the ABCDEF—family history added—mnemonic for nail unit melanoma was completely excluded. Not surprisingly, resident knowledge of melanonychia diagnosis is deficient, with a prior study demonstrating that 62% (88/142) of residents were not confident diagnosing and managing patients with melanonychia, and only 88% (125/142) of residents were aware of the nail melanoma mnemonic.⁴

Similarly, nail biopsy for melanonychia diagnosis was excluded from the curriculum, whereas skin biopsy was thoroughly discussed in the context of a cutaneous melanoma diagnosis. This deficient teaching may track to the dermatology resident curriculum, as a survey of third-year dermatology residents (N=240) showed that 58% performed 10 or fewer nail procedures, and one-third of residents felt incompetent in nail surgery.⁵

We acknowledge that the AAD Basic Dermatology Curriculum is simply an introduction to dermatology. However, given that dermatologists are among the major specialists who care for nail patients, we advocate for more content on nail diseases in this curriculum. Nails can easily be incorporated into existing modules, and a new module specifically dedicated to nail disease should be added. Moreover, we envision that our findings will positively reflect on competence in treating nail disease for dermatology residents.

The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, is launching the first in-human trial of a universal influenza vaccine candidate.

Copyright National Institutes of Health

The experimental vaccine, H1ssF_3928, is derived from the stem of an H1N1 virus and has a surface made from hemagglutinin and ferritin. By including only the stem of the virus, which changes less than the head, the vaccine should require fewer updates. A similar vaccine made from the same materials was shown to be safe and well tolerated in humans.

The clinical trial (NCT03814720) will be conducted at the NIH Clinical Center in Bethesda, Md., and will gradually enroll at least 53 healthy adults aged 18-70 years. The first 5 participants will receive one 20-mcg intramuscular injection of the vaccine; the other 48 participants will receive two 60-mcg vaccinations 16 weeks apart. Patients will return for 9-11 follow-ups over a 12- to 15-month period, and will provide blood samples for analysis of anti-influenza antibodies.

copyright itsmejust/Thinkstock

“Seasonal influenza is a perpetual public health challenge, and we continually face the possibility of an influenza pandemic resulting from the emergence and spread of novel influenza viruses. This phase 1 clinical trial is a step forward in our efforts to develop a durable and broadly protective universal influenza vaccine,” Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said in the press release.

Find the full press release on the NIH website.

lfranki@mdedge.com

The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, is launching the first in-human trial of a universal influenza vaccine candidate.

Copyright National Institutes of Health

The experimental vaccine, H1ssF_3928, is derived from the stem of an H1N1 virus and has a surface made from hemagglutinin and ferritin. By including only the stem of the virus, which changes less than the head, the vaccine should require fewer updates. A similar vaccine made from the same materials was shown to be safe and well tolerated in humans.

The clinical trial (NCT03814720) will be conducted at the NIH Clinical Center in Bethesda, Md., and will gradually enroll at least 53 healthy adults aged 18-70 years. The first 5 participants will receive one 20-mcg intramuscular injection of the vaccine; the other 48 participants will receive two 60-mcg vaccinations 16 weeks apart. Patients will return for 9-11 follow-ups over a 12- to 15-month period, and will provide blood samples for analysis of anti-influenza antibodies.

copyright itsmejust/Thinkstock

“Seasonal influenza is a perpetual public health challenge, and we continually face the possibility of an influenza pandemic resulting from the emergence and spread of novel influenza viruses. This phase 1 clinical trial is a step forward in our efforts to develop a durable and broadly protective universal influenza vaccine,” Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said in the press release.

Find the full press release on the NIH website.

lfranki@mdedge.com

The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, is launching the first in-human trial of a universal influenza vaccine candidate.

Copyright National Institutes of Health

The experimental vaccine, H1ssF_3928, is derived from the stem of an H1N1 virus and has a surface made from hemagglutinin and ferritin. By including only the stem of the virus, which changes less than the head, the vaccine should require fewer updates. A similar vaccine made from the same materials was shown to be safe and well tolerated in humans.

The clinical trial (NCT03814720) will be conducted at the NIH Clinical Center in Bethesda, Md., and will gradually enroll at least 53 healthy adults aged 18-70 years. The first 5 participants will receive one 20-mcg intramuscular injection of the vaccine; the other 48 participants will receive two 60-mcg vaccinations 16 weeks apart. Patients will return for 9-11 follow-ups over a 12- to 15-month period, and will provide blood samples for analysis of anti-influenza antibodies.

copyright itsmejust/Thinkstock

“Seasonal influenza is a perpetual public health challenge, and we continually face the possibility of an influenza pandemic resulting from the emergence and spread of novel influenza viruses. This phase 1 clinical trial is a step forward in our efforts to develop a durable and broadly protective universal influenza vaccine,” Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said in the press release.

Find the full press release on the NIH website.

lfranki@mdedge.com

To the Editor:

I read with interest the informative Cutis case report by Krooks and Weatherall¹ in which the authors not only described the case of a 66-year-old man whose diagnosis of bone marrow biopsy–confirmed acute myeloid leukemia (AML) presented concurrently with skin biopsy–confirmed leukemia cutis but also discussed the poor prognosis of individuals with acute myelogenous leukemia cutis. Their patient died within 5 weeks of establishing the diagnosis. In addition, lateral and frontal photographs of the patient’s face demonstrated diffuse infiltrative plaques of leukemia cutis; he had swollen eyelids and lips with distortion of the nose secondary to dermal infiltration of leukemic myeloid cells.¹ Although not emphasized by the authors, the patient appeared to have a leonine facies and at least partial loss of the lateral eyebrows.

Malignancy-associated leonine facies resulting from infiltration of the skin by neoplastic cells has been reported in a patient with metastatic breast carcinoma.^2,3 However, it predominantly occurs in patients with hematologic dyscrasias such as leukemia cutis, lymphoma (ie, cutaneous B cell, cutaneous T cell, Hodgkin), plasmacytoma, and systemic mastocytosis.^3,4 The report by Krooks and Weatherall¹ adds AML-associated leukemia cutis to the previously observed types of leukemia cutis–related leonine facies in patients with acute lymphocytic leukemia, acute myelomonocytic leukemia, and chronic lymphocytic leukemia.^3,4

Partial or complete loss of eyebrows in the setting of leonine facies has a limited differential diagnosis.^3,5 In addition to cancer, the associated disorders include adnexal mucin deposition (alopecia mucinosis), granulomatous conditions (sarcoidosis), infectious diseases (leprosy), inherited syndromes (Setleis syndrome), photoallergic dermatoses (actinic reticuloid), and viral conditions (viral-associated trichodysplasia).^3-9 Neoplasms associated with leonine facies and eyebrow loss include lymphomas (mycosis fungoides and unspecified cutaneous T-cell lymphoma), systemic mastocytosis and leukemia cutis secondary to acute lymphocytic leukemia, acute myelomonocytic leukemia, and now AML.^1,3-5

The eyebrow loss associated with leonine facies often is not reversible once the causative cell of the associated condition (eg, granulomas of mycobacteria-infected histiocytes in leprosy, neoplastic lymphocytes in cutaneous T-cell lymphoma) has infiltrated the area of the eyebrows and abolished the preexisting hair follicles; however, follow-up descriptions of patients after treatment of other conditions that cause eyebrow loss usually are not reported. Indeed, there was partial reappearance of the eyebrows in a woman with systemic mastocytosis–associated loss of the eyebrows after malignancy-related treatment was reinitiated and the infiltrative facial plaques that had created her leonine facies had decreased in size.⁵ It is reasonable to speculate that the eyebrows may have reappeared in the patient reported by Krooks and Weatherall¹ and his leonine facies–associated facial plaques may have resolved if he had underwent and responded to treatment with antineoplastic chemotherapy.

To the Editor:

I read with interest the informative Cutis case report by Krooks and Weatherall¹ in which the authors not only described the case of a 66-year-old man whose diagnosis of bone marrow biopsy–confirmed acute myeloid leukemia (AML) presented concurrently with skin biopsy–confirmed leukemia cutis but also discussed the poor prognosis of individuals with acute myelogenous leukemia cutis. Their patient died within 5 weeks of establishing the diagnosis. In addition, lateral and frontal photographs of the patient’s face demonstrated diffuse infiltrative plaques of leukemia cutis; he had swollen eyelids and lips with distortion of the nose secondary to dermal infiltration of leukemic myeloid cells.¹ Although not emphasized by the authors, the patient appeared to have a leonine facies and at least partial loss of the lateral eyebrows.

Malignancy-associated leonine facies resulting from infiltration of the skin by neoplastic cells has been reported in a patient with metastatic breast carcinoma.^2,3 However, it predominantly occurs in patients with hematologic dyscrasias such as leukemia cutis, lymphoma (ie, cutaneous B cell, cutaneous T cell, Hodgkin), plasmacytoma, and systemic mastocytosis.^3,4 The report by Krooks and Weatherall¹ adds AML-associated leukemia cutis to the previously observed types of leukemia cutis–related leonine facies in patients with acute lymphocytic leukemia, acute myelomonocytic leukemia, and chronic lymphocytic leukemia.^3,4

Partial or complete loss of eyebrows in the setting of leonine facies has a limited differential diagnosis.^3,5 In addition to cancer, the associated disorders include adnexal mucin deposition (alopecia mucinosis), granulomatous conditions (sarcoidosis), infectious diseases (leprosy), inherited syndromes (Setleis syndrome), photoallergic dermatoses (actinic reticuloid), and viral conditions (viral-associated trichodysplasia).^3-9 Neoplasms associated with leonine facies and eyebrow loss include lymphomas (mycosis fungoides and unspecified cutaneous T-cell lymphoma), systemic mastocytosis and leukemia cutis secondary to acute lymphocytic leukemia, acute myelomonocytic leukemia, and now AML.^1,3-5

The eyebrow loss associated with leonine facies often is not reversible once the causative cell of the associated condition (eg, granulomas of mycobacteria-infected histiocytes in leprosy, neoplastic lymphocytes in cutaneous T-cell lymphoma) has infiltrated the area of the eyebrows and abolished the preexisting hair follicles; however, follow-up descriptions of patients after treatment of other conditions that cause eyebrow loss usually are not reported. Indeed, there was partial reappearance of the eyebrows in a woman with systemic mastocytosis–associated loss of the eyebrows after malignancy-related treatment was reinitiated and the infiltrative facial plaques that had created her leonine facies had decreased in size.⁵ It is reasonable to speculate that the eyebrows may have reappeared in the patient reported by Krooks and Weatherall¹ and his leonine facies–associated facial plaques may have resolved if he had underwent and responded to treatment with antineoplastic chemotherapy.

To the Editor:

I read with interest the informative Cutis case report by Krooks and Weatherall¹ in which the authors not only described the case of a 66-year-old man whose diagnosis of bone marrow biopsy–confirmed acute myeloid leukemia (AML) presented concurrently with skin biopsy–confirmed leukemia cutis but also discussed the poor prognosis of individuals with acute myelogenous leukemia cutis. Their patient died within 5 weeks of establishing the diagnosis. In addition, lateral and frontal photographs of the patient’s face demonstrated diffuse infiltrative plaques of leukemia cutis; he had swollen eyelids and lips with distortion of the nose secondary to dermal infiltration of leukemic myeloid cells.¹ Although not emphasized by the authors, the patient appeared to have a leonine facies and at least partial loss of the lateral eyebrows.

Malignancy-associated leonine facies resulting from infiltration of the skin by neoplastic cells has been reported in a patient with metastatic breast carcinoma.^2,3 However, it predominantly occurs in patients with hematologic dyscrasias such as leukemia cutis, lymphoma (ie, cutaneous B cell, cutaneous T cell, Hodgkin), plasmacytoma, and systemic mastocytosis.^3,4 The report by Krooks and Weatherall¹ adds AML-associated leukemia cutis to the previously observed types of leukemia cutis–related leonine facies in patients with acute lymphocytic leukemia, acute myelomonocytic leukemia, and chronic lymphocytic leukemia.^3,4

Partial or complete loss of eyebrows in the setting of leonine facies has a limited differential diagnosis.^3,5 In addition to cancer, the associated disorders include adnexal mucin deposition (alopecia mucinosis), granulomatous conditions (sarcoidosis), infectious diseases (leprosy), inherited syndromes (Setleis syndrome), photoallergic dermatoses (actinic reticuloid), and viral conditions (viral-associated trichodysplasia).^3-9 Neoplasms associated with leonine facies and eyebrow loss include lymphomas (mycosis fungoides and unspecified cutaneous T-cell lymphoma), systemic mastocytosis and leukemia cutis secondary to acute lymphocytic leukemia, acute myelomonocytic leukemia, and now AML.^1,3-5

The eyebrow loss associated with leonine facies often is not reversible once the causative cell of the associated condition (eg, granulomas of mycobacteria-infected histiocytes in leprosy, neoplastic lymphocytes in cutaneous T-cell lymphoma) has infiltrated the area of the eyebrows and abolished the preexisting hair follicles; however, follow-up descriptions of patients after treatment of other conditions that cause eyebrow loss usually are not reported. Indeed, there was partial reappearance of the eyebrows in a woman with systemic mastocytosis–associated loss of the eyebrows after malignancy-related treatment was reinitiated and the infiltrative facial plaques that had created her leonine facies had decreased in size.⁵ It is reasonable to speculate that the eyebrows may have reappeared in the patient reported by Krooks and Weatherall¹ and his leonine facies–associated facial plaques may have resolved if he had underwent and responded to treatment with antineoplastic chemotherapy.

Practice Gap

Onychocryptosis, or ingrown toenail, is a highly prevalent nail condition characterized by penetration of the periungual skin by the nail plate (Figure, A). Patients may report pain either while at rest or walking, which may be debilitating in severe cases and may adversely affect daily living. Treatment may be approached using conservative or surgical therapies. Conservative methods are noninvasive and appropriate for mild cases but require excellent compliance. Although nail trimming is the simplest method, it may necessitate cutting soft tissue, particularly when the nail is anchored deep within the periungual skin. Another conservative method is taping, which aims to separate the nail fold from the offending nail edge by using an adhesive. In common practice, the adhesive often detaches within a few hours, which is further exacerbated by moisture from sweating or bathing.¹ Therefore, for effective treatment of onychocryptosis, the tape typically must be reapplied multiple times per day, limiting compliance.

Tools

We propose using kinesiology tape to treat onychocryptosis. Kinesiology tape is a highly elastic adhesive that was originally employed by athletes to relieve pain while supporting muscles, tendons, and ligaments during strenuous activity. We hypothesized that its stronger adherent properties and greater elasticity would be advantageous for treatment of onychocryptosis compared to standard tape.

The Technique

A strip of tape is cut to approximately 10 to 15 mm×5 cm and is applied once daily to the lateral nail fold, pulling it away from the nail plate in oblique and proximal directions and then wrapping it around the plantar surface dorsally (Figure, B). Kinesiology tape properties allow for less frequent application and greater tension to be applied to the nail fold while reducing the risk for vasoconstriction, as the tape does not need to be fully wrapped around the digit for reliable adherence.

Practice Implications

Kinesiology tape adheres more firmly than other tapes and requires less frequent applications. Use of kinesiology tape for onychocryptosis therapy often is effective and may negate the need for more invasive procedures and improve quality of life during and after treatment.

Practice Gap

Onychocryptosis, or ingrown toenail, is a highly prevalent nail condition characterized by penetration of the periungual skin by the nail plate (Figure, A). Patients may report pain either while at rest or walking, which may be debilitating in severe cases and may adversely affect daily living. Treatment may be approached using conservative or surgical therapies. Conservative methods are noninvasive and appropriate for mild cases but require excellent compliance. Although nail trimming is the simplest method, it may necessitate cutting soft tissue, particularly when the nail is anchored deep within the periungual skin. Another conservative method is taping, which aims to separate the nail fold from the offending nail edge by using an adhesive. In common practice, the adhesive often detaches within a few hours, which is further exacerbated by moisture from sweating or bathing.¹ Therefore, for effective treatment of onychocryptosis, the tape typically must be reapplied multiple times per day, limiting compliance.

Tools

We propose using kinesiology tape to treat onychocryptosis. Kinesiology tape is a highly elastic adhesive that was originally employed by athletes to relieve pain while supporting muscles, tendons, and ligaments during strenuous activity. We hypothesized that its stronger adherent properties and greater elasticity would be advantageous for treatment of onychocryptosis compared to standard tape.

The Technique

A strip of tape is cut to approximately 10 to 15 mm×5 cm and is applied once daily to the lateral nail fold, pulling it away from the nail plate in oblique and proximal directions and then wrapping it around the plantar surface dorsally (Figure, B). Kinesiology tape properties allow for less frequent application and greater tension to be applied to the nail fold while reducing the risk for vasoconstriction, as the tape does not need to be fully wrapped around the digit for reliable adherence.

Practice Implications

Kinesiology tape adheres more firmly than other tapes and requires less frequent applications. Use of kinesiology tape for onychocryptosis therapy often is effective and may negate the need for more invasive procedures and improve quality of life during and after treatment.

Practice Gap

Onychocryptosis, or ingrown toenail, is a highly prevalent nail condition characterized by penetration of the periungual skin by the nail plate (Figure, A). Patients may report pain either while at rest or walking, which may be debilitating in severe cases and may adversely affect daily living. Treatment may be approached using conservative or surgical therapies. Conservative methods are noninvasive and appropriate for mild cases but require excellent compliance. Although nail trimming is the simplest method, it may necessitate cutting soft tissue, particularly when the nail is anchored deep within the periungual skin. Another conservative method is taping, which aims to separate the nail fold from the offending nail edge by using an adhesive. In common practice, the adhesive often detaches within a few hours, which is further exacerbated by moisture from sweating or bathing.¹ Therefore, for effective treatment of onychocryptosis, the tape typically must be reapplied multiple times per day, limiting compliance.

Tools

We propose using kinesiology tape to treat onychocryptosis. Kinesiology tape is a highly elastic adhesive that was originally employed by athletes to relieve pain while supporting muscles, tendons, and ligaments during strenuous activity. We hypothesized that its stronger adherent properties and greater elasticity would be advantageous for treatment of onychocryptosis compared to standard tape.

The Technique

A strip of tape is cut to approximately 10 to 15 mm×5 cm and is applied once daily to the lateral nail fold, pulling it away from the nail plate in oblique and proximal directions and then wrapping it around the plantar surface dorsally (Figure, B). Kinesiology tape properties allow for less frequent application and greater tension to be applied to the nail fold while reducing the risk for vasoconstriction, as the tape does not need to be fully wrapped around the digit for reliable adherence.

Practice Implications

Kinesiology tape adheres more firmly than other tapes and requires less frequent applications. Use of kinesiology tape for onychocryptosis therapy often is effective and may negate the need for more invasive procedures and improve quality of life during and after treatment.

Which patients are likely to benefit from using aspirin for primary prevention? In this article, we review the evidence to date, summarized for primary care settings in guidelines issued by the US Preventive Services Task Force (USPSTF). We supplement this summary with a rundown of the risks associated with aspirin use. And then we wrap up by identifying a clinical decision tool that is available to help make personalized decisions in a busy clinic setting, where determining an individual’s potential cardiovascular benefits and bleeding risk can be challenging.

The “roadmap” from the guidelines. In 2014, after performing a review of the literature, the US Food and Drug Administration recommended against the routine use of aspirin for primary prevention of cardiovascular disease (CVD).¹ In 2016, the USPSTF published 4 separate systematic reviews along with a decision analysis using a microsimulation model, which informed their position statement on aspirin for primary prevention.^2-6 These USPSTF reviews and recommendations incorporated both CVD and colorectal cancer (CRC) benefits with the bleeding risks from aspirin. Generally, for individuals 50 to 59 years old, the benefits are deemed to outweigh the harms; shared decision making is advised with those 60 to 69 years of age. For patients younger than 50 or 70 and older, evidence is inconclusive.

The benefits of primary prevention with aspirin

Cardiovascular disease

The Antithrombotic Trialists’ (ATT) Collaboration was one of the first meta-analyses that addressed the benefit-to-harm balance and called into question the routine use of aspirin for primary prevention.⁷ The USPSTF systematic review included the studies from the ATT Collaboration as well as trials performed after its publication, bringing the total number of eligible randomized controlled trials reviewed to 11.²

The benefit of aspirin for primary prevention of nonfatal myocardial infarction (MI) has been shown in multiple randomized controlled trials. The USPSTF systematic review showed a statistically significant relative risk reduction of 17% in patients taking low-dose aspirin (≤ 100 mg; relative risk [RR] = 0.83; confidence interval [95% CI], 0.74-0.94), although the heterogeneity of the studies was high. The same low dose of aspirin showed a statistically significant reduction in nonfatal stroke (RR = 0.86; 95% CI, 0.76-0.98), although the same benefit was not observed when all doses of aspirin were included. Cardiovascular disease mortality and all-cause mortality were not statistically different for patients taking low-dose aspirin when compared with placebo (RR = 0.97; 95% CI, 0.85-1.10 for CVD mortality; RR = 0.95; 95% CI, 0.89-1.01 for all-cause mortality).²

One study of more than 14,000 older (≥ 60 years) Japanese patients showed a statistically significant reduction in nonfatal MI (hazard ratio [HR] = 0.53; 95% CI, 0.31-0.91, P = .02) and nonfatal strokes (HR = 0.57; 95% CI, 0.32-0.99; P = .04). The study was stopped early because at 5 years of follow-up there was no statistically significant difference in a composite primary outcome, which included death from cardiovascular causes, nonfatal MI, and nonfatal stroke (HR = 0.94; 95% CI, 0.77-1.15; P = .54).⁸

Preventive benefits of aspirin outweigh risks for those 50-59 years of age who have a 10-year cardiovascular disease risk of ≥ 10%.

Several recent landmark studies have called into question the benefit of aspirin for cardiovascular primary prevention, especially in obese individuals, patients with diabetes, and the elderly. A meta-analysis of 10 trials showed that the effectiveness of aspirin doses between 75 mg and 100 mg for primary prevention decreased as weight increased; patients weighing 70 kg or more received no benefit.⁹ The ASCEND (A Study of Cardiovascular Events in Diabetes) trial included more than 15,000 patients with diabetes but no cardiovascular disease. Patients randomized to receive the low-dose aspirin did have fewer serious vascular events (incidence rate ratio [IRR] = 0.88; 95% CI, 0.79-0.97; P = .01), but they also had high risk of major bleeding events (IRR = 1.29; 95% CI, 1.09-1.52; P = .003).¹⁰ The ASPREE (Aspirin in Reducing Events in the Elderly) trial included more than 19,000 patients ages 70 years and older with no cardiovascular disease and compared low-dose aspirin to placebo. There was no statistically significant cardiovascular benefit, although there was an increase of major hemorrhage (HR = 1.38; 95% CI, 1.18-1.62; P < .001).¹¹ The ARRIVE (A Randomized Trial of Induction Versus Expectant Management) trial included 12,546 moderate atherosclerotic CVD (ASCVD) risk patients. Although a per-protocol analysis showed a decrease in rates of fatal and nonfatal MI (HR = 0.53; 95% CI, 0.36-0.79; P = .0014), the more reliable intention-to-treat analysis showed no improvement for any outcomes.¹²

[polldaddy:10286821]

Colorectal cancer

The literature base on prevention of cancer has been growing rapidly. However, the deluge of findings over the past 2 decades of trials and analyses has also introduced ambiguity and, often, conflicting results. The first journal article suggesting aspirin for primary prevention of cancer, published in 1988, was a case-control study wherein a population with CRC was matched to controls to look for potential protective factors.¹³ The most notable finding was the CRC risk reduction for those taking aspirin or aspirin-containing medications. Since then numerous studies and analyses have explored aspirin’s potential in primary prevention of many types of cancer, with overall unclear findings as denoted in the 2016 USPSTF systemic reviews and recommendations.

Continue to: One major limiting factor...

One major limiting factor is that most data come from CVD prevention trials, and only a limited number of trials have focused specifically on cancer prevention. For the USPSTF, these data showed no statistically significant risk reduction in overall cancer mortality (RR = 0.96; 95% CI, 0.87-1.06) or in total cancer incidence (RR = 0.98; 95% CI, 0.93-1.04).⁴ Other ongoing trials may yield more definitive data.¹⁴

The particular interest in CRC was due to it being the first cancer found to be preventable with aspirin therapy. The USPSTF, while acknowledging the homogeneous nature of supporting studies, noted that their significant number and resulting evidence made CRC the only cancer warranting evaluation. Population studies have now shown more benefit than the few randomized control trials. The Women’s Health Study and the Physicians’ Health Study were both limited by their duration. But such studies conducted over a longer period revealed notable benefits in the second decade of use, with a statistically significant lower CRC incidence (RR = 0.60; 95% CI, 0.47-0.76). Additionally, CRC mortality at 20 years was decreased in patients taking aspirin regularly (RR = 0.67; 95% CI, 0.52-0.86).⁴ Multiple studies are in progress to better establish aspirin’s CRC benefit.

While not directly applicable to the general population, use of aspirin for patients with Lynch syndrome to prevent CRC has strong supporting evidence.¹⁵ Beyond CRC, there is nascent evidence from limited observational studies that aspirin may have a preventive effect on melanoma and ovarian and pancreatic cancers.^16-18 Further studies or compilations of data would be needed to draw more significant conclusions on other types of cancers. Larger studies would prove more difficult to do, given the smaller incidences of these cancers.

Interestingly, a recent study showed that for individuals 70 years and older, aspirin might increase the risk for all-cause mortality, primarily due to increased cancer mortality across all types.¹⁹ Although this result was unexpected, caution should be used when prescribing aspirin particularly for patients 70 or older with active cancer.

A look at the harms associated with aspirin use

Aspirin has long been known to cause clinically significant bleeding. Aspirin inhibits platelet-derived cyclooxygenase-1 (COX-1), a potent vasoconstrictor, and thereby decreases platelet aggregation, reducing thromboembolic potential and prolonging bleeding time. These effects can confer health benefits but also carry the potential for risks. A decision to initiate aspirin therapy for primary prevention relies on an understanding of the benefit-to-harm balance.

Continue to: Initial aspirin studies...

Initial aspirin studies did not show a statistically significant increase in bleeding, likely due to too few events and inadequate powering. Subsequent meta-analyses from multiple evaluations have consistently shown bleeding to be a risk.^3,7 The risk for bleeding with aspirin has also been examined in multiple cohort studies, which has helped elucidate the risk in greater detail.

Gastrointestinal bleeding

Epidemiologic data show that among patients who do not use nonsteroidal anti-inflammatory drugs (NSAIDs), the rate of upper gastrointestinal (GI) complications is 1 case per 1000 patient-years.²⁰ Multiple studies have consistently shown that aspirin use increases the rate of significant upper GI bleeding over baseline risk (odds ratio [OR] = 1.54-1.58).^3,21,22 Interestingly, these increases seem not to be influenced by other factors, such as comorbidities that increase the risk for ASCVD. Analysis of cancer prevention studies showed similar epidemiologic trends, with aspirin use exceeding a baseline bleeding risk of 0.7 cases of upper GI complications per 1000 patient-years (OR = 1.31-1.73).²³

Other risk factors. Evaluation of risk factors for bleeding primarily comes from 2 studies.^3,7 Most data concern the impact of individual factors on significant GI bleeding, with fewer data available for evaluating risk for intracerebral hemorrhage (ICH). Initial analysis of individual prospective studies showed little or no correlation between risk for bleeding and such factors as gender, age, or history of hypertension or ASCVD.²¹ Subsequent analysis of meta-data and large cohorts did show statistically significant impact on rates of bleeding across several factors (TABLE 1^3,7).

Enteric coating on aspirin does appear to lower the rates of gastric mucosal injury.

Of note is a large heterogeneous cohort study conducted in Spain. Data showed significant increases in baseline risk for GI bleeding in older men with a history of GI bleeding and NSAID use. The absolute risk for GI bleed in this group was potentially as high as 150 cases per 1000 patient-years, well above the risk level assumed for the average patient.²⁴ A seemingly small OR of 1.5 could dramatically increase the absolute risk for bleeding in such patients, and it suggests that a generalized risk for bleeding probably shouldn’t be applied to all patients. Individuals may be better served by a baseline risk calculation reflecting multiple factors.

Intracerebral hemorrhage

Due to the comparatively uncommon nature of ICH, fewer data are available to support definitive conclusions about its increased risk with aspirin use. Aspirin use appeared to increase the risk for ICH with ratios between 1.27 and 1.32 in meta-analyses (measured as an OR or as an RR),^3,7,21 with an IRR of 1.54 in a cohort study.²² The only statistically significant factors suspected to increase the risk of ICH at baseline were smoking (RR = 2.18) and mean BP > 20 mm Hg over normal (OR = 2.18). Age, gender, and diabetes all showed a nonsignificant trend toward risk increase.⁷

Continue to: Risk based on dose and formulation

 

 

Risk based on dose and formulation

The effect of aspirin dose and formulation on bleeding risk is uncertain. Some studies have shown an increased risk for bleeding with daily doses of aspirin ≥ 300 mg, while others have shown no significant increase in rates for bleeding with differing doses.^21,25 Enteric coating does appear to lower the rates of gastric mucosal injury, although there are few data on the effect toward reducing clinically significant bleeding.²⁶ Currently, several prospective studies are underway to help clarify the evidence.²⁷

Putting it all together

For the general population, the evidence shows that the benefits and harms of aspirin for primary prevention are relatively even. The USPSTF guidelines are the first to recommend aspirin for both CVD and cancer prevention while taking into account the bleeding risk. According to the findings of the USPSTF, the balance of benefits and harms of aspirin use is contingent on 4 factors: age, baseline CVD risk, risk for bleeding, and preferences about taking aspirin.⁶ The complete recommendations from the USPSTF, along with other leading organizations, are outlined in TABLE 2.^6,28-31

Applying the evidence and varying guidelines in practice can feel daunting. Some practical tools have been developed to help clinicians understand patients’ bleeding risk and potential benefits with aspirin use. One such tool is highlighted below. Others are also available, and each has its own strengths and weaknesses.

Aspirin-Guide (www.aspiringuide.com) is a Web-based clinical decision support tool with an associated mobile application. It uses internal calculators (including the pooled cohort calculator prepared jointly by the American College of Cardiology and the American Heart Association) to assess CVD risk as well as bleeding risk. This tool gives clinicians patient-specific numbers-needed-to-treat and numbers-needed-to-harm when considering starting aspirin for primary prevention. It gives specific recommendations for aspirin use based on the data entered, and it also gives providers information to help guide shared decision-making with patients.³² Unfortunately, this decision support tool and others do not take into account the data from the most recent trials, so they should be used with caution.

CORRESPONDENCE
LCDR Dustin K. Smith, DO, Naval Branch Clinic Diego Garcia, PSC 466, Box 301, FPO, AP 96595; dustinksmith@yahoo.com.

Which patients are likely to benefit from using aspirin for primary prevention? In this article, we review the evidence to date, summarized for primary care settings in guidelines issued by the US Preventive Services Task Force (USPSTF). We supplement this summary with a rundown of the risks associated with aspirin use. And then we wrap up by identifying a clinical decision tool that is available to help make personalized decisions in a busy clinic setting, where determining an individual’s potential cardiovascular benefits and bleeding risk can be challenging.

The “roadmap” from the guidelines. In 2014, after performing a review of the literature, the US Food and Drug Administration recommended against the routine use of aspirin for primary prevention of cardiovascular disease (CVD).¹ In 2016, the USPSTF published 4 separate systematic reviews along with a decision analysis using a microsimulation model, which informed their position statement on aspirin for primary prevention.^2-6 These USPSTF reviews and recommendations incorporated both CVD and colorectal cancer (CRC) benefits with the bleeding risks from aspirin. Generally, for individuals 50 to 59 years old, the benefits are deemed to outweigh the harms; shared decision making is advised with those 60 to 69 years of age. For patients younger than 50 or 70 and older, evidence is inconclusive.

The benefits of primary prevention with aspirin

Cardiovascular disease

The Antithrombotic Trialists’ (ATT) Collaboration was one of the first meta-analyses that addressed the benefit-to-harm balance and called into question the routine use of aspirin for primary prevention.⁷ The USPSTF systematic review included the studies from the ATT Collaboration as well as trials performed after its publication, bringing the total number of eligible randomized controlled trials reviewed to 11.²

The benefit of aspirin for primary prevention of nonfatal myocardial infarction (MI) has been shown in multiple randomized controlled trials. The USPSTF systematic review showed a statistically significant relative risk reduction of 17% in patients taking low-dose aspirin (≤ 100 mg; relative risk [RR] = 0.83; confidence interval [95% CI], 0.74-0.94), although the heterogeneity of the studies was high. The same low dose of aspirin showed a statistically significant reduction in nonfatal stroke (RR = 0.86; 95% CI, 0.76-0.98), although the same benefit was not observed when all doses of aspirin were included. Cardiovascular disease mortality and all-cause mortality were not statistically different for patients taking low-dose aspirin when compared with placebo (RR = 0.97; 95% CI, 0.85-1.10 for CVD mortality; RR = 0.95; 95% CI, 0.89-1.01 for all-cause mortality).²

One study of more than 14,000 older (≥ 60 years) Japanese patients showed a statistically significant reduction in nonfatal MI (hazard ratio [HR] = 0.53; 95% CI, 0.31-0.91, P = .02) and nonfatal strokes (HR = 0.57; 95% CI, 0.32-0.99; P = .04). The study was stopped early because at 5 years of follow-up there was no statistically significant difference in a composite primary outcome, which included death from cardiovascular causes, nonfatal MI, and nonfatal stroke (HR = 0.94; 95% CI, 0.77-1.15; P = .54).⁸

Preventive benefits of aspirin outweigh risks for those 50-59 years of age who have a 10-year cardiovascular disease risk of ≥ 10%.

Several recent landmark studies have called into question the benefit of aspirin for cardiovascular primary prevention, especially in obese individuals, patients with diabetes, and the elderly. A meta-analysis of 10 trials showed that the effectiveness of aspirin doses between 75 mg and 100 mg for primary prevention decreased as weight increased; patients weighing 70 kg or more received no benefit.⁹ The ASCEND (A Study of Cardiovascular Events in Diabetes) trial included more than 15,000 patients with diabetes but no cardiovascular disease. Patients randomized to receive the low-dose aspirin did have fewer serious vascular events (incidence rate ratio [IRR] = 0.88; 95% CI, 0.79-0.97; P = .01), but they also had high risk of major bleeding events (IRR = 1.29; 95% CI, 1.09-1.52; P = .003).¹⁰ The ASPREE (Aspirin in Reducing Events in the Elderly) trial included more than 19,000 patients ages 70 years and older with no cardiovascular disease and compared low-dose aspirin to placebo. There was no statistically significant cardiovascular benefit, although there was an increase of major hemorrhage (HR = 1.38; 95% CI, 1.18-1.62; P < .001).¹¹ The ARRIVE (A Randomized Trial of Induction Versus Expectant Management) trial included 12,546 moderate atherosclerotic CVD (ASCVD) risk patients. Although a per-protocol analysis showed a decrease in rates of fatal and nonfatal MI (HR = 0.53; 95% CI, 0.36-0.79; P = .0014), the more reliable intention-to-treat analysis showed no improvement for any outcomes.¹²

[polldaddy:10286821]

Colorectal cancer

The literature base on prevention of cancer has been growing rapidly. However, the deluge of findings over the past 2 decades of trials and analyses has also introduced ambiguity and, often, conflicting results. The first journal article suggesting aspirin for primary prevention of cancer, published in 1988, was a case-control study wherein a population with CRC was matched to controls to look for potential protective factors.¹³ The most notable finding was the CRC risk reduction for those taking aspirin or aspirin-containing medications. Since then numerous studies and analyses have explored aspirin’s potential in primary prevention of many types of cancer, with overall unclear findings as denoted in the 2016 USPSTF systemic reviews and recommendations.

Continue to: One major limiting factor...

One major limiting factor is that most data come from CVD prevention trials, and only a limited number of trials have focused specifically on cancer prevention. For the USPSTF, these data showed no statistically significant risk reduction in overall cancer mortality (RR = 0.96; 95% CI, 0.87-1.06) or in total cancer incidence (RR = 0.98; 95% CI, 0.93-1.04).⁴ Other ongoing trials may yield more definitive data.¹⁴

The particular interest in CRC was due to it being the first cancer found to be preventable with aspirin therapy. The USPSTF, while acknowledging the homogeneous nature of supporting studies, noted that their significant number and resulting evidence made CRC the only cancer warranting evaluation. Population studies have now shown more benefit than the few randomized control trials. The Women’s Health Study and the Physicians’ Health Study were both limited by their duration. But such studies conducted over a longer period revealed notable benefits in the second decade of use, with a statistically significant lower CRC incidence (RR = 0.60; 95% CI, 0.47-0.76). Additionally, CRC mortality at 20 years was decreased in patients taking aspirin regularly (RR = 0.67; 95% CI, 0.52-0.86).⁴ Multiple studies are in progress to better establish aspirin’s CRC benefit.

While not directly applicable to the general population, use of aspirin for patients with Lynch syndrome to prevent CRC has strong supporting evidence.¹⁵ Beyond CRC, there is nascent evidence from limited observational studies that aspirin may have a preventive effect on melanoma and ovarian and pancreatic cancers.^16-18 Further studies or compilations of data would be needed to draw more significant conclusions on other types of cancers. Larger studies would prove more difficult to do, given the smaller incidences of these cancers.

Interestingly, a recent study showed that for individuals 70 years and older, aspirin might increase the risk for all-cause mortality, primarily due to increased cancer mortality across all types.¹⁹ Although this result was unexpected, caution should be used when prescribing aspirin particularly for patients 70 or older with active cancer.

A look at the harms associated with aspirin use

Aspirin has long been known to cause clinically significant bleeding. Aspirin inhibits platelet-derived cyclooxygenase-1 (COX-1), a potent vasoconstrictor, and thereby decreases platelet aggregation, reducing thromboembolic potential and prolonging bleeding time. These effects can confer health benefits but also carry the potential for risks. A decision to initiate aspirin therapy for primary prevention relies on an understanding of the benefit-to-harm balance.

Continue to: Initial aspirin studies...

Initial aspirin studies did not show a statistically significant increase in bleeding, likely due to too few events and inadequate powering. Subsequent meta-analyses from multiple evaluations have consistently shown bleeding to be a risk.^3,7 The risk for bleeding with aspirin has also been examined in multiple cohort studies, which has helped elucidate the risk in greater detail.

Gastrointestinal bleeding

Epidemiologic data show that among patients who do not use nonsteroidal anti-inflammatory drugs (NSAIDs), the rate of upper gastrointestinal (GI) complications is 1 case per 1000 patient-years.²⁰ Multiple studies have consistently shown that aspirin use increases the rate of significant upper GI bleeding over baseline risk (odds ratio [OR] = 1.54-1.58).^3,21,22 Interestingly, these increases seem not to be influenced by other factors, such as comorbidities that increase the risk for ASCVD. Analysis of cancer prevention studies showed similar epidemiologic trends, with aspirin use exceeding a baseline bleeding risk of 0.7 cases of upper GI complications per 1000 patient-years (OR = 1.31-1.73).²³

Other risk factors. Evaluation of risk factors for bleeding primarily comes from 2 studies.^3,7 Most data concern the impact of individual factors on significant GI bleeding, with fewer data available for evaluating risk for intracerebral hemorrhage (ICH). Initial analysis of individual prospective studies showed little or no correlation between risk for bleeding and such factors as gender, age, or history of hypertension or ASCVD.²¹ Subsequent analysis of meta-data and large cohorts did show statistically significant impact on rates of bleeding across several factors (TABLE 1^3,7).

Enteric coating on aspirin does appear to lower the rates of gastric mucosal injury.

Of note is a large heterogeneous cohort study conducted in Spain. Data showed significant increases in baseline risk for GI bleeding in older men with a history of GI bleeding and NSAID use. The absolute risk for GI bleed in this group was potentially as high as 150 cases per 1000 patient-years, well above the risk level assumed for the average patient.²⁴ A seemingly small OR of 1.5 could dramatically increase the absolute risk for bleeding in such patients, and it suggests that a generalized risk for bleeding probably shouldn’t be applied to all patients. Individuals may be better served by a baseline risk calculation reflecting multiple factors.

Intracerebral hemorrhage

Due to the comparatively uncommon nature of ICH, fewer data are available to support definitive conclusions about its increased risk with aspirin use. Aspirin use appeared to increase the risk for ICH with ratios between 1.27 and 1.32 in meta-analyses (measured as an OR or as an RR),^3,7,21 with an IRR of 1.54 in a cohort study.²² The only statistically significant factors suspected to increase the risk of ICH at baseline were smoking (RR = 2.18) and mean BP > 20 mm Hg over normal (OR = 2.18). Age, gender, and diabetes all showed a nonsignificant trend toward risk increase.⁷

Continue to: Risk based on dose and formulation

 

 

Risk based on dose and formulation

The effect of aspirin dose and formulation on bleeding risk is uncertain. Some studies have shown an increased risk for bleeding with daily doses of aspirin ≥ 300 mg, while others have shown no significant increase in rates for bleeding with differing doses.^21,25 Enteric coating does appear to lower the rates of gastric mucosal injury, although there are few data on the effect toward reducing clinically significant bleeding.²⁶ Currently, several prospective studies are underway to help clarify the evidence.²⁷

Putting it all together

For the general population, the evidence shows that the benefits and harms of aspirin for primary prevention are relatively even. The USPSTF guidelines are the first to recommend aspirin for both CVD and cancer prevention while taking into account the bleeding risk. According to the findings of the USPSTF, the balance of benefits and harms of aspirin use is contingent on 4 factors: age, baseline CVD risk, risk for bleeding, and preferences about taking aspirin.⁶ The complete recommendations from the USPSTF, along with other leading organizations, are outlined in TABLE 2.^6,28-31

Applying the evidence and varying guidelines in practice can feel daunting. Some practical tools have been developed to help clinicians understand patients’ bleeding risk and potential benefits with aspirin use. One such tool is highlighted below. Others are also available, and each has its own strengths and weaknesses.

Aspirin-Guide (www.aspiringuide.com) is a Web-based clinical decision support tool with an associated mobile application. It uses internal calculators (including the pooled cohort calculator prepared jointly by the American College of Cardiology and the American Heart Association) to assess CVD risk as well as bleeding risk. This tool gives clinicians patient-specific numbers-needed-to-treat and numbers-needed-to-harm when considering starting aspirin for primary prevention. It gives specific recommendations for aspirin use based on the data entered, and it also gives providers information to help guide shared decision-making with patients.³² Unfortunately, this decision support tool and others do not take into account the data from the most recent trials, so they should be used with caution.

CORRESPONDENCE
LCDR Dustin K. Smith, DO, Naval Branch Clinic Diego Garcia, PSC 466, Box 301, FPO, AP 96595; dustinksmith@yahoo.com.

Which patients are likely to benefit from using aspirin for primary prevention? In this article, we review the evidence to date, summarized for primary care settings in guidelines issued by the US Preventive Services Task Force (USPSTF). We supplement this summary with a rundown of the risks associated with aspirin use. And then we wrap up by identifying a clinical decision tool that is available to help make personalized decisions in a busy clinic setting, where determining an individual’s potential cardiovascular benefits and bleeding risk can be challenging.

The “roadmap” from the guidelines. In 2014, after performing a review of the literature, the US Food and Drug Administration recommended against the routine use of aspirin for primary prevention of cardiovascular disease (CVD).¹ In 2016, the USPSTF published 4 separate systematic reviews along with a decision analysis using a microsimulation model, which informed their position statement on aspirin for primary prevention.^2-6 These USPSTF reviews and recommendations incorporated both CVD and colorectal cancer (CRC) benefits with the bleeding risks from aspirin. Generally, for individuals 50 to 59 years old, the benefits are deemed to outweigh the harms; shared decision making is advised with those 60 to 69 years of age. For patients younger than 50 or 70 and older, evidence is inconclusive.

The benefits of primary prevention with aspirin

Cardiovascular disease

The Antithrombotic Trialists’ (ATT) Collaboration was one of the first meta-analyses that addressed the benefit-to-harm balance and called into question the routine use of aspirin for primary prevention.⁷ The USPSTF systematic review included the studies from the ATT Collaboration as well as trials performed after its publication, bringing the total number of eligible randomized controlled trials reviewed to 11.²

The benefit of aspirin for primary prevention of nonfatal myocardial infarction (MI) has been shown in multiple randomized controlled trials. The USPSTF systematic review showed a statistically significant relative risk reduction of 17% in patients taking low-dose aspirin (≤ 100 mg; relative risk [RR] = 0.83; confidence interval [95% CI], 0.74-0.94), although the heterogeneity of the studies was high. The same low dose of aspirin showed a statistically significant reduction in nonfatal stroke (RR = 0.86; 95% CI, 0.76-0.98), although the same benefit was not observed when all doses of aspirin were included. Cardiovascular disease mortality and all-cause mortality were not statistically different for patients taking low-dose aspirin when compared with placebo (RR = 0.97; 95% CI, 0.85-1.10 for CVD mortality; RR = 0.95; 95% CI, 0.89-1.01 for all-cause mortality).²

One study of more than 14,000 older (≥ 60 years) Japanese patients showed a statistically significant reduction in nonfatal MI (hazard ratio [HR] = 0.53; 95% CI, 0.31-0.91, P = .02) and nonfatal strokes (HR = 0.57; 95% CI, 0.32-0.99; P = .04). The study was stopped early because at 5 years of follow-up there was no statistically significant difference in a composite primary outcome, which included death from cardiovascular causes, nonfatal MI, and nonfatal stroke (HR = 0.94; 95% CI, 0.77-1.15; P = .54).⁸

Preventive benefits of aspirin outweigh risks for those 50-59 years of age who have a 10-year cardiovascular disease risk of ≥ 10%.

Several recent landmark studies have called into question the benefit of aspirin for cardiovascular primary prevention, especially in obese individuals, patients with diabetes, and the elderly. A meta-analysis of 10 trials showed that the effectiveness of aspirin doses between 75 mg and 100 mg for primary prevention decreased as weight increased; patients weighing 70 kg or more received no benefit.⁹ The ASCEND (A Study of Cardiovascular Events in Diabetes) trial included more than 15,000 patients with diabetes but no cardiovascular disease. Patients randomized to receive the low-dose aspirin did have fewer serious vascular events (incidence rate ratio [IRR] = 0.88; 95% CI, 0.79-0.97; P = .01), but they also had high risk of major bleeding events (IRR = 1.29; 95% CI, 1.09-1.52; P = .003).¹⁰ The ASPREE (Aspirin in Reducing Events in the Elderly) trial included more than 19,000 patients ages 70 years and older with no cardiovascular disease and compared low-dose aspirin to placebo. There was no statistically significant cardiovascular benefit, although there was an increase of major hemorrhage (HR = 1.38; 95% CI, 1.18-1.62; P < .001).¹¹ The ARRIVE (A Randomized Trial of Induction Versus Expectant Management) trial included 12,546 moderate atherosclerotic CVD (ASCVD) risk patients. Although a per-protocol analysis showed a decrease in rates of fatal and nonfatal MI (HR = 0.53; 95% CI, 0.36-0.79; P = .0014), the more reliable intention-to-treat analysis showed no improvement for any outcomes.¹²

[polldaddy:10286821]

Colorectal cancer

The literature base on prevention of cancer has been growing rapidly. However, the deluge of findings over the past 2 decades of trials and analyses has also introduced ambiguity and, often, conflicting results. The first journal article suggesting aspirin for primary prevention of cancer, published in 1988, was a case-control study wherein a population with CRC was matched to controls to look for potential protective factors.¹³ The most notable finding was the CRC risk reduction for those taking aspirin or aspirin-containing medications. Since then numerous studies and analyses have explored aspirin’s potential in primary prevention of many types of cancer, with overall unclear findings as denoted in the 2016 USPSTF systemic reviews and recommendations.

Continue to: One major limiting factor...

One major limiting factor is that most data come from CVD prevention trials, and only a limited number of trials have focused specifically on cancer prevention. For the USPSTF, these data showed no statistically significant risk reduction in overall cancer mortality (RR = 0.96; 95% CI, 0.87-1.06) or in total cancer incidence (RR = 0.98; 95% CI, 0.93-1.04).⁴ Other ongoing trials may yield more definitive data.¹⁴

The particular interest in CRC was due to it being the first cancer found to be preventable with aspirin therapy. The USPSTF, while acknowledging the homogeneous nature of supporting studies, noted that their significant number and resulting evidence made CRC the only cancer warranting evaluation. Population studies have now shown more benefit than the few randomized control trials. The Women’s Health Study and the Physicians’ Health Study were both limited by their duration. But such studies conducted over a longer period revealed notable benefits in the second decade of use, with a statistically significant lower CRC incidence (RR = 0.60; 95% CI, 0.47-0.76). Additionally, CRC mortality at 20 years was decreased in patients taking aspirin regularly (RR = 0.67; 95% CI, 0.52-0.86).⁴ Multiple studies are in progress to better establish aspirin’s CRC benefit.

While not directly applicable to the general population, use of aspirin for patients with Lynch syndrome to prevent CRC has strong supporting evidence.¹⁵ Beyond CRC, there is nascent evidence from limited observational studies that aspirin may have a preventive effect on melanoma and ovarian and pancreatic cancers.^16-18 Further studies or compilations of data would be needed to draw more significant conclusions on other types of cancers. Larger studies would prove more difficult to do, given the smaller incidences of these cancers.

Interestingly, a recent study showed that for individuals 70 years and older, aspirin might increase the risk for all-cause mortality, primarily due to increased cancer mortality across all types.¹⁹ Although this result was unexpected, caution should be used when prescribing aspirin particularly for patients 70 or older with active cancer.

A look at the harms associated with aspirin use

Aspirin has long been known to cause clinically significant bleeding. Aspirin inhibits platelet-derived cyclooxygenase-1 (COX-1), a potent vasoconstrictor, and thereby decreases platelet aggregation, reducing thromboembolic potential and prolonging bleeding time. These effects can confer health benefits but also carry the potential for risks. A decision to initiate aspirin therapy for primary prevention relies on an understanding of the benefit-to-harm balance.

Continue to: Initial aspirin studies...

Initial aspirin studies did not show a statistically significant increase in bleeding, likely due to too few events and inadequate powering. Subsequent meta-analyses from multiple evaluations have consistently shown bleeding to be a risk.^3,7 The risk for bleeding with aspirin has also been examined in multiple cohort studies, which has helped elucidate the risk in greater detail.

Gastrointestinal bleeding

Epidemiologic data show that among patients who do not use nonsteroidal anti-inflammatory drugs (NSAIDs), the rate of upper gastrointestinal (GI) complications is 1 case per 1000 patient-years.²⁰ Multiple studies have consistently shown that aspirin use increases the rate of significant upper GI bleeding over baseline risk (odds ratio [OR] = 1.54-1.58).^3,21,22 Interestingly, these increases seem not to be influenced by other factors, such as comorbidities that increase the risk for ASCVD. Analysis of cancer prevention studies showed similar epidemiologic trends, with aspirin use exceeding a baseline bleeding risk of 0.7 cases of upper GI complications per 1000 patient-years (OR = 1.31-1.73).²³

Other risk factors. Evaluation of risk factors for bleeding primarily comes from 2 studies.^3,7 Most data concern the impact of individual factors on significant GI bleeding, with fewer data available for evaluating risk for intracerebral hemorrhage (ICH). Initial analysis of individual prospective studies showed little or no correlation between risk for bleeding and such factors as gender, age, or history of hypertension or ASCVD.²¹ Subsequent analysis of meta-data and large cohorts did show statistically significant impact on rates of bleeding across several factors (TABLE 1^3,7).

Enteric coating on aspirin does appear to lower the rates of gastric mucosal injury.

Of note is a large heterogeneous cohort study conducted in Spain. Data showed significant increases in baseline risk for GI bleeding in older men with a history of GI bleeding and NSAID use. The absolute risk for GI bleed in this group was potentially as high as 150 cases per 1000 patient-years, well above the risk level assumed for the average patient.²⁴ A seemingly small OR of 1.5 could dramatically increase the absolute risk for bleeding in such patients, and it suggests that a generalized risk for bleeding probably shouldn’t be applied to all patients. Individuals may be better served by a baseline risk calculation reflecting multiple factors.

Intracerebral hemorrhage

Due to the comparatively uncommon nature of ICH, fewer data are available to support definitive conclusions about its increased risk with aspirin use. Aspirin use appeared to increase the risk for ICH with ratios between 1.27 and 1.32 in meta-analyses (measured as an OR or as an RR),^3,7,21 with an IRR of 1.54 in a cohort study.²² The only statistically significant factors suspected to increase the risk of ICH at baseline were smoking (RR = 2.18) and mean BP > 20 mm Hg over normal (OR = 2.18). Age, gender, and diabetes all showed a nonsignificant trend toward risk increase.⁷

Continue to: Risk based on dose and formulation

 

 

Risk based on dose and formulation

The effect of aspirin dose and formulation on bleeding risk is uncertain. Some studies have shown an increased risk for bleeding with daily doses of aspirin ≥ 300 mg, while others have shown no significant increase in rates for bleeding with differing doses.^21,25 Enteric coating does appear to lower the rates of gastric mucosal injury, although there are few data on the effect toward reducing clinically significant bleeding.²⁶ Currently, several prospective studies are underway to help clarify the evidence.²⁷

Putting it all together

For the general population, the evidence shows that the benefits and harms of aspirin for primary prevention are relatively even. The USPSTF guidelines are the first to recommend aspirin for both CVD and cancer prevention while taking into account the bleeding risk. According to the findings of the USPSTF, the balance of benefits and harms of aspirin use is contingent on 4 factors: age, baseline CVD risk, risk for bleeding, and preferences about taking aspirin.⁶ The complete recommendations from the USPSTF, along with other leading organizations, are outlined in TABLE 2.^6,28-31

Applying the evidence and varying guidelines in practice can feel daunting. Some practical tools have been developed to help clinicians understand patients’ bleeding risk and potential benefits with aspirin use. One such tool is highlighted below. Others are also available, and each has its own strengths and weaknesses.

Aspirin-Guide (www.aspiringuide.com) is a Web-based clinical decision support tool with an associated mobile application. It uses internal calculators (including the pooled cohort calculator prepared jointly by the American College of Cardiology and the American Heart Association) to assess CVD risk as well as bleeding risk. This tool gives clinicians patient-specific numbers-needed-to-treat and numbers-needed-to-harm when considering starting aspirin for primary prevention. It gives specific recommendations for aspirin use based on the data entered, and it also gives providers information to help guide shared decision-making with patients.³² Unfortunately, this decision support tool and others do not take into account the data from the most recent trials, so they should be used with caution.

CORRESPONDENCE
LCDR Dustin K. Smith, DO, Naval Branch Clinic Diego Garcia, PSC 466, Box 301, FPO, AP 96595; dustinksmith@yahoo.com.

Clinical Presentation

Millipedes secrete a noxious toxin implicated in millipede burns. The toxic substance is benzoquinone, a strong irritant secreted from the repugnatorial glands contained in each segment of the arthropod (Figure 1). This compound serves as a natural insect repellant, acting as the millipede’s defense mechanism from potential predators.¹ On human skin, benzoquinone causes localized pigmentary changes most commonly presenting on the feet and toes. Local lesions may be associated with pain or burning, but there are no known reports of adverse systemic effects.² Affected patients experience cutaneous pigmentary changes, which may be dark red, blue, or black, and spontaneously resolve over time.² The degree of pigment change may be associated with duration of skin contact with the toxin. The affected areas may resemble burns, dermatitis, or skin necrosis. More distal lesions may present similarly to blue toe syndrome or acute arterial occlusion but can be differentiated by the presence of intact peripheral pulses and lack of temperature discrepancy between the feet.^3,4 Histologic evaluation of the lesions generally reveals nonspecific full-thickness epidermal necrosis, making clinical suspicion and physical examination paramount to the diagnosis of millipede burns.⁵

Diagnostic Difficulties

Accurate diagnosis of millipede burns is more difficult when the burn involves an unusual site. The most common site of involvement is the foot (Figure 2), followed by other commonly exposed areas such as the arms, face, and eyes.^2,3,6,7 Covered parts of the body are much less commonly affected, requiring the arthropod to gain access via infiltration of clothing, often when hanging on a clothesline. In these cases, burns may be mistaken for child abuse, especially if certain areas of the body are involved, such as the groin and genitals.² The well-defined arcuate lesions of the burns may resemble injuries from a wire or belt to the unsuspecting observer.

Conclusion

Although millipedes often are regarded as harmless, they are capable of causing adverse reactions through the secretion of toxic chemicals. Millipede burns cause localized pigmentary changes that may be associated with pain or burning in some patients. Because these burns may resemble child abuse in pediatric patients, physicians should be aware of this diagnosis when unusual parts of the body are involved.

Clinical Presentation

Millipedes secrete a noxious toxin implicated in millipede burns. The toxic substance is benzoquinone, a strong irritant secreted from the repugnatorial glands contained in each segment of the arthropod (Figure 1). This compound serves as a natural insect repellant, acting as the millipede’s defense mechanism from potential predators.¹ On human skin, benzoquinone causes localized pigmentary changes most commonly presenting on the feet and toes. Local lesions may be associated with pain or burning, but there are no known reports of adverse systemic effects.² Affected patients experience cutaneous pigmentary changes, which may be dark red, blue, or black, and spontaneously resolve over time.² The degree of pigment change may be associated with duration of skin contact with the toxin. The affected areas may resemble burns, dermatitis, or skin necrosis. More distal lesions may present similarly to blue toe syndrome or acute arterial occlusion but can be differentiated by the presence of intact peripheral pulses and lack of temperature discrepancy between the feet.^3,4 Histologic evaluation of the lesions generally reveals nonspecific full-thickness epidermal necrosis, making clinical suspicion and physical examination paramount to the diagnosis of millipede burns.⁵

Diagnostic Difficulties

Accurate diagnosis of millipede burns is more difficult when the burn involves an unusual site. The most common site of involvement is the foot (Figure 2), followed by other commonly exposed areas such as the arms, face, and eyes.^2,3,6,7 Covered parts of the body are much less commonly affected, requiring the arthropod to gain access via infiltration of clothing, often when hanging on a clothesline. In these cases, burns may be mistaken for child abuse, especially if certain areas of the body are involved, such as the groin and genitals.² The well-defined arcuate lesions of the burns may resemble injuries from a wire or belt to the unsuspecting observer.

Conclusion

Although millipedes often are regarded as harmless, they are capable of causing adverse reactions through the secretion of toxic chemicals. Millipede burns cause localized pigmentary changes that may be associated with pain or burning in some patients. Because these burns may resemble child abuse in pediatric patients, physicians should be aware of this diagnosis when unusual parts of the body are involved.

Clinical Presentation

Millipedes secrete a noxious toxin implicated in millipede burns. The toxic substance is benzoquinone, a strong irritant secreted from the repugnatorial glands contained in each segment of the arthropod (Figure 1). This compound serves as a natural insect repellant, acting as the millipede’s defense mechanism from potential predators.¹ On human skin, benzoquinone causes localized pigmentary changes most commonly presenting on the feet and toes. Local lesions may be associated with pain or burning, but there are no known reports of adverse systemic effects.² Affected patients experience cutaneous pigmentary changes, which may be dark red, blue, or black, and spontaneously resolve over time.² The degree of pigment change may be associated with duration of skin contact with the toxin. The affected areas may resemble burns, dermatitis, or skin necrosis. More distal lesions may present similarly to blue toe syndrome or acute arterial occlusion but can be differentiated by the presence of intact peripheral pulses and lack of temperature discrepancy between the feet.^3,4 Histologic evaluation of the lesions generally reveals nonspecific full-thickness epidermal necrosis, making clinical suspicion and physical examination paramount to the diagnosis of millipede burns.⁵

Diagnostic Difficulties

Accurate diagnosis of millipede burns is more difficult when the burn involves an unusual site. The most common site of involvement is the foot (Figure 2), followed by other commonly exposed areas such as the arms, face, and eyes.^2,3,6,7 Covered parts of the body are much less commonly affected, requiring the arthropod to gain access via infiltration of clothing, often when hanging on a clothesline. In these cases, burns may be mistaken for child abuse, especially if certain areas of the body are involved, such as the groin and genitals.² The well-defined arcuate lesions of the burns may resemble injuries from a wire or belt to the unsuspecting observer.

Conclusion

Although millipedes often are regarded as harmless, they are capable of causing adverse reactions through the secretion of toxic chemicals. Millipede burns cause localized pigmentary changes that may be associated with pain or burning in some patients. Because these burns may resemble child abuse in pediatric patients, physicians should be aware of this diagnosis when unusual parts of the body are involved.

Intimate partner violence (IPV) is a serious public health problem with considerable harmful health consequences. Decades of research have been dedicated to improving the identification of women in abusive heterosexual relationships and interventions that support healthier outcomes. A result of this work has been the recommendation of the US Preventive Services Task Force that all women of childbearing age be screened for IPV and provided with intervention or referral.¹

The problem extends further, however: Epidemiologic studies and comprehensive reviews show: 1) a high rate of IPV victimization among heterosexual men and lesbian, gay, bisexual, and transsexual (LGBT) men and women^2,3; 2) significant harmful effects on health and greater expectations of prejudice and discrimination among these populations^4-6; and 3) evidence that screening and referral for IPV are likely to confer similar benefits for these populations.⁷ We argue that it is reasonable to ask all patients about abuse in their relationships while the research literature progresses.

We intend this article to serve a number of purposes:

• support national standards for IPV screening of female patients
• highlight the need for piloting universal IPV screening for all patients (ie, male and female, across the lifespan)
• offer recommendations for navigating the process from IPV screening to referral, using insights gained from the substance abuse literature.

We also provide supplemental materials that facilitate establishment of screening and referral protocols for physicians across practice settings.

© Joe Gorman

What is intimate partner violence? How can you identify it?

Intimate partner violence includes physical and sexual violence and nonphysical forms of abuse, such as psychological aggression and emotional abuse, perpetrated by a current or former intimate partner.⁸ TABLE 1^9-14 provides definitions for each of these behavior categories and example behaviors. Nearly 25% of women and 20% of men report having experienced physical violence from a romantic partner and even higher rates of nonphysical IPV.¹⁵ Consequences of IPV victimization include acute and chronic medical illness, injury, and psychological problems, including depression, anxiety, and poor self-esteem.¹⁶

Intimate partner violence is heterogenous, with differences in severity (eg, frequency and intensity of violence) and laterality (ie, is one partner violent? are both partners violent?).

Intimate partner violence is heterogeneous, with differences in severity (eg, frequency and intensity of violence) and laterality (ie, is one partner violent? are both partners violent?). A recent comprehensive review of the literature revealed that, for 49.2%-69.7% of partner-violent couples across diverse samples, IPV is perpetrated by both partners.¹⁷ Furthermore, this bidirectionality is not due entirely to aggression perpetrated in self-defense; rather, across diverse patient samples, that is the case for fewer than one-quarter of males and no more than approximately one-third of females.¹⁸ In the remaining cases, bidirectionality may be attributed to other motivations, such as a maladaptive emotional expression or a means by which to get a partner’s attention.¹⁸

Women are disproportionately susceptible to harmful outcomes as a result of severe violence, including physical injury, psychological distress (eg, depression and anxiety), and substance abuse.^16,19 Some patients in unidirectionally violent relationships experience severe physical violence that may be, or become, life-threatening (0.4%-2.4% of couples in community samples)²⁰—victimization that is traditionally known as “battering.”²¹

Continue to: These tools can facilitate screening for IPV

These tools can facilitate screening for IPV

Physicians might have reservations asking about IPV because of 1) concern whether there is sufficient time during an office visit to interview, screen, and refer, 2) feelings of powerlessness to stop violence by or toward a patient, and 3) general discomfort with the topic.²² Additionally, mandated reporting laws regarding IPV vary by state, making it crucial to know one’s own state laws on this issue to protect the safety of the patient and those around them.

Screening increases the likelihood of engaging the patient in supportive services, thus decreasing the isolation that is typical of abuse.

Research has shown that some patients prefer that their health care providers ask about relationship violence directly²³; others are more willing to acknowledge IPV if asked using a paper-and-pencil measure, rather than face-to-face questions.²⁴ Either way, screening increases the likelihood of engaging the patient in supportive services, thus decreasing the isolation that is typical of abuse.²⁵ Based on this research, screening that utilizes face-valid items embedded within paperwork completed in the waiting room is recommended as an important first step toward identifying and helping patients who are experiencing IPV. Even under these conditions, however, heterosexual men and sexual minorities might be less willing than heterosexual women to admit experiencing IPV.^26,27

A brief vignette that depicts how quickly the screening and referral process can be applied is presented in “IPV screening and referral: A real-world vignette." The vignette is a de-identified composite of heterosexual men experiencing IPV whom we have counseled.

One model that provides a useful framework for IPV assessment is the Screening, Brief Intervention, and Referral to Treatment (SBIRT) model, which was developed to facilitate assessment of, and referral for, substance abuse—another heavily stigmatized health care problem. The SBIRT approach for substance abuse screening is associated with significant reduction in alcohol and drug abuse 6 months postintervention, as well as improvements in well-being, mental health, and functioning across gender, race and ethnicity, and age.²⁸

IPASSPRT. Inspired by the SBIRT model for substance abuse, we created the Intimate Partner Aggression Screening, Safety Planning, and Referral to Treatment, or IPASSPRT (spoken as “i-passport”) project to provide tools that make IPV screening and referral accessible to a range of health care providers. These tools include a script and safety plan that guide providers through screening, safety planning, and referral in a manner that is collaborative and grounded in the spirit of motivational interviewing. We have made these tools available on the Web for ease of distribution (http://bit.ly/ipassprt; open by linking through “IPASSPRT-Script”).

Continue to: The IPASSPRT script appears lengthy...

The IPASSPRT script appears lengthy, but progress through its sections is directed by patient need; most patients will not require that all parts be completed. For example, a patient whose screen for IPV is negative and who feels safe in their relationship does not need assessment beyond page 2; on the other hand, the physician might need more information from a patient who is at greater risk for IPV. This response-based progression through the script makes the screening process dynamic, data-driven, and tailored to the patient’s needs—an approach that aids rapport and optimizes the physician’s limited time during the appointment.

In the sections that follow, we describe key components of this script.

What aggression, if any, is present? From whom? The Hurt, Insult, Threaten, and Scream inventory (HITS) (TABLE 2)²⁹ is a widely used screen for IPV that has been validated for use in family medicine. A 4-item scale asks patients to report how often their partner physically hurts, insults, threatens, and screams at them using a 5-point scale (1 point, “never,” to 5 points, “frequently”). Although a score > 10 is indicative of IPV, item-level analysis is encouraged. Attending to which items the patient acknowledges and how often these behaviors occur yields a richer assessment than a summary score. In regard to simply asking a patient, “Do you feel safe at home?” (sensitivity of this question, 8.8%; specificity, 91.2%), the HITS better detects IPV with male and female patient populations in family practice and emergency care settings (sensitivity, 30%-100%; specificity, 86%-99%).^27,30

What contextual factors and related concerns are present? It is important to understand proximal factors that might influence IPV risk to determine what kind of referral or treatment is appropriate—particularly for patients experiencing or engaging in infrequent, noninjurious, and bidirectional forms of IPV. Environmental and contextual stressors, such as financial hardship, unemployment, pregnancy, and discussion of divorce, can increase the risk for IPV.^31,32 Situational influences, such as alcohol and drug intoxication, can also increase the risk for IPV. Victims of partner violence are at greater risk for mental health problems, including depression, anxiety, trauma- and stressor-related disorders, and substance use disorders. Risk goes both ways, however: Mental illness predicts subsequent IPV perpetration or victimization, and vice versa.³¹

Does the patient feel safe? Assessing the situation. Patient perception of safety in the relationship provides important information about the necessity of referral. Asking a patient if they feel unsafe because of the behavior of a current or former partner sheds light on the need for further safety assessment and immediate connection with appropriate resources.

Continue to: The Danger Assessment-5...

The Danger Assessment-5 (DA-5) (TABLE 3³³) is a useful 5-item tool for quickly assessing the risk for severe IPV.³³ Patients respond to whether:

• the frequency or severity of violence has increased in the past year
• the partner has ever used, or threatened to use, a weapon
• the patient believes the partner is capable of killing her (him)
• the partner has ever tried to choke or strangle her (him)
• the partner is violently and constantly jealous.

Mental illness predicts subsequent IPV perpetration or victimization and vice versa.

Sensitivity and specificity analyses with a high-risk female sample suggested that 3 affirmative responses indicate a high risk for severe IPV and a need for adequate safety planning.

Brief motivational enhancement intervention. There are 3 components to this intervention.

• Assess interest in making changes or seeking help. IPV is paradoxical: Many factors complicate the decision to leave or stay, and patients across the spectrum of victimization might have some motivation to stay with their partner. It is important to assess the patient’s motivation to make changes in their relationship.^4,34
• Provide feedback on screening. Sharing the results of screening with patients makes the assessment and referral process collaborative and transparent; collaborative engagement helps patients feel in control and invested in the follow-through.³⁵ In the spirit of this endeavor, physicians are encouraged to refrain from providing raw or total scores from the measures; instead, share the interpretation of those scores, based on the participant’s responses to the screening items, in a matter-of-fact manner. At this point, elicit the patient’s response to this information, listen empathically, and answer questions before proceeding.

Consistent with screening for other serious health problems, we recommend that all patients be provided with information about abuse in romantic relationships. The National Center for Injury Prevention and Control Division of Violence Prevention has published a useful, easy-to-understand fact sheet (www.cdc.gov/violenceprevention/pdf/ipv-factsheet.pdf) that provides an overview of IPV-related behavior, how it influences health outcomes, who is at risk for IPV, and sources for support.

Continue to: Our IPASSPRT interview script...

Our IPASSPRT interview script (http://bit.ly/ipassprt) outlines how this information can be presented to patients as a typical part of the screening process. Providers are encouraged to share and review the information from the fact sheet with all patients and present it as part of the normal screening process to mitigate the potential for defensiveness on the part of the patient. For patients who screen positive for IPV, it might be important to brainstorm ideas for a safe, secure place to store this fact sheet and other resources from the brief intervention and referral process below (eg, a safety plan and specific referral information) so that the patient can access them quickly and easily, if needed.

For patients who screen negative for IPV, their screen and interview conclude at this point.

• Provide recommendations based on the screen. Evidence suggests that collaborating with the patient on safety planning and referral can increase the likelihood of their engagement.⁷ Furthermore, failure to tailor the referral to the needs of the patient can be detrimental³⁶—ie, overshooting the level of intervention might decrease the patient’s future treatment-seeking behavior and undermine their internal coping strategies, increasing the likelihood of future victimization. For that reason, we provide the following guidance on navigating the referral process for patients who screen positive for IPV.

Screening-based referral: A delicate and collaborative process

Referral for IPV victimization. Individual counseling, with or without an IPV focus, might be appropriate for patients at lower levels of risk; immediate connection with local IPV resources is strongly encouraged for patients at higher risk. This is a delicate, collaborative process, in which the physician offers recommendations for referral commensurate to the patient’s risk but must, ultimately, respect the patient’s autonomy by identifying referrals that fit the patient’s goals. We encourage providers to provide risk-informed recommendations and to elicit the patient’s thoughts about that information.

Several online resources are available to help physicians locate and connect with IPV-related resources in their community, including the National Health Resource Center on Domestic Violence (http://ipvhealth.org/), which provides a step-by-step guide to making such connections. We encourage physicians to develop these collaborative partnerships early to facilitate warm handoffs and increase the likelihood that a patient will follow through with the referral after screening.³⁷

Referral for related concerns. As we’ve noted, IPV has numerous physical and mental health consequences, including depression, low self-esteem, trauma- and non-trauma-related anxiety, and substance abuse. In general, cognitive behavioral therapies appear most efficacious for treating these IPV-related consequences, but evidence is limited that such interventions diminish the likelihood of re-victimization.³⁸ Intervention programs that foster problem-solving, solution-seeking, and cognitive restructuring for self-critical thoughts and misconceptions seem to produce the best physical and mental health outcomes.³⁹ For patients who have a substance use disorder, treatment programs that target substance use have demonstrated a reduction in the rate of IPV recidivism.⁴⁰ These findings indicate that establishing multiple treatment targets might reduce the risk for future aggression in relationships.

Continue to: The Substance Abuse and Mental Health Services Administration...

The Substance Abuse and Mental Health Services Administration of the US Department of Health and Human Services provides a useful online tool (https://findtreatment.samhsa.gov/) for locating local referrals that address behavioral health and substance-related concerns. The agency also provides a hotline (1-800-662-HELP [4357]) as an alternative resource for information and treatment referrals.

Safety planning can improve outcomes

For a patient who screens above low risk, safety planning with the patient is an important part of improving outcomes and can take several forms. Online resources, such as the Path to Safety interactive Web page (www.thehotline.org/help/path-to-safety/) maintained by The National Domestic Violence Hotline ([800]799-SAFE [7233]), provide information regarding important considerations for safety planning when:

• living with an abusive partner
• children are in the home
• the patient is pregnant
• pets are involved.

The Web site also provides information regarding legal options and resources related to IPV (eg, an order of protection) and steps for improving safety when leaving an abusive relationship. Patients at risk for IPV can explore the online tool and call the hotline.

For physicians who want to engage in provider-assisted safety planning, we’ve provided further guidance in the IPASSPRT screening script and safety plan (http://bit.ly/ipassprt) (TABLE 4).

Goal: Affirm patients’ strengths and reinforce hope

Psychological aggression is the most common form of relationship aggression; repeated denigration might leave a person with little confidence in their ability to change their relationship or seek out identified resources. That’s why it’s useful to inquire—with genuine curiosity—about a time in the past when the patient accomplished something challenging. The physician’s enthusiastic reflection on this achievement can be a means of highlighting the patient’s ability to accomplish a meaningful goal; of reinforcing their hope; and of eliciting important resources within and around the patient that can facilitate action on their safety plan. (See “IPV-related resources for physicians and patients.”)

Continue to: Closing the screen and making a referral

Closing the screen and making a referral

The end of the interview should consist of a summary of topics discussed, including:

• changes that the patient wants to make (if any)
• their stated reasons for making those changes
• the patient’s plan for accomplishing changes.

Physicians should also include their own role in next steps—whether providing a warm handoff to a local IPV referral, agreeing to a follow-up schedule with the patient, or making a call as a mandated reporter. To close out the interview, it is important to affirm respect for the patient’s autonomy in executing the plan.

It’s important to screen all patients—here’s why

A major impetus for this article has been to raise awareness about the need for expanded IPV screening across primary care settings. As mentioned, much of the literature on IPV victimization has focused on women; however, the few epidemiological investigations of victimization rates among men and members of LGBT couples show a high rate of victimization and considerable harmful health outcomes. Driven by stigma surrounding IPV, sex, and sexual minority status, patients might have expectations that they will be judged by a provider or “outed.”

Such barriers can lead many to suffer in silence until the problem can no longer be hidden or the danger becomes more emergent. Compassionate, nonjudgmental screening and collaborative safety planning—such as the approach we describe in this article—help ease the concerns of LGBT victims of IPV and improve the likelihood that conversations you have with them will occur earlier, rather than later, in care.*

Underassessment of IPV (ie, underreporting as well as under-inquiry) because of stigma, misconception, and other factors obscures an accurate estimate of the rate of partner violence and its consequences for all couples. As a consequence, we know little about the dynamics of IPV, best practices for screening, and appropriate referral for couples from these populations. Furthermore, few resources are available to these understudied and underserved groups (eg, shelters for men and for transgender people).

Continue to: Although our immediate approach to IPV screening...

Although our immediate approach to IPV screening, safety planning, and referral with understudied patient populations might be informed by what we have learned from the experiences of heterosexual women in abusive relationships, such a practice is unsustainable. Unless we expand our scope of screening to all patients, it is unlikely that we will develop the evidence base necessary to 1) warrant stronger IPV screening recommendations for patient groups apart from women of childbearing age, let alone 2) demonstrate the need for additional community resources, and 3) provide comprehensive care in family practice of comparable quality.

The benefits of screening go beyond the individual patient

Screening for violence in the relationship does not take long; the value of asking about its presence in a relationship might offer benefits beyond the individual patient by raising awareness and providing the field of study with more data to increase attention and resources for under-researched and underserved populations. Screening might also combat the stigma that perpetuates the silence of many who deserve access to care.

CORRESPONDENCE
Joel G. Sprunger, PhD, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, 260 Stetson St, Suite 3200, Cincinnati OH 45219; joel.sprunger@UC.edu.

ACKNOWLEDGMENTS
The authors thank Jeffrey M. Girard, PhD, and Daniel C. Williams, PhD, for their input on the design and content, respectively, of the IPASSPRT screening materials; the authors of the DA-5 and the HITS screening tools, particularly Jacquelyn Campbell, PhD, RN, FAAN, and Kevin Sherin, MD, MPH, MBA, respectively, for permission to include these measures in this article and for their support of its goals; and The Journal of Family Practice’s peer reviewers for their thoughtful feedback throughout the prepublication process.

Intimate partner violence (IPV) is a serious public health problem with considerable harmful health consequences. Decades of research have been dedicated to improving the identification of women in abusive heterosexual relationships and interventions that support healthier outcomes. A result of this work has been the recommendation of the US Preventive Services Task Force that all women of childbearing age be screened for IPV and provided with intervention or referral.¹

The problem extends further, however: Epidemiologic studies and comprehensive reviews show: 1) a high rate of IPV victimization among heterosexual men and lesbian, gay, bisexual, and transsexual (LGBT) men and women^2,3; 2) significant harmful effects on health and greater expectations of prejudice and discrimination among these populations^4-6; and 3) evidence that screening and referral for IPV are likely to confer similar benefits for these populations.⁷ We argue that it is reasonable to ask all patients about abuse in their relationships while the research literature progresses.

We intend this article to serve a number of purposes:

• support national standards for IPV screening of female patients
• highlight the need for piloting universal IPV screening for all patients (ie, male and female, across the lifespan)
• offer recommendations for navigating the process from IPV screening to referral, using insights gained from the substance abuse literature.

We also provide supplemental materials that facilitate establishment of screening and referral protocols for physicians across practice settings.

© Joe Gorman

What is intimate partner violence? How can you identify it?

Intimate partner violence includes physical and sexual violence and nonphysical forms of abuse, such as psychological aggression and emotional abuse, perpetrated by a current or former intimate partner.⁸ TABLE 1^9-14 provides definitions for each of these behavior categories and example behaviors. Nearly 25% of women and 20% of men report having experienced physical violence from a romantic partner and even higher rates of nonphysical IPV.¹⁵ Consequences of IPV victimization include acute and chronic medical illness, injury, and psychological problems, including depression, anxiety, and poor self-esteem.¹⁶

Intimate partner violence is heterogenous, with differences in severity (eg, frequency and intensity of violence) and laterality (ie, is one partner violent? are both partners violent?).

Intimate partner violence is heterogeneous, with differences in severity (eg, frequency and intensity of violence) and laterality (ie, is one partner violent? are both partners violent?). A recent comprehensive review of the literature revealed that, for 49.2%-69.7% of partner-violent couples across diverse samples, IPV is perpetrated by both partners.¹⁷ Furthermore, this bidirectionality is not due entirely to aggression perpetrated in self-defense; rather, across diverse patient samples, that is the case for fewer than one-quarter of males and no more than approximately one-third of females.¹⁸ In the remaining cases, bidirectionality may be attributed to other motivations, such as a maladaptive emotional expression or a means by which to get a partner’s attention.¹⁸

Women are disproportionately susceptible to harmful outcomes as a result of severe violence, including physical injury, psychological distress (eg, depression and anxiety), and substance abuse.^16,19 Some patients in unidirectionally violent relationships experience severe physical violence that may be, or become, life-threatening (0.4%-2.4% of couples in community samples)²⁰—victimization that is traditionally known as “battering.”²¹

Continue to: These tools can facilitate screening for IPV

These tools can facilitate screening for IPV

Physicians might have reservations asking about IPV because of 1) concern whether there is sufficient time during an office visit to interview, screen, and refer, 2) feelings of powerlessness to stop violence by or toward a patient, and 3) general discomfort with the topic.²² Additionally, mandated reporting laws regarding IPV vary by state, making it crucial to know one’s own state laws on this issue to protect the safety of the patient and those around them.

Screening increases the likelihood of engaging the patient in supportive services, thus decreasing the isolation that is typical of abuse.

Research has shown that some patients prefer that their health care providers ask about relationship violence directly²³; others are more willing to acknowledge IPV if asked using a paper-and-pencil measure, rather than face-to-face questions.²⁴ Either way, screening increases the likelihood of engaging the patient in supportive services, thus decreasing the isolation that is typical of abuse.²⁵ Based on this research, screening that utilizes face-valid items embedded within paperwork completed in the waiting room is recommended as an important first step toward identifying and helping patients who are experiencing IPV. Even under these conditions, however, heterosexual men and sexual minorities might be less willing than heterosexual women to admit experiencing IPV.^26,27

A brief vignette that depicts how quickly the screening and referral process can be applied is presented in “IPV screening and referral: A real-world vignette." The vignette is a de-identified composite of heterosexual men experiencing IPV whom we have counseled.

One model that provides a useful framework for IPV assessment is the Screening, Brief Intervention, and Referral to Treatment (SBIRT) model, which was developed to facilitate assessment of, and referral for, substance abuse—another heavily stigmatized health care problem. The SBIRT approach for substance abuse screening is associated with significant reduction in alcohol and drug abuse 6 months postintervention, as well as improvements in well-being, mental health, and functioning across gender, race and ethnicity, and age.²⁸

IPASSPRT. Inspired by the SBIRT model for substance abuse, we created the Intimate Partner Aggression Screening, Safety Planning, and Referral to Treatment, or IPASSPRT (spoken as “i-passport”) project to provide tools that make IPV screening and referral accessible to a range of health care providers. These tools include a script and safety plan that guide providers through screening, safety planning, and referral in a manner that is collaborative and grounded in the spirit of motivational interviewing. We have made these tools available on the Web for ease of distribution (http://bit.ly/ipassprt; open by linking through “IPASSPRT-Script”).

Continue to: The IPASSPRT script appears lengthy...

The IPASSPRT script appears lengthy, but progress through its sections is directed by patient need; most patients will not require that all parts be completed. For example, a patient whose screen for IPV is negative and who feels safe in their relationship does not need assessment beyond page 2; on the other hand, the physician might need more information from a patient who is at greater risk for IPV. This response-based progression through the script makes the screening process dynamic, data-driven, and tailored to the patient’s needs—an approach that aids rapport and optimizes the physician’s limited time during the appointment.

In the sections that follow, we describe key components of this script.

What aggression, if any, is present? From whom? The Hurt, Insult, Threaten, and Scream inventory (HITS) (TABLE 2)²⁹ is a widely used screen for IPV that has been validated for use in family medicine. A 4-item scale asks patients to report how often their partner physically hurts, insults, threatens, and screams at them using a 5-point scale (1 point, “never,” to 5 points, “frequently”). Although a score > 10 is indicative of IPV, item-level analysis is encouraged. Attending to which items the patient acknowledges and how often these behaviors occur yields a richer assessment than a summary score. In regard to simply asking a patient, “Do you feel safe at home?” (sensitivity of this question, 8.8%; specificity, 91.2%), the HITS better detects IPV with male and female patient populations in family practice and emergency care settings (sensitivity, 30%-100%; specificity, 86%-99%).^27,30

What contextual factors and related concerns are present? It is important to understand proximal factors that might influence IPV risk to determine what kind of referral or treatment is appropriate—particularly for patients experiencing or engaging in infrequent, noninjurious, and bidirectional forms of IPV. Environmental and contextual stressors, such as financial hardship, unemployment, pregnancy, and discussion of divorce, can increase the risk for IPV.^31,32 Situational influences, such as alcohol and drug intoxication, can also increase the risk for IPV. Victims of partner violence are at greater risk for mental health problems, including depression, anxiety, trauma- and stressor-related disorders, and substance use disorders. Risk goes both ways, however: Mental illness predicts subsequent IPV perpetration or victimization, and vice versa.³¹

Does the patient feel safe? Assessing the situation. Patient perception of safety in the relationship provides important information about the necessity of referral. Asking a patient if they feel unsafe because of the behavior of a current or former partner sheds light on the need for further safety assessment and immediate connection with appropriate resources.

Continue to: The Danger Assessment-5...

The Danger Assessment-5 (DA-5) (TABLE 3³³) is a useful 5-item tool for quickly assessing the risk for severe IPV.³³ Patients respond to whether:

• the frequency or severity of violence has increased in the past year
• the partner has ever used, or threatened to use, a weapon
• the patient believes the partner is capable of killing her (him)
• the partner has ever tried to choke or strangle her (him)
• the partner is violently and constantly jealous.

Mental illness predicts subsequent IPV perpetration or victimization and vice versa.

Sensitivity and specificity analyses with a high-risk female sample suggested that 3 affirmative responses indicate a high risk for severe IPV and a need for adequate safety planning.

Brief motivational enhancement intervention. There are 3 components to this intervention.

• Assess interest in making changes or seeking help. IPV is paradoxical: Many factors complicate the decision to leave or stay, and patients across the spectrum of victimization might have some motivation to stay with their partner. It is important to assess the patient’s motivation to make changes in their relationship.^4,34
• Provide feedback on screening. Sharing the results of screening with patients makes the assessment and referral process collaborative and transparent; collaborative engagement helps patients feel in control and invested in the follow-through.³⁵ In the spirit of this endeavor, physicians are encouraged to refrain from providing raw or total scores from the measures; instead, share the interpretation of those scores, based on the participant’s responses to the screening items, in a matter-of-fact manner. At this point, elicit the patient’s response to this information, listen empathically, and answer questions before proceeding.

Consistent with screening for other serious health problems, we recommend that all patients be provided with information about abuse in romantic relationships. The National Center for Injury Prevention and Control Division of Violence Prevention has published a useful, easy-to-understand fact sheet (www.cdc.gov/violenceprevention/pdf/ipv-factsheet.pdf) that provides an overview of IPV-related behavior, how it influences health outcomes, who is at risk for IPV, and sources for support.

Continue to: Our IPASSPRT interview script...

Our IPASSPRT interview script (http://bit.ly/ipassprt) outlines how this information can be presented to patients as a typical part of the screening process. Providers are encouraged to share and review the information from the fact sheet with all patients and present it as part of the normal screening process to mitigate the potential for defensiveness on the part of the patient. For patients who screen positive for IPV, it might be important to brainstorm ideas for a safe, secure place to store this fact sheet and other resources from the brief intervention and referral process below (eg, a safety plan and specific referral information) so that the patient can access them quickly and easily, if needed.

For patients who screen negative for IPV, their screen and interview conclude at this point.

• Provide recommendations based on the screen. Evidence suggests that collaborating with the patient on safety planning and referral can increase the likelihood of their engagement.⁷ Furthermore, failure to tailor the referral to the needs of the patient can be detrimental³⁶—ie, overshooting the level of intervention might decrease the patient’s future treatment-seeking behavior and undermine their internal coping strategies, increasing the likelihood of future victimization. For that reason, we provide the following guidance on navigating the referral process for patients who screen positive for IPV.

Screening-based referral: A delicate and collaborative process

Referral for IPV victimization. Individual counseling, with or without an IPV focus, might be appropriate for patients at lower levels of risk; immediate connection with local IPV resources is strongly encouraged for patients at higher risk. This is a delicate, collaborative process, in which the physician offers recommendations for referral commensurate to the patient’s risk but must, ultimately, respect the patient’s autonomy by identifying referrals that fit the patient’s goals. We encourage providers to provide risk-informed recommendations and to elicit the patient’s thoughts about that information.

Several online resources are available to help physicians locate and connect with IPV-related resources in their community, including the National Health Resource Center on Domestic Violence (http://ipvhealth.org/), which provides a step-by-step guide to making such connections. We encourage physicians to develop these collaborative partnerships early to facilitate warm handoffs and increase the likelihood that a patient will follow through with the referral after screening.³⁷

Referral for related concerns. As we’ve noted, IPV has numerous physical and mental health consequences, including depression, low self-esteem, trauma- and non-trauma-related anxiety, and substance abuse. In general, cognitive behavioral therapies appear most efficacious for treating these IPV-related consequences, but evidence is limited that such interventions diminish the likelihood of re-victimization.³⁸ Intervention programs that foster problem-solving, solution-seeking, and cognitive restructuring for self-critical thoughts and misconceptions seem to produce the best physical and mental health outcomes.³⁹ For patients who have a substance use disorder, treatment programs that target substance use have demonstrated a reduction in the rate of IPV recidivism.⁴⁰ These findings indicate that establishing multiple treatment targets might reduce the risk for future aggression in relationships.

Continue to: The Substance Abuse and Mental Health Services Administration...

The Substance Abuse and Mental Health Services Administration of the US Department of Health and Human Services provides a useful online tool (https://findtreatment.samhsa.gov/) for locating local referrals that address behavioral health and substance-related concerns. The agency also provides a hotline (1-800-662-HELP [4357]) as an alternative resource for information and treatment referrals.

Safety planning can improve outcomes

For a patient who screens above low risk, safety planning with the patient is an important part of improving outcomes and can take several forms. Online resources, such as the Path to Safety interactive Web page (www.thehotline.org/help/path-to-safety/) maintained by The National Domestic Violence Hotline ([800]799-SAFE [7233]), provide information regarding important considerations for safety planning when:

• living with an abusive partner
• children are in the home
• the patient is pregnant
• pets are involved.

The Web site also provides information regarding legal options and resources related to IPV (eg, an order of protection) and steps for improving safety when leaving an abusive relationship. Patients at risk for IPV can explore the online tool and call the hotline.

For physicians who want to engage in provider-assisted safety planning, we’ve provided further guidance in the IPASSPRT screening script and safety plan (http://bit.ly/ipassprt) (TABLE 4).

Goal: Affirm patients’ strengths and reinforce hope

Psychological aggression is the most common form of relationship aggression; repeated denigration might leave a person with little confidence in their ability to change their relationship or seek out identified resources. That’s why it’s useful to inquire—with genuine curiosity—about a time in the past when the patient accomplished something challenging. The physician’s enthusiastic reflection on this achievement can be a means of highlighting the patient’s ability to accomplish a meaningful goal; of reinforcing their hope; and of eliciting important resources within and around the patient that can facilitate action on their safety plan. (See “IPV-related resources for physicians and patients.”)

Continue to: Closing the screen and making a referral

Closing the screen and making a referral

The end of the interview should consist of a summary of topics discussed, including:

• changes that the patient wants to make (if any)
• their stated reasons for making those changes
• the patient’s plan for accomplishing changes.

Physicians should also include their own role in next steps—whether providing a warm handoff to a local IPV referral, agreeing to a follow-up schedule with the patient, or making a call as a mandated reporter. To close out the interview, it is important to affirm respect for the patient’s autonomy in executing the plan.

It’s important to screen all patients—here’s why

A major impetus for this article has been to raise awareness about the need for expanded IPV screening across primary care settings. As mentioned, much of the literature on IPV victimization has focused on women; however, the few epidemiological investigations of victimization rates among men and members of LGBT couples show a high rate of victimization and considerable harmful health outcomes. Driven by stigma surrounding IPV, sex, and sexual minority status, patients might have expectations that they will be judged by a provider or “outed.”

Such barriers can lead many to suffer in silence until the problem can no longer be hidden or the danger becomes more emergent. Compassionate, nonjudgmental screening and collaborative safety planning—such as the approach we describe in this article—help ease the concerns of LGBT victims of IPV and improve the likelihood that conversations you have with them will occur earlier, rather than later, in care.*

Underassessment of IPV (ie, underreporting as well as under-inquiry) because of stigma, misconception, and other factors obscures an accurate estimate of the rate of partner violence and its consequences for all couples. As a consequence, we know little about the dynamics of IPV, best practices for screening, and appropriate referral for couples from these populations. Furthermore, few resources are available to these understudied and underserved groups (eg, shelters for men and for transgender people).

Continue to: Although our immediate approach to IPV screening...

Although our immediate approach to IPV screening, safety planning, and referral with understudied patient populations might be informed by what we have learned from the experiences of heterosexual women in abusive relationships, such a practice is unsustainable. Unless we expand our scope of screening to all patients, it is unlikely that we will develop the evidence base necessary to 1) warrant stronger IPV screening recommendations for patient groups apart from women of childbearing age, let alone 2) demonstrate the need for additional community resources, and 3) provide comprehensive care in family practice of comparable quality.

The benefits of screening go beyond the individual patient

Screening for violence in the relationship does not take long; the value of asking about its presence in a relationship might offer benefits beyond the individual patient by raising awareness and providing the field of study with more data to increase attention and resources for under-researched and underserved populations. Screening might also combat the stigma that perpetuates the silence of many who deserve access to care.

CORRESPONDENCE
Joel G. Sprunger, PhD, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, 260 Stetson St, Suite 3200, Cincinnati OH 45219; joel.sprunger@UC.edu.

ACKNOWLEDGMENTS
The authors thank Jeffrey M. Girard, PhD, and Daniel C. Williams, PhD, for their input on the design and content, respectively, of the IPASSPRT screening materials; the authors of the DA-5 and the HITS screening tools, particularly Jacquelyn Campbell, PhD, RN, FAAN, and Kevin Sherin, MD, MPH, MBA, respectively, for permission to include these measures in this article and for their support of its goals; and The Journal of Family Practice’s peer reviewers for their thoughtful feedback throughout the prepublication process.

Intimate partner violence (IPV) is a serious public health problem with considerable harmful health consequences. Decades of research have been dedicated to improving the identification of women in abusive heterosexual relationships and interventions that support healthier outcomes. A result of this work has been the recommendation of the US Preventive Services Task Force that all women of childbearing age be screened for IPV and provided with intervention or referral.¹

The problem extends further, however: Epidemiologic studies and comprehensive reviews show: 1) a high rate of IPV victimization among heterosexual men and lesbian, gay, bisexual, and transsexual (LGBT) men and women^2,3; 2) significant harmful effects on health and greater expectations of prejudice and discrimination among these populations^4-6; and 3) evidence that screening and referral for IPV are likely to confer similar benefits for these populations.⁷ We argue that it is reasonable to ask all patients about abuse in their relationships while the research literature progresses.

We intend this article to serve a number of purposes:

• support national standards for IPV screening of female patients
• highlight the need for piloting universal IPV screening for all patients (ie, male and female, across the lifespan)
• offer recommendations for navigating the process from IPV screening to referral, using insights gained from the substance abuse literature.

We also provide supplemental materials that facilitate establishment of screening and referral protocols for physicians across practice settings.

© Joe Gorman

What is intimate partner violence? How can you identify it?

Intimate partner violence includes physical and sexual violence and nonphysical forms of abuse, such as psychological aggression and emotional abuse, perpetrated by a current or former intimate partner.⁸ TABLE 1^9-14 provides definitions for each of these behavior categories and example behaviors. Nearly 25% of women and 20% of men report having experienced physical violence from a romantic partner and even higher rates of nonphysical IPV.¹⁵ Consequences of IPV victimization include acute and chronic medical illness, injury, and psychological problems, including depression, anxiety, and poor self-esteem.¹⁶

Intimate partner violence is heterogenous, with differences in severity (eg, frequency and intensity of violence) and laterality (ie, is one partner violent? are both partners violent?).

Intimate partner violence is heterogeneous, with differences in severity (eg, frequency and intensity of violence) and laterality (ie, is one partner violent? are both partners violent?). A recent comprehensive review of the literature revealed that, for 49.2%-69.7% of partner-violent couples across diverse samples, IPV is perpetrated by both partners.¹⁷ Furthermore, this bidirectionality is not due entirely to aggression perpetrated in self-defense; rather, across diverse patient samples, that is the case for fewer than one-quarter of males and no more than approximately one-third of females.¹⁸ In the remaining cases, bidirectionality may be attributed to other motivations, such as a maladaptive emotional expression or a means by which to get a partner’s attention.¹⁸

Women are disproportionately susceptible to harmful outcomes as a result of severe violence, including physical injury, psychological distress (eg, depression and anxiety), and substance abuse.^16,19 Some patients in unidirectionally violent relationships experience severe physical violence that may be, or become, life-threatening (0.4%-2.4% of couples in community samples)²⁰—victimization that is traditionally known as “battering.”²¹

Continue to: These tools can facilitate screening for IPV

These tools can facilitate screening for IPV

Physicians might have reservations asking about IPV because of 1) concern whether there is sufficient time during an office visit to interview, screen, and refer, 2) feelings of powerlessness to stop violence by or toward a patient, and 3) general discomfort with the topic.²² Additionally, mandated reporting laws regarding IPV vary by state, making it crucial to know one’s own state laws on this issue to protect the safety of the patient and those around them.

Screening increases the likelihood of engaging the patient in supportive services, thus decreasing the isolation that is typical of abuse.

Research has shown that some patients prefer that their health care providers ask about relationship violence directly²³; others are more willing to acknowledge IPV if asked using a paper-and-pencil measure, rather than face-to-face questions.²⁴ Either way, screening increases the likelihood of engaging the patient in supportive services, thus decreasing the isolation that is typical of abuse.²⁵ Based on this research, screening that utilizes face-valid items embedded within paperwork completed in the waiting room is recommended as an important first step toward identifying and helping patients who are experiencing IPV. Even under these conditions, however, heterosexual men and sexual minorities might be less willing than heterosexual women to admit experiencing IPV.^26,27

A brief vignette that depicts how quickly the screening and referral process can be applied is presented in “IPV screening and referral: A real-world vignette." The vignette is a de-identified composite of heterosexual men experiencing IPV whom we have counseled.

One model that provides a useful framework for IPV assessment is the Screening, Brief Intervention, and Referral to Treatment (SBIRT) model, which was developed to facilitate assessment of, and referral for, substance abuse—another heavily stigmatized health care problem. The SBIRT approach for substance abuse screening is associated with significant reduction in alcohol and drug abuse 6 months postintervention, as well as improvements in well-being, mental health, and functioning across gender, race and ethnicity, and age.²⁸

IPASSPRT. Inspired by the SBIRT model for substance abuse, we created the Intimate Partner Aggression Screening, Safety Planning, and Referral to Treatment, or IPASSPRT (spoken as “i-passport”) project to provide tools that make IPV screening and referral accessible to a range of health care providers. These tools include a script and safety plan that guide providers through screening, safety planning, and referral in a manner that is collaborative and grounded in the spirit of motivational interviewing. We have made these tools available on the Web for ease of distribution (http://bit.ly/ipassprt; open by linking through “IPASSPRT-Script”).

Continue to: The IPASSPRT script appears lengthy...

The IPASSPRT script appears lengthy, but progress through its sections is directed by patient need; most patients will not require that all parts be completed. For example, a patient whose screen for IPV is negative and who feels safe in their relationship does not need assessment beyond page 2; on the other hand, the physician might need more information from a patient who is at greater risk for IPV. This response-based progression through the script makes the screening process dynamic, data-driven, and tailored to the patient’s needs—an approach that aids rapport and optimizes the physician’s limited time during the appointment.

In the sections that follow, we describe key components of this script.

What aggression, if any, is present? From whom? The Hurt, Insult, Threaten, and Scream inventory (HITS) (TABLE 2)²⁹ is a widely used screen for IPV that has been validated for use in family medicine. A 4-item scale asks patients to report how often their partner physically hurts, insults, threatens, and screams at them using a 5-point scale (1 point, “never,” to 5 points, “frequently”). Although a score > 10 is indicative of IPV, item-level analysis is encouraged. Attending to which items the patient acknowledges and how often these behaviors occur yields a richer assessment than a summary score. In regard to simply asking a patient, “Do you feel safe at home?” (sensitivity of this question, 8.8%; specificity, 91.2%), the HITS better detects IPV with male and female patient populations in family practice and emergency care settings (sensitivity, 30%-100%; specificity, 86%-99%).^27,30

What contextual factors and related concerns are present? It is important to understand proximal factors that might influence IPV risk to determine what kind of referral or treatment is appropriate—particularly for patients experiencing or engaging in infrequent, noninjurious, and bidirectional forms of IPV. Environmental and contextual stressors, such as financial hardship, unemployment, pregnancy, and discussion of divorce, can increase the risk for IPV.^31,32 Situational influences, such as alcohol and drug intoxication, can also increase the risk for IPV. Victims of partner violence are at greater risk for mental health problems, including depression, anxiety, trauma- and stressor-related disorders, and substance use disorders. Risk goes both ways, however: Mental illness predicts subsequent IPV perpetration or victimization, and vice versa.³¹

Does the patient feel safe? Assessing the situation. Patient perception of safety in the relationship provides important information about the necessity of referral. Asking a patient if they feel unsafe because of the behavior of a current or former partner sheds light on the need for further safety assessment and immediate connection with appropriate resources.

Continue to: The Danger Assessment-5...

The Danger Assessment-5 (DA-5) (TABLE 3³³) is a useful 5-item tool for quickly assessing the risk for severe IPV.³³ Patients respond to whether:

• the frequency or severity of violence has increased in the past year
• the partner has ever used, or threatened to use, a weapon
• the patient believes the partner is capable of killing her (him)
• the partner has ever tried to choke or strangle her (him)
• the partner is violently and constantly jealous.

Mental illness predicts subsequent IPV perpetration or victimization and vice versa.

Sensitivity and specificity analyses with a high-risk female sample suggested that 3 affirmative responses indicate a high risk for severe IPV and a need for adequate safety planning.

Brief motivational enhancement intervention. There are 3 components to this intervention.

• Assess interest in making changes or seeking help. IPV is paradoxical: Many factors complicate the decision to leave or stay, and patients across the spectrum of victimization might have some motivation to stay with their partner. It is important to assess the patient’s motivation to make changes in their relationship.^4,34
• Provide feedback on screening. Sharing the results of screening with patients makes the assessment and referral process collaborative and transparent; collaborative engagement helps patients feel in control and invested in the follow-through.³⁵ In the spirit of this endeavor, physicians are encouraged to refrain from providing raw or total scores from the measures; instead, share the interpretation of those scores, based on the participant’s responses to the screening items, in a matter-of-fact manner. At this point, elicit the patient’s response to this information, listen empathically, and answer questions before proceeding.

Consistent with screening for other serious health problems, we recommend that all patients be provided with information about abuse in romantic relationships. The National Center for Injury Prevention and Control Division of Violence Prevention has published a useful, easy-to-understand fact sheet (www.cdc.gov/violenceprevention/pdf/ipv-factsheet.pdf) that provides an overview of IPV-related behavior, how it influences health outcomes, who is at risk for IPV, and sources for support.

Continue to: Our IPASSPRT interview script...

Our IPASSPRT interview script (http://bit.ly/ipassprt) outlines how this information can be presented to patients as a typical part of the screening process. Providers are encouraged to share and review the information from the fact sheet with all patients and present it as part of the normal screening process to mitigate the potential for defensiveness on the part of the patient. For patients who screen positive for IPV, it might be important to brainstorm ideas for a safe, secure place to store this fact sheet and other resources from the brief intervention and referral process below (eg, a safety plan and specific referral information) so that the patient can access them quickly and easily, if needed.

For patients who screen negative for IPV, their screen and interview conclude at this point.

• Provide recommendations based on the screen. Evidence suggests that collaborating with the patient on safety planning and referral can increase the likelihood of their engagement.⁷ Furthermore, failure to tailor the referral to the needs of the patient can be detrimental³⁶—ie, overshooting the level of intervention might decrease the patient’s future treatment-seeking behavior and undermine their internal coping strategies, increasing the likelihood of future victimization. For that reason, we provide the following guidance on navigating the referral process for patients who screen positive for IPV.

Screening-based referral: A delicate and collaborative process

Referral for IPV victimization. Individual counseling, with or without an IPV focus, might be appropriate for patients at lower levels of risk; immediate connection with local IPV resources is strongly encouraged for patients at higher risk. This is a delicate, collaborative process, in which the physician offers recommendations for referral commensurate to the patient’s risk but must, ultimately, respect the patient’s autonomy by identifying referrals that fit the patient’s goals. We encourage providers to provide risk-informed recommendations and to elicit the patient’s thoughts about that information.

Several online resources are available to help physicians locate and connect with IPV-related resources in their community, including the National Health Resource Center on Domestic Violence (http://ipvhealth.org/), which provides a step-by-step guide to making such connections. We encourage physicians to develop these collaborative partnerships early to facilitate warm handoffs and increase the likelihood that a patient will follow through with the referral after screening.³⁷

Referral for related concerns. As we’ve noted, IPV has numerous physical and mental health consequences, including depression, low self-esteem, trauma- and non-trauma-related anxiety, and substance abuse. In general, cognitive behavioral therapies appear most efficacious for treating these IPV-related consequences, but evidence is limited that such interventions diminish the likelihood of re-victimization.³⁸ Intervention programs that foster problem-solving, solution-seeking, and cognitive restructuring for self-critical thoughts and misconceptions seem to produce the best physical and mental health outcomes.³⁹ For patients who have a substance use disorder, treatment programs that target substance use have demonstrated a reduction in the rate of IPV recidivism.⁴⁰ These findings indicate that establishing multiple treatment targets might reduce the risk for future aggression in relationships.

Continue to: The Substance Abuse and Mental Health Services Administration...

The Substance Abuse and Mental Health Services Administration of the US Department of Health and Human Services provides a useful online tool (https://findtreatment.samhsa.gov/) for locating local referrals that address behavioral health and substance-related concerns. The agency also provides a hotline (1-800-662-HELP [4357]) as an alternative resource for information and treatment referrals.

Safety planning can improve outcomes

For a patient who screens above low risk, safety planning with the patient is an important part of improving outcomes and can take several forms. Online resources, such as the Path to Safety interactive Web page (www.thehotline.org/help/path-to-safety/) maintained by The National Domestic Violence Hotline ([800]799-SAFE [7233]), provide information regarding important considerations for safety planning when:

• living with an abusive partner
• children are in the home
• the patient is pregnant
• pets are involved.

The Web site also provides information regarding legal options and resources related to IPV (eg, an order of protection) and steps for improving safety when leaving an abusive relationship. Patients at risk for IPV can explore the online tool and call the hotline.

For physicians who want to engage in provider-assisted safety planning, we’ve provided further guidance in the IPASSPRT screening script and safety plan (http://bit.ly/ipassprt) (TABLE 4).

Goal: Affirm patients’ strengths and reinforce hope

Psychological aggression is the most common form of relationship aggression; repeated denigration might leave a person with little confidence in their ability to change their relationship or seek out identified resources. That’s why it’s useful to inquire—with genuine curiosity—about a time in the past when the patient accomplished something challenging. The physician’s enthusiastic reflection on this achievement can be a means of highlighting the patient’s ability to accomplish a meaningful goal; of reinforcing their hope; and of eliciting important resources within and around the patient that can facilitate action on their safety plan. (See “IPV-related resources for physicians and patients.”)

Continue to: Closing the screen and making a referral

Closing the screen and making a referral

The end of the interview should consist of a summary of topics discussed, including:

• changes that the patient wants to make (if any)
• their stated reasons for making those changes
• the patient’s plan for accomplishing changes.

Physicians should also include their own role in next steps—whether providing a warm handoff to a local IPV referral, agreeing to a follow-up schedule with the patient, or making a call as a mandated reporter. To close out the interview, it is important to affirm respect for the patient’s autonomy in executing the plan.

It’s important to screen all patients—here’s why

A major impetus for this article has been to raise awareness about the need for expanded IPV screening across primary care settings. As mentioned, much of the literature on IPV victimization has focused on women; however, the few epidemiological investigations of victimization rates among men and members of LGBT couples show a high rate of victimization and considerable harmful health outcomes. Driven by stigma surrounding IPV, sex, and sexual minority status, patients might have expectations that they will be judged by a provider or “outed.”

Such barriers can lead many to suffer in silence until the problem can no longer be hidden or the danger becomes more emergent. Compassionate, nonjudgmental screening and collaborative safety planning—such as the approach we describe in this article—help ease the concerns of LGBT victims of IPV and improve the likelihood that conversations you have with them will occur earlier, rather than later, in care.*

Underassessment of IPV (ie, underreporting as well as under-inquiry) because of stigma, misconception, and other factors obscures an accurate estimate of the rate of partner violence and its consequences for all couples. As a consequence, we know little about the dynamics of IPV, best practices for screening, and appropriate referral for couples from these populations. Furthermore, few resources are available to these understudied and underserved groups (eg, shelters for men and for transgender people).

Continue to: Although our immediate approach to IPV screening...

Although our immediate approach to IPV screening, safety planning, and referral with understudied patient populations might be informed by what we have learned from the experiences of heterosexual women in abusive relationships, such a practice is unsustainable. Unless we expand our scope of screening to all patients, it is unlikely that we will develop the evidence base necessary to 1) warrant stronger IPV screening recommendations for patient groups apart from women of childbearing age, let alone 2) demonstrate the need for additional community resources, and 3) provide comprehensive care in family practice of comparable quality.

The benefits of screening go beyond the individual patient

Screening for violence in the relationship does not take long; the value of asking about its presence in a relationship might offer benefits beyond the individual patient by raising awareness and providing the field of study with more data to increase attention and resources for under-researched and underserved populations. Screening might also combat the stigma that perpetuates the silence of many who deserve access to care.

CORRESPONDENCE
Joel G. Sprunger, PhD, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, 260 Stetson St, Suite 3200, Cincinnati OH 45219; joel.sprunger@UC.edu.

ACKNOWLEDGMENTS
The authors thank Jeffrey M. Girard, PhD, and Daniel C. Williams, PhD, for their input on the design and content, respectively, of the IPASSPRT screening materials; the authors of the DA-5 and the HITS screening tools, particularly Jacquelyn Campbell, PhD, RN, FAAN, and Kevin Sherin, MD, MPH, MBA, respectively, for permission to include these measures in this article and for their support of its goals; and The Journal of Family Practice’s peer reviewers for their thoughtful feedback throughout the prepublication process.

Each year, the American Contact Dermatitis Society (ACDS) names an allergen of the year with the purpose of promoting greater awareness of a key allergen and its impact on patients. Often, the allergen of the year is an emerging allergen that may represent an underrecognized or novel cause of allergic contact dermatitis (ACD). In 2019, the ACDS chose parabens as the “nonallergen” of the year to draw attention to their low rate of associated ACD despite high public interest in limiting exposure to parabens.¹

What types of products contain parabens?

Parabens are preservatives commonly found in many different categories of personal care products. Preservatives inhibit microbial growth and are necessary ingredients in water-based products. The 4 most common parabens used in personal care products are methylparaben, ethylparaben, propylparaben, and butylparaben.¹ Parabens are metabolized to 4-hydroxybenzoic acid and are excreted in urine. When parabens are applied topically, there is minimal penetration through intact human skin.² In the United States, parabens are allowed as preservatives in cosmetics at concentrations up to 0.4% when used alone or up to 0.8% when used in combination with other parabens.³

Consumers are exposed to parabens in a wide variety of personal care products. The Contact Allergen Management Program (CAMP) is a system owned and managed by the ACDS that typically is used to generate lists of safe personal care products for patients and also can be queried for the presence of individual chemicals in products. According to a 2018 query of the CAMP, parabens were found in 19% of all products.¹ A more recent query of CAMP (http://www.contactderm.org/resources/acds-camp) in March 2019 showed parabens were present in 39.3% of makeup products, especially in eye products, foundations, and concealers; parabens also were found in 34% of moisturizers, 11.5% of soaps, and 19% of sunscreens. Notably, 14.8% of prescription topical steroids listed in the CAMP contained a paraben. Another method for evaluating chemical contents of personal care products is a review of the Voluntary Cosmetic Registration Program, a US Food and Drug Administration–based registry for cosmetic products. Survey data from the Voluntary Cosmetic Registration Program in 2018 documented methylparaben in 11,626 formulations.⁴ Other parabens included propylparaben (8885 products), butylparaben (3915 products), and ethylparaben (3860 products). Parabens were reported more frequently in leave-on rather than rinse-off products.⁴

In medications, parabens are recommended at concentrations of no more than 0.1%.¹ Fransway et al¹ compiled a list of medications that contain parabens, including commonly prescribed dermatologic topical medications such as corticosteroids, several acne preparations, eflornithine, fluorouracil, hydroquinone, imiquimod, urea, and sertaconazole. Oral and parenteral medications including local anesthetics and corticosteroids also may contain parabens.

Consumers also may be exposed to parabens through foodstuffs. Methylparaben and propylparaben have been classified as generally recognized as safe in foods by the US Food and Drug Administration.⁵ The acceptable daily intake of parabens in food is 0 to 10 mg/kg of body weight,¹ and the estimated dietary intake for a typical adult is 307 mg/kg of body weight daily.⁶ Several studies on paraben content in foodstuffs have confirmed their presence in both natural and processed foods.^1,6 Systemic contact dermatitis caused by ingestion of parabens is rare. In general, individuals with positive patch test reactions to parabens should not routinely avoid them in foods or oral medications,¹ but they should, of course, be avoided in topical medications.

What is the rate of ACD with parabens?

One of the main reasons that parabens were designated as the ACDS nonallergen of the year is the very low rate of ACD associated with parabens. The North American Contact Dermatitis Group, a research group with members in the United States and Canada, reported a 0.6% positive reaction rate when patch testing with paraben mix 12%,⁷ which closely compares with a 0.8% positive reaction rate when patch testing with paraben mix 16% using the Mayo Clinic standard series.⁸ From the standpoint of ACD, this very low patch test reaction rate makes parabens one of the safest preservative options for use in cosmetic products.

Are there health risks associated with parabens?

The paraben controversy in the scientific literature and in the lay press centers around potential health risks and endocrine disruption. We will focus on the conversation regarding parabens and the risk for endocrine disruption and association with breast cancer.

Parabens have been reported to have estrogenic effects; however, the bulk of the data is limited to in vitro and animal studies, with less evidence of endocrine disruption in humans.² In vitro studies have demonstrated that the estrogenic potency of parabens is much less than that of estrogen. In one study, parabens were shown to be 10,000-fold less potent than 17β-estradiol⁹; in a separate study, they had a maximum potency of only 1/4000 that of estrogen.¹⁰ Additionally, an in vitro study showed varying ability for parabens to bind estrogen receptors, with a greater ability to bind with longer alkyl side chains.¹¹ The result is decreased or increased estrogen activity, dependent on side chain length and type of receptor.² Finally, some studies add conflicting results that parabens may actually create an antiestrogenic effect in human breast cancer cells.¹² From the standpoint of estrogen mimicry, there are no known studies in humans confirming harmful effects associated with paraben exposure.

The reported association between parabens and breast cancer is closely related to their theoretical estrogenic effects. The conversation regarding parabens and breast cancer has been fueled by the identification of parabens in human breast tumors and their presence in concentrations similar to what is needed to stimulate in vitro breast cancer cells.² The existing data do not confirm causation. An association with parabens in topical axillary personal care products has been theorized but not confirmed; for example, it was shown that paraben levels were highest in the axillary region of breast cancer tissue, including women who had never used deodorant. It was concluded that the presence of axillary parabens was due to sources other than topical axillary personal care products.¹³ Another study confirmed there was not an increased risk for breast cancer in patients who applied personal care products to the axillary area within an hour of shaving.¹⁴ The existing data do not support topical paraben exposure as a risk for breast cancer.

Final Thoughts

Parabens are preservatives frequently found in personal care products and exhibit a very low rate of associated ACD. Consumers may be exposed to parabens through foods, cosmetics, and medications. Although there have been consumer concerns regarding endocrine disruption or carcinogenicity associated with parabens, definite evidence of their harm is lacking in the scientific literature, and many studies confirm their safety.² With their high prevalence in personal care products and low rates of associated contact allergy, parabens remain ideal preservative agents.

Ultimately, contact dermatitis is a common yet often underrecognized dermatologic condition. To address this knowledge gap in clinical practice, we are proud to launch Final Interpretation, a new column in Cutis covering emerging trends in contact dermatitis. We will address pearls, pitfalls, and updates in contact dermatitis. Although our primary focus will be ACD, other important causes of contact dermatitis will be highlighted. Look for the inaugural column in the June 2019 issue of Cutis.

Each year, the American Contact Dermatitis Society (ACDS) names an allergen of the year with the purpose of promoting greater awareness of a key allergen and its impact on patients. Often, the allergen of the year is an emerging allergen that may represent an underrecognized or novel cause of allergic contact dermatitis (ACD). In 2019, the ACDS chose parabens as the “nonallergen” of the year to draw attention to their low rate of associated ACD despite high public interest in limiting exposure to parabens.¹

What types of products contain parabens?

Parabens are preservatives commonly found in many different categories of personal care products. Preservatives inhibit microbial growth and are necessary ingredients in water-based products. The 4 most common parabens used in personal care products are methylparaben, ethylparaben, propylparaben, and butylparaben.¹ Parabens are metabolized to 4-hydroxybenzoic acid and are excreted in urine. When parabens are applied topically, there is minimal penetration through intact human skin.² In the United States, parabens are allowed as preservatives in cosmetics at concentrations up to 0.4% when used alone or up to 0.8% when used in combination with other parabens.³

Consumers are exposed to parabens in a wide variety of personal care products. The Contact Allergen Management Program (CAMP) is a system owned and managed by the ACDS that typically is used to generate lists of safe personal care products for patients and also can be queried for the presence of individual chemicals in products. According to a 2018 query of the CAMP, parabens were found in 19% of all products.¹ A more recent query of CAMP (http://www.contactderm.org/resources/acds-camp) in March 2019 showed parabens were present in 39.3% of makeup products, especially in eye products, foundations, and concealers; parabens also were found in 34% of moisturizers, 11.5% of soaps, and 19% of sunscreens. Notably, 14.8% of prescription topical steroids listed in the CAMP contained a paraben. Another method for evaluating chemical contents of personal care products is a review of the Voluntary Cosmetic Registration Program, a US Food and Drug Administration–based registry for cosmetic products. Survey data from the Voluntary Cosmetic Registration Program in 2018 documented methylparaben in 11,626 formulations.⁴ Other parabens included propylparaben (8885 products), butylparaben (3915 products), and ethylparaben (3860 products). Parabens were reported more frequently in leave-on rather than rinse-off products.⁴

In medications, parabens are recommended at concentrations of no more than 0.1%.¹ Fransway et al¹ compiled a list of medications that contain parabens, including commonly prescribed dermatologic topical medications such as corticosteroids, several acne preparations, eflornithine, fluorouracil, hydroquinone, imiquimod, urea, and sertaconazole. Oral and parenteral medications including local anesthetics and corticosteroids also may contain parabens.

Consumers also may be exposed to parabens through foodstuffs. Methylparaben and propylparaben have been classified as generally recognized as safe in foods by the US Food and Drug Administration.⁵ The acceptable daily intake of parabens in food is 0 to 10 mg/kg of body weight,¹ and the estimated dietary intake for a typical adult is 307 mg/kg of body weight daily.⁶ Several studies on paraben content in foodstuffs have confirmed their presence in both natural and processed foods.^1,6 Systemic contact dermatitis caused by ingestion of parabens is rare. In general, individuals with positive patch test reactions to parabens should not routinely avoid them in foods or oral medications,¹ but they should, of course, be avoided in topical medications.

What is the rate of ACD with parabens?

One of the main reasons that parabens were designated as the ACDS nonallergen of the year is the very low rate of ACD associated with parabens. The North American Contact Dermatitis Group, a research group with members in the United States and Canada, reported a 0.6% positive reaction rate when patch testing with paraben mix 12%,⁷ which closely compares with a 0.8% positive reaction rate when patch testing with paraben mix 16% using the Mayo Clinic standard series.⁸ From the standpoint of ACD, this very low patch test reaction rate makes parabens one of the safest preservative options for use in cosmetic products.

Are there health risks associated with parabens?

The paraben controversy in the scientific literature and in the lay press centers around potential health risks and endocrine disruption. We will focus on the conversation regarding parabens and the risk for endocrine disruption and association with breast cancer.

Parabens have been reported to have estrogenic effects; however, the bulk of the data is limited to in vitro and animal studies, with less evidence of endocrine disruption in humans.² In vitro studies have demonstrated that the estrogenic potency of parabens is much less than that of estrogen. In one study, parabens were shown to be 10,000-fold less potent than 17β-estradiol⁹; in a separate study, they had a maximum potency of only 1/4000 that of estrogen.¹⁰ Additionally, an in vitro study showed varying ability for parabens to bind estrogen receptors, with a greater ability to bind with longer alkyl side chains.¹¹ The result is decreased or increased estrogen activity, dependent on side chain length and type of receptor.² Finally, some studies add conflicting results that parabens may actually create an antiestrogenic effect in human breast cancer cells.¹² From the standpoint of estrogen mimicry, there are no known studies in humans confirming harmful effects associated with paraben exposure.

The reported association between parabens and breast cancer is closely related to their theoretical estrogenic effects. The conversation regarding parabens and breast cancer has been fueled by the identification of parabens in human breast tumors and their presence in concentrations similar to what is needed to stimulate in vitro breast cancer cells.² The existing data do not confirm causation. An association with parabens in topical axillary personal care products has been theorized but not confirmed; for example, it was shown that paraben levels were highest in the axillary region of breast cancer tissue, including women who had never used deodorant. It was concluded that the presence of axillary parabens was due to sources other than topical axillary personal care products.¹³ Another study confirmed there was not an increased risk for breast cancer in patients who applied personal care products to the axillary area within an hour of shaving.¹⁴ The existing data do not support topical paraben exposure as a risk for breast cancer.

Final Thoughts

Parabens are preservatives frequently found in personal care products and exhibit a very low rate of associated ACD. Consumers may be exposed to parabens through foods, cosmetics, and medications. Although there have been consumer concerns regarding endocrine disruption or carcinogenicity associated with parabens, definite evidence of their harm is lacking in the scientific literature, and many studies confirm their safety.² With their high prevalence in personal care products and low rates of associated contact allergy, parabens remain ideal preservative agents.

Ultimately, contact dermatitis is a common yet often underrecognized dermatologic condition. To address this knowledge gap in clinical practice, we are proud to launch Final Interpretation, a new column in Cutis covering emerging trends in contact dermatitis. We will address pearls, pitfalls, and updates in contact dermatitis. Although our primary focus will be ACD, other important causes of contact dermatitis will be highlighted. Look for the inaugural column in the June 2019 issue of Cutis.

Each year, the American Contact Dermatitis Society (ACDS) names an allergen of the year with the purpose of promoting greater awareness of a key allergen and its impact on patients. Often, the allergen of the year is an emerging allergen that may represent an underrecognized or novel cause of allergic contact dermatitis (ACD). In 2019, the ACDS chose parabens as the “nonallergen” of the year to draw attention to their low rate of associated ACD despite high public interest in limiting exposure to parabens.¹

What types of products contain parabens?

Parabens are preservatives commonly found in many different categories of personal care products. Preservatives inhibit microbial growth and are necessary ingredients in water-based products. The 4 most common parabens used in personal care products are methylparaben, ethylparaben, propylparaben, and butylparaben.¹ Parabens are metabolized to 4-hydroxybenzoic acid and are excreted in urine. When parabens are applied topically, there is minimal penetration through intact human skin.² In the United States, parabens are allowed as preservatives in cosmetics at concentrations up to 0.4% when used alone or up to 0.8% when used in combination with other parabens.³

Consumers are exposed to parabens in a wide variety of personal care products. The Contact Allergen Management Program (CAMP) is a system owned and managed by the ACDS that typically is used to generate lists of safe personal care products for patients and also can be queried for the presence of individual chemicals in products. According to a 2018 query of the CAMP, parabens were found in 19% of all products.¹ A more recent query of CAMP (http://www.contactderm.org/resources/acds-camp) in March 2019 showed parabens were present in 39.3% of makeup products, especially in eye products, foundations, and concealers; parabens also were found in 34% of moisturizers, 11.5% of soaps, and 19% of sunscreens. Notably, 14.8% of prescription topical steroids listed in the CAMP contained a paraben. Another method for evaluating chemical contents of personal care products is a review of the Voluntary Cosmetic Registration Program, a US Food and Drug Administration–based registry for cosmetic products. Survey data from the Voluntary Cosmetic Registration Program in 2018 documented methylparaben in 11,626 formulations.⁴ Other parabens included propylparaben (8885 products), butylparaben (3915 products), and ethylparaben (3860 products). Parabens were reported more frequently in leave-on rather than rinse-off products.⁴

In medications, parabens are recommended at concentrations of no more than 0.1%.¹ Fransway et al¹ compiled a list of medications that contain parabens, including commonly prescribed dermatologic topical medications such as corticosteroids, several acne preparations, eflornithine, fluorouracil, hydroquinone, imiquimod, urea, and sertaconazole. Oral and parenteral medications including local anesthetics and corticosteroids also may contain parabens.

Consumers also may be exposed to parabens through foodstuffs. Methylparaben and propylparaben have been classified as generally recognized as safe in foods by the US Food and Drug Administration.⁵ The acceptable daily intake of parabens in food is 0 to 10 mg/kg of body weight,¹ and the estimated dietary intake for a typical adult is 307 mg/kg of body weight daily.⁶ Several studies on paraben content in foodstuffs have confirmed their presence in both natural and processed foods.^1,6 Systemic contact dermatitis caused by ingestion of parabens is rare. In general, individuals with positive patch test reactions to parabens should not routinely avoid them in foods or oral medications,¹ but they should, of course, be avoided in topical medications.

What is the rate of ACD with parabens?

One of the main reasons that parabens were designated as the ACDS nonallergen of the year is the very low rate of ACD associated with parabens. The North American Contact Dermatitis Group, a research group with members in the United States and Canada, reported a 0.6% positive reaction rate when patch testing with paraben mix 12%,⁷ which closely compares with a 0.8% positive reaction rate when patch testing with paraben mix 16% using the Mayo Clinic standard series.⁸ From the standpoint of ACD, this very low patch test reaction rate makes parabens one of the safest preservative options for use in cosmetic products.

Are there health risks associated with parabens?

The paraben controversy in the scientific literature and in the lay press centers around potential health risks and endocrine disruption. We will focus on the conversation regarding parabens and the risk for endocrine disruption and association with breast cancer.

Parabens have been reported to have estrogenic effects; however, the bulk of the data is limited to in vitro and animal studies, with less evidence of endocrine disruption in humans.² In vitro studies have demonstrated that the estrogenic potency of parabens is much less than that of estrogen. In one study, parabens were shown to be 10,000-fold less potent than 17β-estradiol⁹; in a separate study, they had a maximum potency of only 1/4000 that of estrogen.¹⁰ Additionally, an in vitro study showed varying ability for parabens to bind estrogen receptors, with a greater ability to bind with longer alkyl side chains.¹¹ The result is decreased or increased estrogen activity, dependent on side chain length and type of receptor.² Finally, some studies add conflicting results that parabens may actually create an antiestrogenic effect in human breast cancer cells.¹² From the standpoint of estrogen mimicry, there are no known studies in humans confirming harmful effects associated with paraben exposure.

The reported association between parabens and breast cancer is closely related to their theoretical estrogenic effects. The conversation regarding parabens and breast cancer has been fueled by the identification of parabens in human breast tumors and their presence in concentrations similar to what is needed to stimulate in vitro breast cancer cells.² The existing data do not confirm causation. An association with parabens in topical axillary personal care products has been theorized but not confirmed; for example, it was shown that paraben levels were highest in the axillary region of breast cancer tissue, including women who had never used deodorant. It was concluded that the presence of axillary parabens was due to sources other than topical axillary personal care products.¹³ Another study confirmed there was not an increased risk for breast cancer in patients who applied personal care products to the axillary area within an hour of shaving.¹⁴ The existing data do not support topical paraben exposure as a risk for breast cancer.

Final Thoughts

Parabens are preservatives frequently found in personal care products and exhibit a very low rate of associated ACD. Consumers may be exposed to parabens through foods, cosmetics, and medications. Although there have been consumer concerns regarding endocrine disruption or carcinogenicity associated with parabens, definite evidence of their harm is lacking in the scientific literature, and many studies confirm their safety.² With their high prevalence in personal care products and low rates of associated contact allergy, parabens remain ideal preservative agents.

Ultimately, contact dermatitis is a common yet often underrecognized dermatologic condition. To address this knowledge gap in clinical practice, we are proud to launch Final Interpretation, a new column in Cutis covering emerging trends in contact dermatitis. We will address pearls, pitfalls, and updates in contact dermatitis. Although our primary focus will be ACD, other important causes of contact dermatitis will be highlighted. Look for the inaugural column in the June 2019 issue of Cutis.