Mrs. J, a physically frail but mentally sharp 75-year-old with known metastatic gastric cancer was admitted to the hospital 2 days ago with a small bowel obstruction. Despite appropriate conservative management, her symptoms are worsening. Her prior cancer treatment consisted of gastric resection with reconstruction and chemo and radiation therapy. The probability of identifying a treatable cause for her bowel obstruction during exploratory laparotomy is believed to be small.

Mr. S, a debilitated 58-year-old previously treated with primary chemotherapy and radiation for cancer at the base of his tongue, presents to your office with severe pain due to recurrent disease. The cancer is potentially resectable, but it will require an extensive resection necessitating complex free flap reconstruction in this previously irradiated field.

Is an operation indicated in either/both of these patients? The risk of causing harm with these operations may outweigh the potential benefits, so how do you decide?

Surgery residents have a lot to learn during their residency training. Not only must they gain a mastery of the pathophysiology of surgical disease, they must learn a multitude of operations while they hone their manual dexterity skills. And they must learn how to take care of a multitude of patients.

Less understood and explicitly taught is how to determine whether an operation is appropriate for this specific patient. Understanding the pathophysiology of the patient’s illness is not enough; it requires an ability to effectively communicate with the patient, to understand that person’s hopes and goals, and then honestly determine whether an operation is in fact indicated. It may sound like the antithesis of surgical training, but learning when not to operate is as important as learning when to do so.

Sometimes it’s easy. When the underlying condition is easily treatable by an operation and without it the previously healthy patient will likely die, operation is usually warranted and accepted. For the critically ill patient who will not survive transfer to the operating room and induction of anesthesia, an operation would be impossible.

As illustrated by the patients described at the beginning of this piece, the decision making can be a bit more complicated.

These are the type of patients the surgeon intuitively believes will not do well, but they are referred for an operation and what surgeons do, is ... operate. “To cut is to cure,” is the old adage, not “To cut is to care.”

These are some of the toughest decisions a surgeon can make and are the ones surgeons seem to remember. The enormous responsibility that accompanies the decision to take someone to the operating room and through a potentially difficult postoperative period can be burdensome for the surgeon and potentially fraught with suffering for all.

Understanding how to address goals of care with patients and families can make these decisions easier. Yet these communication skills are not necessarily emphasized during surgical training, and in fact, they are not the forte of many physicians in general, which has led to the growth of the specialty of palliative medicine. Palliative medicine specialists are trained experts in these communication techniques.

One of the cardinal goals of palliative medicine is to help patients and families think about and clarify their treatment goals. Asking questions about “code status” is not the same as exploring someone’s overall treatment goals. Goals can range from wanting to stay alive no matter in what condition to wanting to be kept comfortable at home surrounded by loved ones even if it means a potentially shorter lifespan. By having patients clarify their ultimate goals it may become apparent that a high-risk operation is not the best way to proceed. Perhaps aggressive pain management and arranging effective home support better meets the patient’s overall goals.

You don’t have to be a palliative medicine specialist to have these conversations with patients, but it does require specific communication skills, which can be taught.

For example, many clinicians start their patient encounters by giving a brief overview of the current situation or skip straight to discussions concerning the various treatment options. But are you sure you and your patient are really starting from the same place? You can’t assume that the patient/family truly understands the medical condition, no matter what may be implied in the medical record or the referring physician’s notes. And you can’t assume a patient wants an operation just because he or she shows up in your office.

A more effective way to start the conversation is to begin by asking patients what they understand about their conditions. This will ensure your subsequent discussion corrects any misinformation and better clarifies their understanding of the situation. Starting your encounter in this fashion is critical and can avoid misunderstandings that can lead to treatments the patients do not actually want, and mistrust should complications arise.

An elective rotation with palliative medicine providers to learn these skills can be a great addition to surgical residency training. These conversations can be some of the most meaningful patient interactions a physician can experience. Incorporating an elective rotation with a palliative medicine team into surgical residency training can add value to residency training and have long-lasting benefit for future surgeons, and ultimately, for their patients, as they venture on in their surgical careers.

Nadine B. Semer, M.D., MPH, FACS, is board certified in general surgery, plastic surgery, and palliative medicine. As a reconstructive plastic surgeon, she has worked not only in the United States, but has had the privilege of taking her skills to underserved and resource-poor areas throughout the world. She currently is practicing palliative medicine full time, and is an assistant professor at UT Southwestern Medical School, in Dallas, based at Parkland Hospital.

Mrs. J, a physically frail but mentally sharp 75-year-old with known metastatic gastric cancer was admitted to the hospital 2 days ago with a small bowel obstruction. Despite appropriate conservative management, her symptoms are worsening. Her prior cancer treatment consisted of gastric resection with reconstruction and chemo and radiation therapy. The probability of identifying a treatable cause for her bowel obstruction during exploratory laparotomy is believed to be small.

Mr. S, a debilitated 58-year-old previously treated with primary chemotherapy and radiation for cancer at the base of his tongue, presents to your office with severe pain due to recurrent disease. The cancer is potentially resectable, but it will require an extensive resection necessitating complex free flap reconstruction in this previously irradiated field.

Is an operation indicated in either/both of these patients? The risk of causing harm with these operations may outweigh the potential benefits, so how do you decide?

Surgery residents have a lot to learn during their residency training. Not only must they gain a mastery of the pathophysiology of surgical disease, they must learn a multitude of operations while they hone their manual dexterity skills. And they must learn how to take care of a multitude of patients.

Less understood and explicitly taught is how to determine whether an operation is appropriate for this specific patient. Understanding the pathophysiology of the patient’s illness is not enough; it requires an ability to effectively communicate with the patient, to understand that person’s hopes and goals, and then honestly determine whether an operation is in fact indicated. It may sound like the antithesis of surgical training, but learning when not to operate is as important as learning when to do so.

Sometimes it’s easy. When the underlying condition is easily treatable by an operation and without it the previously healthy patient will likely die, operation is usually warranted and accepted. For the critically ill patient who will not survive transfer to the operating room and induction of anesthesia, an operation would be impossible.

As illustrated by the patients described at the beginning of this piece, the decision making can be a bit more complicated.

These are the type of patients the surgeon intuitively believes will not do well, but they are referred for an operation and what surgeons do, is ... operate. “To cut is to cure,” is the old adage, not “To cut is to care.”

These are some of the toughest decisions a surgeon can make and are the ones surgeons seem to remember. The enormous responsibility that accompanies the decision to take someone to the operating room and through a potentially difficult postoperative period can be burdensome for the surgeon and potentially fraught with suffering for all.

Understanding how to address goals of care with patients and families can make these decisions easier. Yet these communication skills are not necessarily emphasized during surgical training, and in fact, they are not the forte of many physicians in general, which has led to the growth of the specialty of palliative medicine. Palliative medicine specialists are trained experts in these communication techniques.

One of the cardinal goals of palliative medicine is to help patients and families think about and clarify their treatment goals. Asking questions about “code status” is not the same as exploring someone’s overall treatment goals. Goals can range from wanting to stay alive no matter in what condition to wanting to be kept comfortable at home surrounded by loved ones even if it means a potentially shorter lifespan. By having patients clarify their ultimate goals it may become apparent that a high-risk operation is not the best way to proceed. Perhaps aggressive pain management and arranging effective home support better meets the patient’s overall goals.

You don’t have to be a palliative medicine specialist to have these conversations with patients, but it does require specific communication skills, which can be taught.

For example, many clinicians start their patient encounters by giving a brief overview of the current situation or skip straight to discussions concerning the various treatment options. But are you sure you and your patient are really starting from the same place? You can’t assume that the patient/family truly understands the medical condition, no matter what may be implied in the medical record or the referring physician’s notes. And you can’t assume a patient wants an operation just because he or she shows up in your office.

A more effective way to start the conversation is to begin by asking patients what they understand about their conditions. This will ensure your subsequent discussion corrects any misinformation and better clarifies their understanding of the situation. Starting your encounter in this fashion is critical and can avoid misunderstandings that can lead to treatments the patients do not actually want, and mistrust should complications arise.

An elective rotation with palliative medicine providers to learn these skills can be a great addition to surgical residency training. These conversations can be some of the most meaningful patient interactions a physician can experience. Incorporating an elective rotation with a palliative medicine team into surgical residency training can add value to residency training and have long-lasting benefit for future surgeons, and ultimately, for their patients, as they venture on in their surgical careers.

Nadine B. Semer, M.D., MPH, FACS, is board certified in general surgery, plastic surgery, and palliative medicine. As a reconstructive plastic surgeon, she has worked not only in the United States, but has had the privilege of taking her skills to underserved and resource-poor areas throughout the world. She currently is practicing palliative medicine full time, and is an assistant professor at UT Southwestern Medical School, in Dallas, based at Parkland Hospital.

Mrs. J, a physically frail but mentally sharp 75-year-old with known metastatic gastric cancer was admitted to the hospital 2 days ago with a small bowel obstruction. Despite appropriate conservative management, her symptoms are worsening. Her prior cancer treatment consisted of gastric resection with reconstruction and chemo and radiation therapy. The probability of identifying a treatable cause for her bowel obstruction during exploratory laparotomy is believed to be small.

Mr. S, a debilitated 58-year-old previously treated with primary chemotherapy and radiation for cancer at the base of his tongue, presents to your office with severe pain due to recurrent disease. The cancer is potentially resectable, but it will require an extensive resection necessitating complex free flap reconstruction in this previously irradiated field.

Is an operation indicated in either/both of these patients? The risk of causing harm with these operations may outweigh the potential benefits, so how do you decide?

Surgery residents have a lot to learn during their residency training. Not only must they gain a mastery of the pathophysiology of surgical disease, they must learn a multitude of operations while they hone their manual dexterity skills. And they must learn how to take care of a multitude of patients.

Less understood and explicitly taught is how to determine whether an operation is appropriate for this specific patient. Understanding the pathophysiology of the patient’s illness is not enough; it requires an ability to effectively communicate with the patient, to understand that person’s hopes and goals, and then honestly determine whether an operation is in fact indicated. It may sound like the antithesis of surgical training, but learning when not to operate is as important as learning when to do so.

Sometimes it’s easy. When the underlying condition is easily treatable by an operation and without it the previously healthy patient will likely die, operation is usually warranted and accepted. For the critically ill patient who will not survive transfer to the operating room and induction of anesthesia, an operation would be impossible.

As illustrated by the patients described at the beginning of this piece, the decision making can be a bit more complicated.

These are the type of patients the surgeon intuitively believes will not do well, but they are referred for an operation and what surgeons do, is ... operate. “To cut is to cure,” is the old adage, not “To cut is to care.”

These are some of the toughest decisions a surgeon can make and are the ones surgeons seem to remember. The enormous responsibility that accompanies the decision to take someone to the operating room and through a potentially difficult postoperative period can be burdensome for the surgeon and potentially fraught with suffering for all.

Understanding how to address goals of care with patients and families can make these decisions easier. Yet these communication skills are not necessarily emphasized during surgical training, and in fact, they are not the forte of many physicians in general, which has led to the growth of the specialty of palliative medicine. Palliative medicine specialists are trained experts in these communication techniques.

One of the cardinal goals of palliative medicine is to help patients and families think about and clarify their treatment goals. Asking questions about “code status” is not the same as exploring someone’s overall treatment goals. Goals can range from wanting to stay alive no matter in what condition to wanting to be kept comfortable at home surrounded by loved ones even if it means a potentially shorter lifespan. By having patients clarify their ultimate goals it may become apparent that a high-risk operation is not the best way to proceed. Perhaps aggressive pain management and arranging effective home support better meets the patient’s overall goals.

You don’t have to be a palliative medicine specialist to have these conversations with patients, but it does require specific communication skills, which can be taught.

For example, many clinicians start their patient encounters by giving a brief overview of the current situation or skip straight to discussions concerning the various treatment options. But are you sure you and your patient are really starting from the same place? You can’t assume that the patient/family truly understands the medical condition, no matter what may be implied in the medical record or the referring physician’s notes. And you can’t assume a patient wants an operation just because he or she shows up in your office.

A more effective way to start the conversation is to begin by asking patients what they understand about their conditions. This will ensure your subsequent discussion corrects any misinformation and better clarifies their understanding of the situation. Starting your encounter in this fashion is critical and can avoid misunderstandings that can lead to treatments the patients do not actually want, and mistrust should complications arise.

An elective rotation with palliative medicine providers to learn these skills can be a great addition to surgical residency training. These conversations can be some of the most meaningful patient interactions a physician can experience. Incorporating an elective rotation with a palliative medicine team into surgical residency training can add value to residency training and have long-lasting benefit for future surgeons, and ultimately, for their patients, as they venture on in their surgical careers.

Nadine B. Semer, M.D., MPH, FACS, is board certified in general surgery, plastic surgery, and palliative medicine. As a reconstructive plastic surgeon, she has worked not only in the United States, but has had the privilege of taking her skills to underserved and resource-poor areas throughout the world. She currently is practicing palliative medicine full time, and is an assistant professor at UT Southwestern Medical School, in Dallas, based at Parkland Hospital.

Researchers have devised a simple and reproducible method of tracking the cellular origin of chronic lymphocytic leukemia (CLL) by applying five epigenetic biomarkers. By using this strategy, CLL patients can be categorized into three epigenetic subgroups with differential clinicobiologic features and outcomes – naive B-cell-like, intermediate, and memory B-cell-like CLL, according to a paper published in Leukemia.

Being able to identify CLL patients early on who are destined to progress would greatly help their clinical management, said Dr. Ana C. Queirós of the University of Barcelona and colleagues (Leukemia. 2015;29:598-605.

Courtesy Wikimedia Commons/Nephron/Creative Commons BY-SA-3.0

“We believe that the most relevant information obtained by the five epigenetic biomarkers is to classify CLL patients based on the putative cell of origin of the disease rather than being a mere additional prognostic biomarker,” the investigators wrote. “The recent advance in the genetics and cellular biology of CLL, including the present epigenetic classification, could result in the use of targeted therapies for specific subgroups of patients.”

In previous research, the authors identified the presence of three subgroups of CLL with different clinicobiologic features, and in this study they hypothesized that DNA methylation patterns associated with normal B cells could be used to classify CLL into three novel subgroups.

To test their hypothesis and to develop a clinically useful strategy, they identified five epigenetic biomarkers and established new quantitative DNA methylation assays, applying them to two independent series of CLL patients of different geographical origin.

The first epigenetic classification was determined in an initial cohort of 211 CLL patients and then validated in a series of 97 additional CLL patients.

To test the stability of these markers over time and after treatment, two or three sequential samples were analyzed from 27 CLL patients with a median difference between samples of 59 months (range, 5-114). In addition, specimens from 13 patients, from before and after treatment, also were analyzed.

In the initial 211 patients, the three subgroups had different levels of immunoglobulin heavy-chain locus (IGHV) mutation (P <.001) and VH gene usage (P <.03). There also were different clinical features and outcomes in regard to their time to first treatment and overall survival (P <.001), Dr. Queirós and associates reported.

After a Cox multivariate analysis, the final model showed that the epigenetic signature related to the cellular origin of CLL was the most important variable in predicting time to first treatment. Other important variables in the model were Binet stage, CD38 expression, LDH levels, and SF3B1 mutations.

The study was funded by the Spanish Ministry of Economy and Competitiveness (MINECO) through the Instituto de Salud Carlos III (ISCIII) and the Red Temática de Investigación del Cáncer (RTICC) of the ISCIII and project SAF2009-08663, the UK Medical Research Council, and the European Union’s Seventh Framework Programme through the Blueprint Consortium. The authors declared no conflicts of interest.

Researchers have devised a simple and reproducible method of tracking the cellular origin of chronic lymphocytic leukemia (CLL) by applying five epigenetic biomarkers. By using this strategy, CLL patients can be categorized into three epigenetic subgroups with differential clinicobiologic features and outcomes – naive B-cell-like, intermediate, and memory B-cell-like CLL, according to a paper published in Leukemia.

Being able to identify CLL patients early on who are destined to progress would greatly help their clinical management, said Dr. Ana C. Queirós of the University of Barcelona and colleagues (Leukemia. 2015;29:598-605.

Courtesy Wikimedia Commons/Nephron/Creative Commons BY-SA-3.0

“We believe that the most relevant information obtained by the five epigenetic biomarkers is to classify CLL patients based on the putative cell of origin of the disease rather than being a mere additional prognostic biomarker,” the investigators wrote. “The recent advance in the genetics and cellular biology of CLL, including the present epigenetic classification, could result in the use of targeted therapies for specific subgroups of patients.”

In previous research, the authors identified the presence of three subgroups of CLL with different clinicobiologic features, and in this study they hypothesized that DNA methylation patterns associated with normal B cells could be used to classify CLL into three novel subgroups.

To test their hypothesis and to develop a clinically useful strategy, they identified five epigenetic biomarkers and established new quantitative DNA methylation assays, applying them to two independent series of CLL patients of different geographical origin.

The first epigenetic classification was determined in an initial cohort of 211 CLL patients and then validated in a series of 97 additional CLL patients.

To test the stability of these markers over time and after treatment, two or three sequential samples were analyzed from 27 CLL patients with a median difference between samples of 59 months (range, 5-114). In addition, specimens from 13 patients, from before and after treatment, also were analyzed.

In the initial 211 patients, the three subgroups had different levels of immunoglobulin heavy-chain locus (IGHV) mutation (P <.001) and VH gene usage (P <.03). There also were different clinical features and outcomes in regard to their time to first treatment and overall survival (P <.001), Dr. Queirós and associates reported.

After a Cox multivariate analysis, the final model showed that the epigenetic signature related to the cellular origin of CLL was the most important variable in predicting time to first treatment. Other important variables in the model were Binet stage, CD38 expression, LDH levels, and SF3B1 mutations.

The study was funded by the Spanish Ministry of Economy and Competitiveness (MINECO) through the Instituto de Salud Carlos III (ISCIII) and the Red Temática de Investigación del Cáncer (RTICC) of the ISCIII and project SAF2009-08663, the UK Medical Research Council, and the European Union’s Seventh Framework Programme through the Blueprint Consortium. The authors declared no conflicts of interest.

Researchers have devised a simple and reproducible method of tracking the cellular origin of chronic lymphocytic leukemia (CLL) by applying five epigenetic biomarkers. By using this strategy, CLL patients can be categorized into three epigenetic subgroups with differential clinicobiologic features and outcomes – naive B-cell-like, intermediate, and memory B-cell-like CLL, according to a paper published in Leukemia.

Being able to identify CLL patients early on who are destined to progress would greatly help their clinical management, said Dr. Ana C. Queirós of the University of Barcelona and colleagues (Leukemia. 2015;29:598-605.

Courtesy Wikimedia Commons/Nephron/Creative Commons BY-SA-3.0

“We believe that the most relevant information obtained by the five epigenetic biomarkers is to classify CLL patients based on the putative cell of origin of the disease rather than being a mere additional prognostic biomarker,” the investigators wrote. “The recent advance in the genetics and cellular biology of CLL, including the present epigenetic classification, could result in the use of targeted therapies for specific subgroups of patients.”

In previous research, the authors identified the presence of three subgroups of CLL with different clinicobiologic features, and in this study they hypothesized that DNA methylation patterns associated with normal B cells could be used to classify CLL into three novel subgroups.

To test their hypothesis and to develop a clinically useful strategy, they identified five epigenetic biomarkers and established new quantitative DNA methylation assays, applying them to two independent series of CLL patients of different geographical origin.

The first epigenetic classification was determined in an initial cohort of 211 CLL patients and then validated in a series of 97 additional CLL patients.

To test the stability of these markers over time and after treatment, two or three sequential samples were analyzed from 27 CLL patients with a median difference between samples of 59 months (range, 5-114). In addition, specimens from 13 patients, from before and after treatment, also were analyzed.

In the initial 211 patients, the three subgroups had different levels of immunoglobulin heavy-chain locus (IGHV) mutation (P <.001) and VH gene usage (P <.03). There also were different clinical features and outcomes in regard to their time to first treatment and overall survival (P <.001), Dr. Queirós and associates reported.

After a Cox multivariate analysis, the final model showed that the epigenetic signature related to the cellular origin of CLL was the most important variable in predicting time to first treatment. Other important variables in the model were Binet stage, CD38 expression, LDH levels, and SF3B1 mutations.

The study was funded by the Spanish Ministry of Economy and Competitiveness (MINECO) through the Instituto de Salud Carlos III (ISCIII) and the Red Temática de Investigación del Cáncer (RTICC) of the ISCIII and project SAF2009-08663, the UK Medical Research Council, and the European Union’s Seventh Framework Programme through the Blueprint Consortium. The authors declared no conflicts of interest.

The Diagnosis: Fixed Cutaneous Sporotrichosis

On further questioning at our dermatology clinic, the patient reported having landed face-first into rocks and gravel during the all-terrain vehicle accident. After his medical history was noted and a physical examination was completed, bacterial and fungal cultures of the wound were taken. The fungal culture was positive for Sporothrix schenckii. The patient was prescribed itraconazole 200 mg 3 times daily for 3 days, then 200 mg twice daily for an additional 4 weeks after the lesions completely resolved. An ophthalmologist was immediately consulted to rule out sinus and periorbital involvement. After computed tomography revealed possible preseptal cellulitis with frontal sinus involvement, the patient was admitted and intravenous amphotericin B was administered. Following consultations with infectious disease specialists and radiologists, amphotericin B was discontinued and the patient was discharged on itraconazole 200 mg twice daily with close monitoring. At 3-month follow-up, the sporotrichosis infection had completely cleared (Figure).

Deep fungal infections comprise 2 distinct groups: systemic and subcutaneous mycoses. Individuals with subcutaneous mycoses present with skin involvement as the primary feature. Sporotrichosis is the most common cause of this type of mycosis¹ and is caused by the dimorphic fungus S schenckii, an environmental saprophyte often residing in soil. Sporothrix schenckii exists as mold in a natural environment but exists as yeast in host tissue, thus causing ensuing infection.

Epidemiology

Sporotrichosis occurs worldwide but most frequently in temperate tropical and subtropical regions. The majority of cases are reported in Mexico and Central and South America¹; however, cases have been seen in the southern United States, Japan, and Australia.² In the United States, sporotrichosis is most commonly found in river valleys of the Midwest.

Sporothrix schenckii is most commonly isolated in hay, sphagnum moss, thorny plants, and soil, but it also has been described in other manifold host environments. Unusual origins of inoculation include an old and rust-stained camping tent in Mexico,³ crawl space joists of a house in Indiana,⁴ and hay bales used as props in a haunted house in Oklahoma.⁵

The incidence of infection is primarily sporadic; however, outbreaks among individuals who share a common environment favorable for the growth of S schenckii are at risk. Those identified to be at risk include rose gardeners, berry pickers, those who work in tree nurseries, horticulturists, landscapers, and miners.

Pathogenesis

As a dimorphic fungus, infection occurs when a conidium in the mold phase is introduced into the skin, usually by traumatic skin injury, and is 
converted to the yeast form in vivo. Distribution of infection by this organism is most commonly 
localized to the cutaneous, subcutaneous, and lymphocutaneous regions in healthy hosts but can involve visceral and osteoarticular structures in immunocompromised hosts.^1,6 Pulmonary and disseminated forms are rare but can occur when 
S schenckii conidia are inhaled. Zoonotic transmission of the fungus also can occur with exposure to infected animals. Sporothrix schenckii has been reported to occur in cats, dogs, horses, donkeys, squirrels, armadillos, and dolphins.^7-11

Pathology

Sporothrix schenckii is typically not visualized on microscopic examination due to the small number of microorganisms present; however, cultures grow rapidly 
(3–5 days) on Sabouraud agar. The fungus most commonly develops as white or off-white compact colonies that progressively darken with age, transitioning to gray and then black.¹ Microscopically, the hyphae produce oval or pyriform conidia, which are assembled 
in a typical bouquetlike manner. Conversion of the organism to yeast on enriched medium such as brain-heart infusion agar or blood-cysteine-glucose agar confirms the diagnosis.

Acute lesions typically show a nonspecific mixed infiltrate, but established lesions may reveal granulomatous formation and neutrophilic microabscesses.^1,2 Asteroid bodies, which are cigar-shaped yeasts surrounded by eosinophilic coronae radiata, may be found. Organisms are sparsely distributed within the lesions, necessitating a thorough examination of the culture for identification.

Clinical Features

Sporotrichosis has 3 main classifications: lymphocutaneous, fixed cutaneous, and disseminated. Lymphocutaneous sporotrichosis is the most common form of the infection.² The disease presents with a small indurated papule occurring approximately 7 to 30 days after inoculation into the skin. The papule slowly enlarges, forms a nodule, and then frequently ulcerates. Over time, draining lymphatics become edematous and inflammatory, and a chain of secondary nodules begins to appear proximal to the initial lesion. The primary and secondary nodules may continue to ulcerate; alternately, they may heal or become chronic.

In fixed cutaneous sporotrichosis, the infection remains localized to one region and a granuloma may develop, which also may ulcerate. Satellite nodules may appear along the periphery of the lesion. Lymphatic spread is not observed in this form of 
the disease.

The disseminated form is a result of hematogenous spread from the primary inoculation site and typically occurs in an immunocompromised host. This form can present as pulmonary disease, sinusitis, and meningitis.¹

Differential Diagnosis

The differential diagnosis for sporotrichosis includes atypical mycobacteria, nocardiosis, blastomycosis, pyogenic bacteria, leishmaniasis, tularemia, 
and tuberculosis.

Treatment

Treatment of sporotrichosis is always required. A saturated solution of potassium iodide has classically been used; however, it is frequently associated with side effects and can be problematic to administer.¹² Given its low cost and traditional efficacy, it may still be used in some parts of the world.

Currently, the treatment of choice for fixed cutaneous and lymphocutaneous sporotrichosis is itraconazole 100 to 200 mg once daily for 3 to 6 months.¹ The recommended treatment of osteoarticular sporotrichosis is itraconazole, but prolonged therapy is required.

Heat therapy is an alternative treatment option, as certain strains of S schenckii do not grow at temperatures higher than 35°C. Hot compresses must be used for at least 1 hour a day for several months, which may affect patient compliance.

Immunocompromised patients often have disseminated infection and require lifelong suppressive therapy with itraconazole and may require initial treatment with amphotericin B.¹³

Conclusion

Subcutaneous sporotrichosis can develop in patients with a traumatic injury involving vegetation, soil, or animals. Although some patients may develop more invasive disease, most infections in immunocompetent patients will resolve after 3 to 6 months of itraconazole 100 to 200 mg once daily.¹

The Diagnosis: Fixed Cutaneous Sporotrichosis

On further questioning at our dermatology clinic, the patient reported having landed face-first into rocks and gravel during the all-terrain vehicle accident. After his medical history was noted and a physical examination was completed, bacterial and fungal cultures of the wound were taken. The fungal culture was positive for Sporothrix schenckii. The patient was prescribed itraconazole 200 mg 3 times daily for 3 days, then 200 mg twice daily for an additional 4 weeks after the lesions completely resolved. An ophthalmologist was immediately consulted to rule out sinus and periorbital involvement. After computed tomography revealed possible preseptal cellulitis with frontal sinus involvement, the patient was admitted and intravenous amphotericin B was administered. Following consultations with infectious disease specialists and radiologists, amphotericin B was discontinued and the patient was discharged on itraconazole 200 mg twice daily with close monitoring. At 3-month follow-up, the sporotrichosis infection had completely cleared (Figure).

Deep fungal infections comprise 2 distinct groups: systemic and subcutaneous mycoses. Individuals with subcutaneous mycoses present with skin involvement as the primary feature. Sporotrichosis is the most common cause of this type of mycosis¹ and is caused by the dimorphic fungus S schenckii, an environmental saprophyte often residing in soil. Sporothrix schenckii exists as mold in a natural environment but exists as yeast in host tissue, thus causing ensuing infection.

Epidemiology

Sporotrichosis occurs worldwide but most frequently in temperate tropical and subtropical regions. The majority of cases are reported in Mexico and Central and South America¹; however, cases have been seen in the southern United States, Japan, and Australia.² In the United States, sporotrichosis is most commonly found in river valleys of the Midwest.

Sporothrix schenckii is most commonly isolated in hay, sphagnum moss, thorny plants, and soil, but it also has been described in other manifold host environments. Unusual origins of inoculation include an old and rust-stained camping tent in Mexico,³ crawl space joists of a house in Indiana,⁴ and hay bales used as props in a haunted house in Oklahoma.⁵

The incidence of infection is primarily sporadic; however, outbreaks among individuals who share a common environment favorable for the growth of S schenckii are at risk. Those identified to be at risk include rose gardeners, berry pickers, those who work in tree nurseries, horticulturists, landscapers, and miners.

Pathogenesis

As a dimorphic fungus, infection occurs when a conidium in the mold phase is introduced into the skin, usually by traumatic skin injury, and is 
converted to the yeast form in vivo. Distribution of infection by this organism is most commonly 
localized to the cutaneous, subcutaneous, and lymphocutaneous regions in healthy hosts but can involve visceral and osteoarticular structures in immunocompromised hosts.^1,6 Pulmonary and disseminated forms are rare but can occur when 
S schenckii conidia are inhaled. Zoonotic transmission of the fungus also can occur with exposure to infected animals. Sporothrix schenckii has been reported to occur in cats, dogs, horses, donkeys, squirrels, armadillos, and dolphins.^7-11

Pathology

Sporothrix schenckii is typically not visualized on microscopic examination due to the small number of microorganisms present; however, cultures grow rapidly 
(3–5 days) on Sabouraud agar. The fungus most commonly develops as white or off-white compact colonies that progressively darken with age, transitioning to gray and then black.¹ Microscopically, the hyphae produce oval or pyriform conidia, which are assembled 
in a typical bouquetlike manner. Conversion of the organism to yeast on enriched medium such as brain-heart infusion agar or blood-cysteine-glucose agar confirms the diagnosis.

Acute lesions typically show a nonspecific mixed infiltrate, but established lesions may reveal granulomatous formation and neutrophilic microabscesses.^1,2 Asteroid bodies, which are cigar-shaped yeasts surrounded by eosinophilic coronae radiata, may be found. Organisms are sparsely distributed within the lesions, necessitating a thorough examination of the culture for identification.

Clinical Features

Sporotrichosis has 3 main classifications: lymphocutaneous, fixed cutaneous, and disseminated. Lymphocutaneous sporotrichosis is the most common form of the infection.² The disease presents with a small indurated papule occurring approximately 7 to 30 days after inoculation into the skin. The papule slowly enlarges, forms a nodule, and then frequently ulcerates. Over time, draining lymphatics become edematous and inflammatory, and a chain of secondary nodules begins to appear proximal to the initial lesion. The primary and secondary nodules may continue to ulcerate; alternately, they may heal or become chronic.

In fixed cutaneous sporotrichosis, the infection remains localized to one region and a granuloma may develop, which also may ulcerate. Satellite nodules may appear along the periphery of the lesion. Lymphatic spread is not observed in this form of 
the disease.

The disseminated form is a result of hematogenous spread from the primary inoculation site and typically occurs in an immunocompromised host. This form can present as pulmonary disease, sinusitis, and meningitis.¹

Differential Diagnosis

The differential diagnosis for sporotrichosis includes atypical mycobacteria, nocardiosis, blastomycosis, pyogenic bacteria, leishmaniasis, tularemia, 
and tuberculosis.

Treatment

Treatment of sporotrichosis is always required. A saturated solution of potassium iodide has classically been used; however, it is frequently associated with side effects and can be problematic to administer.¹² Given its low cost and traditional efficacy, it may still be used in some parts of the world.

Currently, the treatment of choice for fixed cutaneous and lymphocutaneous sporotrichosis is itraconazole 100 to 200 mg once daily for 3 to 6 months.¹ The recommended treatment of osteoarticular sporotrichosis is itraconazole, but prolonged therapy is required.

Heat therapy is an alternative treatment option, as certain strains of S schenckii do not grow at temperatures higher than 35°C. Hot compresses must be used for at least 1 hour a day for several months, which may affect patient compliance.

Immunocompromised patients often have disseminated infection and require lifelong suppressive therapy with itraconazole and may require initial treatment with amphotericin B.¹³

Conclusion

Subcutaneous sporotrichosis can develop in patients with a traumatic injury involving vegetation, soil, or animals. Although some patients may develop more invasive disease, most infections in immunocompetent patients will resolve after 3 to 6 months of itraconazole 100 to 200 mg once daily.¹

The Diagnosis: Fixed Cutaneous Sporotrichosis

On further questioning at our dermatology clinic, the patient reported having landed face-first into rocks and gravel during the all-terrain vehicle accident. After his medical history was noted and a physical examination was completed, bacterial and fungal cultures of the wound were taken. The fungal culture was positive for Sporothrix schenckii. The patient was prescribed itraconazole 200 mg 3 times daily for 3 days, then 200 mg twice daily for an additional 4 weeks after the lesions completely resolved. An ophthalmologist was immediately consulted to rule out sinus and periorbital involvement. After computed tomography revealed possible preseptal cellulitis with frontal sinus involvement, the patient was admitted and intravenous amphotericin B was administered. Following consultations with infectious disease specialists and radiologists, amphotericin B was discontinued and the patient was discharged on itraconazole 200 mg twice daily with close monitoring. At 3-month follow-up, the sporotrichosis infection had completely cleared (Figure).

Deep fungal infections comprise 2 distinct groups: systemic and subcutaneous mycoses. Individuals with subcutaneous mycoses present with skin involvement as the primary feature. Sporotrichosis is the most common cause of this type of mycosis¹ and is caused by the dimorphic fungus S schenckii, an environmental saprophyte often residing in soil. Sporothrix schenckii exists as mold in a natural environment but exists as yeast in host tissue, thus causing ensuing infection.

Epidemiology

Sporotrichosis occurs worldwide but most frequently in temperate tropical and subtropical regions. The majority of cases are reported in Mexico and Central and South America¹; however, cases have been seen in the southern United States, Japan, and Australia.² In the United States, sporotrichosis is most commonly found in river valleys of the Midwest.

Sporothrix schenckii is most commonly isolated in hay, sphagnum moss, thorny plants, and soil, but it also has been described in other manifold host environments. Unusual origins of inoculation include an old and rust-stained camping tent in Mexico,³ crawl space joists of a house in Indiana,⁴ and hay bales used as props in a haunted house in Oklahoma.⁵

The incidence of infection is primarily sporadic; however, outbreaks among individuals who share a common environment favorable for the growth of S schenckii are at risk. Those identified to be at risk include rose gardeners, berry pickers, those who work in tree nurseries, horticulturists, landscapers, and miners.

Pathogenesis

As a dimorphic fungus, infection occurs when a conidium in the mold phase is introduced into the skin, usually by traumatic skin injury, and is 
converted to the yeast form in vivo. Distribution of infection by this organism is most commonly 
localized to the cutaneous, subcutaneous, and lymphocutaneous regions in healthy hosts but can involve visceral and osteoarticular structures in immunocompromised hosts.^1,6 Pulmonary and disseminated forms are rare but can occur when 
S schenckii conidia are inhaled. Zoonotic transmission of the fungus also can occur with exposure to infected animals. Sporothrix schenckii has been reported to occur in cats, dogs, horses, donkeys, squirrels, armadillos, and dolphins.^7-11

Pathology

Sporothrix schenckii is typically not visualized on microscopic examination due to the small number of microorganisms present; however, cultures grow rapidly 
(3–5 days) on Sabouraud agar. The fungus most commonly develops as white or off-white compact colonies that progressively darken with age, transitioning to gray and then black.¹ Microscopically, the hyphae produce oval or pyriform conidia, which are assembled 
in a typical bouquetlike manner. Conversion of the organism to yeast on enriched medium such as brain-heart infusion agar or blood-cysteine-glucose agar confirms the diagnosis.

Acute lesions typically show a nonspecific mixed infiltrate, but established lesions may reveal granulomatous formation and neutrophilic microabscesses.^1,2 Asteroid bodies, which are cigar-shaped yeasts surrounded by eosinophilic coronae radiata, may be found. Organisms are sparsely distributed within the lesions, necessitating a thorough examination of the culture for identification.

Clinical Features

Sporotrichosis has 3 main classifications: lymphocutaneous, fixed cutaneous, and disseminated. Lymphocutaneous sporotrichosis is the most common form of the infection.² The disease presents with a small indurated papule occurring approximately 7 to 30 days after inoculation into the skin. The papule slowly enlarges, forms a nodule, and then frequently ulcerates. Over time, draining lymphatics become edematous and inflammatory, and a chain of secondary nodules begins to appear proximal to the initial lesion. The primary and secondary nodules may continue to ulcerate; alternately, they may heal or become chronic.

In fixed cutaneous sporotrichosis, the infection remains localized to one region and a granuloma may develop, which also may ulcerate. Satellite nodules may appear along the periphery of the lesion. Lymphatic spread is not observed in this form of 
the disease.

The disseminated form is a result of hematogenous spread from the primary inoculation site and typically occurs in an immunocompromised host. This form can present as pulmonary disease, sinusitis, and meningitis.¹

Differential Diagnosis

The differential diagnosis for sporotrichosis includes atypical mycobacteria, nocardiosis, blastomycosis, pyogenic bacteria, leishmaniasis, tularemia, 
and tuberculosis.

Treatment

Treatment of sporotrichosis is always required. A saturated solution of potassium iodide has classically been used; however, it is frequently associated with side effects and can be problematic to administer.¹² Given its low cost and traditional efficacy, it may still be used in some parts of the world.

Currently, the treatment of choice for fixed cutaneous and lymphocutaneous sporotrichosis is itraconazole 100 to 200 mg once daily for 3 to 6 months.¹ The recommended treatment of osteoarticular sporotrichosis is itraconazole, but prolonged therapy is required.

Heat therapy is an alternative treatment option, as certain strains of S schenckii do not grow at temperatures higher than 35°C. Hot compresses must be used for at least 1 hour a day for several months, which may affect patient compliance.

Immunocompromised patients often have disseminated infection and require lifelong suppressive therapy with itraconazole and may require initial treatment with amphotericin B.¹³

Conclusion

Subcutaneous sporotrichosis can develop in patients with a traumatic injury involving vegetation, soil, or animals. Although some patients may develop more invasive disease, most infections in immunocompetent patients will resolve after 3 to 6 months of itraconazole 100 to 200 mg once daily.¹

Case Report

An 18-year-old Iranian man presented to the dermatology clinic with hair loss of 1 night’s duration. He denied pruritus, pain, discharge, or flaking. The patient had no notable personal, family, or surgical history and was not currently taking any medications. He denied recent travel. The patient reported that he found hair on his pillow upon waking up in the morning prior to coming to the clinic. On physical examination, 2 ants 
(Figure 1) were found on the scalp and alopecia with a vertical linear distribution was noted (Figure 2). Hairs of various lengths were found on the scalp within the distribution of the alopecia. No excoriations, crusting, seborrhea, or other areas of hair loss were detected. Wood lamp examination was negative. Based on these findings, which were concordant with similar findings from prior reports,^1-4 a diagnosis of ant-induced alopecia was made. Hair regrowth was noted within 1 week with full appearance of normal-length hair within 2.5 weeks.

Comment

Ant-induced alopecia is a form of localized hair loss caused by the Pheidole genus, the second largest genus of ants in the world.⁵ These ants can be found worldwide, but most cases of ant-induced alopecia have been from Iran, with at least 1 reported case from Turkey.^1-4,6 An early case series of ant-induced alopecia was reported in 1999,⁶ but the causative species was not described at that time.

The majority of reported cases of ant-induced alopecia are attributed to the barber ant (Pheidole pallidula). This type of alopecia is caused by worker ants within the species hierarchy.^1,4,6 The P pallidula worker ants are dimorphic and are classified as major and minor workers.⁷ Major workers have body lengths ranging up to 6 mm, whereas minor workers have body lengths ranging up to 4 mm. Major workers have larger heads and mandibles than minor workers and also have up to 2 pairs of denticles on the cranium.⁵ The minor workers are foragers and mainly collect food, whereas the major workers defend the nest and store food.⁸ These ants have widespread habitats with the ability to live in indoor and outdoor environments.

The presentation of hair loss caused by these ants is acute. Hair loss usually is confined to one specific area. Some patients may report pruritus or may present with erythematous lesions from ant stings or manual scratching.⁵ None of these signs or symptoms were seen in our patient. Some investigators have suggested that the barber ant is attracted to the hair of individuals with seborrheic dermatitis,¹ but our patient had no medical history of seborrheic dermatitis. Most likely, ants are attracted to excess sebum on the scalp in select individuals in their search for food and cause localized hair destruction.

Localized hair loss, as depicted in our case, should warrant a thorough evaluation for alopecia areata, trichotillomania, and tinea capitis.⁹ Alopecia areata should be considered in individuals with multiple focal patches of hair loss that have a positive hair pull test from peripheral sites of active lesions. Tinea capitis usually has localized sites of hair loss with underlying scaling, crusting, pruritus, erythema, and discharge from lesions, with positive potassium hydroxide preparations or fungal cultures. Trichotillomania typically presents with a spared peripheral fringe of hair. Remaining hairs may be thick and hyperpigmented as a response to repeated pulling, and biopsy often demonstrates fracture or degeneration of the hair shaft. A psychiatric evaluation may be warranted in cases of trichotillomania. Other cases of arthropod-induced hair loss include tick bite alopecia^10,11 and hair loss induced by numerous honeybee stings,¹² and these diagnoses should be suspected in patients with a history of ants on their pillow or in those from endemic areas.

No specific treatment is indicated in cases of 
ant-induced alopecia because hair usually regrows to its normal length without intervention.

Case Report

An 18-year-old Iranian man presented to the dermatology clinic with hair loss of 1 night’s duration. He denied pruritus, pain, discharge, or flaking. The patient had no notable personal, family, or surgical history and was not currently taking any medications. He denied recent travel. The patient reported that he found hair on his pillow upon waking up in the morning prior to coming to the clinic. On physical examination, 2 ants 
(Figure 1) were found on the scalp and alopecia with a vertical linear distribution was noted (Figure 2). Hairs of various lengths were found on the scalp within the distribution of the alopecia. No excoriations, crusting, seborrhea, or other areas of hair loss were detected. Wood lamp examination was negative. Based on these findings, which were concordant with similar findings from prior reports,^1-4 a diagnosis of ant-induced alopecia was made. Hair regrowth was noted within 1 week with full appearance of normal-length hair within 2.5 weeks.

Comment

Ant-induced alopecia is a form of localized hair loss caused by the Pheidole genus, the second largest genus of ants in the world.⁵ These ants can be found worldwide, but most cases of ant-induced alopecia have been from Iran, with at least 1 reported case from Turkey.^1-4,6 An early case series of ant-induced alopecia was reported in 1999,⁶ but the causative species was not described at that time.

The majority of reported cases of ant-induced alopecia are attributed to the barber ant (Pheidole pallidula). This type of alopecia is caused by worker ants within the species hierarchy.^1,4,6 The P pallidula worker ants are dimorphic and are classified as major and minor workers.⁷ Major workers have body lengths ranging up to 6 mm, whereas minor workers have body lengths ranging up to 4 mm. Major workers have larger heads and mandibles than minor workers and also have up to 2 pairs of denticles on the cranium.⁵ The minor workers are foragers and mainly collect food, whereas the major workers defend the nest and store food.⁸ These ants have widespread habitats with the ability to live in indoor and outdoor environments.

The presentation of hair loss caused by these ants is acute. Hair loss usually is confined to one specific area. Some patients may report pruritus or may present with erythematous lesions from ant stings or manual scratching.⁵ None of these signs or symptoms were seen in our patient. Some investigators have suggested that the barber ant is attracted to the hair of individuals with seborrheic dermatitis,¹ but our patient had no medical history of seborrheic dermatitis. Most likely, ants are attracted to excess sebum on the scalp in select individuals in their search for food and cause localized hair destruction.

Localized hair loss, as depicted in our case, should warrant a thorough evaluation for alopecia areata, trichotillomania, and tinea capitis.⁹ Alopecia areata should be considered in individuals with multiple focal patches of hair loss that have a positive hair pull test from peripheral sites of active lesions. Tinea capitis usually has localized sites of hair loss with underlying scaling, crusting, pruritus, erythema, and discharge from lesions, with positive potassium hydroxide preparations or fungal cultures. Trichotillomania typically presents with a spared peripheral fringe of hair. Remaining hairs may be thick and hyperpigmented as a response to repeated pulling, and biopsy often demonstrates fracture or degeneration of the hair shaft. A psychiatric evaluation may be warranted in cases of trichotillomania. Other cases of arthropod-induced hair loss include tick bite alopecia^10,11 and hair loss induced by numerous honeybee stings,¹² and these diagnoses should be suspected in patients with a history of ants on their pillow or in those from endemic areas.

No specific treatment is indicated in cases of 
ant-induced alopecia because hair usually regrows to its normal length without intervention.

Case Report

An 18-year-old Iranian man presented to the dermatology clinic with hair loss of 1 night’s duration. He denied pruritus, pain, discharge, or flaking. The patient had no notable personal, family, or surgical history and was not currently taking any medications. He denied recent travel. The patient reported that he found hair on his pillow upon waking up in the morning prior to coming to the clinic. On physical examination, 2 ants 
(Figure 1) were found on the scalp and alopecia with a vertical linear distribution was noted (Figure 2). Hairs of various lengths were found on the scalp within the distribution of the alopecia. No excoriations, crusting, seborrhea, or other areas of hair loss were detected. Wood lamp examination was negative. Based on these findings, which were concordant with similar findings from prior reports,^1-4 a diagnosis of ant-induced alopecia was made. Hair regrowth was noted within 1 week with full appearance of normal-length hair within 2.5 weeks.

Comment

Ant-induced alopecia is a form of localized hair loss caused by the Pheidole genus, the second largest genus of ants in the world.⁵ These ants can be found worldwide, but most cases of ant-induced alopecia have been from Iran, with at least 1 reported case from Turkey.^1-4,6 An early case series of ant-induced alopecia was reported in 1999,⁶ but the causative species was not described at that time.

The majority of reported cases of ant-induced alopecia are attributed to the barber ant (Pheidole pallidula). This type of alopecia is caused by worker ants within the species hierarchy.^1,4,6 The P pallidula worker ants are dimorphic and are classified as major and minor workers.⁷ Major workers have body lengths ranging up to 6 mm, whereas minor workers have body lengths ranging up to 4 mm. Major workers have larger heads and mandibles than minor workers and also have up to 2 pairs of denticles on the cranium.⁵ The minor workers are foragers and mainly collect food, whereas the major workers defend the nest and store food.⁸ These ants have widespread habitats with the ability to live in indoor and outdoor environments.

The presentation of hair loss caused by these ants is acute. Hair loss usually is confined to one specific area. Some patients may report pruritus or may present with erythematous lesions from ant stings or manual scratching.⁵ None of these signs or symptoms were seen in our patient. Some investigators have suggested that the barber ant is attracted to the hair of individuals with seborrheic dermatitis,¹ but our patient had no medical history of seborrheic dermatitis. Most likely, ants are attracted to excess sebum on the scalp in select individuals in their search for food and cause localized hair destruction.

Localized hair loss, as depicted in our case, should warrant a thorough evaluation for alopecia areata, trichotillomania, and tinea capitis.⁹ Alopecia areata should be considered in individuals with multiple focal patches of hair loss that have a positive hair pull test from peripheral sites of active lesions. Tinea capitis usually has localized sites of hair loss with underlying scaling, crusting, pruritus, erythema, and discharge from lesions, with positive potassium hydroxide preparations or fungal cultures. Trichotillomania typically presents with a spared peripheral fringe of hair. Remaining hairs may be thick and hyperpigmented as a response to repeated pulling, and biopsy often demonstrates fracture or degeneration of the hair shaft. A psychiatric evaluation may be warranted in cases of trichotillomania. Other cases of arthropod-induced hair loss include tick bite alopecia^10,11 and hair loss induced by numerous honeybee stings,¹² and these diagnoses should be suspected in patients with a history of ants on their pillow or in those from endemic areas.

No specific treatment is indicated in cases of 
ant-induced alopecia because hair usually regrows to its normal length without intervention.

The percentage of the nonmedical use of prescription opioids decreased among U.S. adults over the last decade, but the prevalence of opioid use disorders, the frequency of opioid abuse, and related mortality all increased, according to a report published online Oct. 13 in JAMA.

These findings, from an analysis of two large nationally representative data sets, paint a picture that is complex and more nuanced than that suggested by some recent reports. For example, a study of the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System found that the abuse and diversion of prescription opioids plateaued or decreased in recent years. “The nationally representative results in our study may be especially important in providing an accurate picture of the current status of the epidemic,” said Dr. Beth Han of the Substance Abuse and Mental Health Services Administration (SAMHSA), Rockville, Md., and her associates.

©PhotoDisk

The nonmedical use of prescription opioids is an acknowledged epidemic, but that epidemic’s changing pattern over time needed to be updated. The investigators assessed the changes in use during the most recent decade for which data are available (2003-2013) using annual surveys conducted by SAMHSA and cause of death files from the National Vital Statistics System.

Based on responses from 472,200 people aged 18-64 years, the 1-year prevalence of nonmedical use of prescription opioids decreased from 5.4% to 4.9% during the study period. However, the 1-year prevalence of use disorders rose from 0.6% to 0.9%, the 1-year prevalence of high-frequency use (200 days or more per year) increased from 0.3% to 0.4%, and the rate of opioid-related deaths increased from 4.5 per 100,000 to 7.8 per 100,000. In addition, the mean number of days of opioid abuse increased from 2.1 to 2.6 per year in the general population and from 40.0 to 54.2 days per year among acknowledged opioid users, the investigators said (JAMA. 2015 Oct 13;314[14]:1468-1478. doi:10.1001/jama.2015.11859).

Compared with white users of prescription opioids, both black and Hispanic users had a lower prevalence of use disorders. The prevalence of use disorders was higher among less-educated than more-educated adults, among those with no health insurance or Medicaid as opposed to private health insurance, and among smokers than nonsmokers, Dr. Han and her associates added.

Previous research has shown that most adults who abuse prescription opioids neither receive treatment nor perceive that they need treatment. Clinicians can help by using prescription-drug monitoring programs to identify inappropriate receipt of prescription opioids, then offering treatments, which are highly effective, for patients who need them, the investigators noted.

The Substance Abuse and Mental Health Services Administration, the National Institute on Drug Abuse, and the Food and Drug Administration sponsored the study. Dr. Han reported having no relevant disclosures; an associate reported owning stock in General Electric, 3M Company, and Pfizer.

The percentage of the nonmedical use of prescription opioids decreased among U.S. adults over the last decade, but the prevalence of opioid use disorders, the frequency of opioid abuse, and related mortality all increased, according to a report published online Oct. 13 in JAMA.

These findings, from an analysis of two large nationally representative data sets, paint a picture that is complex and more nuanced than that suggested by some recent reports. For example, a study of the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System found that the abuse and diversion of prescription opioids plateaued or decreased in recent years. “The nationally representative results in our study may be especially important in providing an accurate picture of the current status of the epidemic,” said Dr. Beth Han of the Substance Abuse and Mental Health Services Administration (SAMHSA), Rockville, Md., and her associates.

©PhotoDisk

The nonmedical use of prescription opioids is an acknowledged epidemic, but that epidemic’s changing pattern over time needed to be updated. The investigators assessed the changes in use during the most recent decade for which data are available (2003-2013) using annual surveys conducted by SAMHSA and cause of death files from the National Vital Statistics System.

Based on responses from 472,200 people aged 18-64 years, the 1-year prevalence of nonmedical use of prescription opioids decreased from 5.4% to 4.9% during the study period. However, the 1-year prevalence of use disorders rose from 0.6% to 0.9%, the 1-year prevalence of high-frequency use (200 days or more per year) increased from 0.3% to 0.4%, and the rate of opioid-related deaths increased from 4.5 per 100,000 to 7.8 per 100,000. In addition, the mean number of days of opioid abuse increased from 2.1 to 2.6 per year in the general population and from 40.0 to 54.2 days per year among acknowledged opioid users, the investigators said (JAMA. 2015 Oct 13;314[14]:1468-1478. doi:10.1001/jama.2015.11859).

Compared with white users of prescription opioids, both black and Hispanic users had a lower prevalence of use disorders. The prevalence of use disorders was higher among less-educated than more-educated adults, among those with no health insurance or Medicaid as opposed to private health insurance, and among smokers than nonsmokers, Dr. Han and her associates added.

Previous research has shown that most adults who abuse prescription opioids neither receive treatment nor perceive that they need treatment. Clinicians can help by using prescription-drug monitoring programs to identify inappropriate receipt of prescription opioids, then offering treatments, which are highly effective, for patients who need them, the investigators noted.

The Substance Abuse and Mental Health Services Administration, the National Institute on Drug Abuse, and the Food and Drug Administration sponsored the study. Dr. Han reported having no relevant disclosures; an associate reported owning stock in General Electric, 3M Company, and Pfizer.

The percentage of the nonmedical use of prescription opioids decreased among U.S. adults over the last decade, but the prevalence of opioid use disorders, the frequency of opioid abuse, and related mortality all increased, according to a report published online Oct. 13 in JAMA.

These findings, from an analysis of two large nationally representative data sets, paint a picture that is complex and more nuanced than that suggested by some recent reports. For example, a study of the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System found that the abuse and diversion of prescription opioids plateaued or decreased in recent years. “The nationally representative results in our study may be especially important in providing an accurate picture of the current status of the epidemic,” said Dr. Beth Han of the Substance Abuse and Mental Health Services Administration (SAMHSA), Rockville, Md., and her associates.

©PhotoDisk

The nonmedical use of prescription opioids is an acknowledged epidemic, but that epidemic’s changing pattern over time needed to be updated. The investigators assessed the changes in use during the most recent decade for which data are available (2003-2013) using annual surveys conducted by SAMHSA and cause of death files from the National Vital Statistics System.

Based on responses from 472,200 people aged 18-64 years, the 1-year prevalence of nonmedical use of prescription opioids decreased from 5.4% to 4.9% during the study period. However, the 1-year prevalence of use disorders rose from 0.6% to 0.9%, the 1-year prevalence of high-frequency use (200 days or more per year) increased from 0.3% to 0.4%, and the rate of opioid-related deaths increased from 4.5 per 100,000 to 7.8 per 100,000. In addition, the mean number of days of opioid abuse increased from 2.1 to 2.6 per year in the general population and from 40.0 to 54.2 days per year among acknowledged opioid users, the investigators said (JAMA. 2015 Oct 13;314[14]:1468-1478. doi:10.1001/jama.2015.11859).

Compared with white users of prescription opioids, both black and Hispanic users had a lower prevalence of use disorders. The prevalence of use disorders was higher among less-educated than more-educated adults, among those with no health insurance or Medicaid as opposed to private health insurance, and among smokers than nonsmokers, Dr. Han and her associates added.

Previous research has shown that most adults who abuse prescription opioids neither receive treatment nor perceive that they need treatment. Clinicians can help by using prescription-drug monitoring programs to identify inappropriate receipt of prescription opioids, then offering treatments, which are highly effective, for patients who need them, the investigators noted.

The Substance Abuse and Mental Health Services Administration, the National Institute on Drug Abuse, and the Food and Drug Administration sponsored the study. Dr. Han reported having no relevant disclosures; an associate reported owning stock in General Electric, 3M Company, and Pfizer.

What should you do during the first 
visit for a patient you may start 
on spironolactone?

Some women will come in asking about spironolactone for acne, so it is important to identify potential candidates for antihormonal therapy:

Evaluation of these women with acne for the possibility of hormonal imbalance may be necessary, with the 2 most common causes of hyperandrogenism being polycystic ovary syndrome and congenital adrenal hyperplasia. The presence of alopecia, hirsutism, acanthosis nigricans, or other signs of androgen excess, in combination with dysmenorrhea or amenorrhea, may be an indication that the patient has an underlying medical condition that needs to be addressed. Blood tests including testosterone, dehydroepiandrosterone, follicle-stimulating hormone, and luteinizing hormone would be appropriate screening tests and should be performed during the menstrual period or week prior; the patient should not be on an OC or have been on one within the last 6 weeks of testing.

Prior to initiating therapy with spironolactone, it is important to establish that there is no history of renal dysfunction; that the patient does not utilize salt substitutes, which may contain potassium in place of sodium; and that the patient is not taking potassium supplements, other potassium-sparing diuretics (ie, amiloride, triamterene), angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers.

Of note, the patient should not be currently or actively trying to become pregnant. Even though it has a category C rating, there is substantial theoretical risk for teratogenicity, especially in a male fetus (ie, feminization of a male fetus). However, there are no reports linking spironolactone with human congenital defects, and no well-controlled, prospective studies evaluating spironolactone exposure in pregnant women.

What does the patient need to know at 
the first visit?

Because patients have Dr. Internet on call within seconds on their smartphones and tablets, there are several points I review with patients as a semipreemptive strike.

Spironolactone is not approved by the US Food and Drug Administration for the treatment of acne; however, it has been used for decades for acne and even longer for the management of high blood pressure (since 1957!). Because it is a potassium-sparing diuretic, patients need to be careful not to get too much of a good thing (ie, potassium). I counsel patients on potassium intake, including sources 
such as diet (ie, fruit/fruit drinks), coconut water (very popular right now), and over-the-counter nutritional supplements.

Spironolactone is used in varying doses depending on the situation (25–200 mg daily), but it is important to start with a lower dose and escalate in a stepwise fashion, if needed, depending on how the patient is doing. I usually tell the patient it requires at least one boost in the dosage (around 50 mg twice daily) to appreciate notable results; however, patients will often have some improvement even at the lowest dose of 25 mg twice daily within 4 weeks of treatment initiation, which is when I have them return for reevaluation.

Spironolactone will help with acne on the face, back, and chest.

The majority of sides effects associated with spironolactone are dose dependent; low-dose therapy (25–50 mg daily) generally is well tolerated, and even 100 mg daily is not problematic in most cases. 
Dose-dependent side effects include frequent urination, menstrual irregularities, breast tenderness and/or enlargement, low blood pressure, hyperkalemia, and reduced libido. Of note, a recent study (Plovanich et al) found that the incidence of hyperkalemia in healthy young women taking spironolactone for acne is equivalent to the baseline rate of hyperkalemia in this specific population. Therefore, routine potassium monitoring is unnecessary for healthy women taking spironolactone for acne. I tend not to check potassium in these patients unless I head to higher doses due to poor response or I am treating female pattern alopecia, which often requires higher dosing.

Spironolactone has sufficient data to suggest that long-term use appears to be safe overall. There was one long-term study with patients who received spironolactone for up to 8 years for the treatment of acne vulgaris (Shaw and White).

Spironolactone can be used as monotherapy or in combination with OCs safely. In fact, by prescribing spironolactone in combination with OCs you can kill 3 birds with 1 stone from efficacy (the synergy between the two often allows for lower dosing of spironolactone without compromising impact), contraception prevention, and dysmenorrhea perspectives. I do offer OCs to eligible patients who are starting on spironolactone. In general, spironolactone can be used safely in combination with oral antibiotics, though oral antibiotic use should be short-term to limit rising rates of antimicrobial resistance. Of note, there may be risk for hyperkalemia when spironolactone is combined with trimethoprim-sulfamethoxazole, so its use should be avoided in this setting.

How do you keep patients compliant 
with treatment?

If androgens are playing a notable role in the patient’s acne, some response is usually noted by even the first return visit, which I always make for 4 weeks later, unlike with other acne treatment regimens, which I usually make for 7 to 8 weeks later. Even though most treatments require at least 8 weeks to show any sign of improvement, even spironolactone at times, close follow-up allows me to increase the dose, which is often needed, or change to another medication if the patient is not tolerating it. Given that I stress it will require taking the medication every day in a consistent fashion to allow me to effectively evaluate it, the short time frame between visits also enhances compliance, as it encourages the patient to actually take the medication and incorporate it into her routine.

What do you do if patients 
refuse treatment?

I always tell my patients they are the captains and I am helping them navigate through their disease. I will, however, discuss the chronicity of acne as well as the long-term sequelae of this inflammatory disease including scarring and postinflammatory pigment alteration for which there are no great treatments. I also tell them that if there is any issue with the medication, we simply stop, and the likelihood for severe adverse events is exceedingly low based on the evidence and anecdotal experience.

What should you do during the first 
visit for a patient you may start 
on spironolactone?

Some women will come in asking about spironolactone for acne, so it is important to identify potential candidates for antihormonal therapy:

Evaluation of these women with acne for the possibility of hormonal imbalance may be necessary, with the 2 most common causes of hyperandrogenism being polycystic ovary syndrome and congenital adrenal hyperplasia. The presence of alopecia, hirsutism, acanthosis nigricans, or other signs of androgen excess, in combination with dysmenorrhea or amenorrhea, may be an indication that the patient has an underlying medical condition that needs to be addressed. Blood tests including testosterone, dehydroepiandrosterone, follicle-stimulating hormone, and luteinizing hormone would be appropriate screening tests and should be performed during the menstrual period or week prior; the patient should not be on an OC or have been on one within the last 6 weeks of testing.

Prior to initiating therapy with spironolactone, it is important to establish that there is no history of renal dysfunction; that the patient does not utilize salt substitutes, which may contain potassium in place of sodium; and that the patient is not taking potassium supplements, other potassium-sparing diuretics (ie, amiloride, triamterene), angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers.

Of note, the patient should not be currently or actively trying to become pregnant. Even though it has a category C rating, there is substantial theoretical risk for teratogenicity, especially in a male fetus (ie, feminization of a male fetus). However, there are no reports linking spironolactone with human congenital defects, and no well-controlled, prospective studies evaluating spironolactone exposure in pregnant women.

What does the patient need to know at 
the first visit?

Because patients have Dr. Internet on call within seconds on their smartphones and tablets, there are several points I review with patients as a semipreemptive strike.

Spironolactone is not approved by the US Food and Drug Administration for the treatment of acne; however, it has been used for decades for acne and even longer for the management of high blood pressure (since 1957!). Because it is a potassium-sparing diuretic, patients need to be careful not to get too much of a good thing (ie, potassium). I counsel patients on potassium intake, including sources 
such as diet (ie, fruit/fruit drinks), coconut water (very popular right now), and over-the-counter nutritional supplements.

Spironolactone is used in varying doses depending on the situation (25–200 mg daily), but it is important to start with a lower dose and escalate in a stepwise fashion, if needed, depending on how the patient is doing. I usually tell the patient it requires at least one boost in the dosage (around 50 mg twice daily) to appreciate notable results; however, patients will often have some improvement even at the lowest dose of 25 mg twice daily within 4 weeks of treatment initiation, which is when I have them return for reevaluation.

Spironolactone will help with acne on the face, back, and chest.

The majority of sides effects associated with spironolactone are dose dependent; low-dose therapy (25–50 mg daily) generally is well tolerated, and even 100 mg daily is not problematic in most cases. 
Dose-dependent side effects include frequent urination, menstrual irregularities, breast tenderness and/or enlargement, low blood pressure, hyperkalemia, and reduced libido. Of note, a recent study (Plovanich et al) found that the incidence of hyperkalemia in healthy young women taking spironolactone for acne is equivalent to the baseline rate of hyperkalemia in this specific population. Therefore, routine potassium monitoring is unnecessary for healthy women taking spironolactone for acne. I tend not to check potassium in these patients unless I head to higher doses due to poor response or I am treating female pattern alopecia, which often requires higher dosing.

Spironolactone has sufficient data to suggest that long-term use appears to be safe overall. There was one long-term study with patients who received spironolactone for up to 8 years for the treatment of acne vulgaris (Shaw and White).

Spironolactone can be used as monotherapy or in combination with OCs safely. In fact, by prescribing spironolactone in combination with OCs you can kill 3 birds with 1 stone from efficacy (the synergy between the two often allows for lower dosing of spironolactone without compromising impact), contraception prevention, and dysmenorrhea perspectives. I do offer OCs to eligible patients who are starting on spironolactone. In general, spironolactone can be used safely in combination with oral antibiotics, though oral antibiotic use should be short-term to limit rising rates of antimicrobial resistance. Of note, there may be risk for hyperkalemia when spironolactone is combined with trimethoprim-sulfamethoxazole, so its use should be avoided in this setting.

How do you keep patients compliant 
with treatment?

If androgens are playing a notable role in the patient’s acne, some response is usually noted by even the first return visit, which I always make for 4 weeks later, unlike with other acne treatment regimens, which I usually make for 7 to 8 weeks later. Even though most treatments require at least 8 weeks to show any sign of improvement, even spironolactone at times, close follow-up allows me to increase the dose, which is often needed, or change to another medication if the patient is not tolerating it. Given that I stress it will require taking the medication every day in a consistent fashion to allow me to effectively evaluate it, the short time frame between visits also enhances compliance, as it encourages the patient to actually take the medication and incorporate it into her routine.

What do you do if patients 
refuse treatment?

I always tell my patients they are the captains and I am helping them navigate through their disease. I will, however, discuss the chronicity of acne as well as the long-term sequelae of this inflammatory disease including scarring and postinflammatory pigment alteration for which there are no great treatments. I also tell them that if there is any issue with the medication, we simply stop, and the likelihood for severe adverse events is exceedingly low based on the evidence and anecdotal experience.

What should you do during the first 
visit for a patient you may start 
on spironolactone?

Some women will come in asking about spironolactone for acne, so it is important to identify potential candidates for antihormonal therapy:

Evaluation of these women with acne for the possibility of hormonal imbalance may be necessary, with the 2 most common causes of hyperandrogenism being polycystic ovary syndrome and congenital adrenal hyperplasia. The presence of alopecia, hirsutism, acanthosis nigricans, or other signs of androgen excess, in combination with dysmenorrhea or amenorrhea, may be an indication that the patient has an underlying medical condition that needs to be addressed. Blood tests including testosterone, dehydroepiandrosterone, follicle-stimulating hormone, and luteinizing hormone would be appropriate screening tests and should be performed during the menstrual period or week prior; the patient should not be on an OC or have been on one within the last 6 weeks of testing.

Prior to initiating therapy with spironolactone, it is important to establish that there is no history of renal dysfunction; that the patient does not utilize salt substitutes, which may contain potassium in place of sodium; and that the patient is not taking potassium supplements, other potassium-sparing diuretics (ie, amiloride, triamterene), angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers.

Of note, the patient should not be currently or actively trying to become pregnant. Even though it has a category C rating, there is substantial theoretical risk for teratogenicity, especially in a male fetus (ie, feminization of a male fetus). However, there are no reports linking spironolactone with human congenital defects, and no well-controlled, prospective studies evaluating spironolactone exposure in pregnant women.

What does the patient need to know at 
the first visit?

Because patients have Dr. Internet on call within seconds on their smartphones and tablets, there are several points I review with patients as a semipreemptive strike.

Spironolactone is not approved by the US Food and Drug Administration for the treatment of acne; however, it has been used for decades for acne and even longer for the management of high blood pressure (since 1957!). Because it is a potassium-sparing diuretic, patients need to be careful not to get too much of a good thing (ie, potassium). I counsel patients on potassium intake, including sources 
such as diet (ie, fruit/fruit drinks), coconut water (very popular right now), and over-the-counter nutritional supplements.

Spironolactone is used in varying doses depending on the situation (25–200 mg daily), but it is important to start with a lower dose and escalate in a stepwise fashion, if needed, depending on how the patient is doing. I usually tell the patient it requires at least one boost in the dosage (around 50 mg twice daily) to appreciate notable results; however, patients will often have some improvement even at the lowest dose of 25 mg twice daily within 4 weeks of treatment initiation, which is when I have them return for reevaluation.

Spironolactone will help with acne on the face, back, and chest.

The majority of sides effects associated with spironolactone are dose dependent; low-dose therapy (25–50 mg daily) generally is well tolerated, and even 100 mg daily is not problematic in most cases. 
Dose-dependent side effects include frequent urination, menstrual irregularities, breast tenderness and/or enlargement, low blood pressure, hyperkalemia, and reduced libido. Of note, a recent study (Plovanich et al) found that the incidence of hyperkalemia in healthy young women taking spironolactone for acne is equivalent to the baseline rate of hyperkalemia in this specific population. Therefore, routine potassium monitoring is unnecessary for healthy women taking spironolactone for acne. I tend not to check potassium in these patients unless I head to higher doses due to poor response or I am treating female pattern alopecia, which often requires higher dosing.

Spironolactone has sufficient data to suggest that long-term use appears to be safe overall. There was one long-term study with patients who received spironolactone for up to 8 years for the treatment of acne vulgaris (Shaw and White).

Spironolactone can be used as monotherapy or in combination with OCs safely. In fact, by prescribing spironolactone in combination with OCs you can kill 3 birds with 1 stone from efficacy (the synergy between the two often allows for lower dosing of spironolactone without compromising impact), contraception prevention, and dysmenorrhea perspectives. I do offer OCs to eligible patients who are starting on spironolactone. In general, spironolactone can be used safely in combination with oral antibiotics, though oral antibiotic use should be short-term to limit rising rates of antimicrobial resistance. Of note, there may be risk for hyperkalemia when spironolactone is combined with trimethoprim-sulfamethoxazole, so its use should be avoided in this setting.

How do you keep patients compliant 
with treatment?

If androgens are playing a notable role in the patient’s acne, some response is usually noted by even the first return visit, which I always make for 4 weeks later, unlike with other acne treatment regimens, which I usually make for 7 to 8 weeks later. Even though most treatments require at least 8 weeks to show any sign of improvement, even spironolactone at times, close follow-up allows me to increase the dose, which is often needed, or change to another medication if the patient is not tolerating it. Given that I stress it will require taking the medication every day in a consistent fashion to allow me to effectively evaluate it, the short time frame between visits also enhances compliance, as it encourages the patient to actually take the medication and incorporate it into her routine.

What do you do if patients 
refuse treatment?

I always tell my patients they are the captains and I am helping them navigate through their disease. I will, however, discuss the chronicity of acne as well as the long-term sequelae of this inflammatory disease including scarring and postinflammatory pigment alteration for which there are no great treatments. I also tell them that if there is any issue with the medication, we simply stop, and the likelihood for severe adverse events is exceedingly low based on the evidence and anecdotal experience.

Fresh produce

New research suggests that cancer survivors in the US may need dietary interventions to improve their health.

The study showed that, overall, cancer survivors did not adhere to federal dietary guidelines as well as a matched control population.

Cancer survivors tended to consume more empty calories and less fiber than controls.

Fang Fang Zhang, MD, PhD, of Tufts University in Boston, Massachusetts, and his colleagues reported these findings in Cancer.

The team evaluated the diets of 1533 adult cancer survivors who participated in the National Health and Nutrition Examination Survey from 1999 to 2010. The investigators also assessed the diets of 3075 individuals who had no history of cancer and were matched to the cancer survivors by age, sex, and race/ethnicity.

The goal was to determine how subjects’ diets aligned with advice from the 2010 Dietary Guidelines for Americans, which was jointly issued by the Department of Agriculture and the Department of Health and Human Services.

Cancer survivors had poor adherence to the guidelines, with a total Healthy Eating Index score of 47.2 out of 100, compared with a score of 48.3 in the adults without a history of cancer (P=0.03).

Cancer survivors had a significantly lower mean score for empty calories compared to the noncancer group—13.6 and 14.4, respectively (P=0.001). This suggested the cancer group had a higher consumption of calories from solid fats, alcohol, and added sugars.

Cancer survivors also had significantly lower dietary intake of fiber than the noncancer group—15.0 and 15.9 g per day, respectively (P=0.02).

Compared to recommended values, cancer survivors had low dietary intakes of vitamin D (31% of the recommended intake), vitamin E (47%), potassium (55%), and calcium (73%) but high intakes of saturated fat (112%) and sodium (133%).

The investigators noted that diet quality in cancer survivors increased linearly with age. The older the age, the better the diet quality.

Survivors with lower education (high school or less) had significantly worse diet quality than those with higher education. And survivors who were current smokers had significantly worse diet quality than non-smokers or former smokers.

For the 4 major cancer types in the US (breast, prostate, lung, and colorectal), breast cancer survivors had the best diet quality, and lung cancer survivors had the worst diet quality.

The investigators said that knowing how well cancer survivors adhere to federal dietary guidelines can help inform evidence-based priorities for improving their nutritional intake.

“Dietary changes that include more fiber, fruit, and vegetables in the diet and less fat, sodium, and added sugar would be important for cancer survivors,” Dr Zhang said.

“Oncology care providers can play critical roles in reinforcing the importance of a healthful diet and can refer patients to registered dietitians who are experts in oncology care or to other reputable sources in order to improve survivors’ overall health.”

Fresh produce

New research suggests that cancer survivors in the US may need dietary interventions to improve their health.

The study showed that, overall, cancer survivors did not adhere to federal dietary guidelines as well as a matched control population.

Cancer survivors tended to consume more empty calories and less fiber than controls.

Fang Fang Zhang, MD, PhD, of Tufts University in Boston, Massachusetts, and his colleagues reported these findings in Cancer.

The team evaluated the diets of 1533 adult cancer survivors who participated in the National Health and Nutrition Examination Survey from 1999 to 2010. The investigators also assessed the diets of 3075 individuals who had no history of cancer and were matched to the cancer survivors by age, sex, and race/ethnicity.

The goal was to determine how subjects’ diets aligned with advice from the 2010 Dietary Guidelines for Americans, which was jointly issued by the Department of Agriculture and the Department of Health and Human Services.

Cancer survivors had poor adherence to the guidelines, with a total Healthy Eating Index score of 47.2 out of 100, compared with a score of 48.3 in the adults without a history of cancer (P=0.03).

Cancer survivors had a significantly lower mean score for empty calories compared to the noncancer group—13.6 and 14.4, respectively (P=0.001). This suggested the cancer group had a higher consumption of calories from solid fats, alcohol, and added sugars.

Cancer survivors also had significantly lower dietary intake of fiber than the noncancer group—15.0 and 15.9 g per day, respectively (P=0.02).

Compared to recommended values, cancer survivors had low dietary intakes of vitamin D (31% of the recommended intake), vitamin E (47%), potassium (55%), and calcium (73%) but high intakes of saturated fat (112%) and sodium (133%).

The investigators noted that diet quality in cancer survivors increased linearly with age. The older the age, the better the diet quality.

Survivors with lower education (high school or less) had significantly worse diet quality than those with higher education. And survivors who were current smokers had significantly worse diet quality than non-smokers or former smokers.

For the 4 major cancer types in the US (breast, prostate, lung, and colorectal), breast cancer survivors had the best diet quality, and lung cancer survivors had the worst diet quality.

The investigators said that knowing how well cancer survivors adhere to federal dietary guidelines can help inform evidence-based priorities for improving their nutritional intake.

“Dietary changes that include more fiber, fruit, and vegetables in the diet and less fat, sodium, and added sugar would be important for cancer survivors,” Dr Zhang said.

“Oncology care providers can play critical roles in reinforcing the importance of a healthful diet and can refer patients to registered dietitians who are experts in oncology care or to other reputable sources in order to improve survivors’ overall health.”

Fresh produce

New research suggests that cancer survivors in the US may need dietary interventions to improve their health.

The study showed that, overall, cancer survivors did not adhere to federal dietary guidelines as well as a matched control population.

Cancer survivors tended to consume more empty calories and less fiber than controls.

Fang Fang Zhang, MD, PhD, of Tufts University in Boston, Massachusetts, and his colleagues reported these findings in Cancer.

The team evaluated the diets of 1533 adult cancer survivors who participated in the National Health and Nutrition Examination Survey from 1999 to 2010. The investigators also assessed the diets of 3075 individuals who had no history of cancer and were matched to the cancer survivors by age, sex, and race/ethnicity.

The goal was to determine how subjects’ diets aligned with advice from the 2010 Dietary Guidelines for Americans, which was jointly issued by the Department of Agriculture and the Department of Health and Human Services.

Cancer survivors had poor adherence to the guidelines, with a total Healthy Eating Index score of 47.2 out of 100, compared with a score of 48.3 in the adults without a history of cancer (P=0.03).

Cancer survivors had a significantly lower mean score for empty calories compared to the noncancer group—13.6 and 14.4, respectively (P=0.001). This suggested the cancer group had a higher consumption of calories from solid fats, alcohol, and added sugars.

Cancer survivors also had significantly lower dietary intake of fiber than the noncancer group—15.0 and 15.9 g per day, respectively (P=0.02).

Compared to recommended values, cancer survivors had low dietary intakes of vitamin D (31% of the recommended intake), vitamin E (47%), potassium (55%), and calcium (73%) but high intakes of saturated fat (112%) and sodium (133%).

The investigators noted that diet quality in cancer survivors increased linearly with age. The older the age, the better the diet quality.

Survivors with lower education (high school or less) had significantly worse diet quality than those with higher education. And survivors who were current smokers had significantly worse diet quality than non-smokers or former smokers.

For the 4 major cancer types in the US (breast, prostate, lung, and colorectal), breast cancer survivors had the best diet quality, and lung cancer survivors had the worst diet quality.

The investigators said that knowing how well cancer survivors adhere to federal dietary guidelines can help inform evidence-based priorities for improving their nutritional intake.

“Dietary changes that include more fiber, fruit, and vegetables in the diet and less fat, sodium, and added sugar would be important for cancer survivors,” Dr Zhang said.

“Oncology care providers can play critical roles in reinforcing the importance of a healthful diet and can refer patients to registered dietitians who are experts in oncology care or to other reputable sources in order to improve survivors’ overall health.”

It was not long ago that acne vulgaris (AV) was commonly considered to be a skin disease that affected teenagers with little attention given to preadolescent and postadolescent AV. This perspective has changed, with more attention being given to AV across a broad range of affected 
age groups, including preadolescent, adolescent, and postadolescent subgroups.^1-5 Earlier onset of adrenarche has led to earlier development of AV in many young girls, with a higher range of dehydroepiandrosterone sulfate (DHEAS) levels observed overall in those with AV as compared to a normal age-matched population.^3,4 At the other end of the age spectrum, AV is a common phenomenon in adult females, with at least half of women estimated to exhibit some form of AV.^1,2,5-8 Based on a 
large survey of females and males (N=1013), the prevalence of AV in adult females has been reported to be 50.9%, 35.2%, 26.3%, and 15.3% among women aged 20 to 29 years, 30 to 39 years, 40 to 49 years, and 50 years and older, respectively.² Acne vulgaris that persists beyond adolescence into adulthood is termed persistent acne, or early-onset acne, and the development of AV in women 25 years and older who have not previously been affected by AV has been termed late-onset acne.^6,8,9 Publications on the management of AV in adult women have focused primarily on systemic hormonal therapies; however, topical therapies more recently have received greater attention in this subpopulation^9-12 and will be discussed in part 2 of this series. Because data on AV in women are 
limited primarily to involvement of the face and neck region, this article does not address truncal AV unless otherwise specified. Table 1 depicts factors that can influence the management of AV in adult women.

Visible Patterns and Considerations for Clinical Evaluation 


Clinical Patterns

Although epidemiologic and demographic data are limited in the subpopulation of women with AV, it is reported that females account for up to 82% of adults with AV, with approximately 75% presenting with AV that is clinically similar to their disease course in adolescence.^2,5,13 Among those women with persistent AV, some state that their AV is worse compared to adolescence, while others report it is not as severe. The pattern of AV often is similar to that seen in adolescence, presenting as mixed comedonal and inflammatory papular/pustular lesions diffusely distributed on the face; in other cases, a more selectively distributed U-shaped pattern is noted, characterized predominantly by inflammatory papules and/or nodules involving the lower cheeks and jawline margin, with lesions also commonly noted on the anterior and lateral neck.^5,8,9,13-16 A U-shaped pattern is believed to be more common in late-onset AV, often with persistence into the mid-40s.^1,15,17 It is important to emphasize the need for additional studies on the demographics and clinical characteristics of AV in adult females, especially correlations between onset, age, and clinical patterns of AV.

An international, prospective, observational study assessed the clinical characteristics of AV in adults (aged ≥25 years) at a dermatology visit for acne (N=374).¹⁶ Participants who were under management for their AV showed severity grades of mild (clear/almost clear) in 47.3% of cases. Involvement of multiple facial sites—cheeks, forehead, mandibular region, and temples—was noted in 89.8% of women, often with both inflammatory and comedonal lesions, which is a pattern similar to adolescent AV. Inflammatory lesions alone were observed in 6.4% of women, 17.1% had comedonal AV only, 
and truncal AV was present in 48.4%.¹⁶ Additional well-designed studies are needed to determine if this study reflects an accurate qualitative and 
quantitative depiction of the spectrum of AV in adult females.

Mandibular Pattern

In the observational study of AV in adults, AV localized to the mandibular area was noted in only 11.2% of participants.¹⁶ Women with localized mandibular AV were more likely than women without localized AV to be employed, noted greater daily stress levels, and tended to report more psychologically stressful jobs. Interestingly, the subgroup with mandibular acne alone was much less likely 
to exhibit a global severity grade of moderate or higher (7.1% vs 50.1%), truncal acne 
(19.0% vs 51.9%), postinflammatory hyperpigmentation (23.8% vs 51.9%), and erythema (19.0% vs 48.4%), suggesting a unique subset of AV presentation.¹⁶

Ethnicity/Skin Color

Women of all ethnicities and skin types may be affected by AV.^1,18-20 Earlier age of onset of AV has been suggested in white women; however, earlier onset of adrenarche may be more frequent in black girls, which supports an earlier age of onset of AV in this subpopulation.^15-17 Women with skin of color usually express greater concern with persistent dyschromia at sites where lesions have resolved, and presence of acne scars is a concern among women regardless of skin color, ethnicity, or race.^18,20-22

Scarring

Acne scarring has been noted to affect up to 
three-fourths of adult women in one report¹⁷ and 
often is stated by patients to be a cause of concern 
and frustration.^1,5,17

Perimenstrual Flaring

Flaring associated with menses is commonly reported in adult females with AV, with 56%, 17%, and 
3% of women in one study (n=230) reporting worsening before, during, or after menses, respectively.²¹

External Factors

Comedogenic products used for skin care, cover-up makeup, or hair care may be important to consider in selected cases as potential etiologic or exacerbating factors in adult females with AV; they also may be used in the management of AV.^23-25 Adult females often are perplexed and frustrated by the presence of AV after their 
teenaged years and anxiously wonder about or search for the potential causes. Many women use cosmetic products to cover up facial AV.^5,23-25 Therefore, even if skin care or personal hygiene products or makeup are not believed to be an etiologic factor, many patients appreciate that their dermatologist addressed skin care and cosmetics as a component of AV management and provided appropriate recommendations.^5,13

Ingestion of dietary supplements containing whey protein have been associated with precipitation of AV.^26,27 Diets with specific content characteristics have been implicated as potential etiologic or exacerbating factors for AV; however, data are limited and specific recommendations remain elusive at present. Individual cases may warrant consideration of dietary factors, especially when treatment resistance is noted.²⁸ Importantly, progestin-only contraceptives (ie, injectables, intrauterine devices) also can exacerbate or induce AV.²⁹

Hyperandrogenism

Although most adult females with AV are reported to have normal serum androgen levels when tested, it is important to explore potential signs and symptoms that are suggestive of underlying hyperandrogenism through both the patient’s history and physical examination.^{9-11,21,29-33} Some investigators have suggested that underlying peripheral hyperandrogenism is the leading cause of AV in adult females, 
with or without concurrent polycystic ovarian syndrome (PCOS), though it is believed that most women with AV exhibit normal results when 
undergoing laboratory testing for androgen excess.^{10,11,21,29,30} Nevertheless, it is important to consider the possibility of underlying causes of androgen excess (Table 2), the most common being PCOS and late-onset congenital adrenal hyperplasia; an androgen-secreting tumor is less common.^11,29-33 It is suggested that screening for underlying endocrinopathy should be conducted in women presenting with (1) AV recalcitrant to conventional treatment, (2) sudden emergence of severe AV, 
(3) concurrent signs/symptoms of androgen 
excess, and/or (4) AV relapse shortly after isotretinoin therapy.^7,11,16,33

Hirsutism and acanthosis nigricans have been reported to be more reliable predictors of hyperandrogenism than androgenic alopecia.²¹ Although it may be subtle in some cases, acanthosis nigricans is harder to camouflage, so the clinician can usually detect it if a thorough physical examination is performed. However, a patient may not voluntarily report to the clinician and their staff that she has hair removed, so despite a thorough examination, the clinician may not detect hirsutism. Therefore, it is important to inquire directly about the presence of hairs (pigmented terminal vs “peach fuzz” hairs), their anatomic location, and any hair removal practices the patient has used. The absence of androgenic alopecia does not exclude underlying hyperandrogenism; however, its presence, especially in younger women, may serve as a clinical marker for underlying hyperandrogenism.⁵ Some women may camouflage more subtle alopecia through hairstyling, but obtaining this history usually is not problematic, as most women are distressed by any degree of hair loss.

Laboratory Evaluation—A relatively straightforward approach to the workup of androgen excess includes assessment of serum DHEAS, free testosterone, and total testosterone levels.^10,30 Elevation of serum DHEAS levels indicates an adrenal source of androgen production. Elevation of testosterone is associated with excess androgens 
produced by the ovaries. Modest elevations of 
DHEAS are most commonly associated with late-onset congenital adrenal hyperplasia that may not have been previously diagnosed. Modest elevation 
of testosterone is most commonly associated with PCOS, which also can be accompanied by an 
elevated luteinizing hormone:follicle-stimulating hormone ratio of 2.5:1 to 3:1.^10,30 Marked elevations of DHEAS or testosterone can be indicative of adrenal or ovarian tumors, respectively.³⁰

In some cases, a woman might have 
elevated DHEAS and testosterone levels. A 17-hydroxyprogesterone test can help discriminate between an adrenal or ovarian source of 
androgen excess in these cases, as elevated 
17-hydroxyprogesterone levels indicate that the androgens are coming from the adrenal gland.^10,30

It is important that laboratory evaluation be performed when ovulation is not occurring. Blood tests can be drawn just prior to or during menses. It is important that a woman is not taking an oral contraceptive at the time of testing, which can mask an underlying endocrine abnormality.^10,11,29,30 Generally, testing can be performed at least 4 to 6 weeks after stopping the oral contraceptive.

Psychosocial Impact

Facial AV exhibits a broad range of adverse psychological and social effects on many adult females.^2,5,13,18 It can be associated with depression, anxiety, psychological stress, and suicidal ideation; therefore, thorough screening for these comorbidities may be warranted in some patients.^2,18

Conclusion

The epidemiology, clinical presentation, and clinical and laboratory evaluation of AV in adult females was reviewed in part 1 of this 3-part series. It is important for the clinician to assess the clinical presentation, psychosocial effects, and the possibility of underlying causes of androgen excess. In part 2, skin care 
and topical management of AV in adult females will be discussed.

It was not long ago that acne vulgaris (AV) was commonly considered to be a skin disease that affected teenagers with little attention given to preadolescent and postadolescent AV. This perspective has changed, with more attention being given to AV across a broad range of affected 
age groups, including preadolescent, adolescent, and postadolescent subgroups.^1-5 Earlier onset of adrenarche has led to earlier development of AV in many young girls, with a higher range of dehydroepiandrosterone sulfate (DHEAS) levels observed overall in those with AV as compared to a normal age-matched population.^3,4 At the other end of the age spectrum, AV is a common phenomenon in adult females, with at least half of women estimated to exhibit some form of AV.^1,2,5-8 Based on a 
large survey of females and males (N=1013), the prevalence of AV in adult females has been reported to be 50.9%, 35.2%, 26.3%, and 15.3% among women aged 20 to 29 years, 30 to 39 years, 40 to 49 years, and 50 years and older, respectively.² Acne vulgaris that persists beyond adolescence into adulthood is termed persistent acne, or early-onset acne, and the development of AV in women 25 years and older who have not previously been affected by AV has been termed late-onset acne.^6,8,9 Publications on the management of AV in adult women have focused primarily on systemic hormonal therapies; however, topical therapies more recently have received greater attention in this subpopulation^9-12 and will be discussed in part 2 of this series. Because data on AV in women are 
limited primarily to involvement of the face and neck region, this article does not address truncal AV unless otherwise specified. Table 1 depicts factors that can influence the management of AV in adult women.

Visible Patterns and Considerations for Clinical Evaluation 


Clinical Patterns

Although epidemiologic and demographic data are limited in the subpopulation of women with AV, it is reported that females account for up to 82% of adults with AV, with approximately 75% presenting with AV that is clinically similar to their disease course in adolescence.^2,5,13 Among those women with persistent AV, some state that their AV is worse compared to adolescence, while others report it is not as severe. The pattern of AV often is similar to that seen in adolescence, presenting as mixed comedonal and inflammatory papular/pustular lesions diffusely distributed on the face; in other cases, a more selectively distributed U-shaped pattern is noted, characterized predominantly by inflammatory papules and/or nodules involving the lower cheeks and jawline margin, with lesions also commonly noted on the anterior and lateral neck.^5,8,9,13-16 A U-shaped pattern is believed to be more common in late-onset AV, often with persistence into the mid-40s.^1,15,17 It is important to emphasize the need for additional studies on the demographics and clinical characteristics of AV in adult females, especially correlations between onset, age, and clinical patterns of AV.

An international, prospective, observational study assessed the clinical characteristics of AV in adults (aged ≥25 years) at a dermatology visit for acne (N=374).¹⁶ Participants who were under management for their AV showed severity grades of mild (clear/almost clear) in 47.3% of cases. Involvement of multiple facial sites—cheeks, forehead, mandibular region, and temples—was noted in 89.8% of women, often with both inflammatory and comedonal lesions, which is a pattern similar to adolescent AV. Inflammatory lesions alone were observed in 6.4% of women, 17.1% had comedonal AV only, 
and truncal AV was present in 48.4%.¹⁶ Additional well-designed studies are needed to determine if this study reflects an accurate qualitative and 
quantitative depiction of the spectrum of AV in adult females.

Mandibular Pattern

In the observational study of AV in adults, AV localized to the mandibular area was noted in only 11.2% of participants.¹⁶ Women with localized mandibular AV were more likely than women without localized AV to be employed, noted greater daily stress levels, and tended to report more psychologically stressful jobs. Interestingly, the subgroup with mandibular acne alone was much less likely 
to exhibit a global severity grade of moderate or higher (7.1% vs 50.1%), truncal acne 
(19.0% vs 51.9%), postinflammatory hyperpigmentation (23.8% vs 51.9%), and erythema (19.0% vs 48.4%), suggesting a unique subset of AV presentation.¹⁶

Ethnicity/Skin Color

Women of all ethnicities and skin types may be affected by AV.^1,18-20 Earlier age of onset of AV has been suggested in white women; however, earlier onset of adrenarche may be more frequent in black girls, which supports an earlier age of onset of AV in this subpopulation.^15-17 Women with skin of color usually express greater concern with persistent dyschromia at sites where lesions have resolved, and presence of acne scars is a concern among women regardless of skin color, ethnicity, or race.^18,20-22

Scarring

Acne scarring has been noted to affect up to 
three-fourths of adult women in one report¹⁷ and 
often is stated by patients to be a cause of concern 
and frustration.^1,5,17

Perimenstrual Flaring

Flaring associated with menses is commonly reported in adult females with AV, with 56%, 17%, and 
3% of women in one study (n=230) reporting worsening before, during, or after menses, respectively.²¹

External Factors

Comedogenic products used for skin care, cover-up makeup, or hair care may be important to consider in selected cases as potential etiologic or exacerbating factors in adult females with AV; they also may be used in the management of AV.^23-25 Adult females often are perplexed and frustrated by the presence of AV after their 
teenaged years and anxiously wonder about or search for the potential causes. Many women use cosmetic products to cover up facial AV.^5,23-25 Therefore, even if skin care or personal hygiene products or makeup are not believed to be an etiologic factor, many patients appreciate that their dermatologist addressed skin care and cosmetics as a component of AV management and provided appropriate recommendations.^5,13

Ingestion of dietary supplements containing whey protein have been associated with precipitation of AV.^26,27 Diets with specific content characteristics have been implicated as potential etiologic or exacerbating factors for AV; however, data are limited and specific recommendations remain elusive at present. Individual cases may warrant consideration of dietary factors, especially when treatment resistance is noted.²⁸ Importantly, progestin-only contraceptives (ie, injectables, intrauterine devices) also can exacerbate or induce AV.²⁹

Hyperandrogenism

Although most adult females with AV are reported to have normal serum androgen levels when tested, it is important to explore potential signs and symptoms that are suggestive of underlying hyperandrogenism through both the patient’s history and physical examination.^{9-11,21,29-33} Some investigators have suggested that underlying peripheral hyperandrogenism is the leading cause of AV in adult females, 
with or without concurrent polycystic ovarian syndrome (PCOS), though it is believed that most women with AV exhibit normal results when 
undergoing laboratory testing for androgen excess.^{10,11,21,29,30} Nevertheless, it is important to consider the possibility of underlying causes of androgen excess (Table 2), the most common being PCOS and late-onset congenital adrenal hyperplasia; an androgen-secreting tumor is less common.^11,29-33 It is suggested that screening for underlying endocrinopathy should be conducted in women presenting with (1) AV recalcitrant to conventional treatment, (2) sudden emergence of severe AV, 
(3) concurrent signs/symptoms of androgen 
excess, and/or (4) AV relapse shortly after isotretinoin therapy.^7,11,16,33

Hirsutism and acanthosis nigricans have been reported to be more reliable predictors of hyperandrogenism than androgenic alopecia.²¹ Although it may be subtle in some cases, acanthosis nigricans is harder to camouflage, so the clinician can usually detect it if a thorough physical examination is performed. However, a patient may not voluntarily report to the clinician and their staff that she has hair removed, so despite a thorough examination, the clinician may not detect hirsutism. Therefore, it is important to inquire directly about the presence of hairs (pigmented terminal vs “peach fuzz” hairs), their anatomic location, and any hair removal practices the patient has used. The absence of androgenic alopecia does not exclude underlying hyperandrogenism; however, its presence, especially in younger women, may serve as a clinical marker for underlying hyperandrogenism.⁵ Some women may camouflage more subtle alopecia through hairstyling, but obtaining this history usually is not problematic, as most women are distressed by any degree of hair loss.

Laboratory Evaluation—A relatively straightforward approach to the workup of androgen excess includes assessment of serum DHEAS, free testosterone, and total testosterone levels.^10,30 Elevation of serum DHEAS levels indicates an adrenal source of androgen production. Elevation of testosterone is associated with excess androgens 
produced by the ovaries. Modest elevations of 
DHEAS are most commonly associated with late-onset congenital adrenal hyperplasia that may not have been previously diagnosed. Modest elevation 
of testosterone is most commonly associated with PCOS, which also can be accompanied by an 
elevated luteinizing hormone:follicle-stimulating hormone ratio of 2.5:1 to 3:1.^10,30 Marked elevations of DHEAS or testosterone can be indicative of adrenal or ovarian tumors, respectively.³⁰

In some cases, a woman might have 
elevated DHEAS and testosterone levels. A 17-hydroxyprogesterone test can help discriminate between an adrenal or ovarian source of 
androgen excess in these cases, as elevated 
17-hydroxyprogesterone levels indicate that the androgens are coming from the adrenal gland.^10,30

It is important that laboratory evaluation be performed when ovulation is not occurring. Blood tests can be drawn just prior to or during menses. It is important that a woman is not taking an oral contraceptive at the time of testing, which can mask an underlying endocrine abnormality.^10,11,29,30 Generally, testing can be performed at least 4 to 6 weeks after stopping the oral contraceptive.

Psychosocial Impact

Facial AV exhibits a broad range of adverse psychological and social effects on many adult females.^2,5,13,18 It can be associated with depression, anxiety, psychological stress, and suicidal ideation; therefore, thorough screening for these comorbidities may be warranted in some patients.^2,18

Conclusion

The epidemiology, clinical presentation, and clinical and laboratory evaluation of AV in adult females was reviewed in part 1 of this 3-part series. It is important for the clinician to assess the clinical presentation, psychosocial effects, and the possibility of underlying causes of androgen excess. In part 2, skin care 
and topical management of AV in adult females will be discussed.

It was not long ago that acne vulgaris (AV) was commonly considered to be a skin disease that affected teenagers with little attention given to preadolescent and postadolescent AV. This perspective has changed, with more attention being given to AV across a broad range of affected 
age groups, including preadolescent, adolescent, and postadolescent subgroups.^1-5 Earlier onset of adrenarche has led to earlier development of AV in many young girls, with a higher range of dehydroepiandrosterone sulfate (DHEAS) levels observed overall in those with AV as compared to a normal age-matched population.^3,4 At the other end of the age spectrum, AV is a common phenomenon in adult females, with at least half of women estimated to exhibit some form of AV.^1,2,5-8 Based on a 
large survey of females and males (N=1013), the prevalence of AV in adult females has been reported to be 50.9%, 35.2%, 26.3%, and 15.3% among women aged 20 to 29 years, 30 to 39 years, 40 to 49 years, and 50 years and older, respectively.² Acne vulgaris that persists beyond adolescence into adulthood is termed persistent acne, or early-onset acne, and the development of AV in women 25 years and older who have not previously been affected by AV has been termed late-onset acne.^6,8,9 Publications on the management of AV in adult women have focused primarily on systemic hormonal therapies; however, topical therapies more recently have received greater attention in this subpopulation^9-12 and will be discussed in part 2 of this series. Because data on AV in women are 
limited primarily to involvement of the face and neck region, this article does not address truncal AV unless otherwise specified. Table 1 depicts factors that can influence the management of AV in adult women.

Visible Patterns and Considerations for Clinical Evaluation 


Clinical Patterns

Although epidemiologic and demographic data are limited in the subpopulation of women with AV, it is reported that females account for up to 82% of adults with AV, with approximately 75% presenting with AV that is clinically similar to their disease course in adolescence.^2,5,13 Among those women with persistent AV, some state that their AV is worse compared to adolescence, while others report it is not as severe. The pattern of AV often is similar to that seen in adolescence, presenting as mixed comedonal and inflammatory papular/pustular lesions diffusely distributed on the face; in other cases, a more selectively distributed U-shaped pattern is noted, characterized predominantly by inflammatory papules and/or nodules involving the lower cheeks and jawline margin, with lesions also commonly noted on the anterior and lateral neck.^5,8,9,13-16 A U-shaped pattern is believed to be more common in late-onset AV, often with persistence into the mid-40s.^1,15,17 It is important to emphasize the need for additional studies on the demographics and clinical characteristics of AV in adult females, especially correlations between onset, age, and clinical patterns of AV.

An international, prospective, observational study assessed the clinical characteristics of AV in adults (aged ≥25 years) at a dermatology visit for acne (N=374).¹⁶ Participants who were under management for their AV showed severity grades of mild (clear/almost clear) in 47.3% of cases. Involvement of multiple facial sites—cheeks, forehead, mandibular region, and temples—was noted in 89.8% of women, often with both inflammatory and comedonal lesions, which is a pattern similar to adolescent AV. Inflammatory lesions alone were observed in 6.4% of women, 17.1% had comedonal AV only, 
and truncal AV was present in 48.4%.¹⁶ Additional well-designed studies are needed to determine if this study reflects an accurate qualitative and 
quantitative depiction of the spectrum of AV in adult females.

Mandibular Pattern

In the observational study of AV in adults, AV localized to the mandibular area was noted in only 11.2% of participants.¹⁶ Women with localized mandibular AV were more likely than women without localized AV to be employed, noted greater daily stress levels, and tended to report more psychologically stressful jobs. Interestingly, the subgroup with mandibular acne alone was much less likely 
to exhibit a global severity grade of moderate or higher (7.1% vs 50.1%), truncal acne 
(19.0% vs 51.9%), postinflammatory hyperpigmentation (23.8% vs 51.9%), and erythema (19.0% vs 48.4%), suggesting a unique subset of AV presentation.¹⁶

Ethnicity/Skin Color

Women of all ethnicities and skin types may be affected by AV.^1,18-20 Earlier age of onset of AV has been suggested in white women; however, earlier onset of adrenarche may be more frequent in black girls, which supports an earlier age of onset of AV in this subpopulation.^15-17 Women with skin of color usually express greater concern with persistent dyschromia at sites where lesions have resolved, and presence of acne scars is a concern among women regardless of skin color, ethnicity, or race.^18,20-22

Scarring

Acne scarring has been noted to affect up to 
three-fourths of adult women in one report¹⁷ and 
often is stated by patients to be a cause of concern 
and frustration.^1,5,17

Perimenstrual Flaring

Flaring associated with menses is commonly reported in adult females with AV, with 56%, 17%, and 
3% of women in one study (n=230) reporting worsening before, during, or after menses, respectively.²¹

External Factors

Comedogenic products used for skin care, cover-up makeup, or hair care may be important to consider in selected cases as potential etiologic or exacerbating factors in adult females with AV; they also may be used in the management of AV.^23-25 Adult females often are perplexed and frustrated by the presence of AV after their 
teenaged years and anxiously wonder about or search for the potential causes. Many women use cosmetic products to cover up facial AV.^5,23-25 Therefore, even if skin care or personal hygiene products or makeup are not believed to be an etiologic factor, many patients appreciate that their dermatologist addressed skin care and cosmetics as a component of AV management and provided appropriate recommendations.^5,13

Ingestion of dietary supplements containing whey protein have been associated with precipitation of AV.^26,27 Diets with specific content characteristics have been implicated as potential etiologic or exacerbating factors for AV; however, data are limited and specific recommendations remain elusive at present. Individual cases may warrant consideration of dietary factors, especially when treatment resistance is noted.²⁸ Importantly, progestin-only contraceptives (ie, injectables, intrauterine devices) also can exacerbate or induce AV.²⁹

Hyperandrogenism

Although most adult females with AV are reported to have normal serum androgen levels when tested, it is important to explore potential signs and symptoms that are suggestive of underlying hyperandrogenism through both the patient’s history and physical examination.^{9-11,21,29-33} Some investigators have suggested that underlying peripheral hyperandrogenism is the leading cause of AV in adult females, 
with or without concurrent polycystic ovarian syndrome (PCOS), though it is believed that most women with AV exhibit normal results when 
undergoing laboratory testing for androgen excess.^{10,11,21,29,30} Nevertheless, it is important to consider the possibility of underlying causes of androgen excess (Table 2), the most common being PCOS and late-onset congenital adrenal hyperplasia; an androgen-secreting tumor is less common.^11,29-33 It is suggested that screening for underlying endocrinopathy should be conducted in women presenting with (1) AV recalcitrant to conventional treatment, (2) sudden emergence of severe AV, 
(3) concurrent signs/symptoms of androgen 
excess, and/or (4) AV relapse shortly after isotretinoin therapy.^7,11,16,33

Hirsutism and acanthosis nigricans have been reported to be more reliable predictors of hyperandrogenism than androgenic alopecia.²¹ Although it may be subtle in some cases, acanthosis nigricans is harder to camouflage, so the clinician can usually detect it if a thorough physical examination is performed. However, a patient may not voluntarily report to the clinician and their staff that she has hair removed, so despite a thorough examination, the clinician may not detect hirsutism. Therefore, it is important to inquire directly about the presence of hairs (pigmented terminal vs “peach fuzz” hairs), their anatomic location, and any hair removal practices the patient has used. The absence of androgenic alopecia does not exclude underlying hyperandrogenism; however, its presence, especially in younger women, may serve as a clinical marker for underlying hyperandrogenism.⁵ Some women may camouflage more subtle alopecia through hairstyling, but obtaining this history usually is not problematic, as most women are distressed by any degree of hair loss.

Laboratory Evaluation—A relatively straightforward approach to the workup of androgen excess includes assessment of serum DHEAS, free testosterone, and total testosterone levels.^10,30 Elevation of serum DHEAS levels indicates an adrenal source of androgen production. Elevation of testosterone is associated with excess androgens 
produced by the ovaries. Modest elevations of 
DHEAS are most commonly associated with late-onset congenital adrenal hyperplasia that may not have been previously diagnosed. Modest elevation 
of testosterone is most commonly associated with PCOS, which also can be accompanied by an 
elevated luteinizing hormone:follicle-stimulating hormone ratio of 2.5:1 to 3:1.^10,30 Marked elevations of DHEAS or testosterone can be indicative of adrenal or ovarian tumors, respectively.³⁰

In some cases, a woman might have 
elevated DHEAS and testosterone levels. A 17-hydroxyprogesterone test can help discriminate between an adrenal or ovarian source of 
androgen excess in these cases, as elevated 
17-hydroxyprogesterone levels indicate that the androgens are coming from the adrenal gland.^10,30

It is important that laboratory evaluation be performed when ovulation is not occurring. Blood tests can be drawn just prior to or during menses. It is important that a woman is not taking an oral contraceptive at the time of testing, which can mask an underlying endocrine abnormality.^10,11,29,30 Generally, testing can be performed at least 4 to 6 weeks after stopping the oral contraceptive.

Psychosocial Impact

Facial AV exhibits a broad range of adverse psychological and social effects on many adult females.^2,5,13,18 It can be associated with depression, anxiety, psychological stress, and suicidal ideation; therefore, thorough screening for these comorbidities may be warranted in some patients.^2,18

Conclusion

The epidemiology, clinical presentation, and clinical and laboratory evaluation of AV in adult females was reviewed in part 1 of this 3-part series. It is important for the clinician to assess the clinical presentation, psychosocial effects, and the possibility of underlying causes of androgen excess. In part 2, skin care 
and topical management of AV in adult females will be discussed.

Blood for transfusion

Photo by Juan D. Alfonso

CHICAGO—Researchers say an electronic tracking system has enabled a group of hospitals to significantly reduce the amount of blood transfused after operations.

This system also cut costs by an estimated $2.5 million over 2 years and contributed to lower infection rates without harming patients.

These results were presented at the 2015 Clinical Congress of the American College of Surgeons and published in the Journal of the American College of Surgeons.

In 2012, Intermountain Healthcare implemented the blood ordering and tracking system, along with a program to educate hospital staff, in 22 hospitals across Utah. This includes trauma centers, small rural hospitals, and large community medical centers.

Intermountain employs approximately 1200 physicians and 550 advanced practice clinicians, and another 3000 to 4000 independent physicians have privileges at Intermountain hospitals.

Before Intermountain implemented its blood tracking system, general surgeons, orthopedic surgeons, and urologists each used different hematocrit levels to order blood.

Now, Intermountain uses a consistent threshold across all disciplines—less than 23%. However, physicians can still order blood for patients with hematocrit above that threshold when they feel it is medically necessary.

Results

In 2011, 6% of all patients at Intermountain facilities received blood. Today, only 4% do, according to study author Mark J. Ott, MD, chief medical director of Intermountain Healthcare’s central region.

“So a third of our patients didn’t get blood who used to,” Dr Ott said. “That’s a giant change. That’s tens of thousands of units of blood a year that didn’t get used.”

Before the program started (January 1, 2012), Intermountain facilities transfused almost 50 units of packed red blood cells per 1000 patient days. By January 31, 2015, that rate had declined to about 35.5 units, a reduction of around 30%.

Over the same time period, the percentage of patients transfused with a hematocrit of 23% or greater decreased from 60% to 34%.

The researchers said these reductions in blood use reduced costs by about $2.5 million over the 2-year period, assuming each unit of packed red blood cells costs $300.

In addition, the rate of hospital-acquired infections for both the general hospital population and patients who received blood declined significantly over the 2-year period.

The overall infection rate fell from 1.66 to 0.81 per 1000 patient days. Among patients who received blood, infection rates declined around 33%.

Dr Ott noted that the reduction in infections was also impacted by other initiatives within the health system aimed at reducing surgical site infections and ambulating patients earlier after operations.

“So I cannot tell you that those decreases in hospital-acquired infections are solely due to patients receiving less blood, but it’s part of the picture,” he said. “And we did not see worse outcomes in patients.”

Blood for transfusion

Photo by Juan D. Alfonso

CHICAGO—Researchers say an electronic tracking system has enabled a group of hospitals to significantly reduce the amount of blood transfused after operations.

This system also cut costs by an estimated $2.5 million over 2 years and contributed to lower infection rates without harming patients.

These results were presented at the 2015 Clinical Congress of the American College of Surgeons and published in the Journal of the American College of Surgeons.

In 2012, Intermountain Healthcare implemented the blood ordering and tracking system, along with a program to educate hospital staff, in 22 hospitals across Utah. This includes trauma centers, small rural hospitals, and large community medical centers.

Intermountain employs approximately 1200 physicians and 550 advanced practice clinicians, and another 3000 to 4000 independent physicians have privileges at Intermountain hospitals.

Before Intermountain implemented its blood tracking system, general surgeons, orthopedic surgeons, and urologists each used different hematocrit levels to order blood.

Now, Intermountain uses a consistent threshold across all disciplines—less than 23%. However, physicians can still order blood for patients with hematocrit above that threshold when they feel it is medically necessary.

Results

In 2011, 6% of all patients at Intermountain facilities received blood. Today, only 4% do, according to study author Mark J. Ott, MD, chief medical director of Intermountain Healthcare’s central region.

“So a third of our patients didn’t get blood who used to,” Dr Ott said. “That’s a giant change. That’s tens of thousands of units of blood a year that didn’t get used.”

Before the program started (January 1, 2012), Intermountain facilities transfused almost 50 units of packed red blood cells per 1000 patient days. By January 31, 2015, that rate had declined to about 35.5 units, a reduction of around 30%.

Over the same time period, the percentage of patients transfused with a hematocrit of 23% or greater decreased from 60% to 34%.

The researchers said these reductions in blood use reduced costs by about $2.5 million over the 2-year period, assuming each unit of packed red blood cells costs $300.

In addition, the rate of hospital-acquired infections for both the general hospital population and patients who received blood declined significantly over the 2-year period.

The overall infection rate fell from 1.66 to 0.81 per 1000 patient days. Among patients who received blood, infection rates declined around 33%.

Dr Ott noted that the reduction in infections was also impacted by other initiatives within the health system aimed at reducing surgical site infections and ambulating patients earlier after operations.

“So I cannot tell you that those decreases in hospital-acquired infections are solely due to patients receiving less blood, but it’s part of the picture,” he said. “And we did not see worse outcomes in patients.”

Blood for transfusion

Photo by Juan D. Alfonso

CHICAGO—Researchers say an electronic tracking system has enabled a group of hospitals to significantly reduce the amount of blood transfused after operations.

This system also cut costs by an estimated $2.5 million over 2 years and contributed to lower infection rates without harming patients.

These results were presented at the 2015 Clinical Congress of the American College of Surgeons and published in the Journal of the American College of Surgeons.

In 2012, Intermountain Healthcare implemented the blood ordering and tracking system, along with a program to educate hospital staff, in 22 hospitals across Utah. This includes trauma centers, small rural hospitals, and large community medical centers.

Intermountain employs approximately 1200 physicians and 550 advanced practice clinicians, and another 3000 to 4000 independent physicians have privileges at Intermountain hospitals.

Before Intermountain implemented its blood tracking system, general surgeons, orthopedic surgeons, and urologists each used different hematocrit levels to order blood.

Now, Intermountain uses a consistent threshold across all disciplines—less than 23%. However, physicians can still order blood for patients with hematocrit above that threshold when they feel it is medically necessary.

Results

In 2011, 6% of all patients at Intermountain facilities received blood. Today, only 4% do, according to study author Mark J. Ott, MD, chief medical director of Intermountain Healthcare’s central region.

“So a third of our patients didn’t get blood who used to,” Dr Ott said. “That’s a giant change. That’s tens of thousands of units of blood a year that didn’t get used.”

Before the program started (January 1, 2012), Intermountain facilities transfused almost 50 units of packed red blood cells per 1000 patient days. By January 31, 2015, that rate had declined to about 35.5 units, a reduction of around 30%.

Over the same time period, the percentage of patients transfused with a hematocrit of 23% or greater decreased from 60% to 34%.

The researchers said these reductions in blood use reduced costs by about $2.5 million over the 2-year period, assuming each unit of packed red blood cells costs $300.

In addition, the rate of hospital-acquired infections for both the general hospital population and patients who received blood declined significantly over the 2-year period.

The overall infection rate fell from 1.66 to 0.81 per 1000 patient days. Among patients who received blood, infection rates declined around 33%.

Dr Ott noted that the reduction in infections was also impacted by other initiatives within the health system aimed at reducing surgical site infections and ambulating patients earlier after operations.

“So I cannot tell you that those decreases in hospital-acquired infections are solely due to patients receiving less blood, but it’s part of the picture,” he said. “And we did not see worse outcomes in patients.”

Doctor examines patient

Photo by Logan Tuttle

Results of 2 studies suggest eltrombopag can be safe and effective in children of all ages affected by chronic immune thrombocytopenia (ITP).

In both trials, patients who received eltrombopag were significantly more likely to achieve stable platelet counts than patients who received placebo.

And eltrombopag did not increase the rate of serious adverse events (AEs).

These studies are the phase 2 PETIT trial, which was published in The Lancet Haematology, and the phase 3 PETIT2 trial, which was published in The Lancet.

“The studies, funded by GlaxoSmithKline, provide clinicians with much-needed evidence to help decide when eltrombopag would benefit pediatric patients and provide dosage regimens suitable for pediatric patients,” said investigator John Grainger, PhD, of The University of Manchester in the UK.

Phase 2 trial

The PETIT trial included 67 ITP patients who were stratified by age cohort (12-17 years, 6-11 years, and 1-5 years) and randomized (2:1) to receive eltrombopag or placebo for 7 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 10⁹/L.

The primary efficacy endpoint was the proportion of subjects achieving platelet counts of 50 x 10⁹/L or higher at least once between days 8 and 43 of the randomized period of the study.

Significantly more patients in the eltrombopag arm met this endpoint—62.2%—compared to 31.8% in the placebo arm (P=0.011).

The most common AEs (in the eltrombopag and placebo groups, respectively) were headache (30% vs 43%), upper respiratory tract infection (25% vs 10%), and diarrhea (16% vs 5%).

Grade 3/4 AEs occurred in 11% of patients receiving eltrombopag and 19% of patients receiving placebo. Serious AEs occurred in 9% and 10%, respectively. There were no thrombotic events or malignancies in either group.

Phase 3 trial

The PETIT2 trial included 92 patients with chronic ITP who were randomized (2:1) to receive eltrombopag or placebo for 13 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 10⁹/L.

The primary efficacy endpoint was the proportion of subjects who achieved platelet counts of 50 x 10⁹/L or higher for at least 6 out of 8 weeks, between weeks 5 and 12 of the randomized period.

Significantly more patients in the eltrombopag arm met this endpoint—41.3%, compared to 3.4% of patients in the placebo arm (P<0.001).

AEs that occurred more frequently with eltrombopag than with placebo included nasopharyngitis (17%), rhinitis (16%), upper respiratory tract infection (11%), and cough (11%).

Serious AEs occurred in 8% of patients who received eltrombopag and 14% who received placebo. There were no deaths, malignancies, or thromboses during this trial.

It was based on these studies that eltrombopag was approved for use in US children older than 1 year of age. The drug is currently under review for this indication in the European Union.

Doctor examines patient

Photo by Logan Tuttle

Results of 2 studies suggest eltrombopag can be safe and effective in children of all ages affected by chronic immune thrombocytopenia (ITP).

In both trials, patients who received eltrombopag were significantly more likely to achieve stable platelet counts than patients who received placebo.

And eltrombopag did not increase the rate of serious adverse events (AEs).

These studies are the phase 2 PETIT trial, which was published in The Lancet Haematology, and the phase 3 PETIT2 trial, which was published in The Lancet.

“The studies, funded by GlaxoSmithKline, provide clinicians with much-needed evidence to help decide when eltrombopag would benefit pediatric patients and provide dosage regimens suitable for pediatric patients,” said investigator John Grainger, PhD, of The University of Manchester in the UK.

Phase 2 trial

The PETIT trial included 67 ITP patients who were stratified by age cohort (12-17 years, 6-11 years, and 1-5 years) and randomized (2:1) to receive eltrombopag or placebo for 7 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 10⁹/L.

The primary efficacy endpoint was the proportion of subjects achieving platelet counts of 50 x 10⁹/L or higher at least once between days 8 and 43 of the randomized period of the study.

Significantly more patients in the eltrombopag arm met this endpoint—62.2%—compared to 31.8% in the placebo arm (P=0.011).

The most common AEs (in the eltrombopag and placebo groups, respectively) were headache (30% vs 43%), upper respiratory tract infection (25% vs 10%), and diarrhea (16% vs 5%).

Grade 3/4 AEs occurred in 11% of patients receiving eltrombopag and 19% of patients receiving placebo. Serious AEs occurred in 9% and 10%, respectively. There were no thrombotic events or malignancies in either group.

Phase 3 trial

The PETIT2 trial included 92 patients with chronic ITP who were randomized (2:1) to receive eltrombopag or placebo for 13 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 10⁹/L.

The primary efficacy endpoint was the proportion of subjects who achieved platelet counts of 50 x 10⁹/L or higher for at least 6 out of 8 weeks, between weeks 5 and 12 of the randomized period.

Significantly more patients in the eltrombopag arm met this endpoint—41.3%, compared to 3.4% of patients in the placebo arm (P<0.001).

AEs that occurred more frequently with eltrombopag than with placebo included nasopharyngitis (17%), rhinitis (16%), upper respiratory tract infection (11%), and cough (11%).

Serious AEs occurred in 8% of patients who received eltrombopag and 14% who received placebo. There were no deaths, malignancies, or thromboses during this trial.

It was based on these studies that eltrombopag was approved for use in US children older than 1 year of age. The drug is currently under review for this indication in the European Union.

Doctor examines patient

Photo by Logan Tuttle

Results of 2 studies suggest eltrombopag can be safe and effective in children of all ages affected by chronic immune thrombocytopenia (ITP).

In both trials, patients who received eltrombopag were significantly more likely to achieve stable platelet counts than patients who received placebo.

And eltrombopag did not increase the rate of serious adverse events (AEs).

These studies are the phase 2 PETIT trial, which was published in The Lancet Haematology, and the phase 3 PETIT2 trial, which was published in The Lancet.

“The studies, funded by GlaxoSmithKline, provide clinicians with much-needed evidence to help decide when eltrombopag would benefit pediatric patients and provide dosage regimens suitable for pediatric patients,” said investigator John Grainger, PhD, of The University of Manchester in the UK.

Phase 2 trial

The PETIT trial included 67 ITP patients who were stratified by age cohort (12-17 years, 6-11 years, and 1-5 years) and randomized (2:1) to receive eltrombopag or placebo for 7 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 10⁹/L.

The primary efficacy endpoint was the proportion of subjects achieving platelet counts of 50 x 10⁹/L or higher at least once between days 8 and 43 of the randomized period of the study.

Significantly more patients in the eltrombopag arm met this endpoint—62.2%—compared to 31.8% in the placebo arm (P=0.011).

The most common AEs (in the eltrombopag and placebo groups, respectively) were headache (30% vs 43%), upper respiratory tract infection (25% vs 10%), and diarrhea (16% vs 5%).

Grade 3/4 AEs occurred in 11% of patients receiving eltrombopag and 19% of patients receiving placebo. Serious AEs occurred in 9% and 10%, respectively. There were no thrombotic events or malignancies in either group.

Phase 3 trial

The PETIT2 trial included 92 patients with chronic ITP who were randomized (2:1) to receive eltrombopag or placebo for 13 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 10⁹/L.

The primary efficacy endpoint was the proportion of subjects who achieved platelet counts of 50 x 10⁹/L or higher for at least 6 out of 8 weeks, between weeks 5 and 12 of the randomized period.

Significantly more patients in the eltrombopag arm met this endpoint—41.3%, compared to 3.4% of patients in the placebo arm (P<0.001).

AEs that occurred more frequently with eltrombopag than with placebo included nasopharyngitis (17%), rhinitis (16%), upper respiratory tract infection (11%), and cough (11%).

Serious AEs occurred in 8% of patients who received eltrombopag and 14% who received placebo. There were no deaths, malignancies, or thromboses during this trial.

It was based on these studies that eltrombopag was approved for use in US children older than 1 year of age. The drug is currently under review for this indication in the European Union.