Atopic Dermatitis

LAS VEGAS – Recent research has provided a rare triple whammy in the world of atopic dermatitis (AD). Over the last few years, studies have provided valuable insight into not just treatments for AD but also its roots and strategies for prevention, Linda F. Stein Gold, MD, said at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

AD affects an estimated 7% of adults in the United States and 13% of children under aged 18 years, according to the National Eczema Association. An estimated one-third of the affected children (3.2 million) have moderate to severe disease.

New information about AD includes more information pinpointing the genetic link. Dr. Stein Gold, director of clinical research in the department of dermatology at the Henry Ford Health System, Detroit, pointed out that about 70% of patients with AD have a family history of atopic conditions.


Mutations in filaggrin appear to play a role in the development of AD, but a significant proportion of people with AD do not have evidence of filaggrin mutations and about 40% of people with defects never develop AD, she noted.

Emollients may be key to preventing AD. To explore the theory that defects on the skin barrier “might be key initiators of atopic dermatitis and possibly allergic sensitization,” investigators conducted a randomized controlled study of 124 babies at risk of AD in the United States and United Kingdom; parents of 55 babies applied emollients to their whole bodies from shortly after birth until 6 months while a control group used nothing (J Allergy Clin Immunol. 2014 Oct; 134[4]:818-23).

At 6 months, those in the emollient group were half as likely to have developed AD (relative risk, 0.50; P = .017).

Bleach baths have received attention on the AD prevention front. Dr. Stein Gold pointed to a 2017 systematic review and meta-analysis of five studies that found both bleach and water baths reduced AD severity. Bleach baths were effective but not more so than water baths (Ann Allergy Asthma Immunol. 2017 Nov;119[5]:435-40). Also, there was no difference in skin infections or colonization with Staphylococcus aureus between the two.


So are water baths just as good as bleach baths? “I’m not 100% sure I buy into this,” Dr. Stein Gold said. “I’m still a bleach bath believer.”

Topical calcineurin inhibitors (TCIs) can be used as a “proactive,” steroid-sparing treatment to prevent relapses in AD, research suggests. For this purpose, the recommended maintenance dosage is two to three applications per week on areas that tend to flare; the TCI drugs can be used in conjunction with topical corticosteroids (J Am Acad Dermatol. 2014 Jul;71[1]:116-32).

TCIs come with boxed warning because of concerns about such cancers as lymphoma. But recent research has not found a higher risk of lymphoma in patients with AD who are treated with the medication. “We’ve had these drugs for a long time, and they do appear to be safe,” Dr. Stein Gold said.

She referred to a 2015 review of 21 studies of almost 6,000 pediatric patients with AD who were treated with a TCI, which concluded that the drugs are safe and efficacious over the long term (Pediatric Allergy Immunol. 2015 Jun;26[4]:306-15).

“Everyone wants to know which ones are better,” Dr. Stein Gold said in regard to TCIs. But there aren’t head-to-head studies, she said, and it’s difficult to compare the available data on response rates between certain topical treatments because the studies are designed differently.

For example, with crisaborole (Eucrisa), the topical phosphodiesterase-4 (PDE4) inhibitor approved in 2016 for mild to moderate AD in patients aged 2 years and up, clear/almost clear rates are 49%-52%, compared with 30%-40% with placebo, a 10%-20% difference. Rates with OPA-15406, an investigational topical selective PDE4 inhibitor, and with the TCI pimecrolimus (Elidel cream 1%) have been about 20% higher than with controls, but studies are designed differently, and the results cannot be compared, according to Dr. Stein Gold.

Dupilumab (Dupixent), a monoclonal antibody that inhibits signaling of both interleukin-4 and interleukin-13, approved in 2017 for adults with moderate to severe AD, has been a “game changer” for this population, Dr. Stein Gold said. “It looks like this drug has a good, durable effect,” she added (Lancet. 2017 Jun 10;389[10086]:2287-303).

However, she cautioned that up to 10% of patients treated with dupilumab – or more – may develop conjunctivitis. Researchers studying dupilumab in asthma have not seen this side effect, she said, so it may be unique to AD. “It’s something that’s real,” she said, noting that it’s not clear if it’s viral, allergic, or bacterial. Researchers are exploring the use of the drug in children, she added.

Dr. Stein Gold said there are other drugs in development for AD, but she cautioned that “the field is crowded ... and not all of them are going to make it.”

Drugs in development for AD include nemolizumab (a humanized monoclonal antibody that inhibits interleukin-31 signaling), upadacitinib (a JAK1 selective inhibitor), baricitinib (an oral JAK1/2 inhibitor), and topical tapinarof (an agonist of the aryl hydrocarbon receptor).

SDEF and this news organization are owned by the same parent company.

Dr. Stein Gold disclosed relationships with Galderma, Valeant, Ranbaxy, Promius, Actavis, Roche, Dermira, Medimetriks, Pfizer, Sanofi/Regeneron, Otsuka, and Taro.

LAS VEGAS – Recent research has provided a rare triple whammy in the world of atopic dermatitis (AD). Over the last few years, studies have provided valuable insight into not just treatments for AD but also its roots and strategies for prevention, Linda F. Stein Gold, MD, said at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

AD affects an estimated 7% of adults in the United States and 13% of children under aged 18 years, according to the National Eczema Association. An estimated one-third of the affected children (3.2 million) have moderate to severe disease.

New information about AD includes more information pinpointing the genetic link. Dr. Stein Gold, director of clinical research in the department of dermatology at the Henry Ford Health System, Detroit, pointed out that about 70% of patients with AD have a family history of atopic conditions.


Mutations in filaggrin appear to play a role in the development of AD, but a significant proportion of people with AD do not have evidence of filaggrin mutations and about 40% of people with defects never develop AD, she noted.

Emollients may be key to preventing AD. To explore the theory that defects on the skin barrier “might be key initiators of atopic dermatitis and possibly allergic sensitization,” investigators conducted a randomized controlled study of 124 babies at risk of AD in the United States and United Kingdom; parents of 55 babies applied emollients to their whole bodies from shortly after birth until 6 months while a control group used nothing (J Allergy Clin Immunol. 2014 Oct; 134[4]:818-23).

At 6 months, those in the emollient group were half as likely to have developed AD (relative risk, 0.50; P = .017).

Bleach baths have received attention on the AD prevention front. Dr. Stein Gold pointed to a 2017 systematic review and meta-analysis of five studies that found both bleach and water baths reduced AD severity. Bleach baths were effective but not more so than water baths (Ann Allergy Asthma Immunol. 2017 Nov;119[5]:435-40). Also, there was no difference in skin infections or colonization with Staphylococcus aureus between the two.


So are water baths just as good as bleach baths? “I’m not 100% sure I buy into this,” Dr. Stein Gold said. “I’m still a bleach bath believer.”

Topical calcineurin inhibitors (TCIs) can be used as a “proactive,” steroid-sparing treatment to prevent relapses in AD, research suggests. For this purpose, the recommended maintenance dosage is two to three applications per week on areas that tend to flare; the TCI drugs can be used in conjunction with topical corticosteroids (J Am Acad Dermatol. 2014 Jul;71[1]:116-32).

TCIs come with boxed warning because of concerns about such cancers as lymphoma. But recent research has not found a higher risk of lymphoma in patients with AD who are treated with the medication. “We’ve had these drugs for a long time, and they do appear to be safe,” Dr. Stein Gold said.

She referred to a 2015 review of 21 studies of almost 6,000 pediatric patients with AD who were treated with a TCI, which concluded that the drugs are safe and efficacious over the long term (Pediatric Allergy Immunol. 2015 Jun;26[4]:306-15).

“Everyone wants to know which ones are better,” Dr. Stein Gold said in regard to TCIs. But there aren’t head-to-head studies, she said, and it’s difficult to compare the available data on response rates between certain topical treatments because the studies are designed differently.

For example, with crisaborole (Eucrisa), the topical phosphodiesterase-4 (PDE4) inhibitor approved in 2016 for mild to moderate AD in patients aged 2 years and up, clear/almost clear rates are 49%-52%, compared with 30%-40% with placebo, a 10%-20% difference. Rates with OPA-15406, an investigational topical selective PDE4 inhibitor, and with the TCI pimecrolimus (Elidel cream 1%) have been about 20% higher than with controls, but studies are designed differently, and the results cannot be compared, according to Dr. Stein Gold.

Dupilumab (Dupixent), a monoclonal antibody that inhibits signaling of both interleukin-4 and interleukin-13, approved in 2017 for adults with moderate to severe AD, has been a “game changer” for this population, Dr. Stein Gold said. “It looks like this drug has a good, durable effect,” she added (Lancet. 2017 Jun 10;389[10086]:2287-303).

However, she cautioned that up to 10% of patients treated with dupilumab – or more – may develop conjunctivitis. Researchers studying dupilumab in asthma have not seen this side effect, she said, so it may be unique to AD. “It’s something that’s real,” she said, noting that it’s not clear if it’s viral, allergic, or bacterial. Researchers are exploring the use of the drug in children, she added.

Dr. Stein Gold said there are other drugs in development for AD, but she cautioned that “the field is crowded ... and not all of them are going to make it.”

Drugs in development for AD include nemolizumab (a humanized monoclonal antibody that inhibits interleukin-31 signaling), upadacitinib (a JAK1 selective inhibitor), baricitinib (an oral JAK1/2 inhibitor), and topical tapinarof (an agonist of the aryl hydrocarbon receptor).

SDEF and this news organization are owned by the same parent company.

Dr. Stein Gold disclosed relationships with Galderma, Valeant, Ranbaxy, Promius, Actavis, Roche, Dermira, Medimetriks, Pfizer, Sanofi/Regeneron, Otsuka, and Taro.

LAS VEGAS – Recent research has provided a rare triple whammy in the world of atopic dermatitis (AD). Over the last few years, studies have provided valuable insight into not just treatments for AD but also its roots and strategies for prevention, Linda F. Stein Gold, MD, said at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

AD affects an estimated 7% of adults in the United States and 13% of children under aged 18 years, according to the National Eczema Association. An estimated one-third of the affected children (3.2 million) have moderate to severe disease.

New information about AD includes more information pinpointing the genetic link. Dr. Stein Gold, director of clinical research in the department of dermatology at the Henry Ford Health System, Detroit, pointed out that about 70% of patients with AD have a family history of atopic conditions.


Mutations in filaggrin appear to play a role in the development of AD, but a significant proportion of people with AD do not have evidence of filaggrin mutations and about 40% of people with defects never develop AD, she noted.

Emollients may be key to preventing AD. To explore the theory that defects on the skin barrier “might be key initiators of atopic dermatitis and possibly allergic sensitization,” investigators conducted a randomized controlled study of 124 babies at risk of AD in the United States and United Kingdom; parents of 55 babies applied emollients to their whole bodies from shortly after birth until 6 months while a control group used nothing (J Allergy Clin Immunol. 2014 Oct; 134[4]:818-23).

At 6 months, those in the emollient group were half as likely to have developed AD (relative risk, 0.50; P = .017).

Bleach baths have received attention on the AD prevention front. Dr. Stein Gold pointed to a 2017 systematic review and meta-analysis of five studies that found both bleach and water baths reduced AD severity. Bleach baths were effective but not more so than water baths (Ann Allergy Asthma Immunol. 2017 Nov;119[5]:435-40). Also, there was no difference in skin infections or colonization with Staphylococcus aureus between the two.


So are water baths just as good as bleach baths? “I’m not 100% sure I buy into this,” Dr. Stein Gold said. “I’m still a bleach bath believer.”

Topical calcineurin inhibitors (TCIs) can be used as a “proactive,” steroid-sparing treatment to prevent relapses in AD, research suggests. For this purpose, the recommended maintenance dosage is two to three applications per week on areas that tend to flare; the TCI drugs can be used in conjunction with topical corticosteroids (J Am Acad Dermatol. 2014 Jul;71[1]:116-32).

TCIs come with boxed warning because of concerns about such cancers as lymphoma. But recent research has not found a higher risk of lymphoma in patients with AD who are treated with the medication. “We’ve had these drugs for a long time, and they do appear to be safe,” Dr. Stein Gold said.

She referred to a 2015 review of 21 studies of almost 6,000 pediatric patients with AD who were treated with a TCI, which concluded that the drugs are safe and efficacious over the long term (Pediatric Allergy Immunol. 2015 Jun;26[4]:306-15).

“Everyone wants to know which ones are better,” Dr. Stein Gold said in regard to TCIs. But there aren’t head-to-head studies, she said, and it’s difficult to compare the available data on response rates between certain topical treatments because the studies are designed differently.

For example, with crisaborole (Eucrisa), the topical phosphodiesterase-4 (PDE4) inhibitor approved in 2016 for mild to moderate AD in patients aged 2 years and up, clear/almost clear rates are 49%-52%, compared with 30%-40% with placebo, a 10%-20% difference. Rates with OPA-15406, an investigational topical selective PDE4 inhibitor, and with the TCI pimecrolimus (Elidel cream 1%) have been about 20% higher than with controls, but studies are designed differently, and the results cannot be compared, according to Dr. Stein Gold.

Dupilumab (Dupixent), a monoclonal antibody that inhibits signaling of both interleukin-4 and interleukin-13, approved in 2017 for adults with moderate to severe AD, has been a “game changer” for this population, Dr. Stein Gold said. “It looks like this drug has a good, durable effect,” she added (Lancet. 2017 Jun 10;389[10086]:2287-303).

However, she cautioned that up to 10% of patients treated with dupilumab – or more – may develop conjunctivitis. Researchers studying dupilumab in asthma have not seen this side effect, she said, so it may be unique to AD. “It’s something that’s real,” she said, noting that it’s not clear if it’s viral, allergic, or bacterial. Researchers are exploring the use of the drug in children, she added.

Dr. Stein Gold said there are other drugs in development for AD, but she cautioned that “the field is crowded ... and not all of them are going to make it.”

Drugs in development for AD include nemolizumab (a humanized monoclonal antibody that inhibits interleukin-31 signaling), upadacitinib (a JAK1 selective inhibitor), baricitinib (an oral JAK1/2 inhibitor), and topical tapinarof (an agonist of the aryl hydrocarbon receptor).

SDEF and this news organization are owned by the same parent company.

Dr. Stein Gold disclosed relationships with Galderma, Valeant, Ranbaxy, Promius, Actavis, Roche, Dermira, Medimetriks, Pfizer, Sanofi/Regeneron, Otsuka, and Taro.

To the Editor:

Autoimmune progesterone dermatitis (APD) is a rare dermatologic condition that can be challenging to diagnose. The associated skin lesions are not only variable in physical presentation but also in the timing of the outbreak. The skin disorder stems from an internal reaction to elevated levels of progesterone during the luteal phase of the menstrual cycle. Autoimmune progesterone dermatitis can be difficult to detect; although the typical menstrual cycle is 28 days, many women have longer or shorter hormonal phases, leading to cyclical irregularity that can cause the lesions to appear sporadic in nature when in fact they are not.¹

A 34-year-old woman with a history of endometriosis, psoriasis, and malignant melanoma presented to our dermatology clinic 2 days after a brief hospitalization during which she was diagnosed with a hypersensitivity reaction. Two days prior to her hospital admission, the patient developed a rash on the lower back with associated myalgia. The rash progressively worsened, spreading laterally to the flanks, which prompted her to seek medical attention. Blood work included a complete blood cell count with differential, complete metabolic panel, antinuclear antibody test, and erythrocyte sedimentation rate, which all were within reference range. A 4-mm punch biopsy from the left lateral flank was performed and was consistent with a neutrophilic dermatosis. The patient’s symptoms diminished and she was discharged the next day with instructions to follow up with a dermatologist.

Physical examination at our clinic revealed multiple minimally indurated, erythematous plaques with superficial scaling along the left lower back and upper buttock (Figure 1). No other skin lesions were present, and palpation of the cervical, axillary, and inguinal lymph nodes was unremarkable. A repeat 6-mm punch biopsy was performed and she was sent for fasting blood work.

Histologic examination of the punch biopsy revealed a superficial and deep perivascular and interstitial dermatitis with scattered neutrophils and eosinophils. Findings were described as nonspecific, possibly representing a dermal hypersensitivity or urticarial reaction.

Glucose-6-phosphate dehydrogenase testing was within reference range, and therapy was initiated with oral dapsone 50 mg once daily as well as fexofenadine 180 mg once daily. The patient initially responded well to the oral therapy, but she experienced recurrence of the skin eruption at infrequent intervals over the next few months, requiring escalating doses of dapsone to control the symptoms. After further questioning at a subsequent visit a few months later, it was discovered that the eruption occurred near the onset of the patient’s irregular menstrual cycle.

Approximately 1 year after her initial presentation, the patient returned for intradermal hormone injections to test for hormonally induced hypersensitivities. An injection of0.1 mL of a 50-mg/mL progesterone solution was administered in the right forearm as well as 0.1 mL of a 5-mg/mL estradiol solution and 0.1 mL of saline in the left forearm as a control. One hour after the injections, a strong positive reaction consisting of a 15-mm indurated plaque with surrounding wheal was noted at the site of the progesterone injection. The estradiol and saline control sites were clear of any dermal reaction (Figure 2). A diagnosis of APD was established, and the patient was referred to her gynecologist for treatment.

Due to the aggressive nature of her endometriosis, the gonadotropin-releasing hormone agonist leuprolide acetate was the first-line treatment prescribed by her gynecologist; however, after 8 months of therapy with leuprolide acetate, she was still experiencing breakthrough myalgia with her menstrual cycle and opted for a hysterectomy with a bilateral salpingo-oophorectomy. Within weeks of surgery, the myalgia ceased and the patient was completely asymptomatic.

Autoimmune progesterone dermatitis was first described in 1921.² In affected women, the body reacts to the progesterone hormone surge during the luteal phase of the menstrual cycle. Symptoms begin approximately 3 to 4 days prior to menses and resolve 2 to 3 days after onset of flow. These progesterone hypersensitivity reactions can present within a spectrum of morphologies and severities. The lesions can appear eczematous, urticarial, as an angioedemalike reaction, as an erythema multiforme–like reaction with targetoid lesions, or in other nonspecific ways.^1,3 Some patients experience a very mild, almost asymptomatic reaction, while others have a profound reaction progressing to anaphylaxis. Originally it was thought that exogenous exposure to progesterone led to a cross-reaction or hypersensitivity to the hormone; however, there have been cases reported in females as young as 12 years of age with no prior exposure.^3,4 Reactions also can vary during pregnancy. There have been reports of spontaneous abortion in some affected females, but symptoms may dissipate in others, possibly due to a slow rise in progesterone causing a desensitization reaction.^3,5

According to Bandino et al,⁶ there are 3 criteria for diagnosis of APD: (1) skin lesions related to the menstrual cycle, (2) positive response to intradermal testing with progesterone, and (3) symptomatic improvement after inhibiting progesterone secretions by suppressing ovulation.Areas checked with intradermal testing need to be evaluated 24 and 48 hours later for possible immediate or delayed-type hypersensitivity reactions. Biopsy typically is not helpful in this diagnosis because results usually are nonspecific.

Treatment of APD is targeted toward suppressing the internal hormonal surge. By suppressing the progesterone hormone, the symptoms are alleviated. The discomfort from the skin reaction typically is unresponsive to steroids or antihistamines. Oral contraceptives are first line in most cases because they suppress ovulation. Gonadotropin-releasing hormone analogues and tamoxifen also have been successful. For patients with severe disease that is recalcitrant to standard therapy or those who are postmenopausal, an oophorectemy is a curative option.^2,4,5,7

Autoimmune progesterone dermatitis is a rare cyclical dermatologic condition in which the body responds to a surge of the patient’s own progesterone hormone. The disorder is difficult to diagnose because it can present with differing morphologies and biopsy is nonspecific. It also can be increasingly difficult to diagnose in women who do not have a typical 28-day menstrual cycle. In our patient, her irregular menstrual cycle may have caused a delay in diagnosis. Although the condition is rare, APD should be included in the differential diagnosis in females with a recurrent, cyclical, or recalcitrant cutaneous eruption.

To the Editor:

Autoimmune progesterone dermatitis (APD) is a rare dermatologic condition that can be challenging to diagnose. The associated skin lesions are not only variable in physical presentation but also in the timing of the outbreak. The skin disorder stems from an internal reaction to elevated levels of progesterone during the luteal phase of the menstrual cycle. Autoimmune progesterone dermatitis can be difficult to detect; although the typical menstrual cycle is 28 days, many women have longer or shorter hormonal phases, leading to cyclical irregularity that can cause the lesions to appear sporadic in nature when in fact they are not.¹

A 34-year-old woman with a history of endometriosis, psoriasis, and malignant melanoma presented to our dermatology clinic 2 days after a brief hospitalization during which she was diagnosed with a hypersensitivity reaction. Two days prior to her hospital admission, the patient developed a rash on the lower back with associated myalgia. The rash progressively worsened, spreading laterally to the flanks, which prompted her to seek medical attention. Blood work included a complete blood cell count with differential, complete metabolic panel, antinuclear antibody test, and erythrocyte sedimentation rate, which all were within reference range. A 4-mm punch biopsy from the left lateral flank was performed and was consistent with a neutrophilic dermatosis. The patient’s symptoms diminished and she was discharged the next day with instructions to follow up with a dermatologist.

Physical examination at our clinic revealed multiple minimally indurated, erythematous plaques with superficial scaling along the left lower back and upper buttock (Figure 1). No other skin lesions were present, and palpation of the cervical, axillary, and inguinal lymph nodes was unremarkable. A repeat 6-mm punch biopsy was performed and she was sent for fasting blood work.

Histologic examination of the punch biopsy revealed a superficial and deep perivascular and interstitial dermatitis with scattered neutrophils and eosinophils. Findings were described as nonspecific, possibly representing a dermal hypersensitivity or urticarial reaction.

Glucose-6-phosphate dehydrogenase testing was within reference range, and therapy was initiated with oral dapsone 50 mg once daily as well as fexofenadine 180 mg once daily. The patient initially responded well to the oral therapy, but she experienced recurrence of the skin eruption at infrequent intervals over the next few months, requiring escalating doses of dapsone to control the symptoms. After further questioning at a subsequent visit a few months later, it was discovered that the eruption occurred near the onset of the patient’s irregular menstrual cycle.

Approximately 1 year after her initial presentation, the patient returned for intradermal hormone injections to test for hormonally induced hypersensitivities. An injection of0.1 mL of a 50-mg/mL progesterone solution was administered in the right forearm as well as 0.1 mL of a 5-mg/mL estradiol solution and 0.1 mL of saline in the left forearm as a control. One hour after the injections, a strong positive reaction consisting of a 15-mm indurated plaque with surrounding wheal was noted at the site of the progesterone injection. The estradiol and saline control sites were clear of any dermal reaction (Figure 2). A diagnosis of APD was established, and the patient was referred to her gynecologist for treatment.

Due to the aggressive nature of her endometriosis, the gonadotropin-releasing hormone agonist leuprolide acetate was the first-line treatment prescribed by her gynecologist; however, after 8 months of therapy with leuprolide acetate, she was still experiencing breakthrough myalgia with her menstrual cycle and opted for a hysterectomy with a bilateral salpingo-oophorectomy. Within weeks of surgery, the myalgia ceased and the patient was completely asymptomatic.

Autoimmune progesterone dermatitis was first described in 1921.² In affected women, the body reacts to the progesterone hormone surge during the luteal phase of the menstrual cycle. Symptoms begin approximately 3 to 4 days prior to menses and resolve 2 to 3 days after onset of flow. These progesterone hypersensitivity reactions can present within a spectrum of morphologies and severities. The lesions can appear eczematous, urticarial, as an angioedemalike reaction, as an erythema multiforme–like reaction with targetoid lesions, or in other nonspecific ways.^1,3 Some patients experience a very mild, almost asymptomatic reaction, while others have a profound reaction progressing to anaphylaxis. Originally it was thought that exogenous exposure to progesterone led to a cross-reaction or hypersensitivity to the hormone; however, there have been cases reported in females as young as 12 years of age with no prior exposure.^3,4 Reactions also can vary during pregnancy. There have been reports of spontaneous abortion in some affected females, but symptoms may dissipate in others, possibly due to a slow rise in progesterone causing a desensitization reaction.^3,5

According to Bandino et al,⁶ there are 3 criteria for diagnosis of APD: (1) skin lesions related to the menstrual cycle, (2) positive response to intradermal testing with progesterone, and (3) symptomatic improvement after inhibiting progesterone secretions by suppressing ovulation.Areas checked with intradermal testing need to be evaluated 24 and 48 hours later for possible immediate or delayed-type hypersensitivity reactions. Biopsy typically is not helpful in this diagnosis because results usually are nonspecific.

Treatment of APD is targeted toward suppressing the internal hormonal surge. By suppressing the progesterone hormone, the symptoms are alleviated. The discomfort from the skin reaction typically is unresponsive to steroids or antihistamines. Oral contraceptives are first line in most cases because they suppress ovulation. Gonadotropin-releasing hormone analogues and tamoxifen also have been successful. For patients with severe disease that is recalcitrant to standard therapy or those who are postmenopausal, an oophorectemy is a curative option.^2,4,5,7

Autoimmune progesterone dermatitis is a rare cyclical dermatologic condition in which the body responds to a surge of the patient’s own progesterone hormone. The disorder is difficult to diagnose because it can present with differing morphologies and biopsy is nonspecific. It also can be increasingly difficult to diagnose in women who do not have a typical 28-day menstrual cycle. In our patient, her irregular menstrual cycle may have caused a delay in diagnosis. Although the condition is rare, APD should be included in the differential diagnosis in females with a recurrent, cyclical, or recalcitrant cutaneous eruption.

To the Editor:

Autoimmune progesterone dermatitis (APD) is a rare dermatologic condition that can be challenging to diagnose. The associated skin lesions are not only variable in physical presentation but also in the timing of the outbreak. The skin disorder stems from an internal reaction to elevated levels of progesterone during the luteal phase of the menstrual cycle. Autoimmune progesterone dermatitis can be difficult to detect; although the typical menstrual cycle is 28 days, many women have longer or shorter hormonal phases, leading to cyclical irregularity that can cause the lesions to appear sporadic in nature when in fact they are not.¹

A 34-year-old woman with a history of endometriosis, psoriasis, and malignant melanoma presented to our dermatology clinic 2 days after a brief hospitalization during which she was diagnosed with a hypersensitivity reaction. Two days prior to her hospital admission, the patient developed a rash on the lower back with associated myalgia. The rash progressively worsened, spreading laterally to the flanks, which prompted her to seek medical attention. Blood work included a complete blood cell count with differential, complete metabolic panel, antinuclear antibody test, and erythrocyte sedimentation rate, which all were within reference range. A 4-mm punch biopsy from the left lateral flank was performed and was consistent with a neutrophilic dermatosis. The patient’s symptoms diminished and she was discharged the next day with instructions to follow up with a dermatologist.

Physical examination at our clinic revealed multiple minimally indurated, erythematous plaques with superficial scaling along the left lower back and upper buttock (Figure 1). No other skin lesions were present, and palpation of the cervical, axillary, and inguinal lymph nodes was unremarkable. A repeat 6-mm punch biopsy was performed and she was sent for fasting blood work.

Histologic examination of the punch biopsy revealed a superficial and deep perivascular and interstitial dermatitis with scattered neutrophils and eosinophils. Findings were described as nonspecific, possibly representing a dermal hypersensitivity or urticarial reaction.

Glucose-6-phosphate dehydrogenase testing was within reference range, and therapy was initiated with oral dapsone 50 mg once daily as well as fexofenadine 180 mg once daily. The patient initially responded well to the oral therapy, but she experienced recurrence of the skin eruption at infrequent intervals over the next few months, requiring escalating doses of dapsone to control the symptoms. After further questioning at a subsequent visit a few months later, it was discovered that the eruption occurred near the onset of the patient’s irregular menstrual cycle.

Approximately 1 year after her initial presentation, the patient returned for intradermal hormone injections to test for hormonally induced hypersensitivities. An injection of0.1 mL of a 50-mg/mL progesterone solution was administered in the right forearm as well as 0.1 mL of a 5-mg/mL estradiol solution and 0.1 mL of saline in the left forearm as a control. One hour after the injections, a strong positive reaction consisting of a 15-mm indurated plaque with surrounding wheal was noted at the site of the progesterone injection. The estradiol and saline control sites were clear of any dermal reaction (Figure 2). A diagnosis of APD was established, and the patient was referred to her gynecologist for treatment.

Due to the aggressive nature of her endometriosis, the gonadotropin-releasing hormone agonist leuprolide acetate was the first-line treatment prescribed by her gynecologist; however, after 8 months of therapy with leuprolide acetate, she was still experiencing breakthrough myalgia with her menstrual cycle and opted for a hysterectomy with a bilateral salpingo-oophorectomy. Within weeks of surgery, the myalgia ceased and the patient was completely asymptomatic.

Autoimmune progesterone dermatitis was first described in 1921.² In affected women, the body reacts to the progesterone hormone surge during the luteal phase of the menstrual cycle. Symptoms begin approximately 3 to 4 days prior to menses and resolve 2 to 3 days after onset of flow. These progesterone hypersensitivity reactions can present within a spectrum of morphologies and severities. The lesions can appear eczematous, urticarial, as an angioedemalike reaction, as an erythema multiforme–like reaction with targetoid lesions, or in other nonspecific ways.^1,3 Some patients experience a very mild, almost asymptomatic reaction, while others have a profound reaction progressing to anaphylaxis. Originally it was thought that exogenous exposure to progesterone led to a cross-reaction or hypersensitivity to the hormone; however, there have been cases reported in females as young as 12 years of age with no prior exposure.^3,4 Reactions also can vary during pregnancy. There have been reports of spontaneous abortion in some affected females, but symptoms may dissipate in others, possibly due to a slow rise in progesterone causing a desensitization reaction.^3,5

According to Bandino et al,⁶ there are 3 criteria for diagnosis of APD: (1) skin lesions related to the menstrual cycle, (2) positive response to intradermal testing with progesterone, and (3) symptomatic improvement after inhibiting progesterone secretions by suppressing ovulation.Areas checked with intradermal testing need to be evaluated 24 and 48 hours later for possible immediate or delayed-type hypersensitivity reactions. Biopsy typically is not helpful in this diagnosis because results usually are nonspecific.

Treatment of APD is targeted toward suppressing the internal hormonal surge. By suppressing the progesterone hormone, the symptoms are alleviated. The discomfort from the skin reaction typically is unresponsive to steroids or antihistamines. Oral contraceptives are first line in most cases because they suppress ovulation. Gonadotropin-releasing hormone analogues and tamoxifen also have been successful. For patients with severe disease that is recalcitrant to standard therapy or those who are postmenopausal, an oophorectemy is a curative option.^2,4,5,7

Autoimmune progesterone dermatitis is a rare cyclical dermatologic condition in which the body responds to a surge of the patient’s own progesterone hormone. The disorder is difficult to diagnose because it can present with differing morphologies and biopsy is nonspecific. It also can be increasingly difficult to diagnose in women who do not have a typical 28-day menstrual cycle. In our patient, her irregular menstrual cycle may have caused a delay in diagnosis. Although the condition is rare, APD should be included in the differential diagnosis in females with a recurrent, cyclical, or recalcitrant cutaneous eruption.

MONTEREY, CALIF. – “Consort dermatitis” – when a patient is allergic to his or her partner. “Lime dermatitis” – when gin and tonics are the culprit. And “sample dermatitis” – when an unprescribed drug sample turns out to be the cause of a mysterious reaction.

Pcholik/getty images

Dermatologist Vincent DeLeo, MD, of the University of Southern California, Los Angeles, has seen them all. He provided insight about how to diagnose these unusual conditions at the Coastal Dermatology Symposium.

The following are a few unusual causes of dermatitis that he discussed:

• Romantic partners. A patient’s partner can be the cause of a reaction, as in the case of a 25-year-old woman who turned out to be allergic to her boyfriend’s cologne. In another case, a 50-year-old man had a 3-year history of recurrent dermatitis on his left arm and the left side of his chest. The cause was a mystery until it became clear that it was caused by exposure to hair dye, but not his. “He didn’t color his hair, but his wife did, and she always slept on that side of him,” Dr. DeLeo recalled. “When she stopped coloring her hair, his disease cleared.”
• Black henna. The dye known as “black henna,” or just “henna,” can cause reactions in adults (who use it as a hair dye or to decorate the skin) and children (who can be exposed to it with temporary tattoos). “Because henna typically produces a brown, orange-brown, or reddish-brown tint, other ingredients must be added to produce other colors, such as those marketed as ‘black henna’ and ‘blue henna,’ ” according to a Food and Drug Administration statement. “Even brown shades of products marketed as henna may contain other ingredients intended to make them darker or make the stain last longer on the skin. The problem? “The extra ingredient used to blacken henna is often a coal-tar hair dye containing p-Phenylenediamine, an ingredient that can cause dangerous skin reactions in some people,” the statement says. Dr. DeLeo said that one good rule of thumb is to consider a reaction to black henna if a patient acknowledges using a henna dye and their hair is any color but red. That’s a sign, he said, that they’re actually using black henna.
• Makeup applicators. Dr. DeLeo has seen two cases of patients with facial dermatitis who turned out to be allergic to thiuram, a component of rubber. Their skin was reacting to the rubber in some sponges used to apply makeup.
• Lime and sun exposure. Patients are impressed when Dr. DeLeo correctly guesses what they were drinking the previous weekend, because of their telltale blisters indicating a lime allergy. Noninflammatory blisters on the fingers or hyperpigmentation can be caused by touching the skin of a lime and then having subsequent exposure to ultraviolet light. It may take days for the blisters to appear, he noted. A weekend after mixing gin and tonics with lime, for example, a patient “may show up on Tuesday of the following week. The patient doesn’t always think of what they did over the weekend.”
• Liquid detergents. As a general rule, laundry detergents do not cause dermatitis, Dr. DeLeo said. “By the time that clothing is rinsed in your washer, there’s not enough left of anything on the clothing to cause a problem.” But there’s an exception: When people hand wash clothing with liquid detergents, such as Woolite. “It’s not the fragrance,” he said. “It’s the preservative in the detergent.”
• Unexpected nickel. Skin allergy to nickel is common, and the metal can lurk in unexpected places, as he discovered when he treated a Columbia University student who was “allergic to his tuba.” The tuba was made of brass, not nickel. But “the little things connecting the tubes to each other are alloy metals,” he said, including nickel.
• Drug samples. Dr. DeLeo recalled the case of a dermatology office administrator with a recurrent neck rash. Dermatologist after dermatologist failed to find the cause. Patch and photopatch testing turned up nothing. Then Dr. DeLeo asked her to bring in every skin product she was using. She returned with a large bag full of dermatologic samples, including Drithocreme (anthralin), which can be an irritant. None of the drugs were prescribed. “This is case of sample dermatitis,” which may occur among employees and family members of dermatologists, he said. “Always think of having patients bring in what they’re using,” he added, “because you can be surprised.”

The Coastal Dermatology Symposium is jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are both owned by Frontline Medical Communications.

Dr. DeLeo disclosed consulting work for Estée Lauder.

MONTEREY, CALIF. – “Consort dermatitis” – when a patient is allergic to his or her partner. “Lime dermatitis” – when gin and tonics are the culprit. And “sample dermatitis” – when an unprescribed drug sample turns out to be the cause of a mysterious reaction.

Pcholik/getty images

Dermatologist Vincent DeLeo, MD, of the University of Southern California, Los Angeles, has seen them all. He provided insight about how to diagnose these unusual conditions at the Coastal Dermatology Symposium.

The following are a few unusual causes of dermatitis that he discussed:

• Romantic partners. A patient’s partner can be the cause of a reaction, as in the case of a 25-year-old woman who turned out to be allergic to her boyfriend’s cologne. In another case, a 50-year-old man had a 3-year history of recurrent dermatitis on his left arm and the left side of his chest. The cause was a mystery until it became clear that it was caused by exposure to hair dye, but not his. “He didn’t color his hair, but his wife did, and she always slept on that side of him,” Dr. DeLeo recalled. “When she stopped coloring her hair, his disease cleared.”
• Black henna. The dye known as “black henna,” or just “henna,” can cause reactions in adults (who use it as a hair dye or to decorate the skin) and children (who can be exposed to it with temporary tattoos). “Because henna typically produces a brown, orange-brown, or reddish-brown tint, other ingredients must be added to produce other colors, such as those marketed as ‘black henna’ and ‘blue henna,’ ” according to a Food and Drug Administration statement. “Even brown shades of products marketed as henna may contain other ingredients intended to make them darker or make the stain last longer on the skin. The problem? “The extra ingredient used to blacken henna is often a coal-tar hair dye containing p-Phenylenediamine, an ingredient that can cause dangerous skin reactions in some people,” the statement says. Dr. DeLeo said that one good rule of thumb is to consider a reaction to black henna if a patient acknowledges using a henna dye and their hair is any color but red. That’s a sign, he said, that they’re actually using black henna.
• Makeup applicators. Dr. DeLeo has seen two cases of patients with facial dermatitis who turned out to be allergic to thiuram, a component of rubber. Their skin was reacting to the rubber in some sponges used to apply makeup.
• Lime and sun exposure. Patients are impressed when Dr. DeLeo correctly guesses what they were drinking the previous weekend, because of their telltale blisters indicating a lime allergy. Noninflammatory blisters on the fingers or hyperpigmentation can be caused by touching the skin of a lime and then having subsequent exposure to ultraviolet light. It may take days for the blisters to appear, he noted. A weekend after mixing gin and tonics with lime, for example, a patient “may show up on Tuesday of the following week. The patient doesn’t always think of what they did over the weekend.”
• Liquid detergents. As a general rule, laundry detergents do not cause dermatitis, Dr. DeLeo said. “By the time that clothing is rinsed in your washer, there’s not enough left of anything on the clothing to cause a problem.” But there’s an exception: When people hand wash clothing with liquid detergents, such as Woolite. “It’s not the fragrance,” he said. “It’s the preservative in the detergent.”
• Unexpected nickel. Skin allergy to nickel is common, and the metal can lurk in unexpected places, as he discovered when he treated a Columbia University student who was “allergic to his tuba.” The tuba was made of brass, not nickel. But “the little things connecting the tubes to each other are alloy metals,” he said, including nickel.
• Drug samples. Dr. DeLeo recalled the case of a dermatology office administrator with a recurrent neck rash. Dermatologist after dermatologist failed to find the cause. Patch and photopatch testing turned up nothing. Then Dr. DeLeo asked her to bring in every skin product she was using. She returned with a large bag full of dermatologic samples, including Drithocreme (anthralin), which can be an irritant. None of the drugs were prescribed. “This is case of sample dermatitis,” which may occur among employees and family members of dermatologists, he said. “Always think of having patients bring in what they’re using,” he added, “because you can be surprised.”

The Coastal Dermatology Symposium is jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are both owned by Frontline Medical Communications.

Dr. DeLeo disclosed consulting work for Estée Lauder.

MONTEREY, CALIF. – “Consort dermatitis” – when a patient is allergic to his or her partner. “Lime dermatitis” – when gin and tonics are the culprit. And “sample dermatitis” – when an unprescribed drug sample turns out to be the cause of a mysterious reaction.

Pcholik/getty images

Dermatologist Vincent DeLeo, MD, of the University of Southern California, Los Angeles, has seen them all. He provided insight about how to diagnose these unusual conditions at the Coastal Dermatology Symposium.

The following are a few unusual causes of dermatitis that he discussed:

• Romantic partners. A patient’s partner can be the cause of a reaction, as in the case of a 25-year-old woman who turned out to be allergic to her boyfriend’s cologne. In another case, a 50-year-old man had a 3-year history of recurrent dermatitis on his left arm and the left side of his chest. The cause was a mystery until it became clear that it was caused by exposure to hair dye, but not his. “He didn’t color his hair, but his wife did, and she always slept on that side of him,” Dr. DeLeo recalled. “When she stopped coloring her hair, his disease cleared.”
• Black henna. The dye known as “black henna,” or just “henna,” can cause reactions in adults (who use it as a hair dye or to decorate the skin) and children (who can be exposed to it with temporary tattoos). “Because henna typically produces a brown, orange-brown, or reddish-brown tint, other ingredients must be added to produce other colors, such as those marketed as ‘black henna’ and ‘blue henna,’ ” according to a Food and Drug Administration statement. “Even brown shades of products marketed as henna may contain other ingredients intended to make them darker or make the stain last longer on the skin. The problem? “The extra ingredient used to blacken henna is often a coal-tar hair dye containing p-Phenylenediamine, an ingredient that can cause dangerous skin reactions in some people,” the statement says. Dr. DeLeo said that one good rule of thumb is to consider a reaction to black henna if a patient acknowledges using a henna dye and their hair is any color but red. That’s a sign, he said, that they’re actually using black henna.
• Makeup applicators. Dr. DeLeo has seen two cases of patients with facial dermatitis who turned out to be allergic to thiuram, a component of rubber. Their skin was reacting to the rubber in some sponges used to apply makeup.
• Lime and sun exposure. Patients are impressed when Dr. DeLeo correctly guesses what they were drinking the previous weekend, because of their telltale blisters indicating a lime allergy. Noninflammatory blisters on the fingers or hyperpigmentation can be caused by touching the skin of a lime and then having subsequent exposure to ultraviolet light. It may take days for the blisters to appear, he noted. A weekend after mixing gin and tonics with lime, for example, a patient “may show up on Tuesday of the following week. The patient doesn’t always think of what they did over the weekend.”
• Liquid detergents. As a general rule, laundry detergents do not cause dermatitis, Dr. DeLeo said. “By the time that clothing is rinsed in your washer, there’s not enough left of anything on the clothing to cause a problem.” But there’s an exception: When people hand wash clothing with liquid detergents, such as Woolite. “It’s not the fragrance,” he said. “It’s the preservative in the detergent.”
• Unexpected nickel. Skin allergy to nickel is common, and the metal can lurk in unexpected places, as he discovered when he treated a Columbia University student who was “allergic to his tuba.” The tuba was made of brass, not nickel. But “the little things connecting the tubes to each other are alloy metals,” he said, including nickel.
• Drug samples. Dr. DeLeo recalled the case of a dermatology office administrator with a recurrent neck rash. Dermatologist after dermatologist failed to find the cause. Patch and photopatch testing turned up nothing. Then Dr. DeLeo asked her to bring in every skin product she was using. She returned with a large bag full of dermatologic samples, including Drithocreme (anthralin), which can be an irritant. None of the drugs were prescribed. “This is case of sample dermatitis,” which may occur among employees and family members of dermatologists, he said. “Always think of having patients bring in what they’re using,” he added, “because you can be surprised.”

The Coastal Dermatology Symposium is jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are both owned by Frontline Medical Communications.

Dr. DeLeo disclosed consulting work for Estée Lauder.

CHICAGO – A common reason why a women stops breastfeeding is the use of medication her doctor has claimed is unsafe during lactation. But most drugs have little or no effect on an infant’s well-being or milk supply, explained Jenny Eileen Murase, MD, of Palo Alto (Calif.) Foundation Medical Group.

“The bottom line I want you to take away from this [session] is that the vast majority of the medicines you are prescribing as a dermatologist are safe during lactation,” Dr. Murase told attendees at the American Academy of Dermatology summer meeting. “I really want everyone in this room to understand that most of the time, you should not be recommending that a woman is pumping and dumping her milk or stopping breastfeeding because she’s on an agent.”

Dr. Murase, also affiliated with the University of California, San Francisco, provided an overview of drug safety during lactation for major categories of medications that dermatologists prescribe. She recommended that physicians get a copy of Medications and Mother’s Milk by Thomas Hale, PhD, which she considers the best reference for looking up specific drugs. It categorizes drugs as L1 (safest) to L5 (contraindicated), and L2 as “safer,” L3 as “moderately safe,” and L4 as “possibly hazardous.”

Steroids

Contrary to what many believe, prednisone is not contraindicated in breastfeeding, Dr. Murase said. Instead of advising patients to “pump and dump their milk,” she said, “the only recommendation you need to make is that they wait 4 hours after taking the medicine to breastfeed.” For example, a mother can take prednisone before bed and then wake 4 hours later to nurse. Higher doses, such as more than 40 mg daily over long periods, may have the potential to affect growth and development, but more typical doses don’t pose the same risk.

Topical steroids (except for those that are class 1) also are safe to apply directly to the nipple in breastfeeding women, she noted.

Biologics and immunosuppressants

One of the few medications that are contraindicated are topical pimecrolimus and tacrolimus if applied directly to the nipple, since “oral consumption in the infant could be significant,” Dr. Murase said.

Biologics, on the other hand, are not a concern during lactation. “They have low oral bioavailability because of their large molecular size,” and are broken down in the stomach “in a proteolytic environment,” Dr. Murase explained. The CRADLE study, for example, examined the concentration of certolizumab (Cimzia) in mothers’ mature breast milk and found the highest concentration to be just 0.077 mcg/mL, resulting in an average daily infant dose of less than 0.01 mg/kg per day.

Antihistamines and cosmetic topicals

The major antihistamines – brompheniramine, chlorpheniramine, diphenhydramine, hydroxyzine, cetirizine, fexofenadine and loratadine – are likewise safe as L1-L3 drugs. It is preferable to prescribe nonsedating antihistamines, opting for loratadine as the first-line choice. But dermatologists should be reassured that no data support concerns about milk supply reduction from antihistamines, Dr. Murase said.

It’s best to avoid cosmetic topical products, but hydroquinone (L3), topical minoxidil (L2), and botulinum toxin A (L3) do not pose significant risk to the infant. Neither do the anesthetics lidocaine (L2) and epinephrine (L1) for breastfeeding women who need surgery.

Antibiotics

The vast majority of antibiotics are safe for women to use while breastfeeding, but a few notable exceptions exist, including erythromycin.

“People associate erythromycin as safe in lactation because it’s safe in pregnancy, but that’s not the case,” Dr. Murase pointed out. Erythromycin has been linked to pyloric stenosis in newborns and therefore should be avoided in the early months of breastfeeding. In older infants, however, erythromycin becomes an L1 medication.”

Tetracyclines fall into a borderline category. “Tetracyclines would be fine for a complicated infection,” but should not be used for more than 3 weeks, at which point they are regarded as L4, Dr. Murase said. “So long-term use of the tetracyclines should be avoided.”

Aside from these, topical antibiotics are considered safe. Women taking other oral antibiotics should be monitored for gastrointestinal symptoms or allergic responses.

Antifungals

As for antifungals, topicals are safe, and nystatin and clotrimazole are the best first-line options (both L1). Oral antifungals are similarly fine, with griseofulvin, fluconazole, ketoconazole, itraconazole, and terbinafine all classified as L2 and amphotericin B as L3.

If antifungals or antibiotics are being prescribed for a breast fungal infection or for mastitis, Dr. Murase underscored the importance of not stopping breastfeeding.

“The most important thing is that they continue to actually breastfeed on the affected breast that has the staph infection,” she said. She then reiterated that physicians should “reassure new mothers that the majority of oral and topical medications are safe.”

Dr. Murase disclosed serving on the advisory boards of Dermira, UCB, and Genzyme/Sanofi, and she has consulted for Ferndale and UpToDate.

CHICAGO – A common reason why a women stops breastfeeding is the use of medication her doctor has claimed is unsafe during lactation. But most drugs have little or no effect on an infant’s well-being or milk supply, explained Jenny Eileen Murase, MD, of Palo Alto (Calif.) Foundation Medical Group.

“The bottom line I want you to take away from this [session] is that the vast majority of the medicines you are prescribing as a dermatologist are safe during lactation,” Dr. Murase told attendees at the American Academy of Dermatology summer meeting. “I really want everyone in this room to understand that most of the time, you should not be recommending that a woman is pumping and dumping her milk or stopping breastfeeding because she’s on an agent.”

Dr. Murase, also affiliated with the University of California, San Francisco, provided an overview of drug safety during lactation for major categories of medications that dermatologists prescribe. She recommended that physicians get a copy of Medications and Mother’s Milk by Thomas Hale, PhD, which she considers the best reference for looking up specific drugs. It categorizes drugs as L1 (safest) to L5 (contraindicated), and L2 as “safer,” L3 as “moderately safe,” and L4 as “possibly hazardous.”

Steroids

Contrary to what many believe, prednisone is not contraindicated in breastfeeding, Dr. Murase said. Instead of advising patients to “pump and dump their milk,” she said, “the only recommendation you need to make is that they wait 4 hours after taking the medicine to breastfeed.” For example, a mother can take prednisone before bed and then wake 4 hours later to nurse. Higher doses, such as more than 40 mg daily over long periods, may have the potential to affect growth and development, but more typical doses don’t pose the same risk.

Topical steroids (except for those that are class 1) also are safe to apply directly to the nipple in breastfeeding women, she noted.

Biologics and immunosuppressants

One of the few medications that are contraindicated are topical pimecrolimus and tacrolimus if applied directly to the nipple, since “oral consumption in the infant could be significant,” Dr. Murase said.

Biologics, on the other hand, are not a concern during lactation. “They have low oral bioavailability because of their large molecular size,” and are broken down in the stomach “in a proteolytic environment,” Dr. Murase explained. The CRADLE study, for example, examined the concentration of certolizumab (Cimzia) in mothers’ mature breast milk and found the highest concentration to be just 0.077 mcg/mL, resulting in an average daily infant dose of less than 0.01 mg/kg per day.

Antihistamines and cosmetic topicals

The major antihistamines – brompheniramine, chlorpheniramine, diphenhydramine, hydroxyzine, cetirizine, fexofenadine and loratadine – are likewise safe as L1-L3 drugs. It is preferable to prescribe nonsedating antihistamines, opting for loratadine as the first-line choice. But dermatologists should be reassured that no data support concerns about milk supply reduction from antihistamines, Dr. Murase said.

It’s best to avoid cosmetic topical products, but hydroquinone (L3), topical minoxidil (L2), and botulinum toxin A (L3) do not pose significant risk to the infant. Neither do the anesthetics lidocaine (L2) and epinephrine (L1) for breastfeeding women who need surgery.

Antibiotics

The vast majority of antibiotics are safe for women to use while breastfeeding, but a few notable exceptions exist, including erythromycin.

“People associate erythromycin as safe in lactation because it’s safe in pregnancy, but that’s not the case,” Dr. Murase pointed out. Erythromycin has been linked to pyloric stenosis in newborns and therefore should be avoided in the early months of breastfeeding. In older infants, however, erythromycin becomes an L1 medication.”

Tetracyclines fall into a borderline category. “Tetracyclines would be fine for a complicated infection,” but should not be used for more than 3 weeks, at which point they are regarded as L4, Dr. Murase said. “So long-term use of the tetracyclines should be avoided.”

Aside from these, topical antibiotics are considered safe. Women taking other oral antibiotics should be monitored for gastrointestinal symptoms or allergic responses.

Antifungals

As for antifungals, topicals are safe, and nystatin and clotrimazole are the best first-line options (both L1). Oral antifungals are similarly fine, with griseofulvin, fluconazole, ketoconazole, itraconazole, and terbinafine all classified as L2 and amphotericin B as L3.

If antifungals or antibiotics are being prescribed for a breast fungal infection or for mastitis, Dr. Murase underscored the importance of not stopping breastfeeding.

“The most important thing is that they continue to actually breastfeed on the affected breast that has the staph infection,” she said. She then reiterated that physicians should “reassure new mothers that the majority of oral and topical medications are safe.”

Dr. Murase disclosed serving on the advisory boards of Dermira, UCB, and Genzyme/Sanofi, and she has consulted for Ferndale and UpToDate.

CHICAGO – A common reason why a women stops breastfeeding is the use of medication her doctor has claimed is unsafe during lactation. But most drugs have little or no effect on an infant’s well-being or milk supply, explained Jenny Eileen Murase, MD, of Palo Alto (Calif.) Foundation Medical Group.

“The bottom line I want you to take away from this [session] is that the vast majority of the medicines you are prescribing as a dermatologist are safe during lactation,” Dr. Murase told attendees at the American Academy of Dermatology summer meeting. “I really want everyone in this room to understand that most of the time, you should not be recommending that a woman is pumping and dumping her milk or stopping breastfeeding because she’s on an agent.”

Dr. Murase, also affiliated with the University of California, San Francisco, provided an overview of drug safety during lactation for major categories of medications that dermatologists prescribe. She recommended that physicians get a copy of Medications and Mother’s Milk by Thomas Hale, PhD, which she considers the best reference for looking up specific drugs. It categorizes drugs as L1 (safest) to L5 (contraindicated), and L2 as “safer,” L3 as “moderately safe,” and L4 as “possibly hazardous.”

Steroids

Contrary to what many believe, prednisone is not contraindicated in breastfeeding, Dr. Murase said. Instead of advising patients to “pump and dump their milk,” she said, “the only recommendation you need to make is that they wait 4 hours after taking the medicine to breastfeed.” For example, a mother can take prednisone before bed and then wake 4 hours later to nurse. Higher doses, such as more than 40 mg daily over long periods, may have the potential to affect growth and development, but more typical doses don’t pose the same risk.

Topical steroids (except for those that are class 1) also are safe to apply directly to the nipple in breastfeeding women, she noted.

Biologics and immunosuppressants

One of the few medications that are contraindicated are topical pimecrolimus and tacrolimus if applied directly to the nipple, since “oral consumption in the infant could be significant,” Dr. Murase said.

Biologics, on the other hand, are not a concern during lactation. “They have low oral bioavailability because of their large molecular size,” and are broken down in the stomach “in a proteolytic environment,” Dr. Murase explained. The CRADLE study, for example, examined the concentration of certolizumab (Cimzia) in mothers’ mature breast milk and found the highest concentration to be just 0.077 mcg/mL, resulting in an average daily infant dose of less than 0.01 mg/kg per day.

Antihistamines and cosmetic topicals

The major antihistamines – brompheniramine, chlorpheniramine, diphenhydramine, hydroxyzine, cetirizine, fexofenadine and loratadine – are likewise safe as L1-L3 drugs. It is preferable to prescribe nonsedating antihistamines, opting for loratadine as the first-line choice. But dermatologists should be reassured that no data support concerns about milk supply reduction from antihistamines, Dr. Murase said.

It’s best to avoid cosmetic topical products, but hydroquinone (L3), topical minoxidil (L2), and botulinum toxin A (L3) do not pose significant risk to the infant. Neither do the anesthetics lidocaine (L2) and epinephrine (L1) for breastfeeding women who need surgery.

Antibiotics

The vast majority of antibiotics are safe for women to use while breastfeeding, but a few notable exceptions exist, including erythromycin.

“People associate erythromycin as safe in lactation because it’s safe in pregnancy, but that’s not the case,” Dr. Murase pointed out. Erythromycin has been linked to pyloric stenosis in newborns and therefore should be avoided in the early months of breastfeeding. In older infants, however, erythromycin becomes an L1 medication.”

Tetracyclines fall into a borderline category. “Tetracyclines would be fine for a complicated infection,” but should not be used for more than 3 weeks, at which point they are regarded as L4, Dr. Murase said. “So long-term use of the tetracyclines should be avoided.”

Aside from these, topical antibiotics are considered safe. Women taking other oral antibiotics should be monitored for gastrointestinal symptoms or allergic responses.

Antifungals

As for antifungals, topicals are safe, and nystatin and clotrimazole are the best first-line options (both L1). Oral antifungals are similarly fine, with griseofulvin, fluconazole, ketoconazole, itraconazole, and terbinafine all classified as L2 and amphotericin B as L3.

If antifungals or antibiotics are being prescribed for a breast fungal infection or for mastitis, Dr. Murase underscored the importance of not stopping breastfeeding.

“The most important thing is that they continue to actually breastfeed on the affected breast that has the staph infection,” she said. She then reiterated that physicians should “reassure new mothers that the majority of oral and topical medications are safe.”

Dr. Murase disclosed serving on the advisory boards of Dermira, UCB, and Genzyme/Sanofi, and she has consulted for Ferndale and UpToDate.

As technology continues to advance, so too does its accessibility to the general population. In 2013, 56% of Americans owned a smartphone versus 77% in 2017.¹With the increase in mobile applications (apps) available, it is no surprise that the market has extended into the medical field, with dermatology being no exception.² The majority of dermatology apps can be classified as teledermatology apps, followed by self-surveillance, disease guide, and reference apps. Additional types of dermatology apps include dermoscopy, conference, education, photograph storage and sharing, and journal apps, and others.² In this study, we examined Apple App Store rankings to determine the types of dermatology apps that are most popular among patients and physicians.

METHODS

A popular app rankings analyzer (App Annie) was used to search for dermatology apps along with their App Store rankings.³ Although iOS is not the most popular mobile device operating system, we chose to evaluate app rankings via the App Store because iPhones are the top-selling individual phones of any kind in the United States.⁴

We performed our analysis on a single day (July 14, 2018) given that app rankings can change daily. We incorporated the following keywords, which were commonly used in other dermatology app studies: dermatology, psoriasis, rosacea, acne, skin cancer, melanoma, eczema, and teledermatology. The category ranking was defined as the rank of a free or paid app in the App Store’s top charts for the selected country (United States), market (Apple), and device (iPhone) within their app category (Medical). Inclusion criteria required a ranking in the top 1500 Medical apps and being categorized in the App Store as a Medical app. Exclusion criteria included apps that focused on cosmetics, private practice, direct advertisements, photograph editing, or claims to cure skin disease, as well as non–English-language apps. The App Store descriptions were assessed to determine the type of each app (eg, teledermatology, disease guide) and target audience (patient, physician, or both).

Another search was performed using the same keywords but within the Health and Fitness category to capture potentially more highly ranked apps among patients. We also conducted separate searches within the Medical category using the keywords billing, coding, and ICD (International Classification of Diseases) to evaluate rankings for billing/coding apps, as well as EMR and electronic medical records for electronic medical record (EMR) apps.

RESULTS

The initial search yielded 851 results, which was narrowed down to 29 apps after applying the exclusion criteria. Of note, prior to application of the exclusion criteria, one dermatology app that was considered to be a direct advertisement app claiming to cure acne was ranked fourth of 1500 apps in the Medical category. However, the majority of the search results were excluded because they were not popular enough to be ranked among the top 1500 apps. There were more ranked dermatology apps in the Medical category targeting patients than physicians; 18 of 29 (62%) qualifying apps targeted patients and 11 (38%) targeted physicians (Tables 1 and 2). No apps targeted both groups. The most common type of ranked app targeting patients was self-surveillance (11/18), and the most common type targeting physicians was reference (8/11). The highest ranked app targeting patients was a teledermatology app with a ranking of 184, and the highest ranked app targeting physicians was educational, ranked 353. The least common type of ranked apps targeting patients were “other” (2/18 [11%]; 1 prescription and 1 UV monitor app) and conference (1/18 [6%]). The least common type of ranked apps targeting physicians were education (2/11 [18%]) and dermoscopy (1/11 [9%]).

Our search of the Health and Fitness category yielded 6 apps, all targeting patients; 3 (50%) were self-surveillance apps, and 3 (50%) were classified as other (2 UV monitors and a conferencing app for cancer emotional support)(Table 3).

Our search of the Medical category for billing/coding and EMR apps yielded 232 and 164 apps, respectively; of them, 49 (21%) and 54 (33%) apps were ranked. These apps did not overlap with the dermatology-related search criteria; thus, we were not able to ascertain how many of these apps were used specifically by health care providers in dermatology.

COMMENT

Patient Apps

The most common apps used by patients are fitness and nutrition tracker apps categorized as Health and Fitness^5,6; however, the majority of ranked dermatology apps are categorized as Medical per our findings. In a study of 557 dermatology patients, it was found that among the health-related apps they used, the most common apps after fitness/nutrition were references, followed by patient portals, self-surveillance, and emotional assistance apps.⁶ Our search was consistent with these findings, suggesting that the most desired dermatology apps by patients are those that allow them to be proactive with their health. It is no surprise that the top-ranked app targeting patients was a teledermatology app, followed by multiple self-surveillance apps. The highest ranked self-surveillance app in the Health and Fitness category focused on monitoring the effects of nutrition on symptoms of diseases including skin disorders, while the highest ranked (as well as the majority of) self-surveillance apps in the Medical category encompassed mole monitoring and cancer risk calculators.

Benefits of the ranked dermatology apps in the Medical and Health and Fitness categories targeting patients include more immediate access to health care and education. Despite this popularity among patients, Masud et al⁷ demonstrated that only 20.5% (9/44) of dermatology apps targeting patients may be reliable resources based on a rubric created by the investigators. Overall, there remains a research gap for a standardized scientific approach to evaluating app validity and reliability.

Teledermatology
Teledermatology apps are the most common dermatology apps,² allowing for remote evaluation of patients through either live consultations or transmittance of medical information for later review by board-certified physicians.⁸ Features common to many teledermatology apps include accessibility on Android (Google Inc) and iOS as well as a web version. Security and Health Insurance Portability and Accountability Act compliance is especially important and is enforced through user authentications, data encryption, and automatic logout features. Data is not stored locally and is secured on a private server with backup. Referring providers and consultants often can communicate within the app. Insurance providers also may cover teledermatology services, and if not, the out-of-pocket costs often are affordable.

The highest-ranked patient app (ranked 184 in the Medical category) was a teledermatology app that did not meet the American Telemedicine Association standards for teledermatology apps.⁹ The popularity of this app among patients may have been attributable to multiple ease-of-use and turnaround time features. The user interface was simplistic, and the design was appealing to the eye. The entry field options were minimal to avoid confusion. The turnaround time to receive a diagnosis depended on 1 of 3 options, including a more rapid response for an increased cost. Ease of use was the highlight of this app at the cost of accuracy, as the limited amount of information that users were required to provide physicians compromised diagnostic accuracy in this app.

For comparison, we chose a nonranked (and thus less frequently used) teledermatology app that had previously undergone scientific evaluation using 13 evaluation criteria specific to teledermatology.¹⁰ The app also met the American Telemedicine Association standard for teledermatology apps.⁹ The app was originally a broader telemedicine app but featured a section specific to teledermatology. The user interface was simple but professional, almost resembling an EMR. The input fields included a comprehensive history that permitted a better evaluation of a lesion but might be tedious for users. This app boasted professionalism and accuracy, but from a user standpoint, it may have been too time-consuming.

Striking a balance between ensuring proper care versus appealing to patients is a difficult but important task. Based on this study, it appears that popular patient apps may in fact have less scientific rationale and therefore potentially less accuracy.

Self-surveillance
Although self-surveillance apps did not account for the highest-ranked app, they were the most frequently ranked app type in our study. Most of the ranked self-surveillance apps in the Medical category were for monitoring lesions over time to assess for changes. These apps help users take photographs that are well organized in a single, easy-to-find location. Some apps were risk calculators that assessed the risk for malignancies using a questionnaire. The majority of these self-surveillance apps were specific to skin cancer detection. Of note, one of the ranked self-surveillance apps assessed drug effectiveness by monitoring clinical appearance and symptoms. The lowest ranked self-surveillance app in the top 1500 ranked Medical apps in our search monitored cancer symptoms not specific to dermatology. Although this app had a low ranking (1380/1500), it received a high number of reviews and was well rated at 4.8 out of 5 stars; therefore, it seemed more helpful than the other higher-ranked apps targeting patients, which had higher rankings but minimal to no reviews or ratings. A comparison of the ease-of-use features of all the ranked patient-targeted self-surveillance apps in the Medical category is provided in Table 4.

Physician Apps

After examining the results of apps targeting physicians, we realized that the data may be accurate but may not be as representative of all currently practicing dermatology providers. Given the increased usage of apps among younger age groups,¹¹ our data may be skewed toward medical students and residents, supported by the fact that the top-ranked physician app in our study was an education app and the majority were reference apps. Future studies are needed to reexamine app ranking as this age group transitions from entry-level health care providers in the next 5 to 10 years. These findings also suggest less frequent app use among more veteran health care providers within our specific search parameters. Therefore, we decided to do subsequent searches for available billing/coding and EMR apps, which were many, but as mentioned above, none were specific to dermatology.

General Dermatology References
Most of the dermatology reference apps were formatted as e-books; however, other apps such as the Amazon Kindle app (categorized under Books) providing access to multiple e-books within one app were not included. Some apps included study aid features (eg, flash cards, quizzes), and topics spanned both dermatology and dermatopathology. Apps provide a unique way for on-the-go studying for dermatologists in training, and if the usage continues to grow, there may be a need for increased formal integration in dermatology education in the future.

Journals
Journal apps were not among those listed in the top-ranked apps we evaluated, which we suspect may be because journals were categorized differently from one journal to the next; for example, the Journal of the American Academy of Dermatology was ranked 1168 in the Magazines and Newspapers category. On the other hand, Dermatology World was ranked 1363 in the Reference category. An article’s citation affects the publishing journal’s impact factor, which is one of the most important variables in measuring a journal’s influence. In the future, there may be other variables that could aid in understanding journal impact as it relates to the journal’s accessibility.

Limitations

Our study did not look at Android apps. The top chart apps in the Android and Apple App Stores use undisclosed algorithms likely involving different characteristics such as number of downloads, frequency of updates, number of reviews, ratings, and more. Thus, the rankings across these different markets would not be comparable. Although our choice of keywords stemmed from the majority of prior studies looking at dermatology apps, our search was limited due to the use of these specific keywords. To avoid skewing data by cross-comparison of noncomparable categories, we could not compare apps in the Medical category versus those in other categories.

CONCLUSION

There seems to be a disconnect between the apps that are popular among patients and the scientific validity of the apps. As app usage increases among dermatology providers, whose demographic is shifting younger and younger, apps may become more incorporated in our education, and as such, it will become more critical to develop formal scientific standards. Given these future trends, we may need to increase our current literature and understanding of apps in dermatology with regard to their impact on both patients and health care providers.

As technology continues to advance, so too does its accessibility to the general population. In 2013, 56% of Americans owned a smartphone versus 77% in 2017.¹With the increase in mobile applications (apps) available, it is no surprise that the market has extended into the medical field, with dermatology being no exception.² The majority of dermatology apps can be classified as teledermatology apps, followed by self-surveillance, disease guide, and reference apps. Additional types of dermatology apps include dermoscopy, conference, education, photograph storage and sharing, and journal apps, and others.² In this study, we examined Apple App Store rankings to determine the types of dermatology apps that are most popular among patients and physicians.

METHODS

A popular app rankings analyzer (App Annie) was used to search for dermatology apps along with their App Store rankings.³ Although iOS is not the most popular mobile device operating system, we chose to evaluate app rankings via the App Store because iPhones are the top-selling individual phones of any kind in the United States.⁴

We performed our analysis on a single day (July 14, 2018) given that app rankings can change daily. We incorporated the following keywords, which were commonly used in other dermatology app studies: dermatology, psoriasis, rosacea, acne, skin cancer, melanoma, eczema, and teledermatology. The category ranking was defined as the rank of a free or paid app in the App Store’s top charts for the selected country (United States), market (Apple), and device (iPhone) within their app category (Medical). Inclusion criteria required a ranking in the top 1500 Medical apps and being categorized in the App Store as a Medical app. Exclusion criteria included apps that focused on cosmetics, private practice, direct advertisements, photograph editing, or claims to cure skin disease, as well as non–English-language apps. The App Store descriptions were assessed to determine the type of each app (eg, teledermatology, disease guide) and target audience (patient, physician, or both).

Another search was performed using the same keywords but within the Health and Fitness category to capture potentially more highly ranked apps among patients. We also conducted separate searches within the Medical category using the keywords billing, coding, and ICD (International Classification of Diseases) to evaluate rankings for billing/coding apps, as well as EMR and electronic medical records for electronic medical record (EMR) apps.

RESULTS

The initial search yielded 851 results, which was narrowed down to 29 apps after applying the exclusion criteria. Of note, prior to application of the exclusion criteria, one dermatology app that was considered to be a direct advertisement app claiming to cure acne was ranked fourth of 1500 apps in the Medical category. However, the majority of the search results were excluded because they were not popular enough to be ranked among the top 1500 apps. There were more ranked dermatology apps in the Medical category targeting patients than physicians; 18 of 29 (62%) qualifying apps targeted patients and 11 (38%) targeted physicians (Tables 1 and 2). No apps targeted both groups. The most common type of ranked app targeting patients was self-surveillance (11/18), and the most common type targeting physicians was reference (8/11). The highest ranked app targeting patients was a teledermatology app with a ranking of 184, and the highest ranked app targeting physicians was educational, ranked 353. The least common type of ranked apps targeting patients were “other” (2/18 [11%]; 1 prescription and 1 UV monitor app) and conference (1/18 [6%]). The least common type of ranked apps targeting physicians were education (2/11 [18%]) and dermoscopy (1/11 [9%]).

Our search of the Health and Fitness category yielded 6 apps, all targeting patients; 3 (50%) were self-surveillance apps, and 3 (50%) were classified as other (2 UV monitors and a conferencing app for cancer emotional support)(Table 3).

Our search of the Medical category for billing/coding and EMR apps yielded 232 and 164 apps, respectively; of them, 49 (21%) and 54 (33%) apps were ranked. These apps did not overlap with the dermatology-related search criteria; thus, we were not able to ascertain how many of these apps were used specifically by health care providers in dermatology.

COMMENT

Patient Apps

The most common apps used by patients are fitness and nutrition tracker apps categorized as Health and Fitness^5,6; however, the majority of ranked dermatology apps are categorized as Medical per our findings. In a study of 557 dermatology patients, it was found that among the health-related apps they used, the most common apps after fitness/nutrition were references, followed by patient portals, self-surveillance, and emotional assistance apps.⁶ Our search was consistent with these findings, suggesting that the most desired dermatology apps by patients are those that allow them to be proactive with their health. It is no surprise that the top-ranked app targeting patients was a teledermatology app, followed by multiple self-surveillance apps. The highest ranked self-surveillance app in the Health and Fitness category focused on monitoring the effects of nutrition on symptoms of diseases including skin disorders, while the highest ranked (as well as the majority of) self-surveillance apps in the Medical category encompassed mole monitoring and cancer risk calculators.

Benefits of the ranked dermatology apps in the Medical and Health and Fitness categories targeting patients include more immediate access to health care and education. Despite this popularity among patients, Masud et al⁷ demonstrated that only 20.5% (9/44) of dermatology apps targeting patients may be reliable resources based on a rubric created by the investigators. Overall, there remains a research gap for a standardized scientific approach to evaluating app validity and reliability.

Teledermatology
Teledermatology apps are the most common dermatology apps,² allowing for remote evaluation of patients through either live consultations or transmittance of medical information for later review by board-certified physicians.⁸ Features common to many teledermatology apps include accessibility on Android (Google Inc) and iOS as well as a web version. Security and Health Insurance Portability and Accountability Act compliance is especially important and is enforced through user authentications, data encryption, and automatic logout features. Data is not stored locally and is secured on a private server with backup. Referring providers and consultants often can communicate within the app. Insurance providers also may cover teledermatology services, and if not, the out-of-pocket costs often are affordable.

The highest-ranked patient app (ranked 184 in the Medical category) was a teledermatology app that did not meet the American Telemedicine Association standards for teledermatology apps.⁹ The popularity of this app among patients may have been attributable to multiple ease-of-use and turnaround time features. The user interface was simplistic, and the design was appealing to the eye. The entry field options were minimal to avoid confusion. The turnaround time to receive a diagnosis depended on 1 of 3 options, including a more rapid response for an increased cost. Ease of use was the highlight of this app at the cost of accuracy, as the limited amount of information that users were required to provide physicians compromised diagnostic accuracy in this app.

For comparison, we chose a nonranked (and thus less frequently used) teledermatology app that had previously undergone scientific evaluation using 13 evaluation criteria specific to teledermatology.¹⁰ The app also met the American Telemedicine Association standard for teledermatology apps.⁹ The app was originally a broader telemedicine app but featured a section specific to teledermatology. The user interface was simple but professional, almost resembling an EMR. The input fields included a comprehensive history that permitted a better evaluation of a lesion but might be tedious for users. This app boasted professionalism and accuracy, but from a user standpoint, it may have been too time-consuming.

Striking a balance between ensuring proper care versus appealing to patients is a difficult but important task. Based on this study, it appears that popular patient apps may in fact have less scientific rationale and therefore potentially less accuracy.

Self-surveillance
Although self-surveillance apps did not account for the highest-ranked app, they were the most frequently ranked app type in our study. Most of the ranked self-surveillance apps in the Medical category were for monitoring lesions over time to assess for changes. These apps help users take photographs that are well organized in a single, easy-to-find location. Some apps were risk calculators that assessed the risk for malignancies using a questionnaire. The majority of these self-surveillance apps were specific to skin cancer detection. Of note, one of the ranked self-surveillance apps assessed drug effectiveness by monitoring clinical appearance and symptoms. The lowest ranked self-surveillance app in the top 1500 ranked Medical apps in our search monitored cancer symptoms not specific to dermatology. Although this app had a low ranking (1380/1500), it received a high number of reviews and was well rated at 4.8 out of 5 stars; therefore, it seemed more helpful than the other higher-ranked apps targeting patients, which had higher rankings but minimal to no reviews or ratings. A comparison of the ease-of-use features of all the ranked patient-targeted self-surveillance apps in the Medical category is provided in Table 4.

Physician Apps

After examining the results of apps targeting physicians, we realized that the data may be accurate but may not be as representative of all currently practicing dermatology providers. Given the increased usage of apps among younger age groups,¹¹ our data may be skewed toward medical students and residents, supported by the fact that the top-ranked physician app in our study was an education app and the majority were reference apps. Future studies are needed to reexamine app ranking as this age group transitions from entry-level health care providers in the next 5 to 10 years. These findings also suggest less frequent app use among more veteran health care providers within our specific search parameters. Therefore, we decided to do subsequent searches for available billing/coding and EMR apps, which were many, but as mentioned above, none were specific to dermatology.

General Dermatology References
Most of the dermatology reference apps were formatted as e-books; however, other apps such as the Amazon Kindle app (categorized under Books) providing access to multiple e-books within one app were not included. Some apps included study aid features (eg, flash cards, quizzes), and topics spanned both dermatology and dermatopathology. Apps provide a unique way for on-the-go studying for dermatologists in training, and if the usage continues to grow, there may be a need for increased formal integration in dermatology education in the future.

Journals
Journal apps were not among those listed in the top-ranked apps we evaluated, which we suspect may be because journals were categorized differently from one journal to the next; for example, the Journal of the American Academy of Dermatology was ranked 1168 in the Magazines and Newspapers category. On the other hand, Dermatology World was ranked 1363 in the Reference category. An article’s citation affects the publishing journal’s impact factor, which is one of the most important variables in measuring a journal’s influence. In the future, there may be other variables that could aid in understanding journal impact as it relates to the journal’s accessibility.

Limitations

Our study did not look at Android apps. The top chart apps in the Android and Apple App Stores use undisclosed algorithms likely involving different characteristics such as number of downloads, frequency of updates, number of reviews, ratings, and more. Thus, the rankings across these different markets would not be comparable. Although our choice of keywords stemmed from the majority of prior studies looking at dermatology apps, our search was limited due to the use of these specific keywords. To avoid skewing data by cross-comparison of noncomparable categories, we could not compare apps in the Medical category versus those in other categories.

CONCLUSION

There seems to be a disconnect between the apps that are popular among patients and the scientific validity of the apps. As app usage increases among dermatology providers, whose demographic is shifting younger and younger, apps may become more incorporated in our education, and as such, it will become more critical to develop formal scientific standards. Given these future trends, we may need to increase our current literature and understanding of apps in dermatology with regard to their impact on both patients and health care providers.

As technology continues to advance, so too does its accessibility to the general population. In 2013, 56% of Americans owned a smartphone versus 77% in 2017.¹With the increase in mobile applications (apps) available, it is no surprise that the market has extended into the medical field, with dermatology being no exception.² The majority of dermatology apps can be classified as teledermatology apps, followed by self-surveillance, disease guide, and reference apps. Additional types of dermatology apps include dermoscopy, conference, education, photograph storage and sharing, and journal apps, and others.² In this study, we examined Apple App Store rankings to determine the types of dermatology apps that are most popular among patients and physicians.

METHODS

A popular app rankings analyzer (App Annie) was used to search for dermatology apps along with their App Store rankings.³ Although iOS is not the most popular mobile device operating system, we chose to evaluate app rankings via the App Store because iPhones are the top-selling individual phones of any kind in the United States.⁴

We performed our analysis on a single day (July 14, 2018) given that app rankings can change daily. We incorporated the following keywords, which were commonly used in other dermatology app studies: dermatology, psoriasis, rosacea, acne, skin cancer, melanoma, eczema, and teledermatology. The category ranking was defined as the rank of a free or paid app in the App Store’s top charts for the selected country (United States), market (Apple), and device (iPhone) within their app category (Medical). Inclusion criteria required a ranking in the top 1500 Medical apps and being categorized in the App Store as a Medical app. Exclusion criteria included apps that focused on cosmetics, private practice, direct advertisements, photograph editing, or claims to cure skin disease, as well as non–English-language apps. The App Store descriptions were assessed to determine the type of each app (eg, teledermatology, disease guide) and target audience (patient, physician, or both).

Another search was performed using the same keywords but within the Health and Fitness category to capture potentially more highly ranked apps among patients. We also conducted separate searches within the Medical category using the keywords billing, coding, and ICD (International Classification of Diseases) to evaluate rankings for billing/coding apps, as well as EMR and electronic medical records for electronic medical record (EMR) apps.

RESULTS

The initial search yielded 851 results, which was narrowed down to 29 apps after applying the exclusion criteria. Of note, prior to application of the exclusion criteria, one dermatology app that was considered to be a direct advertisement app claiming to cure acne was ranked fourth of 1500 apps in the Medical category. However, the majority of the search results were excluded because they were not popular enough to be ranked among the top 1500 apps. There were more ranked dermatology apps in the Medical category targeting patients than physicians; 18 of 29 (62%) qualifying apps targeted patients and 11 (38%) targeted physicians (Tables 1 and 2). No apps targeted both groups. The most common type of ranked app targeting patients was self-surveillance (11/18), and the most common type targeting physicians was reference (8/11). The highest ranked app targeting patients was a teledermatology app with a ranking of 184, and the highest ranked app targeting physicians was educational, ranked 353. The least common type of ranked apps targeting patients were “other” (2/18 [11%]; 1 prescription and 1 UV monitor app) and conference (1/18 [6%]). The least common type of ranked apps targeting physicians were education (2/11 [18%]) and dermoscopy (1/11 [9%]).

Our search of the Health and Fitness category yielded 6 apps, all targeting patients; 3 (50%) were self-surveillance apps, and 3 (50%) were classified as other (2 UV monitors and a conferencing app for cancer emotional support)(Table 3).

Our search of the Medical category for billing/coding and EMR apps yielded 232 and 164 apps, respectively; of them, 49 (21%) and 54 (33%) apps were ranked. These apps did not overlap with the dermatology-related search criteria; thus, we were not able to ascertain how many of these apps were used specifically by health care providers in dermatology.

COMMENT

Patient Apps

The most common apps used by patients are fitness and nutrition tracker apps categorized as Health and Fitness^5,6; however, the majority of ranked dermatology apps are categorized as Medical per our findings. In a study of 557 dermatology patients, it was found that among the health-related apps they used, the most common apps after fitness/nutrition were references, followed by patient portals, self-surveillance, and emotional assistance apps.⁶ Our search was consistent with these findings, suggesting that the most desired dermatology apps by patients are those that allow them to be proactive with their health. It is no surprise that the top-ranked app targeting patients was a teledermatology app, followed by multiple self-surveillance apps. The highest ranked self-surveillance app in the Health and Fitness category focused on monitoring the effects of nutrition on symptoms of diseases including skin disorders, while the highest ranked (as well as the majority of) self-surveillance apps in the Medical category encompassed mole monitoring and cancer risk calculators.

Benefits of the ranked dermatology apps in the Medical and Health and Fitness categories targeting patients include more immediate access to health care and education. Despite this popularity among patients, Masud et al⁷ demonstrated that only 20.5% (9/44) of dermatology apps targeting patients may be reliable resources based on a rubric created by the investigators. Overall, there remains a research gap for a standardized scientific approach to evaluating app validity and reliability.

Teledermatology
Teledermatology apps are the most common dermatology apps,² allowing for remote evaluation of patients through either live consultations or transmittance of medical information for later review by board-certified physicians.⁸ Features common to many teledermatology apps include accessibility on Android (Google Inc) and iOS as well as a web version. Security and Health Insurance Portability and Accountability Act compliance is especially important and is enforced through user authentications, data encryption, and automatic logout features. Data is not stored locally and is secured on a private server with backup. Referring providers and consultants often can communicate within the app. Insurance providers also may cover teledermatology services, and if not, the out-of-pocket costs often are affordable.

The highest-ranked patient app (ranked 184 in the Medical category) was a teledermatology app that did not meet the American Telemedicine Association standards for teledermatology apps.⁹ The popularity of this app among patients may have been attributable to multiple ease-of-use and turnaround time features. The user interface was simplistic, and the design was appealing to the eye. The entry field options were minimal to avoid confusion. The turnaround time to receive a diagnosis depended on 1 of 3 options, including a more rapid response for an increased cost. Ease of use was the highlight of this app at the cost of accuracy, as the limited amount of information that users were required to provide physicians compromised diagnostic accuracy in this app.

For comparison, we chose a nonranked (and thus less frequently used) teledermatology app that had previously undergone scientific evaluation using 13 evaluation criteria specific to teledermatology.¹⁰ The app also met the American Telemedicine Association standard for teledermatology apps.⁹ The app was originally a broader telemedicine app but featured a section specific to teledermatology. The user interface was simple but professional, almost resembling an EMR. The input fields included a comprehensive history that permitted a better evaluation of a lesion but might be tedious for users. This app boasted professionalism and accuracy, but from a user standpoint, it may have been too time-consuming.

Striking a balance between ensuring proper care versus appealing to patients is a difficult but important task. Based on this study, it appears that popular patient apps may in fact have less scientific rationale and therefore potentially less accuracy.

Self-surveillance
Although self-surveillance apps did not account for the highest-ranked app, they were the most frequently ranked app type in our study. Most of the ranked self-surveillance apps in the Medical category were for monitoring lesions over time to assess for changes. These apps help users take photographs that are well organized in a single, easy-to-find location. Some apps were risk calculators that assessed the risk for malignancies using a questionnaire. The majority of these self-surveillance apps were specific to skin cancer detection. Of note, one of the ranked self-surveillance apps assessed drug effectiveness by monitoring clinical appearance and symptoms. The lowest ranked self-surveillance app in the top 1500 ranked Medical apps in our search monitored cancer symptoms not specific to dermatology. Although this app had a low ranking (1380/1500), it received a high number of reviews and was well rated at 4.8 out of 5 stars; therefore, it seemed more helpful than the other higher-ranked apps targeting patients, which had higher rankings but minimal to no reviews or ratings. A comparison of the ease-of-use features of all the ranked patient-targeted self-surveillance apps in the Medical category is provided in Table 4.

Physician Apps

After examining the results of apps targeting physicians, we realized that the data may be accurate but may not be as representative of all currently practicing dermatology providers. Given the increased usage of apps among younger age groups,¹¹ our data may be skewed toward medical students and residents, supported by the fact that the top-ranked physician app in our study was an education app and the majority were reference apps. Future studies are needed to reexamine app ranking as this age group transitions from entry-level health care providers in the next 5 to 10 years. These findings also suggest less frequent app use among more veteran health care providers within our specific search parameters. Therefore, we decided to do subsequent searches for available billing/coding and EMR apps, which were many, but as mentioned above, none were specific to dermatology.

General Dermatology References
Most of the dermatology reference apps were formatted as e-books; however, other apps such as the Amazon Kindle app (categorized under Books) providing access to multiple e-books within one app were not included. Some apps included study aid features (eg, flash cards, quizzes), and topics spanned both dermatology and dermatopathology. Apps provide a unique way for on-the-go studying for dermatologists in training, and if the usage continues to grow, there may be a need for increased formal integration in dermatology education in the future.

Journals
Journal apps were not among those listed in the top-ranked apps we evaluated, which we suspect may be because journals were categorized differently from one journal to the next; for example, the Journal of the American Academy of Dermatology was ranked 1168 in the Magazines and Newspapers category. On the other hand, Dermatology World was ranked 1363 in the Reference category. An article’s citation affects the publishing journal’s impact factor, which is one of the most important variables in measuring a journal’s influence. In the future, there may be other variables that could aid in understanding journal impact as it relates to the journal’s accessibility.

Limitations

Our study did not look at Android apps. The top chart apps in the Android and Apple App Stores use undisclosed algorithms likely involving different characteristics such as number of downloads, frequency of updates, number of reviews, ratings, and more. Thus, the rankings across these different markets would not be comparable. Although our choice of keywords stemmed from the majority of prior studies looking at dermatology apps, our search was limited due to the use of these specific keywords. To avoid skewing data by cross-comparison of noncomparable categories, we could not compare apps in the Medical category versus those in other categories.

CONCLUSION

There seems to be a disconnect between the apps that are popular among patients and the scientific validity of the apps. As app usage increases among dermatology providers, whose demographic is shifting younger and younger, apps may become more incorporated in our education, and as such, it will become more critical to develop formal scientific standards. Given these future trends, we may need to increase our current literature and understanding of apps in dermatology with regard to their impact on both patients and health care providers.

The practice of inpatient dermatology has a rich history rooted in specialized hospital wards that housed patients with chronic dermatoses. Because systemic agents were limited, the care of these patients required skilled nursing and a distinctive knowledge of the application of numerous topical agents, including washes, baths, powders, lotions, and pastes¹; however, with the evolving nature of health care in the last half a century, such dermatologic inpatient units are now rare, with only 2 units remaining in the United States, specifically at the Mayo Clinic in Minnesota and at the University of Miami.²

Although the shift away from a primary dermatologic admitting service is likely multifactorial, what is more sobering is that the majority of inpatients with dermatologic disorders are cared for by nondermatologists.² Although the dynamics for such a diminished presence are due to various personal and professional concerns, the essential outcome for patients hospitalized with a cutaneous concern—whether directly related to their hospitalization or iatrogenic in nature—is the potential for suboptimal care.³

Fortunately, the practice of inpatient dermatology currently is undergoing a renaissance. With this renewed interest in hospital-based dermatology, there is a growing body of evidence that demonstrates how the dermatology hospitalist has become a vital member of the inpatient team, adding value to the care of patients across all specialties.

To explore the impact of consultative dermatology services, there has been a push by members of the Society for Dermatology Hospitalists to elucidate the contributions of dermatologists in the inpatient setting, which has been accomplished primarily by defining and characterizing the types of patients that dermatology hospitalists care for and, more recently, by demonstrating the improved outcomes that result from expert consultation.

Breadth of Inpatient Dermatologic Consultations

With the adaptation of dermatology consultation services, the scope of practice has shifted from the skilled management of chronic dermatoses to one with an emphasis on the identification of various acute dermatologic diseases. Although the extent of such acute disease states in the inpatient setting is vast, it is interesting to note that the majority of consultations are for common conditions, namely cutaneous infections, venous stasis dermatitis, contact dermatitis, atopic dermatitis, and cutaneous drug eruptions (Table).^4,5

Moreover, for the services that obtain dermatologic consultation, the majority of requests originate from internal medicine and hematology/oncology.^4,5 Although internal medicine often is the largest-represented specialty in the hospital and provides a proportional amount of dermatology consultations, hematology/oncology patients represent a distinct cohort who are prone to unique mucocutaneous dermatoses related to underlying malignancies, immunosuppression, and cancer-specific therapies (eg, chemotherapy, immunotherapy, stem cell transplantation). Within this subset of patients, cutaneous infections and drug eruptions constitute the majority of cases, while graft-versus-host disease and neutrophilic dermatoses account for a smaller percentage of dermatologic disease in this population. Given the complex and uncommon nature of these dermatoses, timely intervention by a dermatologist can have a considerable impact on morbidity and mortality associated with such disease states.^6,7

Among pediatric patients, dermatology consultation patterns mimic those seen among adult patients, with common conditions such as atopic dermatitis and contact dermatitis representing the majority of consultations.^8-11 Vascular lesions further represent a unique source of consultation among pediatric patients. Although they often are considered an outpatient concern, one group found that the majority of inpatient consultations for vascular lesions led to early identification of a syndromic association and/or complication (eg, ulceration).¹⁰ Identifying these cases in the hospital provides early opportunities for intervention and multidisciplinary care.

Adding Value to the Care of Hospitalized Patients

Following other inpatient models, hospitalist dermatology has begun to demonstrate feasibility, advances in quality improvement, and most importantly improved health care outcomes. In an effort to better characterize the enhancement of such health care delivery, recent literature around the impact of inpatient dermatology consultation has centered on improving key objective hospital-based quality measures, namely diagnosis and management as well as hospital length of stay (LOS) and readmission rates.^5,12-18

When identifying cutaneous disease, recent evidence points to the increased diagnostic accuracy by way of dermatology consultation. Specifically, diagnoses were changed 30% to 70% of the time when consultations were provided.^6,12-15 Interestingly, misdiagnosis regularly centered on common diagnoses, specifically cellulitis, stasis dermatitis, and hypersensitivity reactions.^6,12-16 In a multi-institutional retrospective study that examined the national incidence of cellulitis misdiagnosis, the authors found that when a dermatology consultation for presumed cellulitis was called, approximately 75% (N=55) of cases represented mimickers of cellulitis, such as stasis dermatitis, contact dermatitis, and cutaneous fungal infections. Moreover, in more than 38% (N=21) of such cellulitis consultations, patients often had more than one ongoing disease process, further speaking to the diagnostic accuracy obtained from expert consultation.¹⁶ The result of such misdiagnosis is not trivial, as unnecessary hospital admission or inappropriate treatment due to misdiagnosis of cutaneous disease often leads to avoidable complications and preventable health care spending. In a cross-sectional analysis of patients diagnosed with presumed lower extremity cellulitis (N=259), approximately 30% were misdiagnosed. In these cases, more than 90% of patients received unnecessary antibiotics, with approximately 30% of them experiencing a complication or avoidable utilization of health care related to their misdiagnosis.¹⁷

Along with the profound impact on diagnostic accuracy, management and treatment are almost universally affected after dermatology consultation.^5,12-14 Such findings bear importance on optimizing hospital LOS as well as readmission rates. For hospital LOS, a recent study demonstrated reductions in LOS by 2.64 days as well as 1-year cutaneous disease-specific readmissions for patients who received dermatologic consultation for their inflammatory skin disease.¹⁸ Similarly, in a recent prospective cohort study of patients diagnosed with presumed lower extremity cellulitis, hospital LOS decreased by 2 days following a diagnosis of pseudocellulitis via timely dermatologic consultation. Across the United States, such reductions in LOS associated with unnecessary hospitalization due to pseudocellulitis can result in annual health care savings of $100 to $200 million.¹³ As such, early dermatologic intervention plays a vital role in diagnostic accuracy, appropriate treatment implementation, expedited discharge, and the overall economics of health care delivery and utilization, thereby supporting the utility of clinical decision support through expert consultation.

Conclusion

There is a clear and distinct value that results in having specialized inpatient dermatology services. Such expert consultation enhances quality of care and reduces health care costs. Although the implementation and success of inpatient dermatology services has primarily been observed at large hospitals/tertiary care centers, there is incredible potential to further our impact through engagement in our community hospitals. With that said, all practicing dermatologists should feel empowered to employ their expert skillset in their own communities, as such access to care and specialty support is desperately needed and can remarkably impact health care outcomes. Moreover, in addition to the direct impact on health care delivery and economics, the intangible benefits of an inpatient dermatology presence are innumerable, as opportunities to promote quality research and improve trainee education also demonstrate our value. These facets together provide a positive perspective on the potential contribution that our field can have on shaping the outlook of hospital medicine. As such, in addition to enjoying the current renaissance of inpatient dermatology, it is imperative that dermatologists build on this momentum and invest in the future of consultative dermatology.

The practice of inpatient dermatology has a rich history rooted in specialized hospital wards that housed patients with chronic dermatoses. Because systemic agents were limited, the care of these patients required skilled nursing and a distinctive knowledge of the application of numerous topical agents, including washes, baths, powders, lotions, and pastes¹; however, with the evolving nature of health care in the last half a century, such dermatologic inpatient units are now rare, with only 2 units remaining in the United States, specifically at the Mayo Clinic in Minnesota and at the University of Miami.²

Although the shift away from a primary dermatologic admitting service is likely multifactorial, what is more sobering is that the majority of inpatients with dermatologic disorders are cared for by nondermatologists.² Although the dynamics for such a diminished presence are due to various personal and professional concerns, the essential outcome for patients hospitalized with a cutaneous concern—whether directly related to their hospitalization or iatrogenic in nature—is the potential for suboptimal care.³

Fortunately, the practice of inpatient dermatology currently is undergoing a renaissance. With this renewed interest in hospital-based dermatology, there is a growing body of evidence that demonstrates how the dermatology hospitalist has become a vital member of the inpatient team, adding value to the care of patients across all specialties.

To explore the impact of consultative dermatology services, there has been a push by members of the Society for Dermatology Hospitalists to elucidate the contributions of dermatologists in the inpatient setting, which has been accomplished primarily by defining and characterizing the types of patients that dermatology hospitalists care for and, more recently, by demonstrating the improved outcomes that result from expert consultation.

Breadth of Inpatient Dermatologic Consultations

With the adaptation of dermatology consultation services, the scope of practice has shifted from the skilled management of chronic dermatoses to one with an emphasis on the identification of various acute dermatologic diseases. Although the extent of such acute disease states in the inpatient setting is vast, it is interesting to note that the majority of consultations are for common conditions, namely cutaneous infections, venous stasis dermatitis, contact dermatitis, atopic dermatitis, and cutaneous drug eruptions (Table).^4,5

Moreover, for the services that obtain dermatologic consultation, the majority of requests originate from internal medicine and hematology/oncology.^4,5 Although internal medicine often is the largest-represented specialty in the hospital and provides a proportional amount of dermatology consultations, hematology/oncology patients represent a distinct cohort who are prone to unique mucocutaneous dermatoses related to underlying malignancies, immunosuppression, and cancer-specific therapies (eg, chemotherapy, immunotherapy, stem cell transplantation). Within this subset of patients, cutaneous infections and drug eruptions constitute the majority of cases, while graft-versus-host disease and neutrophilic dermatoses account for a smaller percentage of dermatologic disease in this population. Given the complex and uncommon nature of these dermatoses, timely intervention by a dermatologist can have a considerable impact on morbidity and mortality associated with such disease states.^6,7

Among pediatric patients, dermatology consultation patterns mimic those seen among adult patients, with common conditions such as atopic dermatitis and contact dermatitis representing the majority of consultations.^8-11 Vascular lesions further represent a unique source of consultation among pediatric patients. Although they often are considered an outpatient concern, one group found that the majority of inpatient consultations for vascular lesions led to early identification of a syndromic association and/or complication (eg, ulceration).¹⁰ Identifying these cases in the hospital provides early opportunities for intervention and multidisciplinary care.

Adding Value to the Care of Hospitalized Patients

Following other inpatient models, hospitalist dermatology has begun to demonstrate feasibility, advances in quality improvement, and most importantly improved health care outcomes. In an effort to better characterize the enhancement of such health care delivery, recent literature around the impact of inpatient dermatology consultation has centered on improving key objective hospital-based quality measures, namely diagnosis and management as well as hospital length of stay (LOS) and readmission rates.^5,12-18

When identifying cutaneous disease, recent evidence points to the increased diagnostic accuracy by way of dermatology consultation. Specifically, diagnoses were changed 30% to 70% of the time when consultations were provided.^6,12-15 Interestingly, misdiagnosis regularly centered on common diagnoses, specifically cellulitis, stasis dermatitis, and hypersensitivity reactions.^6,12-16 In a multi-institutional retrospective study that examined the national incidence of cellulitis misdiagnosis, the authors found that when a dermatology consultation for presumed cellulitis was called, approximately 75% (N=55) of cases represented mimickers of cellulitis, such as stasis dermatitis, contact dermatitis, and cutaneous fungal infections. Moreover, in more than 38% (N=21) of such cellulitis consultations, patients often had more than one ongoing disease process, further speaking to the diagnostic accuracy obtained from expert consultation.¹⁶ The result of such misdiagnosis is not trivial, as unnecessary hospital admission or inappropriate treatment due to misdiagnosis of cutaneous disease often leads to avoidable complications and preventable health care spending. In a cross-sectional analysis of patients diagnosed with presumed lower extremity cellulitis (N=259), approximately 30% were misdiagnosed. In these cases, more than 90% of patients received unnecessary antibiotics, with approximately 30% of them experiencing a complication or avoidable utilization of health care related to their misdiagnosis.¹⁷

Along with the profound impact on diagnostic accuracy, management and treatment are almost universally affected after dermatology consultation.^5,12-14 Such findings bear importance on optimizing hospital LOS as well as readmission rates. For hospital LOS, a recent study demonstrated reductions in LOS by 2.64 days as well as 1-year cutaneous disease-specific readmissions for patients who received dermatologic consultation for their inflammatory skin disease.¹⁸ Similarly, in a recent prospective cohort study of patients diagnosed with presumed lower extremity cellulitis, hospital LOS decreased by 2 days following a diagnosis of pseudocellulitis via timely dermatologic consultation. Across the United States, such reductions in LOS associated with unnecessary hospitalization due to pseudocellulitis can result in annual health care savings of $100 to $200 million.¹³ As such, early dermatologic intervention plays a vital role in diagnostic accuracy, appropriate treatment implementation, expedited discharge, and the overall economics of health care delivery and utilization, thereby supporting the utility of clinical decision support through expert consultation.

Conclusion

There is a clear and distinct value that results in having specialized inpatient dermatology services. Such expert consultation enhances quality of care and reduces health care costs. Although the implementation and success of inpatient dermatology services has primarily been observed at large hospitals/tertiary care centers, there is incredible potential to further our impact through engagement in our community hospitals. With that said, all practicing dermatologists should feel empowered to employ their expert skillset in their own communities, as such access to care and specialty support is desperately needed and can remarkably impact health care outcomes. Moreover, in addition to the direct impact on health care delivery and economics, the intangible benefits of an inpatient dermatology presence are innumerable, as opportunities to promote quality research and improve trainee education also demonstrate our value. These facets together provide a positive perspective on the potential contribution that our field can have on shaping the outlook of hospital medicine. As such, in addition to enjoying the current renaissance of inpatient dermatology, it is imperative that dermatologists build on this momentum and invest in the future of consultative dermatology.

The practice of inpatient dermatology has a rich history rooted in specialized hospital wards that housed patients with chronic dermatoses. Because systemic agents were limited, the care of these patients required skilled nursing and a distinctive knowledge of the application of numerous topical agents, including washes, baths, powders, lotions, and pastes¹; however, with the evolving nature of health care in the last half a century, such dermatologic inpatient units are now rare, with only 2 units remaining in the United States, specifically at the Mayo Clinic in Minnesota and at the University of Miami.²

Although the shift away from a primary dermatologic admitting service is likely multifactorial, what is more sobering is that the majority of inpatients with dermatologic disorders are cared for by nondermatologists.² Although the dynamics for such a diminished presence are due to various personal and professional concerns, the essential outcome for patients hospitalized with a cutaneous concern—whether directly related to their hospitalization or iatrogenic in nature—is the potential for suboptimal care.³

Fortunately, the practice of inpatient dermatology currently is undergoing a renaissance. With this renewed interest in hospital-based dermatology, there is a growing body of evidence that demonstrates how the dermatology hospitalist has become a vital member of the inpatient team, adding value to the care of patients across all specialties.

To explore the impact of consultative dermatology services, there has been a push by members of the Society for Dermatology Hospitalists to elucidate the contributions of dermatologists in the inpatient setting, which has been accomplished primarily by defining and characterizing the types of patients that dermatology hospitalists care for and, more recently, by demonstrating the improved outcomes that result from expert consultation.

Breadth of Inpatient Dermatologic Consultations

With the adaptation of dermatology consultation services, the scope of practice has shifted from the skilled management of chronic dermatoses to one with an emphasis on the identification of various acute dermatologic diseases. Although the extent of such acute disease states in the inpatient setting is vast, it is interesting to note that the majority of consultations are for common conditions, namely cutaneous infections, venous stasis dermatitis, contact dermatitis, atopic dermatitis, and cutaneous drug eruptions (Table).^4,5

Moreover, for the services that obtain dermatologic consultation, the majority of requests originate from internal medicine and hematology/oncology.^4,5 Although internal medicine often is the largest-represented specialty in the hospital and provides a proportional amount of dermatology consultations, hematology/oncology patients represent a distinct cohort who are prone to unique mucocutaneous dermatoses related to underlying malignancies, immunosuppression, and cancer-specific therapies (eg, chemotherapy, immunotherapy, stem cell transplantation). Within this subset of patients, cutaneous infections and drug eruptions constitute the majority of cases, while graft-versus-host disease and neutrophilic dermatoses account for a smaller percentage of dermatologic disease in this population. Given the complex and uncommon nature of these dermatoses, timely intervention by a dermatologist can have a considerable impact on morbidity and mortality associated with such disease states.^6,7

Among pediatric patients, dermatology consultation patterns mimic those seen among adult patients, with common conditions such as atopic dermatitis and contact dermatitis representing the majority of consultations.^8-11 Vascular lesions further represent a unique source of consultation among pediatric patients. Although they often are considered an outpatient concern, one group found that the majority of inpatient consultations for vascular lesions led to early identification of a syndromic association and/or complication (eg, ulceration).¹⁰ Identifying these cases in the hospital provides early opportunities for intervention and multidisciplinary care.

Adding Value to the Care of Hospitalized Patients

Following other inpatient models, hospitalist dermatology has begun to demonstrate feasibility, advances in quality improvement, and most importantly improved health care outcomes. In an effort to better characterize the enhancement of such health care delivery, recent literature around the impact of inpatient dermatology consultation has centered on improving key objective hospital-based quality measures, namely diagnosis and management as well as hospital length of stay (LOS) and readmission rates.^5,12-18

When identifying cutaneous disease, recent evidence points to the increased diagnostic accuracy by way of dermatology consultation. Specifically, diagnoses were changed 30% to 70% of the time when consultations were provided.^6,12-15 Interestingly, misdiagnosis regularly centered on common diagnoses, specifically cellulitis, stasis dermatitis, and hypersensitivity reactions.^6,12-16 In a multi-institutional retrospective study that examined the national incidence of cellulitis misdiagnosis, the authors found that when a dermatology consultation for presumed cellulitis was called, approximately 75% (N=55) of cases represented mimickers of cellulitis, such as stasis dermatitis, contact dermatitis, and cutaneous fungal infections. Moreover, in more than 38% (N=21) of such cellulitis consultations, patients often had more than one ongoing disease process, further speaking to the diagnostic accuracy obtained from expert consultation.¹⁶ The result of such misdiagnosis is not trivial, as unnecessary hospital admission or inappropriate treatment due to misdiagnosis of cutaneous disease often leads to avoidable complications and preventable health care spending. In a cross-sectional analysis of patients diagnosed with presumed lower extremity cellulitis (N=259), approximately 30% were misdiagnosed. In these cases, more than 90% of patients received unnecessary antibiotics, with approximately 30% of them experiencing a complication or avoidable utilization of health care related to their misdiagnosis.¹⁷

Along with the profound impact on diagnostic accuracy, management and treatment are almost universally affected after dermatology consultation.^5,12-14 Such findings bear importance on optimizing hospital LOS as well as readmission rates. For hospital LOS, a recent study demonstrated reductions in LOS by 2.64 days as well as 1-year cutaneous disease-specific readmissions for patients who received dermatologic consultation for their inflammatory skin disease.¹⁸ Similarly, in a recent prospective cohort study of patients diagnosed with presumed lower extremity cellulitis, hospital LOS decreased by 2 days following a diagnosis of pseudocellulitis via timely dermatologic consultation. Across the United States, such reductions in LOS associated with unnecessary hospitalization due to pseudocellulitis can result in annual health care savings of $100 to $200 million.¹³ As such, early dermatologic intervention plays a vital role in diagnostic accuracy, appropriate treatment implementation, expedited discharge, and the overall economics of health care delivery and utilization, thereby supporting the utility of clinical decision support through expert consultation.

Conclusion

There is a clear and distinct value that results in having specialized inpatient dermatology services. Such expert consultation enhances quality of care and reduces health care costs. Although the implementation and success of inpatient dermatology services has primarily been observed at large hospitals/tertiary care centers, there is incredible potential to further our impact through engagement in our community hospitals. With that said, all practicing dermatologists should feel empowered to employ their expert skillset in their own communities, as such access to care and specialty support is desperately needed and can remarkably impact health care outcomes. Moreover, in addition to the direct impact on health care delivery and economics, the intangible benefits of an inpatient dermatology presence are innumerable, as opportunities to promote quality research and improve trainee education also demonstrate our value. These facets together provide a positive perspective on the potential contribution that our field can have on shaping the outlook of hospital medicine. As such, in addition to enjoying the current renaissance of inpatient dermatology, it is imperative that dermatologists build on this momentum and invest in the future of consultative dermatology.

CHICAGO – When topical and oral medications alone don’t meet the needs of patients with atopic dermatitis, nonpharmaceutical options may benefit patients as adjunctive therapies, according to Peter A. Lio, MD, of Northwestern University, Chicago.

Cryotherapy and silk or silver fabrics have seen some good results, according to Dr. Lio, who cited his paper on nonpharmacologic therapies for atopic dermatitis. “There is another world of nonpharmacologic treatments that is perhaps nearly as extensive, though less well known, and likely underutilized by some clinicians.”

Dr. Lio described the treatment options for atopic dermatitis as the four points of a tetrahedron: anti-inflammatories, antibiotics, antipruritics, and moisturization.

Moisturization

“More moisturizer means less eczema,” Dr. Lio said. If patients find the moisturizer too cold, they can float the jar in a hot bath before applying it. On the flip side, patients who feel hotter or itchier when applying moisturizer may prefer keeping it in the refrigerator.

Evidence also supports balneotherapy and spa therapy, Dr. Lio said, though limited data exist to guide clinicians on the frequency or duration of baths or how soon to apply moisturizer after a bath. Research indicates benefit from bath and spa therapy lasting up to 3-6 months for mild to moderate eczema.

However, it’s hard to distinguish between the possible benefits of the spa therapy itself versus possible confounding benefits from what often accompanies spa therapy, such as climatotherapy (warm weather), heliotherapy (sunshine), and relaxation from being in a vacation setting.

It’s also unclear whether the minerals in the water matter. Balneotherapy studies have shown benefits from mineral-rich water, but research has shown no benefit from using a water softener to remove minerals from hard water. Furthermore, balneotherapy and spa therapy are expensive, time-consuming, and temporary.

Using wet wraps overnight is an easy and cheap alternative treatment. Dr. Lio recommended soaking onesies, pajamas, gloves, or socks (depending on the location of affected skin) in warm water and then wringing them out until slightly damp. The person puts on the damp clothes and dry pajamas, gloves, or socks over them, and ensures the room is warm enough before going to sleep.

Antibacterial agents

Some research has found an association between environmental Staphylococcus aureus and severe atopic dermatitis, suggesting a role for antibacterial agents, Dr. Lio said. Though the mechanism is unclear, a dilute bleach bath may help.

In a small, randomized, controlled trial of 31 children with moderate to severe eczema, all received oral antibiotics and were then randomized to receive either intranasal mupirocin and a dilute bleach bath twice weekly for 4 weeks or intranasal vaseline and a placebo bath. Those in the mupirocin/bleach bath group showed significant greater improvement, compared with the placebo group.

Yet other research has shown regular baths are superior to dilute bleach baths. It seems more likely that dilute bleach baths act more as an anti-inflammatory than an antibacterial agent, Dr. Lio said at the American Academy of Dermatology summer meeting.

Probiotics “is an area that’s teeming with potential, but right now we don’t really write a prescription for probiotics,” Dr. Lio told attendees. He shared a systematic review supporting probiotics’ use in pregnant mothers and newborns for preventing atopic dermatitis.

“I’m convinced there actually is significant evidence that, if you give expecting moms probiotics and then give it to the baby as soon as they come out, you can prevent or at least reduce the severity of the atopic dermatitis in a measurable portion of patients,” Dr. Lio said. However, he acknowledged other research suggesting probiotics simply delay onset of atopic dermatitis.

“The bacteria in our gut are quite different than [the bacteria] on our skin,” Dr. Lio said. Topical probiotics are under study, and “could be a nonpharmacologic adjunctive therapy.”

Silver and silver-coated clothing are anecdotally successful in select patients. One small study compared silk with topical steroids and implied good results, but most studies with silk remain small and underpowered. If patients want to try textile therapy, they can purchase small silk sleep sacs similar to a sleeping bag.

Silver-impregnated products display true antibacterial effects and do seem to improve atopic dermatitis and pruritus scores, he added, but there are downsides. “These products are pricey, and there’s an environmental issue when you wash these silver clothes and the silver hangs out in the water supply.”

Anti-inflammatories

Cryotherapy is a potential anti-inflammatory, nonpharmaceutical treatment worth exploring, Dr. Lio said. It’s not exactly clear how or why cryotherapy works, but there are several possibilities: Very cold air may increase the body’s antioxidative capacity or reduce the conduction velocity of peripheral nerves, or the cold may simply relieve itch through local or systemic anti-inflammatory effects. At the same time, treatment-related adverse effects from whole-body cryotherapy are a risk – particularly frostbite, Dr. Lio said.

Vitamin D “is a bit of a controversial topic,” Dr. Lio said. The research has gone up and down supporting its potential benefits, so Dr. Lio errs on the side of recommending it.

“It’s one of those things I just give to everybody,” he said, adding that the risk-benefit ratio makes vitamin D worth trying as adverse events are unlikely.

Antipruritics

Dr. Lio discussed the fourth point of the tetrahedron: anti-itching agents. Much has been tried – antihistamines, various topical agents (camphor, menthol, pramoxine), antidepressants, gabapentin, antipsychotics – but little has panned out from these medications.

One study found significantly less refractory uremic pruritus at 1 and 3 months after receiving acupressure.

Hypnosis and biofeedback appear worthwhile as well, perhaps via stress relief. Stress and sleep deprivation can worsen atopic dermatitis and slow healing of the skin barrier. Some research has found subjective and objective benefits from hypnosis.

Dr. Lio endorsed a “write it down” approach when managing atopic dermatitis patients. An Eczema Action Plan, clearly written and provided to the patient, can reduce anxiety levels and increase understanding of the treatment regimens and their risks and benefits.

Dr. Lio has received honoraria for speaking and/or consulting from Pierre-Fabre, L’Oreal, Regeneron, Sanofi Genzyme, Pfizer, Theraplex, Johnson & Johnson, AbbVie, Eli Lilly, Exeltis, Franklin BioScience, Galderma, Kiniksa Pharmaceuticals, Menlo Therapeutics, and Mission Pharmacal. He has also received research grants from Pierre-Fabre and AOBiome.

CHICAGO – When topical and oral medications alone don’t meet the needs of patients with atopic dermatitis, nonpharmaceutical options may benefit patients as adjunctive therapies, according to Peter A. Lio, MD, of Northwestern University, Chicago.

Cryotherapy and silk or silver fabrics have seen some good results, according to Dr. Lio, who cited his paper on nonpharmacologic therapies for atopic dermatitis. “There is another world of nonpharmacologic treatments that is perhaps nearly as extensive, though less well known, and likely underutilized by some clinicians.”

Dr. Lio described the treatment options for atopic dermatitis as the four points of a tetrahedron: anti-inflammatories, antibiotics, antipruritics, and moisturization.

Moisturization

“More moisturizer means less eczema,” Dr. Lio said. If patients find the moisturizer too cold, they can float the jar in a hot bath before applying it. On the flip side, patients who feel hotter or itchier when applying moisturizer may prefer keeping it in the refrigerator.

Evidence also supports balneotherapy and spa therapy, Dr. Lio said, though limited data exist to guide clinicians on the frequency or duration of baths or how soon to apply moisturizer after a bath. Research indicates benefit from bath and spa therapy lasting up to 3-6 months for mild to moderate eczema.

However, it’s hard to distinguish between the possible benefits of the spa therapy itself versus possible confounding benefits from what often accompanies spa therapy, such as climatotherapy (warm weather), heliotherapy (sunshine), and relaxation from being in a vacation setting.

It’s also unclear whether the minerals in the water matter. Balneotherapy studies have shown benefits from mineral-rich water, but research has shown no benefit from using a water softener to remove minerals from hard water. Furthermore, balneotherapy and spa therapy are expensive, time-consuming, and temporary.

Using wet wraps overnight is an easy and cheap alternative treatment. Dr. Lio recommended soaking onesies, pajamas, gloves, or socks (depending on the location of affected skin) in warm water and then wringing them out until slightly damp. The person puts on the damp clothes and dry pajamas, gloves, or socks over them, and ensures the room is warm enough before going to sleep.

Antibacterial agents

Some research has found an association between environmental Staphylococcus aureus and severe atopic dermatitis, suggesting a role for antibacterial agents, Dr. Lio said. Though the mechanism is unclear, a dilute bleach bath may help.

In a small, randomized, controlled trial of 31 children with moderate to severe eczema, all received oral antibiotics and were then randomized to receive either intranasal mupirocin and a dilute bleach bath twice weekly for 4 weeks or intranasal vaseline and a placebo bath. Those in the mupirocin/bleach bath group showed significant greater improvement, compared with the placebo group.

Yet other research has shown regular baths are superior to dilute bleach baths. It seems more likely that dilute bleach baths act more as an anti-inflammatory than an antibacterial agent, Dr. Lio said at the American Academy of Dermatology summer meeting.

Probiotics “is an area that’s teeming with potential, but right now we don’t really write a prescription for probiotics,” Dr. Lio told attendees. He shared a systematic review supporting probiotics’ use in pregnant mothers and newborns for preventing atopic dermatitis.

“I’m convinced there actually is significant evidence that, if you give expecting moms probiotics and then give it to the baby as soon as they come out, you can prevent or at least reduce the severity of the atopic dermatitis in a measurable portion of patients,” Dr. Lio said. However, he acknowledged other research suggesting probiotics simply delay onset of atopic dermatitis.

“The bacteria in our gut are quite different than [the bacteria] on our skin,” Dr. Lio said. Topical probiotics are under study, and “could be a nonpharmacologic adjunctive therapy.”

Silver and silver-coated clothing are anecdotally successful in select patients. One small study compared silk with topical steroids and implied good results, but most studies with silk remain small and underpowered. If patients want to try textile therapy, they can purchase small silk sleep sacs similar to a sleeping bag.

Silver-impregnated products display true antibacterial effects and do seem to improve atopic dermatitis and pruritus scores, he added, but there are downsides. “These products are pricey, and there’s an environmental issue when you wash these silver clothes and the silver hangs out in the water supply.”

Anti-inflammatories

Cryotherapy is a potential anti-inflammatory, nonpharmaceutical treatment worth exploring, Dr. Lio said. It’s not exactly clear how or why cryotherapy works, but there are several possibilities: Very cold air may increase the body’s antioxidative capacity or reduce the conduction velocity of peripheral nerves, or the cold may simply relieve itch through local or systemic anti-inflammatory effects. At the same time, treatment-related adverse effects from whole-body cryotherapy are a risk – particularly frostbite, Dr. Lio said.

Vitamin D “is a bit of a controversial topic,” Dr. Lio said. The research has gone up and down supporting its potential benefits, so Dr. Lio errs on the side of recommending it.

“It’s one of those things I just give to everybody,” he said, adding that the risk-benefit ratio makes vitamin D worth trying as adverse events are unlikely.

Antipruritics

Dr. Lio discussed the fourth point of the tetrahedron: anti-itching agents. Much has been tried – antihistamines, various topical agents (camphor, menthol, pramoxine), antidepressants, gabapentin, antipsychotics – but little has panned out from these medications.

One study found significantly less refractory uremic pruritus at 1 and 3 months after receiving acupressure.

Hypnosis and biofeedback appear worthwhile as well, perhaps via stress relief. Stress and sleep deprivation can worsen atopic dermatitis and slow healing of the skin barrier. Some research has found subjective and objective benefits from hypnosis.

Dr. Lio endorsed a “write it down” approach when managing atopic dermatitis patients. An Eczema Action Plan, clearly written and provided to the patient, can reduce anxiety levels and increase understanding of the treatment regimens and their risks and benefits.

Dr. Lio has received honoraria for speaking and/or consulting from Pierre-Fabre, L’Oreal, Regeneron, Sanofi Genzyme, Pfizer, Theraplex, Johnson & Johnson, AbbVie, Eli Lilly, Exeltis, Franklin BioScience, Galderma, Kiniksa Pharmaceuticals, Menlo Therapeutics, and Mission Pharmacal. He has also received research grants from Pierre-Fabre and AOBiome.

CHICAGO – When topical and oral medications alone don’t meet the needs of patients with atopic dermatitis, nonpharmaceutical options may benefit patients as adjunctive therapies, according to Peter A. Lio, MD, of Northwestern University, Chicago.

Cryotherapy and silk or silver fabrics have seen some good results, according to Dr. Lio, who cited his paper on nonpharmacologic therapies for atopic dermatitis. “There is another world of nonpharmacologic treatments that is perhaps nearly as extensive, though less well known, and likely underutilized by some clinicians.”

Dr. Lio described the treatment options for atopic dermatitis as the four points of a tetrahedron: anti-inflammatories, antibiotics, antipruritics, and moisturization.

Moisturization

“More moisturizer means less eczema,” Dr. Lio said. If patients find the moisturizer too cold, they can float the jar in a hot bath before applying it. On the flip side, patients who feel hotter or itchier when applying moisturizer may prefer keeping it in the refrigerator.

Evidence also supports balneotherapy and spa therapy, Dr. Lio said, though limited data exist to guide clinicians on the frequency or duration of baths or how soon to apply moisturizer after a bath. Research indicates benefit from bath and spa therapy lasting up to 3-6 months for mild to moderate eczema.

However, it’s hard to distinguish between the possible benefits of the spa therapy itself versus possible confounding benefits from what often accompanies spa therapy, such as climatotherapy (warm weather), heliotherapy (sunshine), and relaxation from being in a vacation setting.

It’s also unclear whether the minerals in the water matter. Balneotherapy studies have shown benefits from mineral-rich water, but research has shown no benefit from using a water softener to remove minerals from hard water. Furthermore, balneotherapy and spa therapy are expensive, time-consuming, and temporary.

Using wet wraps overnight is an easy and cheap alternative treatment. Dr. Lio recommended soaking onesies, pajamas, gloves, or socks (depending on the location of affected skin) in warm water and then wringing them out until slightly damp. The person puts on the damp clothes and dry pajamas, gloves, or socks over them, and ensures the room is warm enough before going to sleep.

Antibacterial agents

Some research has found an association between environmental Staphylococcus aureus and severe atopic dermatitis, suggesting a role for antibacterial agents, Dr. Lio said. Though the mechanism is unclear, a dilute bleach bath may help.

In a small, randomized, controlled trial of 31 children with moderate to severe eczema, all received oral antibiotics and were then randomized to receive either intranasal mupirocin and a dilute bleach bath twice weekly for 4 weeks or intranasal vaseline and a placebo bath. Those in the mupirocin/bleach bath group showed significant greater improvement, compared with the placebo group.

Yet other research has shown regular baths are superior to dilute bleach baths. It seems more likely that dilute bleach baths act more as an anti-inflammatory than an antibacterial agent, Dr. Lio said at the American Academy of Dermatology summer meeting.

Probiotics “is an area that’s teeming with potential, but right now we don’t really write a prescription for probiotics,” Dr. Lio told attendees. He shared a systematic review supporting probiotics’ use in pregnant mothers and newborns for preventing atopic dermatitis.

“I’m convinced there actually is significant evidence that, if you give expecting moms probiotics and then give it to the baby as soon as they come out, you can prevent or at least reduce the severity of the atopic dermatitis in a measurable portion of patients,” Dr. Lio said. However, he acknowledged other research suggesting probiotics simply delay onset of atopic dermatitis.

“The bacteria in our gut are quite different than [the bacteria] on our skin,” Dr. Lio said. Topical probiotics are under study, and “could be a nonpharmacologic adjunctive therapy.”

Silver and silver-coated clothing are anecdotally successful in select patients. One small study compared silk with topical steroids and implied good results, but most studies with silk remain small and underpowered. If patients want to try textile therapy, they can purchase small silk sleep sacs similar to a sleeping bag.

Silver-impregnated products display true antibacterial effects and do seem to improve atopic dermatitis and pruritus scores, he added, but there are downsides. “These products are pricey, and there’s an environmental issue when you wash these silver clothes and the silver hangs out in the water supply.”

Anti-inflammatories

Cryotherapy is a potential anti-inflammatory, nonpharmaceutical treatment worth exploring, Dr. Lio said. It’s not exactly clear how or why cryotherapy works, but there are several possibilities: Very cold air may increase the body’s antioxidative capacity or reduce the conduction velocity of peripheral nerves, or the cold may simply relieve itch through local or systemic anti-inflammatory effects. At the same time, treatment-related adverse effects from whole-body cryotherapy are a risk – particularly frostbite, Dr. Lio said.

Vitamin D “is a bit of a controversial topic,” Dr. Lio said. The research has gone up and down supporting its potential benefits, so Dr. Lio errs on the side of recommending it.

“It’s one of those things I just give to everybody,” he said, adding that the risk-benefit ratio makes vitamin D worth trying as adverse events are unlikely.

Antipruritics

Dr. Lio discussed the fourth point of the tetrahedron: anti-itching agents. Much has been tried – antihistamines, various topical agents (camphor, menthol, pramoxine), antidepressants, gabapentin, antipsychotics – but little has panned out from these medications.

One study found significantly less refractory uremic pruritus at 1 and 3 months after receiving acupressure.

Hypnosis and biofeedback appear worthwhile as well, perhaps via stress relief. Stress and sleep deprivation can worsen atopic dermatitis and slow healing of the skin barrier. Some research has found subjective and objective benefits from hypnosis.

Dr. Lio endorsed a “write it down” approach when managing atopic dermatitis patients. An Eczema Action Plan, clearly written and provided to the patient, can reduce anxiety levels and increase understanding of the treatment regimens and their risks and benefits.

Dr. Lio has received honoraria for speaking and/or consulting from Pierre-Fabre, L’Oreal, Regeneron, Sanofi Genzyme, Pfizer, Theraplex, Johnson & Johnson, AbbVie, Eli Lilly, Exeltis, Franklin BioScience, Galderma, Kiniksa Pharmaceuticals, Menlo Therapeutics, and Mission Pharmacal. He has also received research grants from Pierre-Fabre and AOBiome.

PARIS – Dupilumab scorched its way through a landmark pivotal phase 3 clinical trial in adolescents with moderate to severe atopic dermatitis (AD), achieving unprecedented clinically meaningful improvements in signs and symptoms of the disease along with important quality of life benefits, Eric L. Simpson, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDEdge News

Indeed, dupilumab (Dupixent), a fully human monoclonal antibody that inhibits interleukins-4 and -13, demonstrated safety and efficacy in adolescent patients akin to that previously shown in adults with moderate to severe AD in phase 3 trials that earned the biologic U.S. and European regulatory approval in the adult population, noted Dr. Simpson, professor of dermatology at Oregon Health & Science University, Portland.

This positive phase 3 study represents a major development in pediatric dermatology because of the pressing unmet need for better treatments for teens with moderate to severe AD whose disease can’t be controlled with topical therapies. The adolescent years are, after all, a critical period in growth and development, and a debilitating, uncontrolled disease can reshape that experience in unwelcome ways.

“Atopic dermatitis profoundly affects quality of life in adolescents and their family: The itching affects mood and sleep, these patients commonly have anxiety and depression, and the chronic and relapsing nature of the disease adversely affects the family,” the dermatologist observed.

Currently, no systemic agent is approved for pediatric patients with AD because evidence demonstrating a favorable benefit-to-risk profile has been lacking. The dupilumab study was the first-ever phase 3 trial of a biologic in such a population.

The phase 3 adolescent trial was a 16-week, randomized, double-blind, multicenter, placebo-controlled study of 251 patients aged 12-17 years with moderate to severe AD, which could not be adequately controlled with topical therapies. Participants averaged 14 years of age, with a 12-year history of AD. “These patients had the disease basically their whole life,” Dr. Simpson noted.

They were more severely affected than participants in the adult clinical trials, with mean Eczema Area And Severity Index (EASI) scores in the mid-30s and an average 56% involved body surface area. The adolescent AD patients had a heavy burden of comorbid allergic type 2 immune comorbidity: Fully 92% of them had documented asthma, food allergy, allergic rhinitis, and/or some other form of allergic comorbidity. The majority of the teens were categorized as having severe AD, whereas most participants in the adult phase 3 trials of dupilumab had moderate disease. That distinction becomes relevant in comparing the trial results.

Participants were randomized to once-monthly subcutaneous injections of dupilumab at 300 mg, following a 600-mg loading dose, or to an injection of 200 mg or 300 mg every 2 weeks with an initial dose of 400 mg or 600 mg based upon a body weight cutoff of 60 kg, or to biweekly placebo injections.

The coprimary endpoints were the proportion of patients who achieved an EASI 75 response at week 16 and achievement of an Investigator’s Global Assessment (IGA) score of 0 or 1, meaning clear or almost clear, on a 5-point scale at week 16.

This trial introduced an important new design feature that physicians can expect to see more of in the future: regulatory agencies now want to see the effects of monotherapy in pivotal studies in AD. Previously, participants in AD studies of systemic agents could also utilize topical steroids as needed. No longer. In the adolescent dupilumab study, resort to rescue topical steroids led to exclusion from inclusion in the primary outcome results. Not surprisingly, this lack of access to rescue medication resulted in a 60% dropout rate by 16 weeks in placebo-treated controls, a 30% dropout rate in teens on dupilumab every 4 weeks, and a 20% dropout rate with biweekly dupilumab.

The EASI 75 rate at week 16 was 8.2% with placebo, 38.1% with monthly dupilumab, and 41.5% with biweekly dosing. The other coprimary endpoint – an IGA of 0 or 1 at 16 weeks – was achieved in 2.4% of controls, 17.9% with dupilumab at 300 mg every 4 weeks, and 41.5% with biweekly dosing.

Turning to secondary endpoints, Dr. Simpson reported that baseline peak pruritus Numeric Rating Scale scores dropped by 19% with placebo at 16 weeks, compared with reductions of 45.5% and 47.9% with monthly and biweekly dupilumab, respectively.

An EASI 50 response,while not as impressive as an EASI 75, is nonetheless considered clinically meaningful improvement. It was attained in 12.9% on placebo and 54.8% and 61% on monthly and biweekly dupilumab.

From a mean baseline score of 13.6 on the Children’s Dermatology Life Quality Index, scores improved over the course of 16 weeks by a mean of 5.1 points with placebo, 8.5 points with monthly dupilumab, and 8.8 points with biweekly biologic therapy. The same pattern was noted with regard to the Patient-Oriented Eczema Measure or POEM.

Adverse events mirrored those documented in the pivotal trials in adults: increased rates of mild to moderate conjunctivitis: 4.7% with placebo, 10.8% with monthly dupilumab, and 9.8% with biweekly dupilumab, along with single-digit rates of injection-site reactions. As in adult AD patients, however, these side effects were counterbalanced by significantly reduced rates of skin infections in the adolescent group: 20% during 16 weeks with placebo, and 13.3% and 11% with monthly and biweekly biologic therapy, respectively.

Study participants had a mean baseline score of 12.5 on the Hospital Anxiety and Depression Scale, which is categorized as clinically significant psychiatric disease. The impact of dupilumab therapy on those scores will be the topic of a future presentation, Dr. Simpson said.

Across the board, specific outcomes were consistently numerically better in patients who received dupilumab biweekly than monthly, albeit not statistically significantly so. Dr. Simpson thinks he knows why: Lab studies showed that the mean serum concentration of functional dupilumab in patients who got the biologic biweekly was nearly twice that for the group with monthly dosing.

At first glance, the IGA “clear” or “almost clear” response rates seen with dupilumab in the adolescent study appeared to be less robust than in the adult pivotal phase 3 trials, such as the SOLO 1 and SOLO 2 trials (N Engl J Med. 2016 Dec 15;375[24]:2335-48), also led by Dr. Simpson.

“I think that’s because of the greater severity of that baseline adolescent population,” he commented. “It made for a much lower placebo response rate. But when you correct for the placebo-subtracted difference, the rates are actually pretty similar, and a lot of the other endpoints are the same or even better than in SOLO.”

After his presentation, Dr. Simpson commented, “This is huge. This is the study we’ve been waiting for.”

Elsewhere at the EADV congress, Emma Guttman-Yassky, MD, PhD, deemed the pivotal phase 3 trial in adolescent AD patients one of the meeting’s highlights. And it’s a harbinger of more good things to come, because the investigational drug pipeline for AD is full of promising candidates addressing the disease from a variety of novel directions. The long therapeutic drought in AD appears to have finally ended, observed Dr. Guttman-Yassky, professor and vice-chair of the department of dermatology at Icahn School of Medicine at Mount Sinai, New York.

Bruce Jancin/MDedge News

That’s welcome news because AD is the most common inflammatory skin disease, both in adults, where the latest data puts the prevalence at 7%-10%, and in children, where the global rate is 15%-25%.

And while at the EADV congress only the 16-week data were reported in the new adolescent study, there is reason to be optimistic that the benefits will remain durable over time. Dr. Guttman-Yassky cited the published 52-week data from the large phase 3 CHRONOS trial in adults with moderate to severe AD. In that trial, in which patients could use concomitant topical steroids, the EASI 75 rates at week 16 were 69% in patients on dupilumab at 300 mg every 2 weeks, 64% with 300 mg weekly, and 23% with placebo. Reassuringly, at 52 weeks the EASI 75 response rates were essentially unchanged: 65%, 64%, and 22% (Lancet. 2017 Jun 10;389[10086]:2287-303).

“This is what we are seeking: not just treatment that is able to quickly modify disease, but we want the treatment to be sustained, and of course we want it to be safe for our patients because we know we cannot use cyclosporine for a long time,” Dr. Guttman-Yassky said.

Dr. Simpson reported serving as a consultant to and recipient of research grants from Sanofi and Regeneron, which sponsored the adolescent study, as well as more than a dozen other pharmaceutical companies. Dr. Guttman-Yassky reported serving as an advisor and consultant, and has received grants/research funding from Regeneron, and multiple other companies.

bjancin@mdedge.com

PARIS – Dupilumab scorched its way through a landmark pivotal phase 3 clinical trial in adolescents with moderate to severe atopic dermatitis (AD), achieving unprecedented clinically meaningful improvements in signs and symptoms of the disease along with important quality of life benefits, Eric L. Simpson, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDEdge News

Indeed, dupilumab (Dupixent), a fully human monoclonal antibody that inhibits interleukins-4 and -13, demonstrated safety and efficacy in adolescent patients akin to that previously shown in adults with moderate to severe AD in phase 3 trials that earned the biologic U.S. and European regulatory approval in the adult population, noted Dr. Simpson, professor of dermatology at Oregon Health & Science University, Portland.

This positive phase 3 study represents a major development in pediatric dermatology because of the pressing unmet need for better treatments for teens with moderate to severe AD whose disease can’t be controlled with topical therapies. The adolescent years are, after all, a critical period in growth and development, and a debilitating, uncontrolled disease can reshape that experience in unwelcome ways.

“Atopic dermatitis profoundly affects quality of life in adolescents and their family: The itching affects mood and sleep, these patients commonly have anxiety and depression, and the chronic and relapsing nature of the disease adversely affects the family,” the dermatologist observed.

Currently, no systemic agent is approved for pediatric patients with AD because evidence demonstrating a favorable benefit-to-risk profile has been lacking. The dupilumab study was the first-ever phase 3 trial of a biologic in such a population.

The phase 3 adolescent trial was a 16-week, randomized, double-blind, multicenter, placebo-controlled study of 251 patients aged 12-17 years with moderate to severe AD, which could not be adequately controlled with topical therapies. Participants averaged 14 years of age, with a 12-year history of AD. “These patients had the disease basically their whole life,” Dr. Simpson noted.

They were more severely affected than participants in the adult clinical trials, with mean Eczema Area And Severity Index (EASI) scores in the mid-30s and an average 56% involved body surface area. The adolescent AD patients had a heavy burden of comorbid allergic type 2 immune comorbidity: Fully 92% of them had documented asthma, food allergy, allergic rhinitis, and/or some other form of allergic comorbidity. The majority of the teens were categorized as having severe AD, whereas most participants in the adult phase 3 trials of dupilumab had moderate disease. That distinction becomes relevant in comparing the trial results.

Participants were randomized to once-monthly subcutaneous injections of dupilumab at 300 mg, following a 600-mg loading dose, or to an injection of 200 mg or 300 mg every 2 weeks with an initial dose of 400 mg or 600 mg based upon a body weight cutoff of 60 kg, or to biweekly placebo injections.

The coprimary endpoints were the proportion of patients who achieved an EASI 75 response at week 16 and achievement of an Investigator’s Global Assessment (IGA) score of 0 or 1, meaning clear or almost clear, on a 5-point scale at week 16.

This trial introduced an important new design feature that physicians can expect to see more of in the future: regulatory agencies now want to see the effects of monotherapy in pivotal studies in AD. Previously, participants in AD studies of systemic agents could also utilize topical steroids as needed. No longer. In the adolescent dupilumab study, resort to rescue topical steroids led to exclusion from inclusion in the primary outcome results. Not surprisingly, this lack of access to rescue medication resulted in a 60% dropout rate by 16 weeks in placebo-treated controls, a 30% dropout rate in teens on dupilumab every 4 weeks, and a 20% dropout rate with biweekly dupilumab.

The EASI 75 rate at week 16 was 8.2% with placebo, 38.1% with monthly dupilumab, and 41.5% with biweekly dosing. The other coprimary endpoint – an IGA of 0 or 1 at 16 weeks – was achieved in 2.4% of controls, 17.9% with dupilumab at 300 mg every 4 weeks, and 41.5% with biweekly dosing.

Turning to secondary endpoints, Dr. Simpson reported that baseline peak pruritus Numeric Rating Scale scores dropped by 19% with placebo at 16 weeks, compared with reductions of 45.5% and 47.9% with monthly and biweekly dupilumab, respectively.

An EASI 50 response,while not as impressive as an EASI 75, is nonetheless considered clinically meaningful improvement. It was attained in 12.9% on placebo and 54.8% and 61% on monthly and biweekly dupilumab.

From a mean baseline score of 13.6 on the Children’s Dermatology Life Quality Index, scores improved over the course of 16 weeks by a mean of 5.1 points with placebo, 8.5 points with monthly dupilumab, and 8.8 points with biweekly biologic therapy. The same pattern was noted with regard to the Patient-Oriented Eczema Measure or POEM.

Adverse events mirrored those documented in the pivotal trials in adults: increased rates of mild to moderate conjunctivitis: 4.7% with placebo, 10.8% with monthly dupilumab, and 9.8% with biweekly dupilumab, along with single-digit rates of injection-site reactions. As in adult AD patients, however, these side effects were counterbalanced by significantly reduced rates of skin infections in the adolescent group: 20% during 16 weeks with placebo, and 13.3% and 11% with monthly and biweekly biologic therapy, respectively.

Study participants had a mean baseline score of 12.5 on the Hospital Anxiety and Depression Scale, which is categorized as clinically significant psychiatric disease. The impact of dupilumab therapy on those scores will be the topic of a future presentation, Dr. Simpson said.

Across the board, specific outcomes were consistently numerically better in patients who received dupilumab biweekly than monthly, albeit not statistically significantly so. Dr. Simpson thinks he knows why: Lab studies showed that the mean serum concentration of functional dupilumab in patients who got the biologic biweekly was nearly twice that for the group with monthly dosing.

At first glance, the IGA “clear” or “almost clear” response rates seen with dupilumab in the adolescent study appeared to be less robust than in the adult pivotal phase 3 trials, such as the SOLO 1 and SOLO 2 trials (N Engl J Med. 2016 Dec 15;375[24]:2335-48), also led by Dr. Simpson.

“I think that’s because of the greater severity of that baseline adolescent population,” he commented. “It made for a much lower placebo response rate. But when you correct for the placebo-subtracted difference, the rates are actually pretty similar, and a lot of the other endpoints are the same or even better than in SOLO.”

After his presentation, Dr. Simpson commented, “This is huge. This is the study we’ve been waiting for.”

Elsewhere at the EADV congress, Emma Guttman-Yassky, MD, PhD, deemed the pivotal phase 3 trial in adolescent AD patients one of the meeting’s highlights. And it’s a harbinger of more good things to come, because the investigational drug pipeline for AD is full of promising candidates addressing the disease from a variety of novel directions. The long therapeutic drought in AD appears to have finally ended, observed Dr. Guttman-Yassky, professor and vice-chair of the department of dermatology at Icahn School of Medicine at Mount Sinai, New York.

Bruce Jancin/MDedge News

That’s welcome news because AD is the most common inflammatory skin disease, both in adults, where the latest data puts the prevalence at 7%-10%, and in children, where the global rate is 15%-25%.

And while at the EADV congress only the 16-week data were reported in the new adolescent study, there is reason to be optimistic that the benefits will remain durable over time. Dr. Guttman-Yassky cited the published 52-week data from the large phase 3 CHRONOS trial in adults with moderate to severe AD. In that trial, in which patients could use concomitant topical steroids, the EASI 75 rates at week 16 were 69% in patients on dupilumab at 300 mg every 2 weeks, 64% with 300 mg weekly, and 23% with placebo. Reassuringly, at 52 weeks the EASI 75 response rates were essentially unchanged: 65%, 64%, and 22% (Lancet. 2017 Jun 10;389[10086]:2287-303).

“This is what we are seeking: not just treatment that is able to quickly modify disease, but we want the treatment to be sustained, and of course we want it to be safe for our patients because we know we cannot use cyclosporine for a long time,” Dr. Guttman-Yassky said.

Dr. Simpson reported serving as a consultant to and recipient of research grants from Sanofi and Regeneron, which sponsored the adolescent study, as well as more than a dozen other pharmaceutical companies. Dr. Guttman-Yassky reported serving as an advisor and consultant, and has received grants/research funding from Regeneron, and multiple other companies.

bjancin@mdedge.com

PARIS – Dupilumab scorched its way through a landmark pivotal phase 3 clinical trial in adolescents with moderate to severe atopic dermatitis (AD), achieving unprecedented clinically meaningful improvements in signs and symptoms of the disease along with important quality of life benefits, Eric L. Simpson, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDEdge News

Indeed, dupilumab (Dupixent), a fully human monoclonal antibody that inhibits interleukins-4 and -13, demonstrated safety and efficacy in adolescent patients akin to that previously shown in adults with moderate to severe AD in phase 3 trials that earned the biologic U.S. and European regulatory approval in the adult population, noted Dr. Simpson, professor of dermatology at Oregon Health & Science University, Portland.

This positive phase 3 study represents a major development in pediatric dermatology because of the pressing unmet need for better treatments for teens with moderate to severe AD whose disease can’t be controlled with topical therapies. The adolescent years are, after all, a critical period in growth and development, and a debilitating, uncontrolled disease can reshape that experience in unwelcome ways.

“Atopic dermatitis profoundly affects quality of life in adolescents and their family: The itching affects mood and sleep, these patients commonly have anxiety and depression, and the chronic and relapsing nature of the disease adversely affects the family,” the dermatologist observed.

Currently, no systemic agent is approved for pediatric patients with AD because evidence demonstrating a favorable benefit-to-risk profile has been lacking. The dupilumab study was the first-ever phase 3 trial of a biologic in such a population.

The phase 3 adolescent trial was a 16-week, randomized, double-blind, multicenter, placebo-controlled study of 251 patients aged 12-17 years with moderate to severe AD, which could not be adequately controlled with topical therapies. Participants averaged 14 years of age, with a 12-year history of AD. “These patients had the disease basically their whole life,” Dr. Simpson noted.

They were more severely affected than participants in the adult clinical trials, with mean Eczema Area And Severity Index (EASI) scores in the mid-30s and an average 56% involved body surface area. The adolescent AD patients had a heavy burden of comorbid allergic type 2 immune comorbidity: Fully 92% of them had documented asthma, food allergy, allergic rhinitis, and/or some other form of allergic comorbidity. The majority of the teens were categorized as having severe AD, whereas most participants in the adult phase 3 trials of dupilumab had moderate disease. That distinction becomes relevant in comparing the trial results.

Participants were randomized to once-monthly subcutaneous injections of dupilumab at 300 mg, following a 600-mg loading dose, or to an injection of 200 mg or 300 mg every 2 weeks with an initial dose of 400 mg or 600 mg based upon a body weight cutoff of 60 kg, or to biweekly placebo injections.

The coprimary endpoints were the proportion of patients who achieved an EASI 75 response at week 16 and achievement of an Investigator’s Global Assessment (IGA) score of 0 or 1, meaning clear or almost clear, on a 5-point scale at week 16.

This trial introduced an important new design feature that physicians can expect to see more of in the future: regulatory agencies now want to see the effects of monotherapy in pivotal studies in AD. Previously, participants in AD studies of systemic agents could also utilize topical steroids as needed. No longer. In the adolescent dupilumab study, resort to rescue topical steroids led to exclusion from inclusion in the primary outcome results. Not surprisingly, this lack of access to rescue medication resulted in a 60% dropout rate by 16 weeks in placebo-treated controls, a 30% dropout rate in teens on dupilumab every 4 weeks, and a 20% dropout rate with biweekly dupilumab.

The EASI 75 rate at week 16 was 8.2% with placebo, 38.1% with monthly dupilumab, and 41.5% with biweekly dosing. The other coprimary endpoint – an IGA of 0 or 1 at 16 weeks – was achieved in 2.4% of controls, 17.9% with dupilumab at 300 mg every 4 weeks, and 41.5% with biweekly dosing.

Turning to secondary endpoints, Dr. Simpson reported that baseline peak pruritus Numeric Rating Scale scores dropped by 19% with placebo at 16 weeks, compared with reductions of 45.5% and 47.9% with monthly and biweekly dupilumab, respectively.

An EASI 50 response,while not as impressive as an EASI 75, is nonetheless considered clinically meaningful improvement. It was attained in 12.9% on placebo and 54.8% and 61% on monthly and biweekly dupilumab.

From a mean baseline score of 13.6 on the Children’s Dermatology Life Quality Index, scores improved over the course of 16 weeks by a mean of 5.1 points with placebo, 8.5 points with monthly dupilumab, and 8.8 points with biweekly biologic therapy. The same pattern was noted with regard to the Patient-Oriented Eczema Measure or POEM.

Adverse events mirrored those documented in the pivotal trials in adults: increased rates of mild to moderate conjunctivitis: 4.7% with placebo, 10.8% with monthly dupilumab, and 9.8% with biweekly dupilumab, along with single-digit rates of injection-site reactions. As in adult AD patients, however, these side effects were counterbalanced by significantly reduced rates of skin infections in the adolescent group: 20% during 16 weeks with placebo, and 13.3% and 11% with monthly and biweekly biologic therapy, respectively.

Study participants had a mean baseline score of 12.5 on the Hospital Anxiety and Depression Scale, which is categorized as clinically significant psychiatric disease. The impact of dupilumab therapy on those scores will be the topic of a future presentation, Dr. Simpson said.

Across the board, specific outcomes were consistently numerically better in patients who received dupilumab biweekly than monthly, albeit not statistically significantly so. Dr. Simpson thinks he knows why: Lab studies showed that the mean serum concentration of functional dupilumab in patients who got the biologic biweekly was nearly twice that for the group with monthly dosing.

At first glance, the IGA “clear” or “almost clear” response rates seen with dupilumab in the adolescent study appeared to be less robust than in the adult pivotal phase 3 trials, such as the SOLO 1 and SOLO 2 trials (N Engl J Med. 2016 Dec 15;375[24]:2335-48), also led by Dr. Simpson.

“I think that’s because of the greater severity of that baseline adolescent population,” he commented. “It made for a much lower placebo response rate. But when you correct for the placebo-subtracted difference, the rates are actually pretty similar, and a lot of the other endpoints are the same or even better than in SOLO.”

After his presentation, Dr. Simpson commented, “This is huge. This is the study we’ve been waiting for.”

Elsewhere at the EADV congress, Emma Guttman-Yassky, MD, PhD, deemed the pivotal phase 3 trial in adolescent AD patients one of the meeting’s highlights. And it’s a harbinger of more good things to come, because the investigational drug pipeline for AD is full of promising candidates addressing the disease from a variety of novel directions. The long therapeutic drought in AD appears to have finally ended, observed Dr. Guttman-Yassky, professor and vice-chair of the department of dermatology at Icahn School of Medicine at Mount Sinai, New York.

Bruce Jancin/MDedge News

That’s welcome news because AD is the most common inflammatory skin disease, both in adults, where the latest data puts the prevalence at 7%-10%, and in children, where the global rate is 15%-25%.

And while at the EADV congress only the 16-week data were reported in the new adolescent study, there is reason to be optimistic that the benefits will remain durable over time. Dr. Guttman-Yassky cited the published 52-week data from the large phase 3 CHRONOS trial in adults with moderate to severe AD. In that trial, in which patients could use concomitant topical steroids, the EASI 75 rates at week 16 were 69% in patients on dupilumab at 300 mg every 2 weeks, 64% with 300 mg weekly, and 23% with placebo. Reassuringly, at 52 weeks the EASI 75 response rates were essentially unchanged: 65%, 64%, and 22% (Lancet. 2017 Jun 10;389[10086]:2287-303).

“This is what we are seeking: not just treatment that is able to quickly modify disease, but we want the treatment to be sustained, and of course we want it to be safe for our patients because we know we cannot use cyclosporine for a long time,” Dr. Guttman-Yassky said.

Dr. Simpson reported serving as a consultant to and recipient of research grants from Sanofi and Regeneron, which sponsored the adolescent study, as well as more than a dozen other pharmaceutical companies. Dr. Guttman-Yassky reported serving as an advisor and consultant, and has received grants/research funding from Regeneron, and multiple other companies.

bjancin@mdedge.com

PARIS – A first-of-its-kind cyclosporine topical spray sailed through an initial proof-of-concept study conducted in people aged 2-75 years with mild to moderate atopic dermatitis, Ana M. Giménez-Arnau, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

The 5% cyclosporine topical spray, known as Cyclatop, showed significantly better results across the board than its vehicle, even during the first week of treatment in the 4-week, multicenter, Spanish, double-blind, randomized trial, which included 44 patients with mild or moderate atopic dermatitis (AD), according to Dr. Giménez-Arnau, a dermatologist at Hospital del Mar and the Autonomous University of Barcelona.

“Besides the clinical efficacy, the study also demonstrated that, when cyclosporine was detectable in the blood, the highest blood level was at least 200-fold less than after systemic administration of cyclosporine at therapeutic doses,” she noted.

The motivation to develop a topical formulation of cyclosporine stemmed from the need to find substitutes for topical corticosteroids, especially in the pediatric population, where steroid phobia is rampant among parents. And while systemic cyclosporine is approved by European regulators for treatment of difficult cases of AD and is widely utilized off label for this purpose in the United States, the fact is that it is an immunosuppressant that paints with a broad brush and is best utilized for a matter of weeks as induction therapy.

But developing a topical formulation of cyclosporine suitable for long-term use posed many challenges. Lack of stability in cream and ointment formulations was a recurring issue. “Cyclosporine is a very big molecule, which is not easy to work with topically,” she explained. “The challenge was to find a stable formulation with good skin penetration, but without systemic absorption.”

Indeed, researchers at Barcelona-based Spherium Biomed evaluated more than 100 prototype compounds in animal models before settling on a proprietary oil emulsion formulation of 5% cyclosporine delivered via a spray without propellant gas.
 

Key study findings

The 44 study participants had a mean baseline of 8.3% body surface area involvement. As a condition of participation, they needed to have similar lesional areas bilaterally. They treated involved areas on one side of the body twice daily with Cyclatop, while they sprayed those on the opposite side with its vehicle.

From a mean baseline Eczema Area and Severity Index (EASI) score of 5.5, EASI scores improved by an average of 3.2 points after 28 days of cyclosporine spray, compared with 1.7 points with vehicle. Atopic Dermatitis Area and Severity Index (ADSI) scores improved from a mean baseline of 6.5 by 3.6 points with topical cyclosporine versus 2.4 points with vehicle.

At week 3, an EASI 75 response – that is, at least a 75% reduction from baseline EASI scores – was achieved at 44.4% of actively treated sites, compared with 25.9% of control sites. ADSI 75 rates at 3 weeks were 33.3% and 11.1%, respectively. An Investigator’s Global Assessment of clear or almost clear was reached at week 4 at 61.5% of active treatment sites, compared with 42.3% of vehicle-treated sites.

Itching responded dramatically to topical cyclosporine. From a mean baseline score of 3.3 on a standard 10-point pruritus visual analog scale, cyclosporine spray–treated areas showed a mean 1.2-point decrease at week 4, compared with a 0.4-point reduction at vehicle-treated areas. About 50% of the reduction in pruritus scores was achieved within the first week of active treatment. Moreover, among patients with moderate as opposed to mild itching scores at baseline, who had a mean pruritus score of 5.6, topical cyclosporine spray resulted in a mean 3.3-point reduction at week 4, Dr. Giménez-Arnau continued.

No safety signals emerged in this initial study. Side effects associated with the cyclosporine spray were the same as with its vehicle, and in exit interviews, more than 85% of patients indicated they were satisfied with the comfort and practicality of topical cyclosporine.

Session chair DeDee Murrell, MD, professor of dermatology at the University of New South Wales, Sydney, noted that the study was restricted to patients with less than 10% body surface area of involvement.

“Are you concerned that if you use this product over widespread areas, as is quite common in eczema, that you might get positive blood levels?” she asked.

“We don’t know. We should check that,” Dr. Giménez-Arnau replied. She added that more studies need to be done before cyclosporine spray is ready for the market. These studies will need to address the optimal dosing schedule and duration, the spectrum of disease severity where the topical spray works best, and other key issues.

Cyclatop is being developed by Spherium Biomed, which sponsored the study. Dr. Giménez-Arnau reported receiving research grants from and/or serving as a consultant to roughly half a dozen pharmaceutical companies.

bjancin@mdedge.com

PARIS – A first-of-its-kind cyclosporine topical spray sailed through an initial proof-of-concept study conducted in people aged 2-75 years with mild to moderate atopic dermatitis, Ana M. Giménez-Arnau, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

The 5% cyclosporine topical spray, known as Cyclatop, showed significantly better results across the board than its vehicle, even during the first week of treatment in the 4-week, multicenter, Spanish, double-blind, randomized trial, which included 44 patients with mild or moderate atopic dermatitis (AD), according to Dr. Giménez-Arnau, a dermatologist at Hospital del Mar and the Autonomous University of Barcelona.

“Besides the clinical efficacy, the study also demonstrated that, when cyclosporine was detectable in the blood, the highest blood level was at least 200-fold less than after systemic administration of cyclosporine at therapeutic doses,” she noted.

The motivation to develop a topical formulation of cyclosporine stemmed from the need to find substitutes for topical corticosteroids, especially in the pediatric population, where steroid phobia is rampant among parents. And while systemic cyclosporine is approved by European regulators for treatment of difficult cases of AD and is widely utilized off label for this purpose in the United States, the fact is that it is an immunosuppressant that paints with a broad brush and is best utilized for a matter of weeks as induction therapy.

But developing a topical formulation of cyclosporine suitable for long-term use posed many challenges. Lack of stability in cream and ointment formulations was a recurring issue. “Cyclosporine is a very big molecule, which is not easy to work with topically,” she explained. “The challenge was to find a stable formulation with good skin penetration, but without systemic absorption.”

Indeed, researchers at Barcelona-based Spherium Biomed evaluated more than 100 prototype compounds in animal models before settling on a proprietary oil emulsion formulation of 5% cyclosporine delivered via a spray without propellant gas.
 

Key study findings

The 44 study participants had a mean baseline of 8.3% body surface area involvement. As a condition of participation, they needed to have similar lesional areas bilaterally. They treated involved areas on one side of the body twice daily with Cyclatop, while they sprayed those on the opposite side with its vehicle.

From a mean baseline Eczema Area and Severity Index (EASI) score of 5.5, EASI scores improved by an average of 3.2 points after 28 days of cyclosporine spray, compared with 1.7 points with vehicle. Atopic Dermatitis Area and Severity Index (ADSI) scores improved from a mean baseline of 6.5 by 3.6 points with topical cyclosporine versus 2.4 points with vehicle.

At week 3, an EASI 75 response – that is, at least a 75% reduction from baseline EASI scores – was achieved at 44.4% of actively treated sites, compared with 25.9% of control sites. ADSI 75 rates at 3 weeks were 33.3% and 11.1%, respectively. An Investigator’s Global Assessment of clear or almost clear was reached at week 4 at 61.5% of active treatment sites, compared with 42.3% of vehicle-treated sites.

Itching responded dramatically to topical cyclosporine. From a mean baseline score of 3.3 on a standard 10-point pruritus visual analog scale, cyclosporine spray–treated areas showed a mean 1.2-point decrease at week 4, compared with a 0.4-point reduction at vehicle-treated areas. About 50% of the reduction in pruritus scores was achieved within the first week of active treatment. Moreover, among patients with moderate as opposed to mild itching scores at baseline, who had a mean pruritus score of 5.6, topical cyclosporine spray resulted in a mean 3.3-point reduction at week 4, Dr. Giménez-Arnau continued.

No safety signals emerged in this initial study. Side effects associated with the cyclosporine spray were the same as with its vehicle, and in exit interviews, more than 85% of patients indicated they were satisfied with the comfort and practicality of topical cyclosporine.

Session chair DeDee Murrell, MD, professor of dermatology at the University of New South Wales, Sydney, noted that the study was restricted to patients with less than 10% body surface area of involvement.

“Are you concerned that if you use this product over widespread areas, as is quite common in eczema, that you might get positive blood levels?” she asked.

“We don’t know. We should check that,” Dr. Giménez-Arnau replied. She added that more studies need to be done before cyclosporine spray is ready for the market. These studies will need to address the optimal dosing schedule and duration, the spectrum of disease severity where the topical spray works best, and other key issues.

Cyclatop is being developed by Spherium Biomed, which sponsored the study. Dr. Giménez-Arnau reported receiving research grants from and/or serving as a consultant to roughly half a dozen pharmaceutical companies.

bjancin@mdedge.com

PARIS – A first-of-its-kind cyclosporine topical spray sailed through an initial proof-of-concept study conducted in people aged 2-75 years with mild to moderate atopic dermatitis, Ana M. Giménez-Arnau, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

The 5% cyclosporine topical spray, known as Cyclatop, showed significantly better results across the board than its vehicle, even during the first week of treatment in the 4-week, multicenter, Spanish, double-blind, randomized trial, which included 44 patients with mild or moderate atopic dermatitis (AD), according to Dr. Giménez-Arnau, a dermatologist at Hospital del Mar and the Autonomous University of Barcelona.

“Besides the clinical efficacy, the study also demonstrated that, when cyclosporine was detectable in the blood, the highest blood level was at least 200-fold less than after systemic administration of cyclosporine at therapeutic doses,” she noted.

The motivation to develop a topical formulation of cyclosporine stemmed from the need to find substitutes for topical corticosteroids, especially in the pediatric population, where steroid phobia is rampant among parents. And while systemic cyclosporine is approved by European regulators for treatment of difficult cases of AD and is widely utilized off label for this purpose in the United States, the fact is that it is an immunosuppressant that paints with a broad brush and is best utilized for a matter of weeks as induction therapy.

But developing a topical formulation of cyclosporine suitable for long-term use posed many challenges. Lack of stability in cream and ointment formulations was a recurring issue. “Cyclosporine is a very big molecule, which is not easy to work with topically,” she explained. “The challenge was to find a stable formulation with good skin penetration, but without systemic absorption.”

Indeed, researchers at Barcelona-based Spherium Biomed evaluated more than 100 prototype compounds in animal models before settling on a proprietary oil emulsion formulation of 5% cyclosporine delivered via a spray without propellant gas.
 

Key study findings

The 44 study participants had a mean baseline of 8.3% body surface area involvement. As a condition of participation, they needed to have similar lesional areas bilaterally. They treated involved areas on one side of the body twice daily with Cyclatop, while they sprayed those on the opposite side with its vehicle.

From a mean baseline Eczema Area and Severity Index (EASI) score of 5.5, EASI scores improved by an average of 3.2 points after 28 days of cyclosporine spray, compared with 1.7 points with vehicle. Atopic Dermatitis Area and Severity Index (ADSI) scores improved from a mean baseline of 6.5 by 3.6 points with topical cyclosporine versus 2.4 points with vehicle.

At week 3, an EASI 75 response – that is, at least a 75% reduction from baseline EASI scores – was achieved at 44.4% of actively treated sites, compared with 25.9% of control sites. ADSI 75 rates at 3 weeks were 33.3% and 11.1%, respectively. An Investigator’s Global Assessment of clear or almost clear was reached at week 4 at 61.5% of active treatment sites, compared with 42.3% of vehicle-treated sites.

Itching responded dramatically to topical cyclosporine. From a mean baseline score of 3.3 on a standard 10-point pruritus visual analog scale, cyclosporine spray–treated areas showed a mean 1.2-point decrease at week 4, compared with a 0.4-point reduction at vehicle-treated areas. About 50% of the reduction in pruritus scores was achieved within the first week of active treatment. Moreover, among patients with moderate as opposed to mild itching scores at baseline, who had a mean pruritus score of 5.6, topical cyclosporine spray resulted in a mean 3.3-point reduction at week 4, Dr. Giménez-Arnau continued.

No safety signals emerged in this initial study. Side effects associated with the cyclosporine spray were the same as with its vehicle, and in exit interviews, more than 85% of patients indicated they were satisfied with the comfort and practicality of topical cyclosporine.

Session chair DeDee Murrell, MD, professor of dermatology at the University of New South Wales, Sydney, noted that the study was restricted to patients with less than 10% body surface area of involvement.

“Are you concerned that if you use this product over widespread areas, as is quite common in eczema, that you might get positive blood levels?” she asked.

“We don’t know. We should check that,” Dr. Giménez-Arnau replied. She added that more studies need to be done before cyclosporine spray is ready for the market. These studies will need to address the optimal dosing schedule and duration, the spectrum of disease severity where the topical spray works best, and other key issues.

Cyclatop is being developed by Spherium Biomed, which sponsored the study. Dr. Giménez-Arnau reported receiving research grants from and/or serving as a consultant to roughly half a dozen pharmaceutical companies.

bjancin@mdedge.com

LAKE TAHOE, CALIF. – Strong associations exist between intestinal dysbiosis and a wide variety of gut and systemic diseases, according to Mark A. Underwood, MD.

Doug Brunk/MDedge News

“Antibiotic exposure changes the composition of the intestinal microbiota,” he said at the annual meeting of the Society for Pediatric Dermatology. “That clearly causes both antibiotic-associated diarrhea and Clostridium difficile colitis. The bigger question is, is it possible that intestinal dysbiosis is related to a whole bunch of other systemic diseases? In other words, does an insult during a critical window of development cause changes in the intestinal microbiota that can lead to systemic diseases in the brain, the lung, the liver, or the immune system?”

According Dr. Underwood, a pediatrician who is chief of the division of neonatology at the University of California, Davis, the prevalence of dysbiosis is increasing worldwide, particularly in developed countries, where Bifidobacteria are decreasing and Enterobacteriaceae are increasing. “Those changes are associated with gut permeability and alterations in both local and systemic inflammation, and the risk for a number of diseases, including atopic dermatitis,” he said. Key reasons for the increasing prevalence of dysbiosis, he continued, include the use of antibiotics, cesarean section delivery, formula feeding, changes in hygiene that alter the intestinal biota, the high-fat, high-sugar Western diet, and a loss of vertical and horizontal transmission over generations.

In an effort to evaluate the association between early childhood antibiotic use with allergic diseases in later childhood, Japanese researchers followed 1,200 infants to the age of 5 years (Ann Allergy Asthma Immunol. 2017;119:54-8). They found that antibiotic exposure within the first 2 years of life was associated with an increased risk of asthma (adjusted odds ratio 1.72), allergic rhinitis (adjusted OR 1.65), and atopic dermatitis (adjusted OR 1.40). In a more recent, smaller prospective study, 436 Dutch infants were followed to 1 year of age (Pediatr Allergy Immunol. 2018;29[2]:151-8). The researchers found that antibiotic exposure within the first week of life was associated with allergic sensitization (adjusted OR 3.26), colic (adjusted OR 1.66), and wheezing (adjusted OR 1.56).

In a study of 44 term infants with a family history of allergy, changes in the fecal microbiota, especially colonization with Ruminococcus gnavus, preceded the onset of allergic symptoms (Gastroenterol. 2018;154[1]:154-67). The same researchers observed similar findings in an animal model.

One potential mechanism by which intestinal dysbiosis causes systemic disease is stimulation of toll-like receptor 4 (TLR4), “which is a receptor on a variety of mucosal cells that senses the presence of a microbial pathogen-associated patterns, particularly those of Gram-negative Enterobacteriaceae,” Dr. Underwood explained. Other potential mechanisms include increased intestinal permeability, an increase in the pH and decreases in short-chain fatty acids within the gut lumen, and a loss of intraluminal hypoxia. “Think of the colon as an anaerobic chamber,” he said. “The colon lumen should be very low in oxygen. It should be dominated by obligate anaerobes.”

Efforts to prevent or treat dysbiosis-related diseases include the use of probiotics and fecal transplantation. A recent Cochrane review of 8,672 patients found “moderate certainty evidence” that probiotics are effective for preventing C. difficile-associated diarrhea. The analysis included 31 randomized, controlled trials of adults who were treated either with a probiotic or with a placebo. When pooled, the risk ratio was 0.40, which represented a significant protection. In addition, a summary of 7 randomized controlled trials and 30 case series suggests that fecal microbial transplantation is superior to vancomycin for adults with recurrent C. difficile colitis (relative risk 0.23) (Aliment Pharmacol Ther. 2017;46[5]:470-93).

To date, the effect of giving probiotics to pregnant women who have a family history of allergy is less clear. One pooled analysis of such studies put the overall risk ratio at 0.74 (Mil Med. 2014;179[6]:580-92). “While I think the jury’s still out on how to best prevent atopic dermatitis in these families, it looks like there is some potential benefit in treating these moms during pregnancy with probiotics and treating the infant during the first few months of life,” Dr. Underwood said. The most effective were mixtures including one or more Lactobacillus species or L. rhamnosus, mixtures including one or more Bifidobacterium species, or B. lactis by itself. The use of probiotics also has been found to prevent necrotizing enterocolitis, sepsis, and death in premature infants (Semin Pediatr Surg. 2018;27[1]:39-46).

Dr. Underwood disclosed that he has received honoraria from Abbott and that he was a member of the scientific review board for Avexegen. He also chaired the data safety and monitoring board for Infant Bacterial Therapeutics and has received support from Evolve BioSystems to perform a clinical trial.

dbrunk@mdedge.com

LAKE TAHOE, CALIF. – Strong associations exist between intestinal dysbiosis and a wide variety of gut and systemic diseases, according to Mark A. Underwood, MD.

Doug Brunk/MDedge News

“Antibiotic exposure changes the composition of the intestinal microbiota,” he said at the annual meeting of the Society for Pediatric Dermatology. “That clearly causes both antibiotic-associated diarrhea and Clostridium difficile colitis. The bigger question is, is it possible that intestinal dysbiosis is related to a whole bunch of other systemic diseases? In other words, does an insult during a critical window of development cause changes in the intestinal microbiota that can lead to systemic diseases in the brain, the lung, the liver, or the immune system?”

According Dr. Underwood, a pediatrician who is chief of the division of neonatology at the University of California, Davis, the prevalence of dysbiosis is increasing worldwide, particularly in developed countries, where Bifidobacteria are decreasing and Enterobacteriaceae are increasing. “Those changes are associated with gut permeability and alterations in both local and systemic inflammation, and the risk for a number of diseases, including atopic dermatitis,” he said. Key reasons for the increasing prevalence of dysbiosis, he continued, include the use of antibiotics, cesarean section delivery, formula feeding, changes in hygiene that alter the intestinal biota, the high-fat, high-sugar Western diet, and a loss of vertical and horizontal transmission over generations.

In an effort to evaluate the association between early childhood antibiotic use with allergic diseases in later childhood, Japanese researchers followed 1,200 infants to the age of 5 years (Ann Allergy Asthma Immunol. 2017;119:54-8). They found that antibiotic exposure within the first 2 years of life was associated with an increased risk of asthma (adjusted odds ratio 1.72), allergic rhinitis (adjusted OR 1.65), and atopic dermatitis (adjusted OR 1.40). In a more recent, smaller prospective study, 436 Dutch infants were followed to 1 year of age (Pediatr Allergy Immunol. 2018;29[2]:151-8). The researchers found that antibiotic exposure within the first week of life was associated with allergic sensitization (adjusted OR 3.26), colic (adjusted OR 1.66), and wheezing (adjusted OR 1.56).

In a study of 44 term infants with a family history of allergy, changes in the fecal microbiota, especially colonization with Ruminococcus gnavus, preceded the onset of allergic symptoms (Gastroenterol. 2018;154[1]:154-67). The same researchers observed similar findings in an animal model.

One potential mechanism by which intestinal dysbiosis causes systemic disease is stimulation of toll-like receptor 4 (TLR4), “which is a receptor on a variety of mucosal cells that senses the presence of a microbial pathogen-associated patterns, particularly those of Gram-negative Enterobacteriaceae,” Dr. Underwood explained. Other potential mechanisms include increased intestinal permeability, an increase in the pH and decreases in short-chain fatty acids within the gut lumen, and a loss of intraluminal hypoxia. “Think of the colon as an anaerobic chamber,” he said. “The colon lumen should be very low in oxygen. It should be dominated by obligate anaerobes.”

Efforts to prevent or treat dysbiosis-related diseases include the use of probiotics and fecal transplantation. A recent Cochrane review of 8,672 patients found “moderate certainty evidence” that probiotics are effective for preventing C. difficile-associated diarrhea. The analysis included 31 randomized, controlled trials of adults who were treated either with a probiotic or with a placebo. When pooled, the risk ratio was 0.40, which represented a significant protection. In addition, a summary of 7 randomized controlled trials and 30 case series suggests that fecal microbial transplantation is superior to vancomycin for adults with recurrent C. difficile colitis (relative risk 0.23) (Aliment Pharmacol Ther. 2017;46[5]:470-93).

To date, the effect of giving probiotics to pregnant women who have a family history of allergy is less clear. One pooled analysis of such studies put the overall risk ratio at 0.74 (Mil Med. 2014;179[6]:580-92). “While I think the jury’s still out on how to best prevent atopic dermatitis in these families, it looks like there is some potential benefit in treating these moms during pregnancy with probiotics and treating the infant during the first few months of life,” Dr. Underwood said. The most effective were mixtures including one or more Lactobacillus species or L. rhamnosus, mixtures including one or more Bifidobacterium species, or B. lactis by itself. The use of probiotics also has been found to prevent necrotizing enterocolitis, sepsis, and death in premature infants (Semin Pediatr Surg. 2018;27[1]:39-46).

Dr. Underwood disclosed that he has received honoraria from Abbott and that he was a member of the scientific review board for Avexegen. He also chaired the data safety and monitoring board for Infant Bacterial Therapeutics and has received support from Evolve BioSystems to perform a clinical trial.

dbrunk@mdedge.com

LAKE TAHOE, CALIF. – Strong associations exist between intestinal dysbiosis and a wide variety of gut and systemic diseases, according to Mark A. Underwood, MD.

Doug Brunk/MDedge News

“Antibiotic exposure changes the composition of the intestinal microbiota,” he said at the annual meeting of the Society for Pediatric Dermatology. “That clearly causes both antibiotic-associated diarrhea and Clostridium difficile colitis. The bigger question is, is it possible that intestinal dysbiosis is related to a whole bunch of other systemic diseases? In other words, does an insult during a critical window of development cause changes in the intestinal microbiota that can lead to systemic diseases in the brain, the lung, the liver, or the immune system?”

According Dr. Underwood, a pediatrician who is chief of the division of neonatology at the University of California, Davis, the prevalence of dysbiosis is increasing worldwide, particularly in developed countries, where Bifidobacteria are decreasing and Enterobacteriaceae are increasing. “Those changes are associated with gut permeability and alterations in both local and systemic inflammation, and the risk for a number of diseases, including atopic dermatitis,” he said. Key reasons for the increasing prevalence of dysbiosis, he continued, include the use of antibiotics, cesarean section delivery, formula feeding, changes in hygiene that alter the intestinal biota, the high-fat, high-sugar Western diet, and a loss of vertical and horizontal transmission over generations.

In an effort to evaluate the association between early childhood antibiotic use with allergic diseases in later childhood, Japanese researchers followed 1,200 infants to the age of 5 years (Ann Allergy Asthma Immunol. 2017;119:54-8). They found that antibiotic exposure within the first 2 years of life was associated with an increased risk of asthma (adjusted odds ratio 1.72), allergic rhinitis (adjusted OR 1.65), and atopic dermatitis (adjusted OR 1.40). In a more recent, smaller prospective study, 436 Dutch infants were followed to 1 year of age (Pediatr Allergy Immunol. 2018;29[2]:151-8). The researchers found that antibiotic exposure within the first week of life was associated with allergic sensitization (adjusted OR 3.26), colic (adjusted OR 1.66), and wheezing (adjusted OR 1.56).

In a study of 44 term infants with a family history of allergy, changes in the fecal microbiota, especially colonization with Ruminococcus gnavus, preceded the onset of allergic symptoms (Gastroenterol. 2018;154[1]:154-67). The same researchers observed similar findings in an animal model.

One potential mechanism by which intestinal dysbiosis causes systemic disease is stimulation of toll-like receptor 4 (TLR4), “which is a receptor on a variety of mucosal cells that senses the presence of a microbial pathogen-associated patterns, particularly those of Gram-negative Enterobacteriaceae,” Dr. Underwood explained. Other potential mechanisms include increased intestinal permeability, an increase in the pH and decreases in short-chain fatty acids within the gut lumen, and a loss of intraluminal hypoxia. “Think of the colon as an anaerobic chamber,” he said. “The colon lumen should be very low in oxygen. It should be dominated by obligate anaerobes.”

Efforts to prevent or treat dysbiosis-related diseases include the use of probiotics and fecal transplantation. A recent Cochrane review of 8,672 patients found “moderate certainty evidence” that probiotics are effective for preventing C. difficile-associated diarrhea. The analysis included 31 randomized, controlled trials of adults who were treated either with a probiotic or with a placebo. When pooled, the risk ratio was 0.40, which represented a significant protection. In addition, a summary of 7 randomized controlled trials and 30 case series suggests that fecal microbial transplantation is superior to vancomycin for adults with recurrent C. difficile colitis (relative risk 0.23) (Aliment Pharmacol Ther. 2017;46[5]:470-93).

To date, the effect of giving probiotics to pregnant women who have a family history of allergy is less clear. One pooled analysis of such studies put the overall risk ratio at 0.74 (Mil Med. 2014;179[6]:580-92). “While I think the jury’s still out on how to best prevent atopic dermatitis in these families, it looks like there is some potential benefit in treating these moms during pregnancy with probiotics and treating the infant during the first few months of life,” Dr. Underwood said. The most effective were mixtures including one or more Lactobacillus species or L. rhamnosus, mixtures including one or more Bifidobacterium species, or B. lactis by itself. The use of probiotics also has been found to prevent necrotizing enterocolitis, sepsis, and death in premature infants (Semin Pediatr Surg. 2018;27[1]:39-46).

Dr. Underwood disclosed that he has received honoraria from Abbott and that he was a member of the scientific review board for Avexegen. He also chaired the data safety and monitoring board for Infant Bacterial Therapeutics and has received support from Evolve BioSystems to perform a clinical trial.

dbrunk@mdedge.com