Cutis

To the Editor:

A 65-year-old man with severe atherosclerotic disease developed multiple painful eschars on the lower abdomen, thighs, sacrum, and perineum. He initially presented with myocardial ischemia and claudication and underwent 3 cardiac catheterizations as well as stenting of the superficial femoral artery. Within 2 weeks, he developed exquisitely tender nodules on the lower abdomen, clinically presumed to be sites of enoxaparin injections. These lesions gradually expanded and ulcerated to involve the sacrum, buttock, perineum, and upper thighs (Figure 1). Two punch biopsies from ulcerated skin taken 10 days apart demonstrated necrosis of skin and subcutaneous fat without evidence of vasculitis, vasculopathy, emboli, or notable inflammation despite examination of multiple levels of all submitted tissue. A definitive cause for the ulcerations remained elusive with development of new lesions. A third incisional biopsy of a newly developed, nonulcerated, subcutaneous nodule performed 8 weeks after presentation revealed multiple cholesterol emboli (Figure 2). He was treated with warfarin and clopidogrel bisulfate as well as local wound care. The lesions slowly resolved over the next 4 to 6 months.

Cholesterol embolization syndrome occurs when disrupted atherosclerotic plaques embolize from large proximal arteries to more distal arterioles, resulting in ischemic damage to 1 or more organ systems.¹ It can occur spontaneously but often is a consequence of thrombolytic therapy, anticoagulation, and angioinvasive procedures.^2,3 Cutaneous manifestations include livedo reticularis, retiform purpura, nodules, and gangrene. Although livedo reticularis may extend from the legs to the trunk, gangrenous lesions predominantly involve the distal digits.

This case illustrates the challenge in diagnosis of cholesterol emboli, both clinically and histologically. Cutaneous lesions are morphologically variable and often occur with systemic manifestations, mimicking numerous conditions.¹ Lower extremity involvement is a well-known occurrence in cholesterol embolization (ie, blue toe syndrome); however, periumbilical and lumbosacral lesions have not been emphasized in the dermatologic or peripheral vascular literature. Our patient’s initial diagnosis was enoxaparin necrosis at abdominal injection sites; however, this unusual distribution of lesions was ultimately determined to be the consequence of cholesterol embolization from the inferior epigastric and superficial external pudendal arteries at the time of stenting of the superficial femoral artery. Proximal truncal involvement should be recognized as an atypical but important cutaneous manifestation to facilitate timely diagnosis and treatment.^4,5

Our patient’s course also highlights the potential need for multiple biopsies. Although the gold standard for diagnosis is histologic confirmation, a negative biopsy does not always exclude cholesterol emboli, and one should have a low threshold to perform additional biopsies in the appropriate clinical setting.

To the Editor:

A 65-year-old man with severe atherosclerotic disease developed multiple painful eschars on the lower abdomen, thighs, sacrum, and perineum. He initially presented with myocardial ischemia and claudication and underwent 3 cardiac catheterizations as well as stenting of the superficial femoral artery. Within 2 weeks, he developed exquisitely tender nodules on the lower abdomen, clinically presumed to be sites of enoxaparin injections. These lesions gradually expanded and ulcerated to involve the sacrum, buttock, perineum, and upper thighs (Figure 1). Two punch biopsies from ulcerated skin taken 10 days apart demonstrated necrosis of skin and subcutaneous fat without evidence of vasculitis, vasculopathy, emboli, or notable inflammation despite examination of multiple levels of all submitted tissue. A definitive cause for the ulcerations remained elusive with development of new lesions. A third incisional biopsy of a newly developed, nonulcerated, subcutaneous nodule performed 8 weeks after presentation revealed multiple cholesterol emboli (Figure 2). He was treated with warfarin and clopidogrel bisulfate as well as local wound care. The lesions slowly resolved over the next 4 to 6 months.

Cholesterol embolization syndrome occurs when disrupted atherosclerotic plaques embolize from large proximal arteries to more distal arterioles, resulting in ischemic damage to 1 or more organ systems.¹ It can occur spontaneously but often is a consequence of thrombolytic therapy, anticoagulation, and angioinvasive procedures.^2,3 Cutaneous manifestations include livedo reticularis, retiform purpura, nodules, and gangrene. Although livedo reticularis may extend from the legs to the trunk, gangrenous lesions predominantly involve the distal digits.

This case illustrates the challenge in diagnosis of cholesterol emboli, both clinically and histologically. Cutaneous lesions are morphologically variable and often occur with systemic manifestations, mimicking numerous conditions.¹ Lower extremity involvement is a well-known occurrence in cholesterol embolization (ie, blue toe syndrome); however, periumbilical and lumbosacral lesions have not been emphasized in the dermatologic or peripheral vascular literature. Our patient’s initial diagnosis was enoxaparin necrosis at abdominal injection sites; however, this unusual distribution of lesions was ultimately determined to be the consequence of cholesterol embolization from the inferior epigastric and superficial external pudendal arteries at the time of stenting of the superficial femoral artery. Proximal truncal involvement should be recognized as an atypical but important cutaneous manifestation to facilitate timely diagnosis and treatment.^4,5

Our patient’s course also highlights the potential need for multiple biopsies. Although the gold standard for diagnosis is histologic confirmation, a negative biopsy does not always exclude cholesterol emboli, and one should have a low threshold to perform additional biopsies in the appropriate clinical setting.

To the Editor:

A 65-year-old man with severe atherosclerotic disease developed multiple painful eschars on the lower abdomen, thighs, sacrum, and perineum. He initially presented with myocardial ischemia and claudication and underwent 3 cardiac catheterizations as well as stenting of the superficial femoral artery. Within 2 weeks, he developed exquisitely tender nodules on the lower abdomen, clinically presumed to be sites of enoxaparin injections. These lesions gradually expanded and ulcerated to involve the sacrum, buttock, perineum, and upper thighs (Figure 1). Two punch biopsies from ulcerated skin taken 10 days apart demonstrated necrosis of skin and subcutaneous fat without evidence of vasculitis, vasculopathy, emboli, or notable inflammation despite examination of multiple levels of all submitted tissue. A definitive cause for the ulcerations remained elusive with development of new lesions. A third incisional biopsy of a newly developed, nonulcerated, subcutaneous nodule performed 8 weeks after presentation revealed multiple cholesterol emboli (Figure 2). He was treated with warfarin and clopidogrel bisulfate as well as local wound care. The lesions slowly resolved over the next 4 to 6 months.

Cholesterol embolization syndrome occurs when disrupted atherosclerotic plaques embolize from large proximal arteries to more distal arterioles, resulting in ischemic damage to 1 or more organ systems.¹ It can occur spontaneously but often is a consequence of thrombolytic therapy, anticoagulation, and angioinvasive procedures.^2,3 Cutaneous manifestations include livedo reticularis, retiform purpura, nodules, and gangrene. Although livedo reticularis may extend from the legs to the trunk, gangrenous lesions predominantly involve the distal digits.

This case illustrates the challenge in diagnosis of cholesterol emboli, both clinically and histologically. Cutaneous lesions are morphologically variable and often occur with systemic manifestations, mimicking numerous conditions.¹ Lower extremity involvement is a well-known occurrence in cholesterol embolization (ie, blue toe syndrome); however, periumbilical and lumbosacral lesions have not been emphasized in the dermatologic or peripheral vascular literature. Our patient’s initial diagnosis was enoxaparin necrosis at abdominal injection sites; however, this unusual distribution of lesions was ultimately determined to be the consequence of cholesterol embolization from the inferior epigastric and superficial external pudendal arteries at the time of stenting of the superficial femoral artery. Proximal truncal involvement should be recognized as an atypical but important cutaneous manifestation to facilitate timely diagnosis and treatment.^4,5

Our patient’s course also highlights the potential need for multiple biopsies. Although the gold standard for diagnosis is histologic confirmation, a negative biopsy does not always exclude cholesterol emboli, and one should have a low threshold to perform additional biopsies in the appropriate clinical setting.

To the Editor:

Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by the development of painful abscesses, fistulous tracts, and scars. It most commonly affects the apocrine gland–bearing areas of the body such as the axillary, inguinal, and anogenital regions. With a prevalence of approximately 1%, HS can lead to notable morbidity.¹ The pathogenesis is thought to be due to occlusion of terminal hair follicles that subsequently stimulates release of proinflammatory cytokines from nearby keratinocytes. The mechanism of initial occlusion is not well understood but may be due to friction or trauma. An inflammatory mechanism of disease also has been hypothesized; however, the exact cytokine profile is not known. Treatment of HS consists of several different modalities, including oral retinoids, antibiotics, antiandrogenic therapy, and surgery.^1,2 Adalimumab is a well-known biologic that has been approved by the US Food and Drug Administration for the treatment of HS.

Adalimumab is a human monoclonal antibody against tumor necrosis factor (TNF) α and is thought to improve HS by several mechanisms. Inhibition of TNF-α and other proinflammatory cytokines found in inflammatory lesions and apocrine glands directly decreases the severity of lesion size and the frequency of recurrence.³ Adalimumab also is thought to downregulate expression of keratin 6 and prevent the hyperkeratinization seen in HS.⁴ Additionally, TNF-α inhibition decreases production of IL-1, which has been shown to cause hypercornification of follicles and perpetuate HS pathogenesis.⁵

Adalimumab is considered a safe medication with a low toxicity profile and rarely is associated with serious adverse effects. The most common adverse effects are injection-site reaction, headache, and rash. However, as with any immunosuppressant, there is an elevated incidence of opportunistic infections. Anti-TNF medications have been associated with an increased incidence of viral, bacterial, and fungal infections. We present a patient who developed Candida esophagitis 6 weeks after starting treatment with adalimumab for the treatment of HS. This case highlights the development of esophageal candidiasis as a notable adverse event.

A 41-year-old woman with a history of endometriosis, adenomyosis, polycystic ovary syndrome, interstitial cystitis, asthma, fibromyalgia, depression, and Hashimoto thyroiditis presented to our dermatology clinic with active draining lesions and sinus tracts in the perivaginal area that were consistent with HS, which initially was treated with doxycycline 100 mg twice daily. She experienced minimal improvement of the HS lesions at 2-month follow-up.

Due to disease severity, adalimumab was started. The patient received a loading dose of 4 injections totaling 160 mg and 80 mg on day 15, followed by a maintenance dose of 40 mg/0.4 mL weekly. The patient reported substantial improvement of pain, and complete resolution of active lesions was noted on physical examination after 4 weeks of treatment with adalimumab.

Six weeks after adalimumab was started, the patient developed severe dysphagia. She was evaluated by a gastroenterologist and underwent endoscopy (Figure), which led to a diagnosis of esophageal candidiasis. Adalimumab was discontinued immediately thereafter. The patient started treatment with nystatin oral rinse 4 times daily and oral fluconazole 200 mg daily. The candidiasis resolved within 2 weeks; however, she experienced recurrence of HS with draining lesions in the perivaginal area approximately 8 weeks after discontinuation of adalimumab. The patient requested to restart adalimumab treatment despite the recent history of esophagitis. Adalimumab 40 mg/0.4 mL weekly was restarted along with oral fluconazole 200 mg twice weekly and nystatin oral rinse 4 times daily. This regimen resulted in complete resolution of HS symptoms within 6 weeks with no recurrence of esophageal candidiasis during 6 months of follow-up.

Patients receiving adalimumab for dermatologic or other conditions should be closely monitored for opportunistic infections. Although immunomodulatory medications offer promising therapeutic benefits in patients with HS, larger studies regarding treatment with anti-TNF agents in HS are warranted to prevent complications from treatment and promote long-term efficacy and safety.

To the Editor:

Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by the development of painful abscesses, fistulous tracts, and scars. It most commonly affects the apocrine gland–bearing areas of the body such as the axillary, inguinal, and anogenital regions. With a prevalence of approximately 1%, HS can lead to notable morbidity.¹ The pathogenesis is thought to be due to occlusion of terminal hair follicles that subsequently stimulates release of proinflammatory cytokines from nearby keratinocytes. The mechanism of initial occlusion is not well understood but may be due to friction or trauma. An inflammatory mechanism of disease also has been hypothesized; however, the exact cytokine profile is not known. Treatment of HS consists of several different modalities, including oral retinoids, antibiotics, antiandrogenic therapy, and surgery.^1,2 Adalimumab is a well-known biologic that has been approved by the US Food and Drug Administration for the treatment of HS.

Adalimumab is a human monoclonal antibody against tumor necrosis factor (TNF) α and is thought to improve HS by several mechanisms. Inhibition of TNF-α and other proinflammatory cytokines found in inflammatory lesions and apocrine glands directly decreases the severity of lesion size and the frequency of recurrence.³ Adalimumab also is thought to downregulate expression of keratin 6 and prevent the hyperkeratinization seen in HS.⁴ Additionally, TNF-α inhibition decreases production of IL-1, which has been shown to cause hypercornification of follicles and perpetuate HS pathogenesis.⁵

Adalimumab is considered a safe medication with a low toxicity profile and rarely is associated with serious adverse effects. The most common adverse effects are injection-site reaction, headache, and rash. However, as with any immunosuppressant, there is an elevated incidence of opportunistic infections. Anti-TNF medications have been associated with an increased incidence of viral, bacterial, and fungal infections. We present a patient who developed Candida esophagitis 6 weeks after starting treatment with adalimumab for the treatment of HS. This case highlights the development of esophageal candidiasis as a notable adverse event.

A 41-year-old woman with a history of endometriosis, adenomyosis, polycystic ovary syndrome, interstitial cystitis, asthma, fibromyalgia, depression, and Hashimoto thyroiditis presented to our dermatology clinic with active draining lesions and sinus tracts in the perivaginal area that were consistent with HS, which initially was treated with doxycycline 100 mg twice daily. She experienced minimal improvement of the HS lesions at 2-month follow-up.

Due to disease severity, adalimumab was started. The patient received a loading dose of 4 injections totaling 160 mg and 80 mg on day 15, followed by a maintenance dose of 40 mg/0.4 mL weekly. The patient reported substantial improvement of pain, and complete resolution of active lesions was noted on physical examination after 4 weeks of treatment with adalimumab.

Six weeks after adalimumab was started, the patient developed severe dysphagia. She was evaluated by a gastroenterologist and underwent endoscopy (Figure), which led to a diagnosis of esophageal candidiasis. Adalimumab was discontinued immediately thereafter. The patient started treatment with nystatin oral rinse 4 times daily and oral fluconazole 200 mg daily. The candidiasis resolved within 2 weeks; however, she experienced recurrence of HS with draining lesions in the perivaginal area approximately 8 weeks after discontinuation of adalimumab. The patient requested to restart adalimumab treatment despite the recent history of esophagitis. Adalimumab 40 mg/0.4 mL weekly was restarted along with oral fluconazole 200 mg twice weekly and nystatin oral rinse 4 times daily. This regimen resulted in complete resolution of HS symptoms within 6 weeks with no recurrence of esophageal candidiasis during 6 months of follow-up.

Patients receiving adalimumab for dermatologic or other conditions should be closely monitored for opportunistic infections. Although immunomodulatory medications offer promising therapeutic benefits in patients with HS, larger studies regarding treatment with anti-TNF agents in HS are warranted to prevent complications from treatment and promote long-term efficacy and safety.

To the Editor:

Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by the development of painful abscesses, fistulous tracts, and scars. It most commonly affects the apocrine gland–bearing areas of the body such as the axillary, inguinal, and anogenital regions. With a prevalence of approximately 1%, HS can lead to notable morbidity.¹ The pathogenesis is thought to be due to occlusion of terminal hair follicles that subsequently stimulates release of proinflammatory cytokines from nearby keratinocytes. The mechanism of initial occlusion is not well understood but may be due to friction or trauma. An inflammatory mechanism of disease also has been hypothesized; however, the exact cytokine profile is not known. Treatment of HS consists of several different modalities, including oral retinoids, antibiotics, antiandrogenic therapy, and surgery.^1,2 Adalimumab is a well-known biologic that has been approved by the US Food and Drug Administration for the treatment of HS.

Adalimumab is a human monoclonal antibody against tumor necrosis factor (TNF) α and is thought to improve HS by several mechanisms. Inhibition of TNF-α and other proinflammatory cytokines found in inflammatory lesions and apocrine glands directly decreases the severity of lesion size and the frequency of recurrence.³ Adalimumab also is thought to downregulate expression of keratin 6 and prevent the hyperkeratinization seen in HS.⁴ Additionally, TNF-α inhibition decreases production of IL-1, which has been shown to cause hypercornification of follicles and perpetuate HS pathogenesis.⁵

Adalimumab is considered a safe medication with a low toxicity profile and rarely is associated with serious adverse effects. The most common adverse effects are injection-site reaction, headache, and rash. However, as with any immunosuppressant, there is an elevated incidence of opportunistic infections. Anti-TNF medications have been associated with an increased incidence of viral, bacterial, and fungal infections. We present a patient who developed Candida esophagitis 6 weeks after starting treatment with adalimumab for the treatment of HS. This case highlights the development of esophageal candidiasis as a notable adverse event.

A 41-year-old woman with a history of endometriosis, adenomyosis, polycystic ovary syndrome, interstitial cystitis, asthma, fibromyalgia, depression, and Hashimoto thyroiditis presented to our dermatology clinic with active draining lesions and sinus tracts in the perivaginal area that were consistent with HS, which initially was treated with doxycycline 100 mg twice daily. She experienced minimal improvement of the HS lesions at 2-month follow-up.

Due to disease severity, adalimumab was started. The patient received a loading dose of 4 injections totaling 160 mg and 80 mg on day 15, followed by a maintenance dose of 40 mg/0.4 mL weekly. The patient reported substantial improvement of pain, and complete resolution of active lesions was noted on physical examination after 4 weeks of treatment with adalimumab.

Six weeks after adalimumab was started, the patient developed severe dysphagia. She was evaluated by a gastroenterologist and underwent endoscopy (Figure), which led to a diagnosis of esophageal candidiasis. Adalimumab was discontinued immediately thereafter. The patient started treatment with nystatin oral rinse 4 times daily and oral fluconazole 200 mg daily. The candidiasis resolved within 2 weeks; however, she experienced recurrence of HS with draining lesions in the perivaginal area approximately 8 weeks after discontinuation of adalimumab. The patient requested to restart adalimumab treatment despite the recent history of esophagitis. Adalimumab 40 mg/0.4 mL weekly was restarted along with oral fluconazole 200 mg twice weekly and nystatin oral rinse 4 times daily. This regimen resulted in complete resolution of HS symptoms within 6 weeks with no recurrence of esophageal candidiasis during 6 months of follow-up.

Patients receiving adalimumab for dermatologic or other conditions should be closely monitored for opportunistic infections. Although immunomodulatory medications offer promising therapeutic benefits in patients with HS, larger studies regarding treatment with anti-TNF agents in HS are warranted to prevent complications from treatment and promote long-term efficacy and safety.

Generalized pustular psoriasis of pregnancy (GPPP), formerly known as impetigo herpetiformis, is a rare dermatosis that causes maternal and fetal morbidity and mortality. It is characterized by widespread, circular, erythematous plaques with pustules at the periphery.¹ Conventional first-line treatment includes systemic corticosteroids and cyclosporine. The National Psoriasis Foundation Medical Board also has included infliximab among the first-line treatment options for GPPP.² Herein, we report a case of GPPP treated with infliximab at 30 weeks’ gestation and during the postpartum period.

Case Report

A 22-year-old woman was admitted to our inpatient clinic at 20 weeks’ gestation in her second pregnancy for evaluation of cutaneous eruptions covering the entire body. The lesions first appeared 3 to 4 days prior to her admission and dramatically progressed. She had a history of psoriasis vulgaris diagnosed during her first pregnancy 2 years prior that was treated with topical steroids throughout the pregnancy and methotrexate during lactation for a total of 11 months. She then was started on cyclosporine, which she used for 6 months due to ineffectiveness of the methotrexate, but she stopped treatment 4 months before the second pregnancy.

At the current presentation, physical examination revealed erythroderma and widespread pustules on the chest, abdomen, arms, and legs, including the intertriginous regions, that tended to coalesce and form lakes of pus over an erythematous base (Figure 1). The mucosae were normal. She exhibited a low blood pressure (85/50 mmHg) and high body temperature (102 °F [38.9 °C]). Routine laboratory examination revealed anemia and a normal leukocyte count. Her erythrocyte sedimentation rate (57 mm/h [reference range, <20 mm/h]) and C-reactive protein level (102 mg/L [reference range, <6 mg/L]) were elevated, whereas total calcium (8.11 mg/dL [reference range, 8.2–10.6 mg/dL]) and albumin (3.15 g/dL [reference range, >4.0 g/dL]) levels were low.

The patient returned to the clinic 3 weeks postpartum with a few pustules on erythematous plaques on the chest, abdomen, and back. At this time, she received a third infusion of infliximab 8 weeks after the second dose. For the past 5 years, the patient has been undergoing infliximab maintenance treatment, which she receives at the hospital every 8 weeks with excellent response. She has had no further pregnancies to date.

Comment

Generalized pustular psoriasis of pregnancy is a rare condition that typically occurs in the third trimester but also can start in the first and second trimesters. It may result in maternal and fetal morbidity by causing fluid and electrolyte imbalance and/or placental insufficiency, resulting in an increased risk for fetal abnormalities, stillbirth, and neonatal death.³ In subsequent pregnancies, GPPP has been observed to recur at an earlier gestational age with a more severe presentation.^1,3

Generalized pustular psoriasis of pregnancy usually involves an eruption that begins symmetrically in the intertriginous areas and spreads to the rest of the body. The lesions present as erythematous annular plaques with pustules on the periphery and desquamation in the center due to older pustules.^1,3 The mucous membranes also may be involved with erosive and exfoliative plaques, and there may be nail involvement. Patients often present with systemic symptoms such as fever, malaise, diarrhea, and vomiting.¹ Laboratory investigations may reveal neutrophilic leukocytosis, high erythrocyte sedimentation rate, hypocalcemia, and hypoalbuminemia.⁴ Cultures from blood and pustules show no bacterial growth. A skin biopsy is helpful in diagnosis, with features similar to generalized pustular psoriasis, demonstrating spongiform pustules containing neutrophils, lymphocytic and neutrophilic infiltrates in the papillary dermis, and negative direct immunofluorescence.³

The differential diagnosis of GPPP includes subcorneal pustular dermatosis, dermatitis herpetiformis, herpes gestationis, impetigo, and acute generalized exanthematous pustulosis.^1,3 Due to concerns of fetal implications, treatment options in GPPP are somewhat limited; however, the condition requires treatment because it may result in unfavorable pregnancy outcomes. Topical corticosteroids may be an option for limited disease.^5,6 Systemic corticosteroids (eg, prednisone 60–80 mg/d) were previously considered as first-line agents, although they have shown limited efficacy in our case as well as in other case reports.⁷ Their ineffectiveness and risk for flare-up after dose tapering should be kept in mind when starting GPPP patients on systemic corticosteroids. Systemic cyclosporine (2–3 mg/kg/d) may be added to increase the efficacy of systemic steroids, which was done in several cases in literature.^1,6,8 Although cyclosporine has been classified as a pregnancy category C drug, an analysis of pregnancy outcomes of 629 renal transplant patients revealed no association with adverse pregnancy outcomes compared to the general population and no increase in fetal malformations.⁹ Therefore, cyclosporine is a safe treatment option and was classified as a first-line drug for GPPP in a 2012 review by the National Psoriasis Foundation Medical Board.² Narrowband UVB also has been reported to be used for the treatment of GPPP.¹⁰ Methotrexate and retinoids have been used in cases with lesions that persisted postpartum.¹

Anti–tumor necrosis factor (TNF) α agents are another effective option for treatment of GPPP. Anti-TNF agents are classified as pregnancy category B due to results showing that anti-mouse TNF-α monoclonal antibodies did not cause embryotoxicity or teratogenicity in pregnant mice.¹¹ Although Carter et al¹² published a review of US Food and Drug Administration data on pregnant women receiving anti-TNF treatment and concluded that these agents were associated with the VACTERL group of malformations (vertebral defects, anal atresia, cardiac defect, tracheoesophageal fistula with esophageal atresia, cardiac defects, renal and limb anomalies), no such association was found in further studies. A 2014 study showed no difference in the rate of major malformations in infants born to women who were treated with anti-TNF drugs compared to the disease-matched group not treated with these agents and pregnant women counselled for nonteratogenic exposure.¹³ The same study detected an increase in preterm and low-birth-weight deliveries and suggested this might be caused by the increased severity of disease in patients requiring anti-TNF medication. The British Society of Rheumatology Biologics Register published data on pregnancy outcomes in 130 rheumatoid arthritis patients who had been exposed to anti-TNF agents.¹⁴ The results suggested an increased rate of spontaneous abortions in women exposed to anti-TNF treatment around the time of conception, especially in those taking these medications together with methotrexate or leflunomide; however, results also indicated that disease activity may have had an impact on the rate of spontaneous abortions in these patients. In a 2013 review of 462 women with inflammatory bowel disease who had been exposed to anti-TNF agents during pregnancy, the investigators concluded that pregnancy outcomes and the rate of congenital anomalies did not significantly differ from other inflammatory bowel disease patients not receiving anti-TNF drugs or the general population.¹⁵

In 2012, the National Board of the National Psoriasis Foundation put infliximab amongst the first-line treatment modalities for GPPP.² In one case of GPPP in which the eruption persisted after delivery, the patient was treated with infliximab 7 weeks postpartum due to failure to control the disease with prednisolone 60 mg daily and cyclosporine 7.5 mg/kg daily. Unlike our patient, this patient was only started on an infliximab regimen after delivery.¹⁶ In another case reported in 2010, the patient was started on infliximab during the postpartum period of her first pregnancy following a pustular flare of previously diagnosed plaque psoriasis (not a generalized pustular psoriasis, as in our case).¹⁷ As a good response was obtained, infliximab treatment was continued in the patient throughout her second pregnancy.

Our case is unique in that infliximab was started during pregnancy because of intractable disease leading to systemic symptoms. Our patient showed an excellent response to infliximab after a 10-week disease course with repeated flare-ups and impairment to her overall condition. Delivery occurred at 36 weeks’ gestation due to suspected intrauterine growth retardation; however, the neonate was born with a 5-minute APGAR score of 10 and required no special medical care, which suggests that the low birth weight was constitutional due to the patient’s small frame (her height was 4 ft 11 in). The breast milk of patients with inflammatory bowel disease has been detected to contain very small amounts of infliximab (101 ng/mL, about 1/200 of the therapeutic blood level).¹⁸ Considering the large molecular weight of this agent and possible proteolysis in the stomach and intestines, infliximab is unlikely to affect the neonate.¹⁵ Thus, we encouraged our patient to breastfeed her baby. A case of fatal disseminated Bacille-Calmette-Guérin infection in an infant whose mother received infliximab treatment during pregnancy has been reported.¹⁹ It has been suggested that live vaccines should be avoided in neonates exposed to anti-TNF agents at least for the first 6 months of life or until the agent is no longer detectable in their blood.¹⁵ We therefore informed our patient’s family practitioner about this data.

Conclusion

We report a case of infliximab treatment for GPPP that was continued during the postpartum period. Infliximab was an effective treatment option in our patient with no detected serious adverse events and may be considered in other cases of GPPP that are not responsive to systemic steroids. However, further studies are warranted to evaluate the safety and efficacy of infliximab treatment for GPPP and psoriasis in pregnancy.

Generalized pustular psoriasis of pregnancy (GPPP), formerly known as impetigo herpetiformis, is a rare dermatosis that causes maternal and fetal morbidity and mortality. It is characterized by widespread, circular, erythematous plaques with pustules at the periphery.¹ Conventional first-line treatment includes systemic corticosteroids and cyclosporine. The National Psoriasis Foundation Medical Board also has included infliximab among the first-line treatment options for GPPP.² Herein, we report a case of GPPP treated with infliximab at 30 weeks’ gestation and during the postpartum period.

Case Report

A 22-year-old woman was admitted to our inpatient clinic at 20 weeks’ gestation in her second pregnancy for evaluation of cutaneous eruptions covering the entire body. The lesions first appeared 3 to 4 days prior to her admission and dramatically progressed. She had a history of psoriasis vulgaris diagnosed during her first pregnancy 2 years prior that was treated with topical steroids throughout the pregnancy and methotrexate during lactation for a total of 11 months. She then was started on cyclosporine, which she used for 6 months due to ineffectiveness of the methotrexate, but she stopped treatment 4 months before the second pregnancy.

At the current presentation, physical examination revealed erythroderma and widespread pustules on the chest, abdomen, arms, and legs, including the intertriginous regions, that tended to coalesce and form lakes of pus over an erythematous base (Figure 1). The mucosae were normal. She exhibited a low blood pressure (85/50 mmHg) and high body temperature (102 °F [38.9 °C]). Routine laboratory examination revealed anemia and a normal leukocyte count. Her erythrocyte sedimentation rate (57 mm/h [reference range, <20 mm/h]) and C-reactive protein level (102 mg/L [reference range, <6 mg/L]) were elevated, whereas total calcium (8.11 mg/dL [reference range, 8.2–10.6 mg/dL]) and albumin (3.15 g/dL [reference range, >4.0 g/dL]) levels were low.

The patient returned to the clinic 3 weeks postpartum with a few pustules on erythematous plaques on the chest, abdomen, and back. At this time, she received a third infusion of infliximab 8 weeks after the second dose. For the past 5 years, the patient has been undergoing infliximab maintenance treatment, which she receives at the hospital every 8 weeks with excellent response. She has had no further pregnancies to date.

Comment

Generalized pustular psoriasis of pregnancy is a rare condition that typically occurs in the third trimester but also can start in the first and second trimesters. It may result in maternal and fetal morbidity by causing fluid and electrolyte imbalance and/or placental insufficiency, resulting in an increased risk for fetal abnormalities, stillbirth, and neonatal death.³ In subsequent pregnancies, GPPP has been observed to recur at an earlier gestational age with a more severe presentation.^1,3

Generalized pustular psoriasis of pregnancy usually involves an eruption that begins symmetrically in the intertriginous areas and spreads to the rest of the body. The lesions present as erythematous annular plaques with pustules on the periphery and desquamation in the center due to older pustules.^1,3 The mucous membranes also may be involved with erosive and exfoliative plaques, and there may be nail involvement. Patients often present with systemic symptoms such as fever, malaise, diarrhea, and vomiting.¹ Laboratory investigations may reveal neutrophilic leukocytosis, high erythrocyte sedimentation rate, hypocalcemia, and hypoalbuminemia.⁴ Cultures from blood and pustules show no bacterial growth. A skin biopsy is helpful in diagnosis, with features similar to generalized pustular psoriasis, demonstrating spongiform pustules containing neutrophils, lymphocytic and neutrophilic infiltrates in the papillary dermis, and negative direct immunofluorescence.³

The differential diagnosis of GPPP includes subcorneal pustular dermatosis, dermatitis herpetiformis, herpes gestationis, impetigo, and acute generalized exanthematous pustulosis.^1,3 Due to concerns of fetal implications, treatment options in GPPP are somewhat limited; however, the condition requires treatment because it may result in unfavorable pregnancy outcomes. Topical corticosteroids may be an option for limited disease.^5,6 Systemic corticosteroids (eg, prednisone 60–80 mg/d) were previously considered as first-line agents, although they have shown limited efficacy in our case as well as in other case reports.⁷ Their ineffectiveness and risk for flare-up after dose tapering should be kept in mind when starting GPPP patients on systemic corticosteroids. Systemic cyclosporine (2–3 mg/kg/d) may be added to increase the efficacy of systemic steroids, which was done in several cases in literature.^1,6,8 Although cyclosporine has been classified as a pregnancy category C drug, an analysis of pregnancy outcomes of 629 renal transplant patients revealed no association with adverse pregnancy outcomes compared to the general population and no increase in fetal malformations.⁹ Therefore, cyclosporine is a safe treatment option and was classified as a first-line drug for GPPP in a 2012 review by the National Psoriasis Foundation Medical Board.² Narrowband UVB also has been reported to be used for the treatment of GPPP.¹⁰ Methotrexate and retinoids have been used in cases with lesions that persisted postpartum.¹

Anti–tumor necrosis factor (TNF) α agents are another effective option for treatment of GPPP. Anti-TNF agents are classified as pregnancy category B due to results showing that anti-mouse TNF-α monoclonal antibodies did not cause embryotoxicity or teratogenicity in pregnant mice.¹¹ Although Carter et al¹² published a review of US Food and Drug Administration data on pregnant women receiving anti-TNF treatment and concluded that these agents were associated with the VACTERL group of malformations (vertebral defects, anal atresia, cardiac defect, tracheoesophageal fistula with esophageal atresia, cardiac defects, renal and limb anomalies), no such association was found in further studies. A 2014 study showed no difference in the rate of major malformations in infants born to women who were treated with anti-TNF drugs compared to the disease-matched group not treated with these agents and pregnant women counselled for nonteratogenic exposure.¹³ The same study detected an increase in preterm and low-birth-weight deliveries and suggested this might be caused by the increased severity of disease in patients requiring anti-TNF medication. The British Society of Rheumatology Biologics Register published data on pregnancy outcomes in 130 rheumatoid arthritis patients who had been exposed to anti-TNF agents.¹⁴ The results suggested an increased rate of spontaneous abortions in women exposed to anti-TNF treatment around the time of conception, especially in those taking these medications together with methotrexate or leflunomide; however, results also indicated that disease activity may have had an impact on the rate of spontaneous abortions in these patients. In a 2013 review of 462 women with inflammatory bowel disease who had been exposed to anti-TNF agents during pregnancy, the investigators concluded that pregnancy outcomes and the rate of congenital anomalies did not significantly differ from other inflammatory bowel disease patients not receiving anti-TNF drugs or the general population.¹⁵

In 2012, the National Board of the National Psoriasis Foundation put infliximab amongst the first-line treatment modalities for GPPP.² In one case of GPPP in which the eruption persisted after delivery, the patient was treated with infliximab 7 weeks postpartum due to failure to control the disease with prednisolone 60 mg daily and cyclosporine 7.5 mg/kg daily. Unlike our patient, this patient was only started on an infliximab regimen after delivery.¹⁶ In another case reported in 2010, the patient was started on infliximab during the postpartum period of her first pregnancy following a pustular flare of previously diagnosed plaque psoriasis (not a generalized pustular psoriasis, as in our case).¹⁷ As a good response was obtained, infliximab treatment was continued in the patient throughout her second pregnancy.

Our case is unique in that infliximab was started during pregnancy because of intractable disease leading to systemic symptoms. Our patient showed an excellent response to infliximab after a 10-week disease course with repeated flare-ups and impairment to her overall condition. Delivery occurred at 36 weeks’ gestation due to suspected intrauterine growth retardation; however, the neonate was born with a 5-minute APGAR score of 10 and required no special medical care, which suggests that the low birth weight was constitutional due to the patient’s small frame (her height was 4 ft 11 in). The breast milk of patients with inflammatory bowel disease has been detected to contain very small amounts of infliximab (101 ng/mL, about 1/200 of the therapeutic blood level).¹⁸ Considering the large molecular weight of this agent and possible proteolysis in the stomach and intestines, infliximab is unlikely to affect the neonate.¹⁵ Thus, we encouraged our patient to breastfeed her baby. A case of fatal disseminated Bacille-Calmette-Guérin infection in an infant whose mother received infliximab treatment during pregnancy has been reported.¹⁹ It has been suggested that live vaccines should be avoided in neonates exposed to anti-TNF agents at least for the first 6 months of life or until the agent is no longer detectable in their blood.¹⁵ We therefore informed our patient’s family practitioner about this data.

Conclusion

We report a case of infliximab treatment for GPPP that was continued during the postpartum period. Infliximab was an effective treatment option in our patient with no detected serious adverse events and may be considered in other cases of GPPP that are not responsive to systemic steroids. However, further studies are warranted to evaluate the safety and efficacy of infliximab treatment for GPPP and psoriasis in pregnancy.

Generalized pustular psoriasis of pregnancy (GPPP), formerly known as impetigo herpetiformis, is a rare dermatosis that causes maternal and fetal morbidity and mortality. It is characterized by widespread, circular, erythematous plaques with pustules at the periphery.¹ Conventional first-line treatment includes systemic corticosteroids and cyclosporine. The National Psoriasis Foundation Medical Board also has included infliximab among the first-line treatment options for GPPP.² Herein, we report a case of GPPP treated with infliximab at 30 weeks’ gestation and during the postpartum period.

Case Report

A 22-year-old woman was admitted to our inpatient clinic at 20 weeks’ gestation in her second pregnancy for evaluation of cutaneous eruptions covering the entire body. The lesions first appeared 3 to 4 days prior to her admission and dramatically progressed. She had a history of psoriasis vulgaris diagnosed during her first pregnancy 2 years prior that was treated with topical steroids throughout the pregnancy and methotrexate during lactation for a total of 11 months. She then was started on cyclosporine, which she used for 6 months due to ineffectiveness of the methotrexate, but she stopped treatment 4 months before the second pregnancy.

At the current presentation, physical examination revealed erythroderma and widespread pustules on the chest, abdomen, arms, and legs, including the intertriginous regions, that tended to coalesce and form lakes of pus over an erythematous base (Figure 1). The mucosae were normal. She exhibited a low blood pressure (85/50 mmHg) and high body temperature (102 °F [38.9 °C]). Routine laboratory examination revealed anemia and a normal leukocyte count. Her erythrocyte sedimentation rate (57 mm/h [reference range, <20 mm/h]) and C-reactive protein level (102 mg/L [reference range, <6 mg/L]) were elevated, whereas total calcium (8.11 mg/dL [reference range, 8.2–10.6 mg/dL]) and albumin (3.15 g/dL [reference range, >4.0 g/dL]) levels were low.

The patient returned to the clinic 3 weeks postpartum with a few pustules on erythematous plaques on the chest, abdomen, and back. At this time, she received a third infusion of infliximab 8 weeks after the second dose. For the past 5 years, the patient has been undergoing infliximab maintenance treatment, which she receives at the hospital every 8 weeks with excellent response. She has had no further pregnancies to date.

Comment

Generalized pustular psoriasis of pregnancy is a rare condition that typically occurs in the third trimester but also can start in the first and second trimesters. It may result in maternal and fetal morbidity by causing fluid and electrolyte imbalance and/or placental insufficiency, resulting in an increased risk for fetal abnormalities, stillbirth, and neonatal death.³ In subsequent pregnancies, GPPP has been observed to recur at an earlier gestational age with a more severe presentation.^1,3

Generalized pustular psoriasis of pregnancy usually involves an eruption that begins symmetrically in the intertriginous areas and spreads to the rest of the body. The lesions present as erythematous annular plaques with pustules on the periphery and desquamation in the center due to older pustules.^1,3 The mucous membranes also may be involved with erosive and exfoliative plaques, and there may be nail involvement. Patients often present with systemic symptoms such as fever, malaise, diarrhea, and vomiting.¹ Laboratory investigations may reveal neutrophilic leukocytosis, high erythrocyte sedimentation rate, hypocalcemia, and hypoalbuminemia.⁴ Cultures from blood and pustules show no bacterial growth. A skin biopsy is helpful in diagnosis, with features similar to generalized pustular psoriasis, demonstrating spongiform pustules containing neutrophils, lymphocytic and neutrophilic infiltrates in the papillary dermis, and negative direct immunofluorescence.³

The differential diagnosis of GPPP includes subcorneal pustular dermatosis, dermatitis herpetiformis, herpes gestationis, impetigo, and acute generalized exanthematous pustulosis.^1,3 Due to concerns of fetal implications, treatment options in GPPP are somewhat limited; however, the condition requires treatment because it may result in unfavorable pregnancy outcomes. Topical corticosteroids may be an option for limited disease.^5,6 Systemic corticosteroids (eg, prednisone 60–80 mg/d) were previously considered as first-line agents, although they have shown limited efficacy in our case as well as in other case reports.⁷ Their ineffectiveness and risk for flare-up after dose tapering should be kept in mind when starting GPPP patients on systemic corticosteroids. Systemic cyclosporine (2–3 mg/kg/d) may be added to increase the efficacy of systemic steroids, which was done in several cases in literature.^1,6,8 Although cyclosporine has been classified as a pregnancy category C drug, an analysis of pregnancy outcomes of 629 renal transplant patients revealed no association with adverse pregnancy outcomes compared to the general population and no increase in fetal malformations.⁹ Therefore, cyclosporine is a safe treatment option and was classified as a first-line drug for GPPP in a 2012 review by the National Psoriasis Foundation Medical Board.² Narrowband UVB also has been reported to be used for the treatment of GPPP.¹⁰ Methotrexate and retinoids have been used in cases with lesions that persisted postpartum.¹

Anti–tumor necrosis factor (TNF) α agents are another effective option for treatment of GPPP. Anti-TNF agents are classified as pregnancy category B due to results showing that anti-mouse TNF-α monoclonal antibodies did not cause embryotoxicity or teratogenicity in pregnant mice.¹¹ Although Carter et al¹² published a review of US Food and Drug Administration data on pregnant women receiving anti-TNF treatment and concluded that these agents were associated with the VACTERL group of malformations (vertebral defects, anal atresia, cardiac defect, tracheoesophageal fistula with esophageal atresia, cardiac defects, renal and limb anomalies), no such association was found in further studies. A 2014 study showed no difference in the rate of major malformations in infants born to women who were treated with anti-TNF drugs compared to the disease-matched group not treated with these agents and pregnant women counselled for nonteratogenic exposure.¹³ The same study detected an increase in preterm and low-birth-weight deliveries and suggested this might be caused by the increased severity of disease in patients requiring anti-TNF medication. The British Society of Rheumatology Biologics Register published data on pregnancy outcomes in 130 rheumatoid arthritis patients who had been exposed to anti-TNF agents.¹⁴ The results suggested an increased rate of spontaneous abortions in women exposed to anti-TNF treatment around the time of conception, especially in those taking these medications together with methotrexate or leflunomide; however, results also indicated that disease activity may have had an impact on the rate of spontaneous abortions in these patients. In a 2013 review of 462 women with inflammatory bowel disease who had been exposed to anti-TNF agents during pregnancy, the investigators concluded that pregnancy outcomes and the rate of congenital anomalies did not significantly differ from other inflammatory bowel disease patients not receiving anti-TNF drugs or the general population.¹⁵

In 2012, the National Board of the National Psoriasis Foundation put infliximab amongst the first-line treatment modalities for GPPP.² In one case of GPPP in which the eruption persisted after delivery, the patient was treated with infliximab 7 weeks postpartum due to failure to control the disease with prednisolone 60 mg daily and cyclosporine 7.5 mg/kg daily. Unlike our patient, this patient was only started on an infliximab regimen after delivery.¹⁶ In another case reported in 2010, the patient was started on infliximab during the postpartum period of her first pregnancy following a pustular flare of previously diagnosed plaque psoriasis (not a generalized pustular psoriasis, as in our case).¹⁷ As a good response was obtained, infliximab treatment was continued in the patient throughout her second pregnancy.

Our case is unique in that infliximab was started during pregnancy because of intractable disease leading to systemic symptoms. Our patient showed an excellent response to infliximab after a 10-week disease course with repeated flare-ups and impairment to her overall condition. Delivery occurred at 36 weeks’ gestation due to suspected intrauterine growth retardation; however, the neonate was born with a 5-minute APGAR score of 10 and required no special medical care, which suggests that the low birth weight was constitutional due to the patient’s small frame (her height was 4 ft 11 in). The breast milk of patients with inflammatory bowel disease has been detected to contain very small amounts of infliximab (101 ng/mL, about 1/200 of the therapeutic blood level).¹⁸ Considering the large molecular weight of this agent and possible proteolysis in the stomach and intestines, infliximab is unlikely to affect the neonate.¹⁵ Thus, we encouraged our patient to breastfeed her baby. A case of fatal disseminated Bacille-Calmette-Guérin infection in an infant whose mother received infliximab treatment during pregnancy has been reported.¹⁹ It has been suggested that live vaccines should be avoided in neonates exposed to anti-TNF agents at least for the first 6 months of life or until the agent is no longer detectable in their blood.¹⁵ We therefore informed our patient’s family practitioner about this data.

Conclusion

We report a case of infliximab treatment for GPPP that was continued during the postpartum period. Infliximab was an effective treatment option in our patient with no detected serious adverse events and may be considered in other cases of GPPP that are not responsive to systemic steroids. However, further studies are warranted to evaluate the safety and efficacy of infliximab treatment for GPPP and psoriasis in pregnancy.

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The Diagnosis: Cutaneous Collagenous Vasculopathy 

Cutaneous collagenous vasculopathy (CCV) is an idiopathic microangiopathy of the small vessels in the superficial dermis. A condition first identified by Salama and Rosenthal¹ in 2000, CCV likely is underreported, as its clinical mimickers are not routinely biopsied.² It presents as asymptomatic telangiectatic macules, initially on the lower extremities and often spreading to the trunk. Cutaneous collagenous vasculopathy often is seen in middle-aged adults, and most patients have comorbidities such as hypertension, diabetes mellitus, or cardiovascular disease. The exact etiology of this disease is unknown.^3,4 

Histopathologically, CCV is characterized by dilated superficial vessels with thickened eosinophilic walls. The eosinophilic material is composed of hyalinized type IV collagen, which is periodic acid-Schiff positive and diastase resistant (Figure 1).^3,4 Stains for amyloid are negative.  

Generalized essential telangiectasia (GET) is a condition that presents with symmetric, blanchable, erythematous telangiectases.⁵ These lesions can occur alone or can accompany systemic diseases. Similar to CCV, the telangiectases tend to begin on the legs before gradually spreading to the trunk; however, this process more often is seen in females and occurs at an earlier age. Unlike CCV, GET can occur on mucosal surfaces, with cases of conjunctival and oral involvement reported.⁶ Generalized essential telangiectasia usually is a diagnosis of exclusion.^7,8 It is thought that many CCV lesions have been misclassified clinically as GET, which highlights the importance of biopsy. Microscopically, GET is distinct from CCV in that the superficial dermis lacks thick-walled vessels.^5,7 Although usually not associated with systemic diseases or progressive morbidity, treatment options are limited.⁸ 

Livedoid vasculopathy, also known as atrophie blanche, is caused by fibrin thrombi occlusion of dermal vessels. Clinically, patients have recurrent telangiectatic papules and painful ulcers on the lower extremities that gradually heal, leaving behind white stellate scars. It is caused by an underlying prothrombotic state with a superimposed inflammatory response.⁹ Livedoid vasculopathy primarily affects middle-aged women, and many patients have comorbidities such as scleroderma or systemic lupus erythematosus. Histologically, the epidermis often is ulcerated, and thrombi are visualized within small vessels. Eosinophilic fibrinoid material is deposited in vessel walls, including but not confined to vessels at the base of the epidermal ulcer (Figure 2). The fibrinoid material is periodic acid-Schiff positive and diastase resistant and can be highlighted with immunofluorescence, which may help to distinguish this entity from CCV.^1,9 As the disease progresses, vessels are diffusely hyalinized, and there is epidermal atrophy and dermal sclerosis. Treatment options include antiplatelet and fibrinolytic drugs with a multidisciplinary approach to resolve pain and scarring.⁹ 

Primary systemic amyloidosis is a rare condition, and cutaneous manifestations are seen in approximately one-third of affected individuals. Amyloid deposition results in waxy papules that predominantly affect the face and periorbital areas but also may occur on the neck, flexural areas, and genitalia.⁵ Because the amyloid deposits also can be found within vessel walls, hemorrhagic lesions may occur. Microscopically, amorphous eosinophilic material can be found within the vessel walls, similar to CCV (Figure 3A); however, when stained with Congo red, cutaneous amyloidosis shows waxy red-orange material involving the vessel walls and exhibits apple green birefringence under polarization (Figure 3B).¹⁰ Amyloid also will be negative for type IV collagen, fibronectin, and laminin, whereas CCV will be positive.⁵

The Diagnosis: Cutaneous Collagenous Vasculopathy 

Cutaneous collagenous vasculopathy (CCV) is an idiopathic microangiopathy of the small vessels in the superficial dermis. A condition first identified by Salama and Rosenthal¹ in 2000, CCV likely is underreported, as its clinical mimickers are not routinely biopsied.² It presents as asymptomatic telangiectatic macules, initially on the lower extremities and often spreading to the trunk. Cutaneous collagenous vasculopathy often is seen in middle-aged adults, and most patients have comorbidities such as hypertension, diabetes mellitus, or cardiovascular disease. The exact etiology of this disease is unknown.^3,4 

Histopathologically, CCV is characterized by dilated superficial vessels with thickened eosinophilic walls. The eosinophilic material is composed of hyalinized type IV collagen, which is periodic acid-Schiff positive and diastase resistant (Figure 1).^3,4 Stains for amyloid are negative.  

Generalized essential telangiectasia (GET) is a condition that presents with symmetric, blanchable, erythematous telangiectases.⁵ These lesions can occur alone or can accompany systemic diseases. Similar to CCV, the telangiectases tend to begin on the legs before gradually spreading to the trunk; however, this process more often is seen in females and occurs at an earlier age. Unlike CCV, GET can occur on mucosal surfaces, with cases of conjunctival and oral involvement reported.⁶ Generalized essential telangiectasia usually is a diagnosis of exclusion.^7,8 It is thought that many CCV lesions have been misclassified clinically as GET, which highlights the importance of biopsy. Microscopically, GET is distinct from CCV in that the superficial dermis lacks thick-walled vessels.^5,7 Although usually not associated with systemic diseases or progressive morbidity, treatment options are limited.⁸ 

Livedoid vasculopathy, also known as atrophie blanche, is caused by fibrin thrombi occlusion of dermal vessels. Clinically, patients have recurrent telangiectatic papules and painful ulcers on the lower extremities that gradually heal, leaving behind white stellate scars. It is caused by an underlying prothrombotic state with a superimposed inflammatory response.⁹ Livedoid vasculopathy primarily affects middle-aged women, and many patients have comorbidities such as scleroderma or systemic lupus erythematosus. Histologically, the epidermis often is ulcerated, and thrombi are visualized within small vessels. Eosinophilic fibrinoid material is deposited in vessel walls, including but not confined to vessels at the base of the epidermal ulcer (Figure 2). The fibrinoid material is periodic acid-Schiff positive and diastase resistant and can be highlighted with immunofluorescence, which may help to distinguish this entity from CCV.^1,9 As the disease progresses, vessels are diffusely hyalinized, and there is epidermal atrophy and dermal sclerosis. Treatment options include antiplatelet and fibrinolytic drugs with a multidisciplinary approach to resolve pain and scarring.⁹ 

Primary systemic amyloidosis is a rare condition, and cutaneous manifestations are seen in approximately one-third of affected individuals. Amyloid deposition results in waxy papules that predominantly affect the face and periorbital areas but also may occur on the neck, flexural areas, and genitalia.⁵ Because the amyloid deposits also can be found within vessel walls, hemorrhagic lesions may occur. Microscopically, amorphous eosinophilic material can be found within the vessel walls, similar to CCV (Figure 3A); however, when stained with Congo red, cutaneous amyloidosis shows waxy red-orange material involving the vessel walls and exhibits apple green birefringence under polarization (Figure 3B).¹⁰ Amyloid also will be negative for type IV collagen, fibronectin, and laminin, whereas CCV will be positive.⁵

The Diagnosis: Cutaneous Collagenous Vasculopathy 

Cutaneous collagenous vasculopathy (CCV) is an idiopathic microangiopathy of the small vessels in the superficial dermis. A condition first identified by Salama and Rosenthal¹ in 2000, CCV likely is underreported, as its clinical mimickers are not routinely biopsied.² It presents as asymptomatic telangiectatic macules, initially on the lower extremities and often spreading to the trunk. Cutaneous collagenous vasculopathy often is seen in middle-aged adults, and most patients have comorbidities such as hypertension, diabetes mellitus, or cardiovascular disease. The exact etiology of this disease is unknown.^3,4 

Histopathologically, CCV is characterized by dilated superficial vessels with thickened eosinophilic walls. The eosinophilic material is composed of hyalinized type IV collagen, which is periodic acid-Schiff positive and diastase resistant (Figure 1).^3,4 Stains for amyloid are negative.  

Generalized essential telangiectasia (GET) is a condition that presents with symmetric, blanchable, erythematous telangiectases.⁵ These lesions can occur alone or can accompany systemic diseases. Similar to CCV, the telangiectases tend to begin on the legs before gradually spreading to the trunk; however, this process more often is seen in females and occurs at an earlier age. Unlike CCV, GET can occur on mucosal surfaces, with cases of conjunctival and oral involvement reported.⁶ Generalized essential telangiectasia usually is a diagnosis of exclusion.^7,8 It is thought that many CCV lesions have been misclassified clinically as GET, which highlights the importance of biopsy. Microscopically, GET is distinct from CCV in that the superficial dermis lacks thick-walled vessels.^5,7 Although usually not associated with systemic diseases or progressive morbidity, treatment options are limited.⁸ 

Livedoid vasculopathy, also known as atrophie blanche, is caused by fibrin thrombi occlusion of dermal vessels. Clinically, patients have recurrent telangiectatic papules and painful ulcers on the lower extremities that gradually heal, leaving behind white stellate scars. It is caused by an underlying prothrombotic state with a superimposed inflammatory response.⁹ Livedoid vasculopathy primarily affects middle-aged women, and many patients have comorbidities such as scleroderma or systemic lupus erythematosus. Histologically, the epidermis often is ulcerated, and thrombi are visualized within small vessels. Eosinophilic fibrinoid material is deposited in vessel walls, including but not confined to vessels at the base of the epidermal ulcer (Figure 2). The fibrinoid material is periodic acid-Schiff positive and diastase resistant and can be highlighted with immunofluorescence, which may help to distinguish this entity from CCV.^1,9 As the disease progresses, vessels are diffusely hyalinized, and there is epidermal atrophy and dermal sclerosis. Treatment options include antiplatelet and fibrinolytic drugs with a multidisciplinary approach to resolve pain and scarring.⁹ 

Primary systemic amyloidosis is a rare condition, and cutaneous manifestations are seen in approximately one-third of affected individuals. Amyloid deposition results in waxy papules that predominantly affect the face and periorbital areas but also may occur on the neck, flexural areas, and genitalia.⁵ Because the amyloid deposits also can be found within vessel walls, hemorrhagic lesions may occur. Microscopically, amorphous eosinophilic material can be found within the vessel walls, similar to CCV (Figure 3A); however, when stained with Congo red, cutaneous amyloidosis shows waxy red-orange material involving the vessel walls and exhibits apple green birefringence under polarization (Figure 3B).¹⁰ Amyloid also will be negative for type IV collagen, fibronectin, and laminin, whereas CCV will be positive.⁵

The Diagnosis: Keratoderma Climactericum 

Keratoderma climactericum was first reported in 1934 by Haxthausen¹ as nonpruritic circumscribed hyperkeratosis located mainly on the palms and soles. The initial eruption was described as discrete lesions with an oval or round shape that progressed to less-defined, confluent, hyperkeratotic patches with fissures.¹ Keratoderma climactericum also may be referred to as Haxthausen disease and is considered an acquired palmoplantar keratoderma.² 

Keratoderma climactericum is a rare dermatologic disorder that presents in women of menopausal age who have no family or personal history of skin disease. Keratoderma climactericum is associated with hypertension and obesity.² Keratotic lesions usually first occur on the plantar surfaces with eventual development of fissuring and hyperkeratosis that causes painful walking. The keratotic lesions on the plantar surfaces often are nonpruritic and gradually become confluent over time. As the disease progresses, keratotic lesions appear on the central palms, which can lead to confluent hyperkeratosis on the palmar surfaces (Figure 1).² The exact mechanism of keratoderma climactericum has not been described but is believed to be due to hormonal dysregulation.²  

Treatment options for keratoderma climactericum include salicylic acid, emollients, oral retinoids, urea ointments, estriol cream, and topical steroids.^5,6 Our patient was prescribed acitretin 25 mg daily and ammonium lactate to apply topically as needed for dry skin. Five months after the initial presentation, fissures and dry skin on the bilateral soles were still present. Ammonium lactate was discontinued, and the patient was prescribed urea cream 40%. Fifteen months after the initial presentation, the patient reported substantial improvement on the hands and feet and noted that she no longer needed the urea cream. Physical examination revealed no presence of hyperkeratosis or fissuring on the palms (Figure 2), and mild hyperkeratosis was present on the plantar surfaces of the feet (Figure 3). The patient continued to use acitretin to prevent disease relapse.  

The Diagnosis: Keratoderma Climactericum 

Keratoderma climactericum was first reported in 1934 by Haxthausen¹ as nonpruritic circumscribed hyperkeratosis located mainly on the palms and soles. The initial eruption was described as discrete lesions with an oval or round shape that progressed to less-defined, confluent, hyperkeratotic patches with fissures.¹ Keratoderma climactericum also may be referred to as Haxthausen disease and is considered an acquired palmoplantar keratoderma.² 

Keratoderma climactericum is a rare dermatologic disorder that presents in women of menopausal age who have no family or personal history of skin disease. Keratoderma climactericum is associated with hypertension and obesity.² Keratotic lesions usually first occur on the plantar surfaces with eventual development of fissuring and hyperkeratosis that causes painful walking. The keratotic lesions on the plantar surfaces often are nonpruritic and gradually become confluent over time. As the disease progresses, keratotic lesions appear on the central palms, which can lead to confluent hyperkeratosis on the palmar surfaces (Figure 1).² The exact mechanism of keratoderma climactericum has not been described but is believed to be due to hormonal dysregulation.²  

Treatment options for keratoderma climactericum include salicylic acid, emollients, oral retinoids, urea ointments, estriol cream, and topical steroids.^5,6 Our patient was prescribed acitretin 25 mg daily and ammonium lactate to apply topically as needed for dry skin. Five months after the initial presentation, fissures and dry skin on the bilateral soles were still present. Ammonium lactate was discontinued, and the patient was prescribed urea cream 40%. Fifteen months after the initial presentation, the patient reported substantial improvement on the hands and feet and noted that she no longer needed the urea cream. Physical examination revealed no presence of hyperkeratosis or fissuring on the palms (Figure 2), and mild hyperkeratosis was present on the plantar surfaces of the feet (Figure 3). The patient continued to use acitretin to prevent disease relapse.  

The Diagnosis: Keratoderma Climactericum 

Keratoderma climactericum was first reported in 1934 by Haxthausen¹ as nonpruritic circumscribed hyperkeratosis located mainly on the palms and soles. The initial eruption was described as discrete lesions with an oval or round shape that progressed to less-defined, confluent, hyperkeratotic patches with fissures.¹ Keratoderma climactericum also may be referred to as Haxthausen disease and is considered an acquired palmoplantar keratoderma.² 

Keratoderma climactericum is a rare dermatologic disorder that presents in women of menopausal age who have no family or personal history of skin disease. Keratoderma climactericum is associated with hypertension and obesity.² Keratotic lesions usually first occur on the plantar surfaces with eventual development of fissuring and hyperkeratosis that causes painful walking. The keratotic lesions on the plantar surfaces often are nonpruritic and gradually become confluent over time. As the disease progresses, keratotic lesions appear on the central palms, which can lead to confluent hyperkeratosis on the palmar surfaces (Figure 1).² The exact mechanism of keratoderma climactericum has not been described but is believed to be due to hormonal dysregulation.²  

Treatment options for keratoderma climactericum include salicylic acid, emollients, oral retinoids, urea ointments, estriol cream, and topical steroids.^5,6 Our patient was prescribed acitretin 25 mg daily and ammonium lactate to apply topically as needed for dry skin. Five months after the initial presentation, fissures and dry skin on the bilateral soles were still present. Ammonium lactate was discontinued, and the patient was prescribed urea cream 40%. Fifteen months after the initial presentation, the patient reported substantial improvement on the hands and feet and noted that she no longer needed the urea cream. Physical examination revealed no presence of hyperkeratosis or fissuring on the palms (Figure 2), and mild hyperkeratosis was present on the plantar surfaces of the feet (Figure 3). The patient continued to use acitretin to prevent disease relapse.  

There has been a rise in the prevalence of perniolike lesions—erythematous to violaceous, edematous papules or nodules on the fingers or toes—during the coronavirus disease 2019 (COVID-19) pandemic. These lesions are referred to as “COVID toes.” Although several studies have suggested an association with these lesions and COVID-19, and coronavirus particles have been identified in endothelial cells of biopsies of pernio lesions, questions remain on the management, pathophysiology, and implications of these lesions.¹ We provide a practical review for primary care clinicians and dermatologists on the current management, recommendations, and remaining questions, with particular attention to the distinctions for children vs adults presenting with pernio lesions.

Hypothetical Case of a Child Presenting With Acral Lesions

A 7-year-old boy presents with acute-onset, violaceous, mildly painful and pruritic macules on the distal toes that began 3 days earlier and have progressed to involve more toes and appear more purpuric. A review of symptoms reveals no fever, cough, fatigue, or viral symptoms. He has been staying at home for the last few weeks with his brother, mother, and father. His father is working in delivery services and is social distancing at work but not at home. His mother is concerned about the lesions, if they could be COVID toes, and if testing is needed for the patient or family. In your assessment and management of this patient, you consider the following questions.

What Is the Relationship Between These Clinical Findings and COVID-19?
Despite negative polymerase chain reaction (PCR) tests reported in cases of chilblains during the COVID-19 pandemic as well as the possibility that these lesions are an indirect result of environmental factors or behavioral changes during quarantine, the majority of studies favor an association between these chilblains lesions and COVID-19 infection.^2,3 Most compellingly, COVID-19 viral particles have been identified by immunohistochemistry and electron microscopy in the endothelial cells of biopsies of these lesions.¹ Additionally, there is evidence for possible associations of other viruses, including Epstein-Barr virus and parvovirus B19, with chilblains lesions.^4,5 In sum, with the lack of any large prospective study, the weight of current evidence suggests that these perniolike skin lesions are not specific markers of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).⁶

Published studies differ in reporting the coincidence of perniolike lesions with typical COVID-19 symptoms, including fever, dyspnea, cough, fatigue, myalgia, headache, and anosmia, among others. Some studies have reported that up to 63% of patients with reported perniolike lesions developed typical COVID-19 symptoms, but other studies found that no patients with these lesions developed symptoms.^6-11 Studies with younger cohorts tended to report lower prevalence of COVID-19 symptoms, and within cohorts, younger patients tended to have less severe symptoms. For example, 78.8% of patients in a cohort (n=58) with an average age of 14 years did not experience COVID-19–related symptoms.⁶ Based on these data, it has been hypothesized that patients with chilblainslike lesions may represent a subpopulation who will have a robust interferon response that is protective from more symptomatic and severe COVID-19.^12-14

Current evidence suggests that these lesions are most likely to occur between 9 days and 2 months after the onset of COVID-19 symptoms.^4,9,10 Most cases have been only mildly symptomatic, with an overall favorable prognosis of both lesions and any viral symptoms.^8,10 The lesions typically resolve without treatment within a few days of initial onset.^15,16

What Should Be the Workup and Management of These Lesions?
Given the currently available information and favorable prognosis, usually no further workup specific to the perniolike lesions is required in the case of an asymptomatic child presenting with acral lesions, and the majority of management will center around patient and parent/guardian education and reassurance. When asked by the patient’s parent, “What does it mean that my child has these lesions?”, clinicians can provide information on the possible association with COVID-19 and the excellent, self-resolving prognosis. An example of honest and reasonable phrasing with current understanding might be, “We are currently not certain if COVID-19 causes these lesions, although there are data to suggest that they are associated. There are a lot of data showing that children with these lesions either do not have any symptoms or have very mild symptoms that resolve without treatment.”

For management, important considerations include how painful the lesions are to the individual patient and how they affect quality of life. If less severe, clinicians can reassure patients and parents/guardians that the lesions will likely self-resolve without treatment. If worsening or symptomatic, clinicians can try typical treatments for chilblains, such as topical steroids, whole-body warming, and nifedipine.^17-19 Obtaining a review of symptoms, including COVID-19 symptoms and general viral symptoms, is important given the rare cases of children with severe COVID-19.^20,21

The question of COVID-19 testing as related to these lesions remains controversial, and currently there are still differing perspectives on the need for biopsy, PCR for COVID-19, or serologies for COVID-19 in patients presenting with these lesions. Some experts report that additional testing is not needed in the pediatric population because of the high frequency of negative testing reported to date.^22,23 However, these children may be silent carriers, and until more is known about their potential to transmit the virus, testing may be considered if resources allow, particularly if the patient has a known exposure.^10,12,16,24 The ultimate decision to pursue biopsy or serologic workup for COVID-19 remains up to clinical discretion with consideration of symptoms, severity, and immunocompromised household contacts. If lesions developed after infection, PCR likely will result negative, whereas serologic testing may reveal antibodies.

Hypothetical Case of an Adult Presenting With Acral Lesions and COVID-19 Symptoms

A 50-year-old man presents with acute-onset, violaceous, painful, edematous plaques on the distal toes that began 3 days earlier and have progressed to include the soles. A review of symptoms reveals fever (temperature, 38.4 °C [101 °F]), cough, dyspnea, diarrhea, and severe asthenia. He has had interactions with a coworker who recently tested positive for COVID-19.

How Should You Consider These Lesions in the Context of the Other Symptoms Concerning for COVID-19?
In contrast to the asymptomatic child above, this adult has chilblainslike lesions and viral symptoms. In adults, chilblainslike lesions have been associated with relatively mild COVID-19, and patients with these lesions who are otherwise asymptomatic have largely tested negative for COVID-19 by PCR and serologic antibody testing.^11,25,26

True acral ischemia, which is more severe and should be differentiated from chilblains, has been reported in critically ill patients.⁹ Additionally, studies have found that retiform purpura is the most common cutaneous finding in patients with severe COVID-19.²⁷ For this patient, who has an examination consistent with progressive and severe chilblainslike lesions and suspicion for COVID-19 infection, it is important to observe and monitor these lesions, as clinical progression suggestive of acral ischemia or retiform purpura should be taken seriously and may indicate worsening of the underlying disease. Early intervention with anticoagulation might be considered, though there currently is no evidence of successful treatment.²⁸

What Causes These Lesions in a Patient With COVID-19?
The underlying pathophysiology has been proposed to be a monocytic-macrophage–induced hyperinflammatory systemic state that damages the lungs, as well as the gastrointestinal, renal, and endothelial systems. The activation of the innate immune system triggers a cytokine storm that creates a hypercoagulable state that ultimately can manifest as superficial thromboses, leading to gangrene of the extremities. Additionally, interferon response and resulting hypercytokinemia may cause direct cytopathic damage to the endothelium of arterioles and capillaries, causing the development of papulovesicular lesions that resemble the chilblainslike lesions observed in children.²⁹ In contrast to children, who typically have no or mild COVID-19 symptoms, adults may have a delayed interferon response, which has been proposed to allow for more severe manifestations of infection.^12,30

How Should an Adult With Perniolike Lesions Be Managed?
Adults with chilblainslike lesions and no other signs or symptoms of COVID-19 infection do not necessarily need be tested for COVID-19, given the reports demonstrating most patients in this clinical situation will have negative PCRs and serologies for antibodies. However, there have been several reports of adults with acro-ischemic skin findings who also had severe COVID-19, with an observed incidence of 23% in intensive care unit patients with COVID-19.^27,28,31,32 If there is suspicion of infection with COVID-19, it is advisable to first obtain workup for COVID-19 and other viruses that can cause acral lesions, including Epstein-Barr virus and parvovirus. Other pertinent laboratory tests may include D-dimer, fibrinogen, prothrombin time, activated partial thromboplastin time, antithrombin activity, platelet count, neutrophil count, procalcitonin, triglycerides, ferritin, C-reactive protein, and hemoglobin. For patients with evidence of worsening acro-ischemia, regular monitoring of these values up to several times per week can allow for initiation of vascular intervention, including angiontensin-converting enzyme inhibitors, statins, or antiplatelet drugs.³² The presence of antiphospholipid antibodies also has been associated with critically ill patients who develop digit ischemia as part of the sequelae of COVID-19 infection and therefore may act as an important marker for the potential to develop disseminated intravascular coagulation in this patient.³³ Even if COVID-19 infection is not suspected, a thorough review of systems is important to look for an underlying connective tissue disease, such as systemic lupus erythematosus, which is associated with pernio. Associated symptoms may warrant workup with antinuclear antibodies and other appropriate autoimmune serologies.

If there is any doubt of the diagnosis, the patient is experiencing symptoms from the lesion, or the patient is experiencing other viral symptoms, it is appropriate to biopsy immediately to confirm the diagnosis. Prior studies have identified fibrin clots, angiocentric and eccrinotropic lymphocytic infiltrates, lymphocytic vasculopathy, and papillary dermal edema as the most common features in chilblainslike lesions during the COVID-19 pandemic.⁹

For COVID-19 testing, many studies have revealed adult patients with an acute hypercoagulable state testing positive by SARS-CoV-2 PCR. These same patients also experienced thromboembolic events shortly after testing positive for COVID-19, which suggests that patients with elevated D-dimer and fibrinogen likely will have a viral load that is sufficient to test positive for COVID-19.^32,34-36 It is appropriate to test all patients with suspected COVID-19, especially adults who are more likely to experience adverse complications secondary to infection.

This patient experiencing COVID-19 symptoms with signs of acral ischemia is likely to test positive by PCR, and additional testing for serologic antibodies is unlikely to be clinically meaningful in this patient’s state. Furthermore, there is little evidence that serology is reliable because of the markedly high levels of both false-negative and false-positive results when using the available antibody testing kits.³⁷ The latter evidence makes serology testing of little value for the general population, but particularly for patients with acute COVID-19.

Conclusion and Outstanding Questions

There is evidence suggesting an association between chilblainslike lesions and COVID-19.^11,22,38,39 Children presenting with these lesions have an excellent prognosis and only need a workup or treatment if there are other symptoms, as the lesions self-resolve in the majority of reported cases.^7-9 Adults presenting with these lesions and without symptoms likewise are unlikely to test positive for COVID-19, and the lesions typically resolve spontaneously or with first-line treatment. However, adults presenting with these lesions and COVID-19 symptoms should raise clinical concern for evolving skin manifestations of acro-ischemia. If the diagnosis is uncertain or systemic symptoms are concerning, biopsy, COVID-19 PCR, and other appropriate laboratory workup should be obtained.

There remains controversy and uncertainty over the relationship between these skin findings and SARS-CoV-2 infection, with clinical evidence to support both a direct relationship representing convalescent-phase cutaneous reaction as well as an indirect epiphenomenon. If there was a direct relationship, we would have expected to see a rise in the incidence of acral lesions proportionate to the rising caseload of COVID-19 after the reopening of many states in the summer of 2020. Similarly, because young adults represent the largest demographic of increasing cases and as some schools have remained open for in-person instruction during the current academic year, we also would have expected the incidence of chilblains-like lesions presenting to dermatologists and pediatricians to increase alongside these cases. Continued evaluation of emerging literature and ongoing efforts to understand the cause of this observed phenomenon will hopefully help us arrive at a future understanding of the pathophysiology of this puzzling skin manifestation.⁴⁰

There has been a rise in the prevalence of perniolike lesions—erythematous to violaceous, edematous papules or nodules on the fingers or toes—during the coronavirus disease 2019 (COVID-19) pandemic. These lesions are referred to as “COVID toes.” Although several studies have suggested an association with these lesions and COVID-19, and coronavirus particles have been identified in endothelial cells of biopsies of pernio lesions, questions remain on the management, pathophysiology, and implications of these lesions.¹ We provide a practical review for primary care clinicians and dermatologists on the current management, recommendations, and remaining questions, with particular attention to the distinctions for children vs adults presenting with pernio lesions.

Hypothetical Case of a Child Presenting With Acral Lesions

A 7-year-old boy presents with acute-onset, violaceous, mildly painful and pruritic macules on the distal toes that began 3 days earlier and have progressed to involve more toes and appear more purpuric. A review of symptoms reveals no fever, cough, fatigue, or viral symptoms. He has been staying at home for the last few weeks with his brother, mother, and father. His father is working in delivery services and is social distancing at work but not at home. His mother is concerned about the lesions, if they could be COVID toes, and if testing is needed for the patient or family. In your assessment and management of this patient, you consider the following questions.

What Is the Relationship Between These Clinical Findings and COVID-19?
Despite negative polymerase chain reaction (PCR) tests reported in cases of chilblains during the COVID-19 pandemic as well as the possibility that these lesions are an indirect result of environmental factors or behavioral changes during quarantine, the majority of studies favor an association between these chilblains lesions and COVID-19 infection.^2,3 Most compellingly, COVID-19 viral particles have been identified by immunohistochemistry and electron microscopy in the endothelial cells of biopsies of these lesions.¹ Additionally, there is evidence for possible associations of other viruses, including Epstein-Barr virus and parvovirus B19, with chilblains lesions.^4,5 In sum, with the lack of any large prospective study, the weight of current evidence suggests that these perniolike skin lesions are not specific markers of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).⁶

Published studies differ in reporting the coincidence of perniolike lesions with typical COVID-19 symptoms, including fever, dyspnea, cough, fatigue, myalgia, headache, and anosmia, among others. Some studies have reported that up to 63% of patients with reported perniolike lesions developed typical COVID-19 symptoms, but other studies found that no patients with these lesions developed symptoms.^6-11 Studies with younger cohorts tended to report lower prevalence of COVID-19 symptoms, and within cohorts, younger patients tended to have less severe symptoms. For example, 78.8% of patients in a cohort (n=58) with an average age of 14 years did not experience COVID-19–related symptoms.⁶ Based on these data, it has been hypothesized that patients with chilblainslike lesions may represent a subpopulation who will have a robust interferon response that is protective from more symptomatic and severe COVID-19.^12-14

Current evidence suggests that these lesions are most likely to occur between 9 days and 2 months after the onset of COVID-19 symptoms.^4,9,10 Most cases have been only mildly symptomatic, with an overall favorable prognosis of both lesions and any viral symptoms.^8,10 The lesions typically resolve without treatment within a few days of initial onset.^15,16

What Should Be the Workup and Management of These Lesions?
Given the currently available information and favorable prognosis, usually no further workup specific to the perniolike lesions is required in the case of an asymptomatic child presenting with acral lesions, and the majority of management will center around patient and parent/guardian education and reassurance. When asked by the patient’s parent, “What does it mean that my child has these lesions?”, clinicians can provide information on the possible association with COVID-19 and the excellent, self-resolving prognosis. An example of honest and reasonable phrasing with current understanding might be, “We are currently not certain if COVID-19 causes these lesions, although there are data to suggest that they are associated. There are a lot of data showing that children with these lesions either do not have any symptoms or have very mild symptoms that resolve without treatment.”

For management, important considerations include how painful the lesions are to the individual patient and how they affect quality of life. If less severe, clinicians can reassure patients and parents/guardians that the lesions will likely self-resolve without treatment. If worsening or symptomatic, clinicians can try typical treatments for chilblains, such as topical steroids, whole-body warming, and nifedipine.^17-19 Obtaining a review of symptoms, including COVID-19 symptoms and general viral symptoms, is important given the rare cases of children with severe COVID-19.^20,21

The question of COVID-19 testing as related to these lesions remains controversial, and currently there are still differing perspectives on the need for biopsy, PCR for COVID-19, or serologies for COVID-19 in patients presenting with these lesions. Some experts report that additional testing is not needed in the pediatric population because of the high frequency of negative testing reported to date.^22,23 However, these children may be silent carriers, and until more is known about their potential to transmit the virus, testing may be considered if resources allow, particularly if the patient has a known exposure.^10,12,16,24 The ultimate decision to pursue biopsy or serologic workup for COVID-19 remains up to clinical discretion with consideration of symptoms, severity, and immunocompromised household contacts. If lesions developed after infection, PCR likely will result negative, whereas serologic testing may reveal antibodies.

Hypothetical Case of an Adult Presenting With Acral Lesions and COVID-19 Symptoms

A 50-year-old man presents with acute-onset, violaceous, painful, edematous plaques on the distal toes that began 3 days earlier and have progressed to include the soles. A review of symptoms reveals fever (temperature, 38.4 °C [101 °F]), cough, dyspnea, diarrhea, and severe asthenia. He has had interactions with a coworker who recently tested positive for COVID-19.

How Should You Consider These Lesions in the Context of the Other Symptoms Concerning for COVID-19?
In contrast to the asymptomatic child above, this adult has chilblainslike lesions and viral symptoms. In adults, chilblainslike lesions have been associated with relatively mild COVID-19, and patients with these lesions who are otherwise asymptomatic have largely tested negative for COVID-19 by PCR and serologic antibody testing.^11,25,26

True acral ischemia, which is more severe and should be differentiated from chilblains, has been reported in critically ill patients.⁹ Additionally, studies have found that retiform purpura is the most common cutaneous finding in patients with severe COVID-19.²⁷ For this patient, who has an examination consistent with progressive and severe chilblainslike lesions and suspicion for COVID-19 infection, it is important to observe and monitor these lesions, as clinical progression suggestive of acral ischemia or retiform purpura should be taken seriously and may indicate worsening of the underlying disease. Early intervention with anticoagulation might be considered, though there currently is no evidence of successful treatment.²⁸

What Causes These Lesions in a Patient With COVID-19?
The underlying pathophysiology has been proposed to be a monocytic-macrophage–induced hyperinflammatory systemic state that damages the lungs, as well as the gastrointestinal, renal, and endothelial systems. The activation of the innate immune system triggers a cytokine storm that creates a hypercoagulable state that ultimately can manifest as superficial thromboses, leading to gangrene of the extremities. Additionally, interferon response and resulting hypercytokinemia may cause direct cytopathic damage to the endothelium of arterioles and capillaries, causing the development of papulovesicular lesions that resemble the chilblainslike lesions observed in children.²⁹ In contrast to children, who typically have no or mild COVID-19 symptoms, adults may have a delayed interferon response, which has been proposed to allow for more severe manifestations of infection.^12,30

How Should an Adult With Perniolike Lesions Be Managed?
Adults with chilblainslike lesions and no other signs or symptoms of COVID-19 infection do not necessarily need be tested for COVID-19, given the reports demonstrating most patients in this clinical situation will have negative PCRs and serologies for antibodies. However, there have been several reports of adults with acro-ischemic skin findings who also had severe COVID-19, with an observed incidence of 23% in intensive care unit patients with COVID-19.^27,28,31,32 If there is suspicion of infection with COVID-19, it is advisable to first obtain workup for COVID-19 and other viruses that can cause acral lesions, including Epstein-Barr virus and parvovirus. Other pertinent laboratory tests may include D-dimer, fibrinogen, prothrombin time, activated partial thromboplastin time, antithrombin activity, platelet count, neutrophil count, procalcitonin, triglycerides, ferritin, C-reactive protein, and hemoglobin. For patients with evidence of worsening acro-ischemia, regular monitoring of these values up to several times per week can allow for initiation of vascular intervention, including angiontensin-converting enzyme inhibitors, statins, or antiplatelet drugs.³² The presence of antiphospholipid antibodies also has been associated with critically ill patients who develop digit ischemia as part of the sequelae of COVID-19 infection and therefore may act as an important marker for the potential to develop disseminated intravascular coagulation in this patient.³³ Even if COVID-19 infection is not suspected, a thorough review of systems is important to look for an underlying connective tissue disease, such as systemic lupus erythematosus, which is associated with pernio. Associated symptoms may warrant workup with antinuclear antibodies and other appropriate autoimmune serologies.

If there is any doubt of the diagnosis, the patient is experiencing symptoms from the lesion, or the patient is experiencing other viral symptoms, it is appropriate to biopsy immediately to confirm the diagnosis. Prior studies have identified fibrin clots, angiocentric and eccrinotropic lymphocytic infiltrates, lymphocytic vasculopathy, and papillary dermal edema as the most common features in chilblainslike lesions during the COVID-19 pandemic.⁹

For COVID-19 testing, many studies have revealed adult patients with an acute hypercoagulable state testing positive by SARS-CoV-2 PCR. These same patients also experienced thromboembolic events shortly after testing positive for COVID-19, which suggests that patients with elevated D-dimer and fibrinogen likely will have a viral load that is sufficient to test positive for COVID-19.^32,34-36 It is appropriate to test all patients with suspected COVID-19, especially adults who are more likely to experience adverse complications secondary to infection.

This patient experiencing COVID-19 symptoms with signs of acral ischemia is likely to test positive by PCR, and additional testing for serologic antibodies is unlikely to be clinically meaningful in this patient’s state. Furthermore, there is little evidence that serology is reliable because of the markedly high levels of both false-negative and false-positive results when using the available antibody testing kits.³⁷ The latter evidence makes serology testing of little value for the general population, but particularly for patients with acute COVID-19.

Conclusion and Outstanding Questions

There is evidence suggesting an association between chilblainslike lesions and COVID-19.^11,22,38,39 Children presenting with these lesions have an excellent prognosis and only need a workup or treatment if there are other symptoms, as the lesions self-resolve in the majority of reported cases.^7-9 Adults presenting with these lesions and without symptoms likewise are unlikely to test positive for COVID-19, and the lesions typically resolve spontaneously or with first-line treatment. However, adults presenting with these lesions and COVID-19 symptoms should raise clinical concern for evolving skin manifestations of acro-ischemia. If the diagnosis is uncertain or systemic symptoms are concerning, biopsy, COVID-19 PCR, and other appropriate laboratory workup should be obtained.

There remains controversy and uncertainty over the relationship between these skin findings and SARS-CoV-2 infection, with clinical evidence to support both a direct relationship representing convalescent-phase cutaneous reaction as well as an indirect epiphenomenon. If there was a direct relationship, we would have expected to see a rise in the incidence of acral lesions proportionate to the rising caseload of COVID-19 after the reopening of many states in the summer of 2020. Similarly, because young adults represent the largest demographic of increasing cases and as some schools have remained open for in-person instruction during the current academic year, we also would have expected the incidence of chilblains-like lesions presenting to dermatologists and pediatricians to increase alongside these cases. Continued evaluation of emerging literature and ongoing efforts to understand the cause of this observed phenomenon will hopefully help us arrive at a future understanding of the pathophysiology of this puzzling skin manifestation.⁴⁰

There has been a rise in the prevalence of perniolike lesions—erythematous to violaceous, edematous papules or nodules on the fingers or toes—during the coronavirus disease 2019 (COVID-19) pandemic. These lesions are referred to as “COVID toes.” Although several studies have suggested an association with these lesions and COVID-19, and coronavirus particles have been identified in endothelial cells of biopsies of pernio lesions, questions remain on the management, pathophysiology, and implications of these lesions.¹ We provide a practical review for primary care clinicians and dermatologists on the current management, recommendations, and remaining questions, with particular attention to the distinctions for children vs adults presenting with pernio lesions.

Hypothetical Case of a Child Presenting With Acral Lesions

A 7-year-old boy presents with acute-onset, violaceous, mildly painful and pruritic macules on the distal toes that began 3 days earlier and have progressed to involve more toes and appear more purpuric. A review of symptoms reveals no fever, cough, fatigue, or viral symptoms. He has been staying at home for the last few weeks with his brother, mother, and father. His father is working in delivery services and is social distancing at work but not at home. His mother is concerned about the lesions, if they could be COVID toes, and if testing is needed for the patient or family. In your assessment and management of this patient, you consider the following questions.

What Is the Relationship Between These Clinical Findings and COVID-19?
Despite negative polymerase chain reaction (PCR) tests reported in cases of chilblains during the COVID-19 pandemic as well as the possibility that these lesions are an indirect result of environmental factors or behavioral changes during quarantine, the majority of studies favor an association between these chilblains lesions and COVID-19 infection.^2,3 Most compellingly, COVID-19 viral particles have been identified by immunohistochemistry and electron microscopy in the endothelial cells of biopsies of these lesions.¹ Additionally, there is evidence for possible associations of other viruses, including Epstein-Barr virus and parvovirus B19, with chilblains lesions.^4,5 In sum, with the lack of any large prospective study, the weight of current evidence suggests that these perniolike skin lesions are not specific markers of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).⁶

Published studies differ in reporting the coincidence of perniolike lesions with typical COVID-19 symptoms, including fever, dyspnea, cough, fatigue, myalgia, headache, and anosmia, among others. Some studies have reported that up to 63% of patients with reported perniolike lesions developed typical COVID-19 symptoms, but other studies found that no patients with these lesions developed symptoms.^6-11 Studies with younger cohorts tended to report lower prevalence of COVID-19 symptoms, and within cohorts, younger patients tended to have less severe symptoms. For example, 78.8% of patients in a cohort (n=58) with an average age of 14 years did not experience COVID-19–related symptoms.⁶ Based on these data, it has been hypothesized that patients with chilblainslike lesions may represent a subpopulation who will have a robust interferon response that is protective from more symptomatic and severe COVID-19.^12-14

Current evidence suggests that these lesions are most likely to occur between 9 days and 2 months after the onset of COVID-19 symptoms.^4,9,10 Most cases have been only mildly symptomatic, with an overall favorable prognosis of both lesions and any viral symptoms.^8,10 The lesions typically resolve without treatment within a few days of initial onset.^15,16

What Should Be the Workup and Management of These Lesions?
Given the currently available information and favorable prognosis, usually no further workup specific to the perniolike lesions is required in the case of an asymptomatic child presenting with acral lesions, and the majority of management will center around patient and parent/guardian education and reassurance. When asked by the patient’s parent, “What does it mean that my child has these lesions?”, clinicians can provide information on the possible association with COVID-19 and the excellent, self-resolving prognosis. An example of honest and reasonable phrasing with current understanding might be, “We are currently not certain if COVID-19 causes these lesions, although there are data to suggest that they are associated. There are a lot of data showing that children with these lesions either do not have any symptoms or have very mild symptoms that resolve without treatment.”

For management, important considerations include how painful the lesions are to the individual patient and how they affect quality of life. If less severe, clinicians can reassure patients and parents/guardians that the lesions will likely self-resolve without treatment. If worsening or symptomatic, clinicians can try typical treatments for chilblains, such as topical steroids, whole-body warming, and nifedipine.^17-19 Obtaining a review of symptoms, including COVID-19 symptoms and general viral symptoms, is important given the rare cases of children with severe COVID-19.^20,21

The question of COVID-19 testing as related to these lesions remains controversial, and currently there are still differing perspectives on the need for biopsy, PCR for COVID-19, or serologies for COVID-19 in patients presenting with these lesions. Some experts report that additional testing is not needed in the pediatric population because of the high frequency of negative testing reported to date.^22,23 However, these children may be silent carriers, and until more is known about their potential to transmit the virus, testing may be considered if resources allow, particularly if the patient has a known exposure.^10,12,16,24 The ultimate decision to pursue biopsy or serologic workup for COVID-19 remains up to clinical discretion with consideration of symptoms, severity, and immunocompromised household contacts. If lesions developed after infection, PCR likely will result negative, whereas serologic testing may reveal antibodies.

Hypothetical Case of an Adult Presenting With Acral Lesions and COVID-19 Symptoms

A 50-year-old man presents with acute-onset, violaceous, painful, edematous plaques on the distal toes that began 3 days earlier and have progressed to include the soles. A review of symptoms reveals fever (temperature, 38.4 °C [101 °F]), cough, dyspnea, diarrhea, and severe asthenia. He has had interactions with a coworker who recently tested positive for COVID-19.

How Should You Consider These Lesions in the Context of the Other Symptoms Concerning for COVID-19?
In contrast to the asymptomatic child above, this adult has chilblainslike lesions and viral symptoms. In adults, chilblainslike lesions have been associated with relatively mild COVID-19, and patients with these lesions who are otherwise asymptomatic have largely tested negative for COVID-19 by PCR and serologic antibody testing.^11,25,26

True acral ischemia, which is more severe and should be differentiated from chilblains, has been reported in critically ill patients.⁹ Additionally, studies have found that retiform purpura is the most common cutaneous finding in patients with severe COVID-19.²⁷ For this patient, who has an examination consistent with progressive and severe chilblainslike lesions and suspicion for COVID-19 infection, it is important to observe and monitor these lesions, as clinical progression suggestive of acral ischemia or retiform purpura should be taken seriously and may indicate worsening of the underlying disease. Early intervention with anticoagulation might be considered, though there currently is no evidence of successful treatment.²⁸

What Causes These Lesions in a Patient With COVID-19?
The underlying pathophysiology has been proposed to be a monocytic-macrophage–induced hyperinflammatory systemic state that damages the lungs, as well as the gastrointestinal, renal, and endothelial systems. The activation of the innate immune system triggers a cytokine storm that creates a hypercoagulable state that ultimately can manifest as superficial thromboses, leading to gangrene of the extremities. Additionally, interferon response and resulting hypercytokinemia may cause direct cytopathic damage to the endothelium of arterioles and capillaries, causing the development of papulovesicular lesions that resemble the chilblainslike lesions observed in children.²⁹ In contrast to children, who typically have no or mild COVID-19 symptoms, adults may have a delayed interferon response, which has been proposed to allow for more severe manifestations of infection.^12,30

How Should an Adult With Perniolike Lesions Be Managed?
Adults with chilblainslike lesions and no other signs or symptoms of COVID-19 infection do not necessarily need be tested for COVID-19, given the reports demonstrating most patients in this clinical situation will have negative PCRs and serologies for antibodies. However, there have been several reports of adults with acro-ischemic skin findings who also had severe COVID-19, with an observed incidence of 23% in intensive care unit patients with COVID-19.^27,28,31,32 If there is suspicion of infection with COVID-19, it is advisable to first obtain workup for COVID-19 and other viruses that can cause acral lesions, including Epstein-Barr virus and parvovirus. Other pertinent laboratory tests may include D-dimer, fibrinogen, prothrombin time, activated partial thromboplastin time, antithrombin activity, platelet count, neutrophil count, procalcitonin, triglycerides, ferritin, C-reactive protein, and hemoglobin. For patients with evidence of worsening acro-ischemia, regular monitoring of these values up to several times per week can allow for initiation of vascular intervention, including angiontensin-converting enzyme inhibitors, statins, or antiplatelet drugs.³² The presence of antiphospholipid antibodies also has been associated with critically ill patients who develop digit ischemia as part of the sequelae of COVID-19 infection and therefore may act as an important marker for the potential to develop disseminated intravascular coagulation in this patient.³³ Even if COVID-19 infection is not suspected, a thorough review of systems is important to look for an underlying connective tissue disease, such as systemic lupus erythematosus, which is associated with pernio. Associated symptoms may warrant workup with antinuclear antibodies and other appropriate autoimmune serologies.

If there is any doubt of the diagnosis, the patient is experiencing symptoms from the lesion, or the patient is experiencing other viral symptoms, it is appropriate to biopsy immediately to confirm the diagnosis. Prior studies have identified fibrin clots, angiocentric and eccrinotropic lymphocytic infiltrates, lymphocytic vasculopathy, and papillary dermal edema as the most common features in chilblainslike lesions during the COVID-19 pandemic.⁹

For COVID-19 testing, many studies have revealed adult patients with an acute hypercoagulable state testing positive by SARS-CoV-2 PCR. These same patients also experienced thromboembolic events shortly after testing positive for COVID-19, which suggests that patients with elevated D-dimer and fibrinogen likely will have a viral load that is sufficient to test positive for COVID-19.^32,34-36 It is appropriate to test all patients with suspected COVID-19, especially adults who are more likely to experience adverse complications secondary to infection.

This patient experiencing COVID-19 symptoms with signs of acral ischemia is likely to test positive by PCR, and additional testing for serologic antibodies is unlikely to be clinically meaningful in this patient’s state. Furthermore, there is little evidence that serology is reliable because of the markedly high levels of both false-negative and false-positive results when using the available antibody testing kits.³⁷ The latter evidence makes serology testing of little value for the general population, but particularly for patients with acute COVID-19.

Conclusion and Outstanding Questions

There is evidence suggesting an association between chilblainslike lesions and COVID-19.^11,22,38,39 Children presenting with these lesions have an excellent prognosis and only need a workup or treatment if there are other symptoms, as the lesions self-resolve in the majority of reported cases.^7-9 Adults presenting with these lesions and without symptoms likewise are unlikely to test positive for COVID-19, and the lesions typically resolve spontaneously or with first-line treatment. However, adults presenting with these lesions and COVID-19 symptoms should raise clinical concern for evolving skin manifestations of acro-ischemia. If the diagnosis is uncertain or systemic symptoms are concerning, biopsy, COVID-19 PCR, and other appropriate laboratory workup should be obtained.

There remains controversy and uncertainty over the relationship between these skin findings and SARS-CoV-2 infection, with clinical evidence to support both a direct relationship representing convalescent-phase cutaneous reaction as well as an indirect epiphenomenon. If there was a direct relationship, we would have expected to see a rise in the incidence of acral lesions proportionate to the rising caseload of COVID-19 after the reopening of many states in the summer of 2020. Similarly, because young adults represent the largest demographic of increasing cases and as some schools have remained open for in-person instruction during the current academic year, we also would have expected the incidence of chilblains-like lesions presenting to dermatologists and pediatricians to increase alongside these cases. Continued evaluation of emerging literature and ongoing efforts to understand the cause of this observed phenomenon will hopefully help us arrive at a future understanding of the pathophysiology of this puzzling skin manifestation.⁴⁰

Hidradenitis suppurativa (HS)(also known as acne inversa) is a chronic, recurrent, and debilitating inflammatory dermatologic disease of the hair follicle. It usually presents after puberty, with painful, deep-seated, inflamed lesions in apocrine gland–bearing areas of the body, most commonly the axillae and inguinal and anogenital regions.¹

Hidradenitis suppurativa patients have a high rate of psychologic and psychiatric comorbidities that often are interrelated and multidirectional. Approximately 1 in 4 adults with HS also experience depression (prevalence among all HS patients, 16.9%), and 1 in 5 experience anxiety (prevalence, 4.9%).^2,3 Hidradenitis suppurativa has been associated with bipolar disorder, schizophrenia, and suicidality.^2,4

These comorbidity factors have a remarkable impact on HS patients’ quality of life (QOL). Compared to other diseases, including psoriasis, stroke, and conditions that create candidacy for heart transplantation, HS was identified as the most impairing condition.^5,6 It is estimated that more than 50% of HS patients experience a very or extremely large effect on their QOL, as measured by the dermatology life quality index.⁶

Pain, a major component of low QOL in HS patients, has an adverse impact on emotional health. Hidradenitis suppurativa causes body image dissatisfaction, leading to shame, embarrassment, lack of self-confidence, stigmatization, and social isolation.^7-9 Furthermore, patients with HS have an increased risk for antidepressant drug use, completed suicide, and suicidal behavior compared to the general population.¹⁰

Focusing therapy on physical manifestations of HS only while ignoring the psychologic aspect could lead to a vicious cycle in which stress triggers flares, leading to worsening HS, leading to more stress, and so on.¹¹ Therefore, psychological support for HS patients is critical, and we believe it should be an integral part of managing the disease.

There is no evidence to support effective therapeutic intervention for psychological aspects of HS. We conducted a PubMed search of articles indexed for MEDLINE using the term hidradenitis in combination with psychology, psychological, mindfulness, and cognitive behavioral therapy. No relevant articles were found. Most articles on HS focused on the low QOL associated with the disease and patient coping mechanisms. However, there are a number of psychological therapies to consider and evaluate for the management of HS.

Psychological Therapies to Consider in HS

Cognitive Behavioral Treatment
Cognitive behavioral treatment has been successfully used to manage skin diseases other than HS.¹² Patients’ shame and stigmatization due to body dissatisfaction often cause social isolation, which might appear as social anxiety.^9,13 Cognitive behavioral treatment, or compassion-focused therapy, could increase patients’ self-acceptance and reduce shameful feelings.¹³

Group Therapy
Alternatively, group therapy might be beneficial for HS patients. Research has shown that most HS patients know others affected by the same disease or attend an HS support group, and patients value the support of peers with the disease.¹³ Therefore, group therapy meetings with HS patients that are directed by a health care professional might reduce feelings of shame and stigmatization and increase feelings of social acceptance.

Mindfulness
Another approach for managing psychological aspects of skin diseases that might be useful in HS is mindfulness-based stress reduction (MBSR), developed by Kabat-Zinn and colleagues,¹⁴ which helps patients develop mindfulness through training in meditation. It is an intensive, structured, patient-centered approach that has been successfully used in a variety of settings.^14,15

Current evidence supports the use of MBSR in the adjunct treatment of chronic pain, anxiety, and depression—symptoms that have a great impact on HS patients’ QOL.¹⁶ Furthermore, MBSR is offered in a group setting, which is potentially an opportunity for peer support and understanding; social support has been reported to be highly beneficial for HS patients.¹⁷

Can the Placebo Effect Aid in Managing HS?

A recent review that assessed the placebo effect in randomized clinical trials (RCTs) of treatments for cutaneous disease demonstrated that the placebo effect in HS therapy trials is higher than in RCTs of therapies for psoriasis and eczema. This finding highlights the importance of the physician-patient relationship when managing HS, which can result in greater treatment adherence and more patient education, empowerment, and encouragement toward beneficial lifestyle changes.¹⁸

Complementary psychological interventions for managing HS might maximize the placebo effect in clinical practice.¹⁸ The placebo effect in RCTs is higher for HS treatments than for psoriasis treatments, and if patients with psoriasis improved with psychological interventions,¹² it would be reasonable to expect an improvement in QOL with psychological interventions for HS.

Final Thoughts

Although a number of studies have been published in the medical literature regarding psychological intervention in psoriasis management,¹² we found no clinical studies assessing the psychological management of HS. We conclude that more research is necessary to develop psychological interventions targeting HS patients because a multidisciplinary and patient-centered approach is essential for the management of HS.

Hidradenitis suppurativa (HS)(also known as acne inversa) is a chronic, recurrent, and debilitating inflammatory dermatologic disease of the hair follicle. It usually presents after puberty, with painful, deep-seated, inflamed lesions in apocrine gland–bearing areas of the body, most commonly the axillae and inguinal and anogenital regions.¹

Hidradenitis suppurativa patients have a high rate of psychologic and psychiatric comorbidities that often are interrelated and multidirectional. Approximately 1 in 4 adults with HS also experience depression (prevalence among all HS patients, 16.9%), and 1 in 5 experience anxiety (prevalence, 4.9%).^2,3 Hidradenitis suppurativa has been associated with bipolar disorder, schizophrenia, and suicidality.^2,4

These comorbidity factors have a remarkable impact on HS patients’ quality of life (QOL). Compared to other diseases, including psoriasis, stroke, and conditions that create candidacy for heart transplantation, HS was identified as the most impairing condition.^5,6 It is estimated that more than 50% of HS patients experience a very or extremely large effect on their QOL, as measured by the dermatology life quality index.⁶

Pain, a major component of low QOL in HS patients, has an adverse impact on emotional health. Hidradenitis suppurativa causes body image dissatisfaction, leading to shame, embarrassment, lack of self-confidence, stigmatization, and social isolation.^7-9 Furthermore, patients with HS have an increased risk for antidepressant drug use, completed suicide, and suicidal behavior compared to the general population.¹⁰

Focusing therapy on physical manifestations of HS only while ignoring the psychologic aspect could lead to a vicious cycle in which stress triggers flares, leading to worsening HS, leading to more stress, and so on.¹¹ Therefore, psychological support for HS patients is critical, and we believe it should be an integral part of managing the disease.

There is no evidence to support effective therapeutic intervention for psychological aspects of HS. We conducted a PubMed search of articles indexed for MEDLINE using the term hidradenitis in combination with psychology, psychological, mindfulness, and cognitive behavioral therapy. No relevant articles were found. Most articles on HS focused on the low QOL associated with the disease and patient coping mechanisms. However, there are a number of psychological therapies to consider and evaluate for the management of HS.

Psychological Therapies to Consider in HS

Cognitive Behavioral Treatment
Cognitive behavioral treatment has been successfully used to manage skin diseases other than HS.¹² Patients’ shame and stigmatization due to body dissatisfaction often cause social isolation, which might appear as social anxiety.^9,13 Cognitive behavioral treatment, or compassion-focused therapy, could increase patients’ self-acceptance and reduce shameful feelings.¹³

Group Therapy
Alternatively, group therapy might be beneficial for HS patients. Research has shown that most HS patients know others affected by the same disease or attend an HS support group, and patients value the support of peers with the disease.¹³ Therefore, group therapy meetings with HS patients that are directed by a health care professional might reduce feelings of shame and stigmatization and increase feelings of social acceptance.

Mindfulness
Another approach for managing psychological aspects of skin diseases that might be useful in HS is mindfulness-based stress reduction (MBSR), developed by Kabat-Zinn and colleagues,¹⁴ which helps patients develop mindfulness through training in meditation. It is an intensive, structured, patient-centered approach that has been successfully used in a variety of settings.^14,15

Current evidence supports the use of MBSR in the adjunct treatment of chronic pain, anxiety, and depression—symptoms that have a great impact on HS patients’ QOL.¹⁶ Furthermore, MBSR is offered in a group setting, which is potentially an opportunity for peer support and understanding; social support has been reported to be highly beneficial for HS patients.¹⁷

Can the Placebo Effect Aid in Managing HS?

A recent review that assessed the placebo effect in randomized clinical trials (RCTs) of treatments for cutaneous disease demonstrated that the placebo effect in HS therapy trials is higher than in RCTs of therapies for psoriasis and eczema. This finding highlights the importance of the physician-patient relationship when managing HS, which can result in greater treatment adherence and more patient education, empowerment, and encouragement toward beneficial lifestyle changes.¹⁸

Complementary psychological interventions for managing HS might maximize the placebo effect in clinical practice.¹⁸ The placebo effect in RCTs is higher for HS treatments than for psoriasis treatments, and if patients with psoriasis improved with psychological interventions,¹² it would be reasonable to expect an improvement in QOL with psychological interventions for HS.

Final Thoughts

Although a number of studies have been published in the medical literature regarding psychological intervention in psoriasis management,¹² we found no clinical studies assessing the psychological management of HS. We conclude that more research is necessary to develop psychological interventions targeting HS patients because a multidisciplinary and patient-centered approach is essential for the management of HS.

Hidradenitis suppurativa (HS)(also known as acne inversa) is a chronic, recurrent, and debilitating inflammatory dermatologic disease of the hair follicle. It usually presents after puberty, with painful, deep-seated, inflamed lesions in apocrine gland–bearing areas of the body, most commonly the axillae and inguinal and anogenital regions.¹

Hidradenitis suppurativa patients have a high rate of psychologic and psychiatric comorbidities that often are interrelated and multidirectional. Approximately 1 in 4 adults with HS also experience depression (prevalence among all HS patients, 16.9%), and 1 in 5 experience anxiety (prevalence, 4.9%).^2,3 Hidradenitis suppurativa has been associated with bipolar disorder, schizophrenia, and suicidality.^2,4

These comorbidity factors have a remarkable impact on HS patients’ quality of life (QOL). Compared to other diseases, including psoriasis, stroke, and conditions that create candidacy for heart transplantation, HS was identified as the most impairing condition.^5,6 It is estimated that more than 50% of HS patients experience a very or extremely large effect on their QOL, as measured by the dermatology life quality index.⁶

Pain, a major component of low QOL in HS patients, has an adverse impact on emotional health. Hidradenitis suppurativa causes body image dissatisfaction, leading to shame, embarrassment, lack of self-confidence, stigmatization, and social isolation.^7-9 Furthermore, patients with HS have an increased risk for antidepressant drug use, completed suicide, and suicidal behavior compared to the general population.¹⁰

Focusing therapy on physical manifestations of HS only while ignoring the psychologic aspect could lead to a vicious cycle in which stress triggers flares, leading to worsening HS, leading to more stress, and so on.¹¹ Therefore, psychological support for HS patients is critical, and we believe it should be an integral part of managing the disease.

There is no evidence to support effective therapeutic intervention for psychological aspects of HS. We conducted a PubMed search of articles indexed for MEDLINE using the term hidradenitis in combination with psychology, psychological, mindfulness, and cognitive behavioral therapy. No relevant articles were found. Most articles on HS focused on the low QOL associated with the disease and patient coping mechanisms. However, there are a number of psychological therapies to consider and evaluate for the management of HS.

Psychological Therapies to Consider in HS

Cognitive Behavioral Treatment
Cognitive behavioral treatment has been successfully used to manage skin diseases other than HS.¹² Patients’ shame and stigmatization due to body dissatisfaction often cause social isolation, which might appear as social anxiety.^9,13 Cognitive behavioral treatment, or compassion-focused therapy, could increase patients’ self-acceptance and reduce shameful feelings.¹³

Group Therapy
Alternatively, group therapy might be beneficial for HS patients. Research has shown that most HS patients know others affected by the same disease or attend an HS support group, and patients value the support of peers with the disease.¹³ Therefore, group therapy meetings with HS patients that are directed by a health care professional might reduce feelings of shame and stigmatization and increase feelings of social acceptance.

Mindfulness
Another approach for managing psychological aspects of skin diseases that might be useful in HS is mindfulness-based stress reduction (MBSR), developed by Kabat-Zinn and colleagues,¹⁴ which helps patients develop mindfulness through training in meditation. It is an intensive, structured, patient-centered approach that has been successfully used in a variety of settings.^14,15

Current evidence supports the use of MBSR in the adjunct treatment of chronic pain, anxiety, and depression—symptoms that have a great impact on HS patients’ QOL.¹⁶ Furthermore, MBSR is offered in a group setting, which is potentially an opportunity for peer support and understanding; social support has been reported to be highly beneficial for HS patients.¹⁷

Can the Placebo Effect Aid in Managing HS?

A recent review that assessed the placebo effect in randomized clinical trials (RCTs) of treatments for cutaneous disease demonstrated that the placebo effect in HS therapy trials is higher than in RCTs of therapies for psoriasis and eczema. This finding highlights the importance of the physician-patient relationship when managing HS, which can result in greater treatment adherence and more patient education, empowerment, and encouragement toward beneficial lifestyle changes.¹⁸

Complementary psychological interventions for managing HS might maximize the placebo effect in clinical practice.¹⁸ The placebo effect in RCTs is higher for HS treatments than for psoriasis treatments, and if patients with psoriasis improved with psychological interventions,¹² it would be reasonable to expect an improvement in QOL with psychological interventions for HS.

Final Thoughts

Although a number of studies have been published in the medical literature regarding psychological intervention in psoriasis management,¹² we found no clinical studies assessing the psychological management of HS. We conclude that more research is necessary to develop psychological interventions targeting HS patients because a multidisciplinary and patient-centered approach is essential for the management of HS.

Recent studies have found poor representation of darker skin types (defined as Fitzpatrick skin types V–VI) in dermatology textbooks and online resources.^1,2 We sought to evaluate representation of darker skin types in the Basic Dermatology Curriculum of the American Academy of Dermatology (AAD), an online curriculum of 35 lectures that serves as a standard curriculum for dermatologic education, particularly for medical students and residents without a home dermatology program.³ Although core dermatology knowledge was specified as a curricular goal, knowledge of how dermatologic conditions manifest across various skin types was not.³

Methods

Photographs from all Basic Dermatology Curriculum online lectures showing background skin were independently labeled by 3 investigators (B.C., R.F., and G.O.) as light skin (Fitzpatrick types I–IV) or dark skin (Fitzpatrick types V–VI), along with the associated diagnosis. Photographs without visible background skin were excluded (eg, mucous membranes, palms and soles, genitalia, scalp, dermoscopic images). Photographs with indeterminate skin type were evaluated by consensus and excluded if consensus could not be reached. Inter-rater reliability for labeling skin type was determined on an overlapping sample of 24 photographs (Fleiss’s κ, 0.80).

Results

Of 666 included photographs, 104 (15.6%) featured dark skin. Of all photographs of light skin (Fitzpatrick type I–IV), 80.8% were Fitzpatrick types I and II. One-quarter of lectures featured no photographs of dark skin (Figure 1). When the associated diagnoses of photographs were organized into 20 categories, 4 categories—pigmentary disorders, HIV infection, sexually transmitted infections and warts, and papulosquamous eruptions (Figure 2)—each featured 25% or more photographs of dark skin.

Comment

Our analysis of curricular photographs found dark skin representation in 16% of photographs, mirroring earlier findings in other educational resources.^1,2 There was little (<5%) representation of skin cancer in individuals with darker skin, which may merely reflect lower incidence, but there is concern that lack of education about skin cancer might contribute to disparities in care, such as delayed diagnosis.²

For some conditions common in darker-skinned patients, such as acne vulgaris, representation was low; the lecture “Acne vulgaris” featured only 1 photograph of dark skin. In contrast, dark skin types were well represented in photographs of sexually transmitted infections, such as HIV infection, syphilis, and warts, which may suggest bias when dark skin is chosen to represent diseases, as noted in prior findings.^1,2

Limitations of this study included individual judgment of skin type and use of the Fitzpatrick scale. Although inter-rater reliability was excellent, the validity of Fitzpatrick classification of skin color is controversial, given that it was intended to describe propensity for sunburn and that types V to VI were added later to describe darker skin.⁴

Suggestions for Improvement
Given the abundance of resources with depictions of skin of color in teaching materials (eg, Taylor and Kelly’s Dermatology for Skin of Color, Ethnic Dermatology: Principles and Practice) and digital resources (eg, VisualDx [https://www.visualdx.com]), a logical solution might be to add a greater percentage of photographs depicting darker skin from outside resources to address the imbalance. Still, this might be challenging with limited space. Often, there is only room for a single representative photograph. Therefore, greater effort must be made to consistently show how diseases might present variably on different background skin types or, at the least, to create new resources showing greater skin type diversity.

Furthermore, given the lack of representation of skin of color, authors of educational resources can prioritize capturing images of skin pathology presenting in darker skin during their clinical work. Authors who do not have access to a substantial census of patients with darker skin can collaborate with dermatologists who specialize in skin of color to gather such images.

Technical issues include difficulty capturing high-quality images of dermatologic conditions in darker skin because eruptions in these patients might have a narrower range of contrast. Although resources on taking high-quality clinical images are widely available, specific advice for photographing darker skin is lacking and warrants future research.^5-7 Collaboration with professional photographers who are experienced with clients with darker skin might be useful in developing guidelines.

Conclusion

Given recent guidance by the AAD to “include common skin disorders and diseases requiring special consideration in people with skin of color” and highlight “current disparities in health outcomes within dermatology,”⁸ our findings might guide future improvements in curricula.

Recent studies have found poor representation of darker skin types (defined as Fitzpatrick skin types V–VI) in dermatology textbooks and online resources.^1,2 We sought to evaluate representation of darker skin types in the Basic Dermatology Curriculum of the American Academy of Dermatology (AAD), an online curriculum of 35 lectures that serves as a standard curriculum for dermatologic education, particularly for medical students and residents without a home dermatology program.³ Although core dermatology knowledge was specified as a curricular goal, knowledge of how dermatologic conditions manifest across various skin types was not.³

Methods

Photographs from all Basic Dermatology Curriculum online lectures showing background skin were independently labeled by 3 investigators (B.C., R.F., and G.O.) as light skin (Fitzpatrick types I–IV) or dark skin (Fitzpatrick types V–VI), along with the associated diagnosis. Photographs without visible background skin were excluded (eg, mucous membranes, palms and soles, genitalia, scalp, dermoscopic images). Photographs with indeterminate skin type were evaluated by consensus and excluded if consensus could not be reached. Inter-rater reliability for labeling skin type was determined on an overlapping sample of 24 photographs (Fleiss’s κ, 0.80).

Results

Of 666 included photographs, 104 (15.6%) featured dark skin. Of all photographs of light skin (Fitzpatrick type I–IV), 80.8% were Fitzpatrick types I and II. One-quarter of lectures featured no photographs of dark skin (Figure 1). When the associated diagnoses of photographs were organized into 20 categories, 4 categories—pigmentary disorders, HIV infection, sexually transmitted infections and warts, and papulosquamous eruptions (Figure 2)—each featured 25% or more photographs of dark skin.

Comment

Our analysis of curricular photographs found dark skin representation in 16% of photographs, mirroring earlier findings in other educational resources.^1,2 There was little (<5%) representation of skin cancer in individuals with darker skin, which may merely reflect lower incidence, but there is concern that lack of education about skin cancer might contribute to disparities in care, such as delayed diagnosis.²

For some conditions common in darker-skinned patients, such as acne vulgaris, representation was low; the lecture “Acne vulgaris” featured only 1 photograph of dark skin. In contrast, dark skin types were well represented in photographs of sexually transmitted infections, such as HIV infection, syphilis, and warts, which may suggest bias when dark skin is chosen to represent diseases, as noted in prior findings.^1,2

Limitations of this study included individual judgment of skin type and use of the Fitzpatrick scale. Although inter-rater reliability was excellent, the validity of Fitzpatrick classification of skin color is controversial, given that it was intended to describe propensity for sunburn and that types V to VI were added later to describe darker skin.⁴

Suggestions for Improvement
Given the abundance of resources with depictions of skin of color in teaching materials (eg, Taylor and Kelly’s Dermatology for Skin of Color, Ethnic Dermatology: Principles and Practice) and digital resources (eg, VisualDx [https://www.visualdx.com]), a logical solution might be to add a greater percentage of photographs depicting darker skin from outside resources to address the imbalance. Still, this might be challenging with limited space. Often, there is only room for a single representative photograph. Therefore, greater effort must be made to consistently show how diseases might present variably on different background skin types or, at the least, to create new resources showing greater skin type diversity.

Furthermore, given the lack of representation of skin of color, authors of educational resources can prioritize capturing images of skin pathology presenting in darker skin during their clinical work. Authors who do not have access to a substantial census of patients with darker skin can collaborate with dermatologists who specialize in skin of color to gather such images.

Technical issues include difficulty capturing high-quality images of dermatologic conditions in darker skin because eruptions in these patients might have a narrower range of contrast. Although resources on taking high-quality clinical images are widely available, specific advice for photographing darker skin is lacking and warrants future research.^5-7 Collaboration with professional photographers who are experienced with clients with darker skin might be useful in developing guidelines.

Conclusion

Given recent guidance by the AAD to “include common skin disorders and diseases requiring special consideration in people with skin of color” and highlight “current disparities in health outcomes within dermatology,”⁸ our findings might guide future improvements in curricula.

Recent studies have found poor representation of darker skin types (defined as Fitzpatrick skin types V–VI) in dermatology textbooks and online resources.^1,2 We sought to evaluate representation of darker skin types in the Basic Dermatology Curriculum of the American Academy of Dermatology (AAD), an online curriculum of 35 lectures that serves as a standard curriculum for dermatologic education, particularly for medical students and residents without a home dermatology program.³ Although core dermatology knowledge was specified as a curricular goal, knowledge of how dermatologic conditions manifest across various skin types was not.³

Methods

Photographs from all Basic Dermatology Curriculum online lectures showing background skin were independently labeled by 3 investigators (B.C., R.F., and G.O.) as light skin (Fitzpatrick types I–IV) or dark skin (Fitzpatrick types V–VI), along with the associated diagnosis. Photographs without visible background skin were excluded (eg, mucous membranes, palms and soles, genitalia, scalp, dermoscopic images). Photographs with indeterminate skin type were evaluated by consensus and excluded if consensus could not be reached. Inter-rater reliability for labeling skin type was determined on an overlapping sample of 24 photographs (Fleiss’s κ, 0.80).

Results

Of 666 included photographs, 104 (15.6%) featured dark skin. Of all photographs of light skin (Fitzpatrick type I–IV), 80.8% were Fitzpatrick types I and II. One-quarter of lectures featured no photographs of dark skin (Figure 1). When the associated diagnoses of photographs were organized into 20 categories, 4 categories—pigmentary disorders, HIV infection, sexually transmitted infections and warts, and papulosquamous eruptions (Figure 2)—each featured 25% or more photographs of dark skin.

Comment

Our analysis of curricular photographs found dark skin representation in 16% of photographs, mirroring earlier findings in other educational resources.^1,2 There was little (<5%) representation of skin cancer in individuals with darker skin, which may merely reflect lower incidence, but there is concern that lack of education about skin cancer might contribute to disparities in care, such as delayed diagnosis.²

For some conditions common in darker-skinned patients, such as acne vulgaris, representation was low; the lecture “Acne vulgaris” featured only 1 photograph of dark skin. In contrast, dark skin types were well represented in photographs of sexually transmitted infections, such as HIV infection, syphilis, and warts, which may suggest bias when dark skin is chosen to represent diseases, as noted in prior findings.^1,2

Limitations of this study included individual judgment of skin type and use of the Fitzpatrick scale. Although inter-rater reliability was excellent, the validity of Fitzpatrick classification of skin color is controversial, given that it was intended to describe propensity for sunburn and that types V to VI were added later to describe darker skin.⁴

Suggestions for Improvement
Given the abundance of resources with depictions of skin of color in teaching materials (eg, Taylor and Kelly’s Dermatology for Skin of Color, Ethnic Dermatology: Principles and Practice) and digital resources (eg, VisualDx [https://www.visualdx.com]), a logical solution might be to add a greater percentage of photographs depicting darker skin from outside resources to address the imbalance. Still, this might be challenging with limited space. Often, there is only room for a single representative photograph. Therefore, greater effort must be made to consistently show how diseases might present variably on different background skin types or, at the least, to create new resources showing greater skin type diversity.

Furthermore, given the lack of representation of skin of color, authors of educational resources can prioritize capturing images of skin pathology presenting in darker skin during their clinical work. Authors who do not have access to a substantial census of patients with darker skin can collaborate with dermatologists who specialize in skin of color to gather such images.

Technical issues include difficulty capturing high-quality images of dermatologic conditions in darker skin because eruptions in these patients might have a narrower range of contrast. Although resources on taking high-quality clinical images are widely available, specific advice for photographing darker skin is lacking and warrants future research.^5-7 Collaboration with professional photographers who are experienced with clients with darker skin might be useful in developing guidelines.

Conclusion

Given recent guidance by the AAD to “include common skin disorders and diseases requiring special consideration in people with skin of color” and highlight “current disparities in health outcomes within dermatology,”⁸ our findings might guide future improvements in curricula.

The use of mobile devices in health care settings has enhanced clinical practice through real-time communication and direct patient monitoring.¹ With advancements in technology, improving the accessibility and quality of patient care using mobile devices is a hot topic. In 2018, 261.34 million people worldwide used smartphones compared to 280.54 million in 2021—a 7.3% increase.² Revenue from sales of mobile applications (apps) is projected to reach $693 billion in 2021.³

A range of apps targeted to patients is available for acne, melanoma, and teledermatology.^4-6 Nail disorders are a common concern, representing 21.1 million outpatient visits in 2007 to 2016,⁷ but, to date, the availability of apps related to nail disorders has not been explored. In this study, we investigated iOS (Apple’s iPhone Operating System) and Android apps to determine the types of nail health apps that are available, using psoriasis and hair loss apps as comparator groups.

Methods

A standard app analytics and market data tool (App Annie; https://www.appannie.com/en/) was utilized to search for iOS and Android nail mobile apps.^4,5 The analysis was performed on a single day (March 23, 2020), given that app searches can change on a daily basis. Our search included the following keywords: nail, nail health, toenail fungus, nail tumor, brittle nails, onychomycosis, onycholysis, subungual melanoma, nail melanoma, paronychia, and nail squamous cell carcinoma. App Annie app descriptions were assessed to determine the type of each app (Lifestyle, Medical, Health & Fitness) and target audience (patient, physician, or both). Psoriasis and hair loss topics were chosen as controls for comparison, based on a prior study.⁸ For psoriasis, the keywords psoriasis and chronic skin disease were searched. Hair loss was searched using the keywords alopecia, hair loss, hair health, and scalp.

Results

Nail-Related Apps
Using keywords for nail-related terms on iOS and Android platforms, our search returned few specific and informative apps related to nail disorders (Table 1). When the terms brittle nails, nail, nail health, nail squamous cell carcinoma, and nail tumor were searched, all available nail apps were either nail games or virtual nail salons for entertainment purposes. For the terms nail melanoma and subungual melanoma, there were no specific nail apps that appeared in the search results; rather, the App Annie search yielded only general dermatology and melanoma apps. The terms onycholysis and paronychia both yielded 0 hits for iOS and Android.

The only search terms that returned specific nail apps were onychomycosis and toenail fungus. Initially, when onychomycosis was searched, only 1 Google Play Medical category app was found: “Nail fungal infection (model onychomycosis).” Although this app recently was removed from the app store, it previously allowed the user to upload a nail photograph, with which a computing algorithm assessed whether the presentation was a fungal nail infection. Toenail fungus returned 1 iOS Medical category app and 5 Android Health & Fitness category apps with reference material for patients. Neither of the 2 medical apps for onychomycosis and toenail fungus referenced a physician involved in the app development.

Psoriasis Comparator
On the contrary, a search for psoriasis yielded 22 hits for iOS and 34 hits for Android within the Health & Fitness, Medical, and Social Networking categories (Table 2). The search term chronic skin disease returned 18 apps for iOS and 60 apps for Android related to psoriasis; 100% were classified as Medical apps.

Other Findings
Most apps for psoriasis and hair health were identified as patient focused. Although iOS and Android are different operating systems, some health apps overlapped: subungual melanoma and toenail fungus had a 20% overlap; psoriasis, 19%; chronic skin disease, 2%; alopecia, 0%; hair loss and hair health, 10%; and scalp, 18%. iOS and Android nail entertainment games had approximately a 30% overlap. Tables 1 and 2 also compare the number of free and paid apps; most available apps were free.

Comment

With continued growth in mobile device ownership and app development has been parallel growth in the creation and use of apps to enhance medical care.¹ In a study analyzing the most popular dermatology apps, 62% (18/29) and 38% (11/29) of apps targeted patients and physicians, respectively.⁶ Our study showed that (1) there are few nail disorder apps available for patient education and (2) there is no evidence that a physician was consulted for content input. Because patients who can effectively communicate their health concerns before and after seeing a physician have better self-reported clinical outcomes,⁹ it is important to have nail disorder apps available to patients for referencing. The nail health app options differ notably from psoriasis and hair loss apps, with apps for the latter 2 topics found in Medical and Health & Fitness categories—targeting patients who seek immediate access to health care and education.

Although there are several general dermatology apps that contain reference information for patients pertaining to nail conditions,⁶ using any of those apps would require a patient to have prior knowledge that dermatologists specialize in nail disorders and necessitate several steps to find nail-relevant information. For example, the patient would have to search dermatology in the iOS and Android app stores, select the available app (eg, Dermatology Database), and then search within that app for nail disorders. Therefore, a patient who is concerned about a possible subungual melanoma would not be able to easily find clinical images and explanations using an app.

Study Limitations
This study was subject to several limitations. Android and iOS app stores have undisclosed computing algorithms that might have filtered apps based on specific word inquiry. Also, our queries were based on specific relevant keywords for nail conditions, psoriasis, and hair loss; use of different keywords might have yielded different results. Additionally, app options change on a daily basis, so a search today (ie, any given day) might yield slightly different results than it did on March 23, 2020.

Conclusion

Specific nail disorder apps available for patient reference are limited. App developers should consider accessibility (ie, clear language, ease of use, cost-effectiveness, usability on iOS- and Android-operated devices) and content (accurate medical information from experts) when considering new apps. A solution to this problem is for established medical organizations to create nail disorder apps specifically for patients.¹⁰ For example, the American Academy of Dermatology has iOS and Android apps that are relevant to physicians (MyDermPath+, Dialogues in Dermatology, Mohs Surgery Appropriate Use Criteria) but no comparable apps for patients; patient-appropriate nail apps are necessary.¹¹ In addition, it would be beneficial to patients if established app companies consulted with dermatologists on pertinent nail content.

In sum, we found few available nail health apps on the iOS or Android platforms that provided accessible and timely information to patients regarding nail disorders. There is an immediate need to produce apps related to nail health for appropriate patient education.

The use of mobile devices in health care settings has enhanced clinical practice through real-time communication and direct patient monitoring.¹ With advancements in technology, improving the accessibility and quality of patient care using mobile devices is a hot topic. In 2018, 261.34 million people worldwide used smartphones compared to 280.54 million in 2021—a 7.3% increase.² Revenue from sales of mobile applications (apps) is projected to reach $693 billion in 2021.³

A range of apps targeted to patients is available for acne, melanoma, and teledermatology.^4-6 Nail disorders are a common concern, representing 21.1 million outpatient visits in 2007 to 2016,⁷ but, to date, the availability of apps related to nail disorders has not been explored. In this study, we investigated iOS (Apple’s iPhone Operating System) and Android apps to determine the types of nail health apps that are available, using psoriasis and hair loss apps as comparator groups.

Methods

A standard app analytics and market data tool (App Annie; https://www.appannie.com/en/) was utilized to search for iOS and Android nail mobile apps.^4,5 The analysis was performed on a single day (March 23, 2020), given that app searches can change on a daily basis. Our search included the following keywords: nail, nail health, toenail fungus, nail tumor, brittle nails, onychomycosis, onycholysis, subungual melanoma, nail melanoma, paronychia, and nail squamous cell carcinoma. App Annie app descriptions were assessed to determine the type of each app (Lifestyle, Medical, Health & Fitness) and target audience (patient, physician, or both). Psoriasis and hair loss topics were chosen as controls for comparison, based on a prior study.⁸ For psoriasis, the keywords psoriasis and chronic skin disease were searched. Hair loss was searched using the keywords alopecia, hair loss, hair health, and scalp.

Results

Nail-Related Apps
Using keywords for nail-related terms on iOS and Android platforms, our search returned few specific and informative apps related to nail disorders (Table 1). When the terms brittle nails, nail, nail health, nail squamous cell carcinoma, and nail tumor were searched, all available nail apps were either nail games or virtual nail salons for entertainment purposes. For the terms nail melanoma and subungual melanoma, there were no specific nail apps that appeared in the search results; rather, the App Annie search yielded only general dermatology and melanoma apps. The terms onycholysis and paronychia both yielded 0 hits for iOS and Android.

The only search terms that returned specific nail apps were onychomycosis and toenail fungus. Initially, when onychomycosis was searched, only 1 Google Play Medical category app was found: “Nail fungal infection (model onychomycosis).” Although this app recently was removed from the app store, it previously allowed the user to upload a nail photograph, with which a computing algorithm assessed whether the presentation was a fungal nail infection. Toenail fungus returned 1 iOS Medical category app and 5 Android Health & Fitness category apps with reference material for patients. Neither of the 2 medical apps for onychomycosis and toenail fungus referenced a physician involved in the app development.

Psoriasis Comparator
On the contrary, a search for psoriasis yielded 22 hits for iOS and 34 hits for Android within the Health & Fitness, Medical, and Social Networking categories (Table 2). The search term chronic skin disease returned 18 apps for iOS and 60 apps for Android related to psoriasis; 100% were classified as Medical apps.

Other Findings
Most apps for psoriasis and hair health were identified as patient focused. Although iOS and Android are different operating systems, some health apps overlapped: subungual melanoma and toenail fungus had a 20% overlap; psoriasis, 19%; chronic skin disease, 2%; alopecia, 0%; hair loss and hair health, 10%; and scalp, 18%. iOS and Android nail entertainment games had approximately a 30% overlap. Tables 1 and 2 also compare the number of free and paid apps; most available apps were free.

Comment

With continued growth in mobile device ownership and app development has been parallel growth in the creation and use of apps to enhance medical care.¹ In a study analyzing the most popular dermatology apps, 62% (18/29) and 38% (11/29) of apps targeted patients and physicians, respectively.⁶ Our study showed that (1) there are few nail disorder apps available for patient education and (2) there is no evidence that a physician was consulted for content input. Because patients who can effectively communicate their health concerns before and after seeing a physician have better self-reported clinical outcomes,⁹ it is important to have nail disorder apps available to patients for referencing. The nail health app options differ notably from psoriasis and hair loss apps, with apps for the latter 2 topics found in Medical and Health & Fitness categories—targeting patients who seek immediate access to health care and education.

Although there are several general dermatology apps that contain reference information for patients pertaining to nail conditions,⁶ using any of those apps would require a patient to have prior knowledge that dermatologists specialize in nail disorders and necessitate several steps to find nail-relevant information. For example, the patient would have to search dermatology in the iOS and Android app stores, select the available app (eg, Dermatology Database), and then search within that app for nail disorders. Therefore, a patient who is concerned about a possible subungual melanoma would not be able to easily find clinical images and explanations using an app.

Study Limitations
This study was subject to several limitations. Android and iOS app stores have undisclosed computing algorithms that might have filtered apps based on specific word inquiry. Also, our queries were based on specific relevant keywords for nail conditions, psoriasis, and hair loss; use of different keywords might have yielded different results. Additionally, app options change on a daily basis, so a search today (ie, any given day) might yield slightly different results than it did on March 23, 2020.

Conclusion

Specific nail disorder apps available for patient reference are limited. App developers should consider accessibility (ie, clear language, ease of use, cost-effectiveness, usability on iOS- and Android-operated devices) and content (accurate medical information from experts) when considering new apps. A solution to this problem is for established medical organizations to create nail disorder apps specifically for patients.¹⁰ For example, the American Academy of Dermatology has iOS and Android apps that are relevant to physicians (MyDermPath+, Dialogues in Dermatology, Mohs Surgery Appropriate Use Criteria) but no comparable apps for patients; patient-appropriate nail apps are necessary.¹¹ In addition, it would be beneficial to patients if established app companies consulted with dermatologists on pertinent nail content.

In sum, we found few available nail health apps on the iOS or Android platforms that provided accessible and timely information to patients regarding nail disorders. There is an immediate need to produce apps related to nail health for appropriate patient education.

The use of mobile devices in health care settings has enhanced clinical practice through real-time communication and direct patient monitoring.¹ With advancements in technology, improving the accessibility and quality of patient care using mobile devices is a hot topic. In 2018, 261.34 million people worldwide used smartphones compared to 280.54 million in 2021—a 7.3% increase.² Revenue from sales of mobile applications (apps) is projected to reach $693 billion in 2021.³

A range of apps targeted to patients is available for acne, melanoma, and teledermatology.^4-6 Nail disorders are a common concern, representing 21.1 million outpatient visits in 2007 to 2016,⁷ but, to date, the availability of apps related to nail disorders has not been explored. In this study, we investigated iOS (Apple’s iPhone Operating System) and Android apps to determine the types of nail health apps that are available, using psoriasis and hair loss apps as comparator groups.

Methods

A standard app analytics and market data tool (App Annie; https://www.appannie.com/en/) was utilized to search for iOS and Android nail mobile apps.^4,5 The analysis was performed on a single day (March 23, 2020), given that app searches can change on a daily basis. Our search included the following keywords: nail, nail health, toenail fungus, nail tumor, brittle nails, onychomycosis, onycholysis, subungual melanoma, nail melanoma, paronychia, and nail squamous cell carcinoma. App Annie app descriptions were assessed to determine the type of each app (Lifestyle, Medical, Health & Fitness) and target audience (patient, physician, or both). Psoriasis and hair loss topics were chosen as controls for comparison, based on a prior study.⁸ For psoriasis, the keywords psoriasis and chronic skin disease were searched. Hair loss was searched using the keywords alopecia, hair loss, hair health, and scalp.

Results

Nail-Related Apps
Using keywords for nail-related terms on iOS and Android platforms, our search returned few specific and informative apps related to nail disorders (Table 1). When the terms brittle nails, nail, nail health, nail squamous cell carcinoma, and nail tumor were searched, all available nail apps were either nail games or virtual nail salons for entertainment purposes. For the terms nail melanoma and subungual melanoma, there were no specific nail apps that appeared in the search results; rather, the App Annie search yielded only general dermatology and melanoma apps. The terms onycholysis and paronychia both yielded 0 hits for iOS and Android.

The only search terms that returned specific nail apps were onychomycosis and toenail fungus. Initially, when onychomycosis was searched, only 1 Google Play Medical category app was found: “Nail fungal infection (model onychomycosis).” Although this app recently was removed from the app store, it previously allowed the user to upload a nail photograph, with which a computing algorithm assessed whether the presentation was a fungal nail infection. Toenail fungus returned 1 iOS Medical category app and 5 Android Health & Fitness category apps with reference material for patients. Neither of the 2 medical apps for onychomycosis and toenail fungus referenced a physician involved in the app development.

Psoriasis Comparator
On the contrary, a search for psoriasis yielded 22 hits for iOS and 34 hits for Android within the Health & Fitness, Medical, and Social Networking categories (Table 2). The search term chronic skin disease returned 18 apps for iOS and 60 apps for Android related to psoriasis; 100% were classified as Medical apps.

Other Findings
Most apps for psoriasis and hair health were identified as patient focused. Although iOS and Android are different operating systems, some health apps overlapped: subungual melanoma and toenail fungus had a 20% overlap; psoriasis, 19%; chronic skin disease, 2%; alopecia, 0%; hair loss and hair health, 10%; and scalp, 18%. iOS and Android nail entertainment games had approximately a 30% overlap. Tables 1 and 2 also compare the number of free and paid apps; most available apps were free.

Comment

With continued growth in mobile device ownership and app development has been parallel growth in the creation and use of apps to enhance medical care.¹ In a study analyzing the most popular dermatology apps, 62% (18/29) and 38% (11/29) of apps targeted patients and physicians, respectively.⁶ Our study showed that (1) there are few nail disorder apps available for patient education and (2) there is no evidence that a physician was consulted for content input. Because patients who can effectively communicate their health concerns before and after seeing a physician have better self-reported clinical outcomes,⁹ it is important to have nail disorder apps available to patients for referencing. The nail health app options differ notably from psoriasis and hair loss apps, with apps for the latter 2 topics found in Medical and Health & Fitness categories—targeting patients who seek immediate access to health care and education.

Although there are several general dermatology apps that contain reference information for patients pertaining to nail conditions,⁶ using any of those apps would require a patient to have prior knowledge that dermatologists specialize in nail disorders and necessitate several steps to find nail-relevant information. For example, the patient would have to search dermatology in the iOS and Android app stores, select the available app (eg, Dermatology Database), and then search within that app for nail disorders. Therefore, a patient who is concerned about a possible subungual melanoma would not be able to easily find clinical images and explanations using an app.

Study Limitations
This study was subject to several limitations. Android and iOS app stores have undisclosed computing algorithms that might have filtered apps based on specific word inquiry. Also, our queries were based on specific relevant keywords for nail conditions, psoriasis, and hair loss; use of different keywords might have yielded different results. Additionally, app options change on a daily basis, so a search today (ie, any given day) might yield slightly different results than it did on March 23, 2020.

Conclusion

Specific nail disorder apps available for patient reference are limited. App developers should consider accessibility (ie, clear language, ease of use, cost-effectiveness, usability on iOS- and Android-operated devices) and content (accurate medical information from experts) when considering new apps. A solution to this problem is for established medical organizations to create nail disorder apps specifically for patients.¹⁰ For example, the American Academy of Dermatology has iOS and Android apps that are relevant to physicians (MyDermPath+, Dialogues in Dermatology, Mohs Surgery Appropriate Use Criteria) but no comparable apps for patients; patient-appropriate nail apps are necessary.¹¹ In addition, it would be beneficial to patients if established app companies consulted with dermatologists on pertinent nail content.

In sum, we found few available nail health apps on the iOS or Android platforms that provided accessible and timely information to patients regarding nail disorders. There is an immediate need to produce apps related to nail health for appropriate patient education.