Case Letter

To the Editor:

A 42-year-old woman with Crohn disease of 10 years’ duration presented to the clinic with a chief concern of nonpruritic pustular lesions on the bilateral arms. Physical examination revealed several pustules on the arms with secondary excoriation. She also had a warm tender nodule on the left upper shin and subungual hemorrhages under the fingernails (Figure 1). The patient had previously undergone infliximab therapy, which was discontinued 10 months prior to presentation in anticipation of a partial colectomy and temporary ileostomy that was performed 8 months prior to presentation. She recently had developed bilateral, radiating, sharp lower extremity pain extending from the feet to the hips over the last 2 weeks and swelling of the bilateral legs that impaired her ability to ambulate. Additionally, she had recently traveled to Colorado and a Lyme disease workup was initiated at an outside hospital in Colorado; however, the results were pending. The outside hospital also performed a spinal tap that was negative. At our clinic, biopsies were performed on the shin nodule and a right palmar pustule (Figure 2). There was clinical suspicion of erythema nodosum and subcorneal pustular dermatosis or a vesiculopustular skin manifestation of the patient’s Crohn disease. The patient was switched from generic doxycycline to a brand name variant 150 mg every night at bedtime for 2 weeks. She subsequently was admitted to the inpatient rheumatology service for a complete systemic workup.

The punch biopsy of the left upper shin demonstrated operative hemorrhage and periadnexal lymphocytic inflammation without evidence of fungal or bacterial elements by Gram or Gomori methenamine-silver stain. Clinically, the diagnosis was most likely erythema nodosum, though insufficient hypodermis was present to make the diagnosis with pathology. The shave biopsy of the right medial palm was nondiagnostic but showed a transected pustule with no bacterial or fungal elements by Gram or Gomori methenamine-silver stain (Figure 3). Given the clinical context, the likely pathologic diagnosis was vesiculopustular Crohn disease.

Our patient was started on an empiric steroid trial with rapid improvement of the arthralgia and rash. The presumed diagnosis was a Crohn disease flare and the patient was discharged on an 8-week steroid taper. Three weeks later at a follow-up appointment, the patient’s skin lesions had nearly resolved. The swelling of the legs and feet had substantially decreased, but the joint pain, primarily in the ankles, persisted.

Routine laboratory studies showed a hemoglobin level of 11.6 g/dL (reference range, 12–15 g/dL), white blood cell count of 9.1 K/μL (reference range, 4.5–11.0 K/μL), C-reactive protein level of 20.15 mg/dL (reference range, <1.0 mg/dL), and an antinuclear antibody titer of 160 (<80). Serology for Lyme disease was negative. Serum chemistries were all within reference range and an echocardiogram was normal.

Up to one-third of patients with inflammatory bowel disease (IBD) experience extraintestinal manifestations of their condition. Of these patients, nearly one-third will develop cutaneous manifestations.¹ The most common skin diseases associated with IBD are pyoderma gangrenosum and erythema nodosum.² The differential diagnoses considered in this unique case included early pyoderma gangrenosum, subcorneal pustular dermatosis (Sneddon-Wilkinson disease), and vesiculopustular Crohn disease. Vesiculopustular Crohn disease is a rare component of IBD and also can be present in bowel-associated dermatosis-arthritis syndrome (BADAS). In BADAS, symptoms often include arthritis and systemic symptoms such as fever and malaise. The skin manifestations typically involve the arms and trunk. It often is seen after intestinal bypass surgery but also can be present in patients with gastrointestinal diseases such as IBD.³ Due to its early association with bypass surgery, BADAS previously was referred to as bowel bypass syndrome but has since been seen in relation to other intestinal surgeries and IBD.⁴ Patients with BADAS often present with episodes of fever, fatigue, and malaise, in addition to arthralgia and cutaneous eruptions. Cases of BADAS related to IBD instead of bypass surgery often can be less severe in nature. Unlike many of these previously reported cases, our patient’s joint pain primarily was in the knees and ankles, whereas typical cases of BADAS cause upper extremity (ie, shoulder, elbow) arthralgia. Our patient occasionally experienced upper extremity pain, but it was less frequent and less severe than the knee and ankle pain. The vesiculopustular lesions in BADAS usually begin as 3- to 10-mm painful macules that then develop into aseptic pustular lesions. These manifestations arise on the upper arms and chest or trunk and can be accompanied by erythema nodosum on the legs.⁴

It has been hypothesized that BADAS occurs as an immune reaction to bacterial overgrowth in the bowel from IBD, infection, or surgery. The reaction is in response to a bacterial antigen and manifests cutaneously.⁵ This same pathogenesis is thought to cause various other manifestations of Crohn disease such as erythema nodosum. Bacteria that incite this immune response include Bacteroides fragilis, Escherichia coli, and Streptococcus.

Resolution of both vesiculopustular Crohn disease and of BADAS often occurs with treatment of the underlying IBD but also can be improved with steroids and antibiotics. However, response to antibiotics often is variable.^5,6 The mainstay for treatment remains steroids and management of underlying bowel disease.

Bowel-associated dermatosis-arthritis syndrome often is overlooked when compiling differential diagnoses for neutrophilic dermatoses but should be considered in patients with bowel disease or recent surgery. Because the syndrome can be recurrent, early diagnosis can help to prevent and treat relapsing courses of BADAS.

To the Editor:

A 42-year-old woman with Crohn disease of 10 years’ duration presented to the clinic with a chief concern of nonpruritic pustular lesions on the bilateral arms. Physical examination revealed several pustules on the arms with secondary excoriation. She also had a warm tender nodule on the left upper shin and subungual hemorrhages under the fingernails (Figure 1). The patient had previously undergone infliximab therapy, which was discontinued 10 months prior to presentation in anticipation of a partial colectomy and temporary ileostomy that was performed 8 months prior to presentation. She recently had developed bilateral, radiating, sharp lower extremity pain extending from the feet to the hips over the last 2 weeks and swelling of the bilateral legs that impaired her ability to ambulate. Additionally, she had recently traveled to Colorado and a Lyme disease workup was initiated at an outside hospital in Colorado; however, the results were pending. The outside hospital also performed a spinal tap that was negative. At our clinic, biopsies were performed on the shin nodule and a right palmar pustule (Figure 2). There was clinical suspicion of erythema nodosum and subcorneal pustular dermatosis or a vesiculopustular skin manifestation of the patient’s Crohn disease. The patient was switched from generic doxycycline to a brand name variant 150 mg every night at bedtime for 2 weeks. She subsequently was admitted to the inpatient rheumatology service for a complete systemic workup.

The punch biopsy of the left upper shin demonstrated operative hemorrhage and periadnexal lymphocytic inflammation without evidence of fungal or bacterial elements by Gram or Gomori methenamine-silver stain. Clinically, the diagnosis was most likely erythema nodosum, though insufficient hypodermis was present to make the diagnosis with pathology. The shave biopsy of the right medial palm was nondiagnostic but showed a transected pustule with no bacterial or fungal elements by Gram or Gomori methenamine-silver stain (Figure 3). Given the clinical context, the likely pathologic diagnosis was vesiculopustular Crohn disease.

Our patient was started on an empiric steroid trial with rapid improvement of the arthralgia and rash. The presumed diagnosis was a Crohn disease flare and the patient was discharged on an 8-week steroid taper. Three weeks later at a follow-up appointment, the patient’s skin lesions had nearly resolved. The swelling of the legs and feet had substantially decreased, but the joint pain, primarily in the ankles, persisted.

Routine laboratory studies showed a hemoglobin level of 11.6 g/dL (reference range, 12–15 g/dL), white blood cell count of 9.1 K/μL (reference range, 4.5–11.0 K/μL), C-reactive protein level of 20.15 mg/dL (reference range, <1.0 mg/dL), and an antinuclear antibody titer of 160 (<80). Serology for Lyme disease was negative. Serum chemistries were all within reference range and an echocardiogram was normal.

Up to one-third of patients with inflammatory bowel disease (IBD) experience extraintestinal manifestations of their condition. Of these patients, nearly one-third will develop cutaneous manifestations.¹ The most common skin diseases associated with IBD are pyoderma gangrenosum and erythema nodosum.² The differential diagnoses considered in this unique case included early pyoderma gangrenosum, subcorneal pustular dermatosis (Sneddon-Wilkinson disease), and vesiculopustular Crohn disease. Vesiculopustular Crohn disease is a rare component of IBD and also can be present in bowel-associated dermatosis-arthritis syndrome (BADAS). In BADAS, symptoms often include arthritis and systemic symptoms such as fever and malaise. The skin manifestations typically involve the arms and trunk. It often is seen after intestinal bypass surgery but also can be present in patients with gastrointestinal diseases such as IBD.³ Due to its early association with bypass surgery, BADAS previously was referred to as bowel bypass syndrome but has since been seen in relation to other intestinal surgeries and IBD.⁴ Patients with BADAS often present with episodes of fever, fatigue, and malaise, in addition to arthralgia and cutaneous eruptions. Cases of BADAS related to IBD instead of bypass surgery often can be less severe in nature. Unlike many of these previously reported cases, our patient’s joint pain primarily was in the knees and ankles, whereas typical cases of BADAS cause upper extremity (ie, shoulder, elbow) arthralgia. Our patient occasionally experienced upper extremity pain, but it was less frequent and less severe than the knee and ankle pain. The vesiculopustular lesions in BADAS usually begin as 3- to 10-mm painful macules that then develop into aseptic pustular lesions. These manifestations arise on the upper arms and chest or trunk and can be accompanied by erythema nodosum on the legs.⁴

It has been hypothesized that BADAS occurs as an immune reaction to bacterial overgrowth in the bowel from IBD, infection, or surgery. The reaction is in response to a bacterial antigen and manifests cutaneously.⁵ This same pathogenesis is thought to cause various other manifestations of Crohn disease such as erythema nodosum. Bacteria that incite this immune response include Bacteroides fragilis, Escherichia coli, and Streptococcus.

Resolution of both vesiculopustular Crohn disease and of BADAS often occurs with treatment of the underlying IBD but also can be improved with steroids and antibiotics. However, response to antibiotics often is variable.^5,6 The mainstay for treatment remains steroids and management of underlying bowel disease.

Bowel-associated dermatosis-arthritis syndrome often is overlooked when compiling differential diagnoses for neutrophilic dermatoses but should be considered in patients with bowel disease or recent surgery. Because the syndrome can be recurrent, early diagnosis can help to prevent and treat relapsing courses of BADAS.

To the Editor:

A 42-year-old woman with Crohn disease of 10 years’ duration presented to the clinic with a chief concern of nonpruritic pustular lesions on the bilateral arms. Physical examination revealed several pustules on the arms with secondary excoriation. She also had a warm tender nodule on the left upper shin and subungual hemorrhages under the fingernails (Figure 1). The patient had previously undergone infliximab therapy, which was discontinued 10 months prior to presentation in anticipation of a partial colectomy and temporary ileostomy that was performed 8 months prior to presentation. She recently had developed bilateral, radiating, sharp lower extremity pain extending from the feet to the hips over the last 2 weeks and swelling of the bilateral legs that impaired her ability to ambulate. Additionally, she had recently traveled to Colorado and a Lyme disease workup was initiated at an outside hospital in Colorado; however, the results were pending. The outside hospital also performed a spinal tap that was negative. At our clinic, biopsies were performed on the shin nodule and a right palmar pustule (Figure 2). There was clinical suspicion of erythema nodosum and subcorneal pustular dermatosis or a vesiculopustular skin manifestation of the patient’s Crohn disease. The patient was switched from generic doxycycline to a brand name variant 150 mg every night at bedtime for 2 weeks. She subsequently was admitted to the inpatient rheumatology service for a complete systemic workup.

The punch biopsy of the left upper shin demonstrated operative hemorrhage and periadnexal lymphocytic inflammation without evidence of fungal or bacterial elements by Gram or Gomori methenamine-silver stain. Clinically, the diagnosis was most likely erythema nodosum, though insufficient hypodermis was present to make the diagnosis with pathology. The shave biopsy of the right medial palm was nondiagnostic but showed a transected pustule with no bacterial or fungal elements by Gram or Gomori methenamine-silver stain (Figure 3). Given the clinical context, the likely pathologic diagnosis was vesiculopustular Crohn disease.

Our patient was started on an empiric steroid trial with rapid improvement of the arthralgia and rash. The presumed diagnosis was a Crohn disease flare and the patient was discharged on an 8-week steroid taper. Three weeks later at a follow-up appointment, the patient’s skin lesions had nearly resolved. The swelling of the legs and feet had substantially decreased, but the joint pain, primarily in the ankles, persisted.

Routine laboratory studies showed a hemoglobin level of 11.6 g/dL (reference range, 12–15 g/dL), white blood cell count of 9.1 K/μL (reference range, 4.5–11.0 K/μL), C-reactive protein level of 20.15 mg/dL (reference range, <1.0 mg/dL), and an antinuclear antibody titer of 160 (<80). Serology for Lyme disease was negative. Serum chemistries were all within reference range and an echocardiogram was normal.

Up to one-third of patients with inflammatory bowel disease (IBD) experience extraintestinal manifestations of their condition. Of these patients, nearly one-third will develop cutaneous manifestations.¹ The most common skin diseases associated with IBD are pyoderma gangrenosum and erythema nodosum.² The differential diagnoses considered in this unique case included early pyoderma gangrenosum, subcorneal pustular dermatosis (Sneddon-Wilkinson disease), and vesiculopustular Crohn disease. Vesiculopustular Crohn disease is a rare component of IBD and also can be present in bowel-associated dermatosis-arthritis syndrome (BADAS). In BADAS, symptoms often include arthritis and systemic symptoms such as fever and malaise. The skin manifestations typically involve the arms and trunk. It often is seen after intestinal bypass surgery but also can be present in patients with gastrointestinal diseases such as IBD.³ Due to its early association with bypass surgery, BADAS previously was referred to as bowel bypass syndrome but has since been seen in relation to other intestinal surgeries and IBD.⁴ Patients with BADAS often present with episodes of fever, fatigue, and malaise, in addition to arthralgia and cutaneous eruptions. Cases of BADAS related to IBD instead of bypass surgery often can be less severe in nature. Unlike many of these previously reported cases, our patient’s joint pain primarily was in the knees and ankles, whereas typical cases of BADAS cause upper extremity (ie, shoulder, elbow) arthralgia. Our patient occasionally experienced upper extremity pain, but it was less frequent and less severe than the knee and ankle pain. The vesiculopustular lesions in BADAS usually begin as 3- to 10-mm painful macules that then develop into aseptic pustular lesions. These manifestations arise on the upper arms and chest or trunk and can be accompanied by erythema nodosum on the legs.⁴

It has been hypothesized that BADAS occurs as an immune reaction to bacterial overgrowth in the bowel from IBD, infection, or surgery. The reaction is in response to a bacterial antigen and manifests cutaneously.⁵ This same pathogenesis is thought to cause various other manifestations of Crohn disease such as erythema nodosum. Bacteria that incite this immune response include Bacteroides fragilis, Escherichia coli, and Streptococcus.

Resolution of both vesiculopustular Crohn disease and of BADAS often occurs with treatment of the underlying IBD but also can be improved with steroids and antibiotics. However, response to antibiotics often is variable.^5,6 The mainstay for treatment remains steroids and management of underlying bowel disease.

Bowel-associated dermatosis-arthritis syndrome often is overlooked when compiling differential diagnoses for neutrophilic dermatoses but should be considered in patients with bowel disease or recent surgery. Because the syndrome can be recurrent, early diagnosis can help to prevent and treat relapsing courses of BADAS.

To the Editor:

There are a wide variety of zoonotic diseases that can be transmitted from birds to humans. Pigeons, chickens, starlings, canaries, and parakeets are known reservoirs of one particular zoonotic infection caused by the parasitic arthropod Dermanyssus gallinae.¹ Dermanyssus gallinae (chicken mite) and Ornithonyssus sylviarum (northern fowl mite) are collectively referred to as bird mites. When these mites are unable to take blood meals from birds, they search out alternative hosts²; in humans, this often leads to the development of pruritic dermatitis.³

A 30-year-old woman presented to our clinic for evaluation of severe generalized pruritus accompanied by a sensation of “bugs on the skin” of 2 weeks’ duration. She noted the pruritus worsened when she was sitting outside on her porch. A few days prior to presentation, she noticed a small, “pinpoint-sized bug” on her arm (<1 mm in size), which she brought in for identification (Figure).

The bug was identified as a bird mite (Dermanyssus gallinae) on light microscopy, which was later confirmed by a medical entomologist. After the diagnosis of bird mite dermatitis was made, the patient noted there was a nest of starlings above the light on her porch. When she later investigated the nest following the current presentation, she noted many small mites crawling around the nest. The nest was removed and her symptoms resolved completely within 2 weeks without treatment.

Bird mites belong to the Arachnida class, under the order Acari. In 1958, Williams⁴ noted D gallinae’s ability to feed on human blood. Bird mites have 5 stages of development: egg, larva, protonymph, deutonymph, and adult. Protonymphs, deutonymphs, and adults can bite humans for a blood meal.⁵ Bird mites range from 0.3 to 1 mm in length and have nonsegmented, egg-shaped bodies with 4 pairs of legs. Before taking a blood meal, bird mites generally are a translucent brown color, and appear red when engorged with blood.² Their small size makes them barely visible to the unaided eye. Of note, D gallinae and O sylviarum can be distinguished from each other based on subtle differences in morphology; for instance, the posterior genitoventral shield of O sylviarum is narrowly rounded, whereas it is broadly rounded in D gallinae. The dorsal shield of O sylviarum abruptly narrows posteriorly but is more smoothly narrowed in D gallinae.⁶ Additionally, O sylviarum tends to cause more irritating dermatitis in humans than D gallinae.³

Although they can be found worldwide, D gallinae and O sylviarum undergo optimal development at 20°C to 25°C and 70% humidity.^3,5,7 Bird mites generally develop over the course of 5 to 12 days; thus, the population of bird mites in a single nest may grow to the tens of thousands before young birds permanently leave. Dermanyssus gallinae can survive for months in abandoned nests without a blood meal, while O sylviarum can survive for several weeks.⁸ It is important to note that humans are not ideal hosts for bird mites, as they are unable to survive for extended periods of time or reproduce on human hosts.⁹

When bird mites are no longer able to obtain blood meals from nesting birds, they begin their nocturnal migration to find suitable hosts. Bird nests generally are abandoned in late spring; thus, most patients with bird mite dermatitis present to clinics with bird mite dermatitis in late spring and early summer.¹⁰ Mites often travel through cracks in doors, floors, walls, and ceilings but also can gain access to living areas through ventilation ducts and air conditioning units.¹ The mite’s bite and crawling on the skin is sometimes noticed by the patient. In general, however, intense itching is not observed until about 1 to 3 days after the mite makes contact with the skin. Patients often report that pruritus is worst at night.⁹ Papules and vesicles (bite reactions) may accompany the pruritus, and physicians commonly find bloody crust and excoriations in particularly pruritic areas.⁵ Urticarial plaques and diffuse erythema occasionally also may be present.⁹ Bird mites sometimes can be scraped from the skin and observed under light microscopy.¹¹ Blood eosinophilia is not found in bird mite dermatitis. On histologic examination, perivascular eosinophilic infiltration can be seen in the upper part of the dermis.¹²

The differential diagnosis in patients with pruritic dermatitis of unknown origin generally includes scabies, pediculosis, and dermatitis caused by other types of infestation. However, unlike scabies, bird mites do not cause burrows to form on the skin.⁹ The presence of a bird’s nest near the area where the patient lives places bird mite dermatitis higher in the differential.

Dermanyssus gallinae is a known vector of bacteria (eg, Salmonella, Shigella, Staphylococcus, Spirochaete, Rickettsia, Pasteurella, Chlamydia psittaci, Erysipelothrix rhusiopathiae) as well as the viruses that cause Eastern and Western equine encephalitis and St. Louis encephalitis. Transmission of these bacteria and viruses is known in birds, but transmission to humans has not been reported.^2,5,9,13

The management of bird mite dermatitis is straightforward. Usually mites can be successfully removed from the skin simply by bathing. Symptomatic treatment for bites with antihistamines and topical corticosteroids is sometimes but not always necessary.² Unlike scabies or lice, there is no need for treatment with lindane.¹ In terms of the prevention of additional bites, any bird nests located near living areas should be removed. Because bird mites often retreat back to nests between blood meals, insecticide sprays generally are unnecessary in interior spaces. Synthetic pyrethroids (eg, bifenthrin, cyfluthrin, cypermethrin, deltamethrin, cyhalothrin) can be used outside and in attics where nests may be located.^2,14,15 However, the ability of bird mites to develop resistance to repeated chemical control could become a future concern.¹⁶

Research regarding the true incidence of bird mite dermatitis is lacking. Some researchers believe that the condition is underreported, possibly due to its uncommon environmental origin.³ Reports of bird mite dermatitis in the literature also are scarce. Our case demonstrates the importance of taking a thorough patient history to rule out exposure to bird mites. All patients with pruritic dermatitis of unknown origin should be questioned about possible contact or proximity to bird nests. These simple questions can lead to the correct diagnosis and a treatment plan that will quickly and effectively resolve the pruritic skin eruption.

To the Editor:

There are a wide variety of zoonotic diseases that can be transmitted from birds to humans. Pigeons, chickens, starlings, canaries, and parakeets are known reservoirs of one particular zoonotic infection caused by the parasitic arthropod Dermanyssus gallinae.¹ Dermanyssus gallinae (chicken mite) and Ornithonyssus sylviarum (northern fowl mite) are collectively referred to as bird mites. When these mites are unable to take blood meals from birds, they search out alternative hosts²; in humans, this often leads to the development of pruritic dermatitis.³

A 30-year-old woman presented to our clinic for evaluation of severe generalized pruritus accompanied by a sensation of “bugs on the skin” of 2 weeks’ duration. She noted the pruritus worsened when she was sitting outside on her porch. A few days prior to presentation, she noticed a small, “pinpoint-sized bug” on her arm (<1 mm in size), which she brought in for identification (Figure).

The bug was identified as a bird mite (Dermanyssus gallinae) on light microscopy, which was later confirmed by a medical entomologist. After the diagnosis of bird mite dermatitis was made, the patient noted there was a nest of starlings above the light on her porch. When she later investigated the nest following the current presentation, she noted many small mites crawling around the nest. The nest was removed and her symptoms resolved completely within 2 weeks without treatment.

Bird mites belong to the Arachnida class, under the order Acari. In 1958, Williams⁴ noted D gallinae’s ability to feed on human blood. Bird mites have 5 stages of development: egg, larva, protonymph, deutonymph, and adult. Protonymphs, deutonymphs, and adults can bite humans for a blood meal.⁵ Bird mites range from 0.3 to 1 mm in length and have nonsegmented, egg-shaped bodies with 4 pairs of legs. Before taking a blood meal, bird mites generally are a translucent brown color, and appear red when engorged with blood.² Their small size makes them barely visible to the unaided eye. Of note, D gallinae and O sylviarum can be distinguished from each other based on subtle differences in morphology; for instance, the posterior genitoventral shield of O sylviarum is narrowly rounded, whereas it is broadly rounded in D gallinae. The dorsal shield of O sylviarum abruptly narrows posteriorly but is more smoothly narrowed in D gallinae.⁶ Additionally, O sylviarum tends to cause more irritating dermatitis in humans than D gallinae.³

Although they can be found worldwide, D gallinae and O sylviarum undergo optimal development at 20°C to 25°C and 70% humidity.^3,5,7 Bird mites generally develop over the course of 5 to 12 days; thus, the population of bird mites in a single nest may grow to the tens of thousands before young birds permanently leave. Dermanyssus gallinae can survive for months in abandoned nests without a blood meal, while O sylviarum can survive for several weeks.⁸ It is important to note that humans are not ideal hosts for bird mites, as they are unable to survive for extended periods of time or reproduce on human hosts.⁹

When bird mites are no longer able to obtain blood meals from nesting birds, they begin their nocturnal migration to find suitable hosts. Bird nests generally are abandoned in late spring; thus, most patients with bird mite dermatitis present to clinics with bird mite dermatitis in late spring and early summer.¹⁰ Mites often travel through cracks in doors, floors, walls, and ceilings but also can gain access to living areas through ventilation ducts and air conditioning units.¹ The mite’s bite and crawling on the skin is sometimes noticed by the patient. In general, however, intense itching is not observed until about 1 to 3 days after the mite makes contact with the skin. Patients often report that pruritus is worst at night.⁹ Papules and vesicles (bite reactions) may accompany the pruritus, and physicians commonly find bloody crust and excoriations in particularly pruritic areas.⁵ Urticarial plaques and diffuse erythema occasionally also may be present.⁹ Bird mites sometimes can be scraped from the skin and observed under light microscopy.¹¹ Blood eosinophilia is not found in bird mite dermatitis. On histologic examination, perivascular eosinophilic infiltration can be seen in the upper part of the dermis.¹²

The differential diagnosis in patients with pruritic dermatitis of unknown origin generally includes scabies, pediculosis, and dermatitis caused by other types of infestation. However, unlike scabies, bird mites do not cause burrows to form on the skin.⁹ The presence of a bird’s nest near the area where the patient lives places bird mite dermatitis higher in the differential.

Dermanyssus gallinae is a known vector of bacteria (eg, Salmonella, Shigella, Staphylococcus, Spirochaete, Rickettsia, Pasteurella, Chlamydia psittaci, Erysipelothrix rhusiopathiae) as well as the viruses that cause Eastern and Western equine encephalitis and St. Louis encephalitis. Transmission of these bacteria and viruses is known in birds, but transmission to humans has not been reported.^2,5,9,13

The management of bird mite dermatitis is straightforward. Usually mites can be successfully removed from the skin simply by bathing. Symptomatic treatment for bites with antihistamines and topical corticosteroids is sometimes but not always necessary.² Unlike scabies or lice, there is no need for treatment with lindane.¹ In terms of the prevention of additional bites, any bird nests located near living areas should be removed. Because bird mites often retreat back to nests between blood meals, insecticide sprays generally are unnecessary in interior spaces. Synthetic pyrethroids (eg, bifenthrin, cyfluthrin, cypermethrin, deltamethrin, cyhalothrin) can be used outside and in attics where nests may be located.^2,14,15 However, the ability of bird mites to develop resistance to repeated chemical control could become a future concern.¹⁶

Research regarding the true incidence of bird mite dermatitis is lacking. Some researchers believe that the condition is underreported, possibly due to its uncommon environmental origin.³ Reports of bird mite dermatitis in the literature also are scarce. Our case demonstrates the importance of taking a thorough patient history to rule out exposure to bird mites. All patients with pruritic dermatitis of unknown origin should be questioned about possible contact or proximity to bird nests. These simple questions can lead to the correct diagnosis and a treatment plan that will quickly and effectively resolve the pruritic skin eruption.

To the Editor:

There are a wide variety of zoonotic diseases that can be transmitted from birds to humans. Pigeons, chickens, starlings, canaries, and parakeets are known reservoirs of one particular zoonotic infection caused by the parasitic arthropod Dermanyssus gallinae.¹ Dermanyssus gallinae (chicken mite) and Ornithonyssus sylviarum (northern fowl mite) are collectively referred to as bird mites. When these mites are unable to take blood meals from birds, they search out alternative hosts²; in humans, this often leads to the development of pruritic dermatitis.³

A 30-year-old woman presented to our clinic for evaluation of severe generalized pruritus accompanied by a sensation of “bugs on the skin” of 2 weeks’ duration. She noted the pruritus worsened when she was sitting outside on her porch. A few days prior to presentation, she noticed a small, “pinpoint-sized bug” on her arm (<1 mm in size), which she brought in for identification (Figure).

The bug was identified as a bird mite (Dermanyssus gallinae) on light microscopy, which was later confirmed by a medical entomologist. After the diagnosis of bird mite dermatitis was made, the patient noted there was a nest of starlings above the light on her porch. When she later investigated the nest following the current presentation, she noted many small mites crawling around the nest. The nest was removed and her symptoms resolved completely within 2 weeks without treatment.

Bird mites belong to the Arachnida class, under the order Acari. In 1958, Williams⁴ noted D gallinae’s ability to feed on human blood. Bird mites have 5 stages of development: egg, larva, protonymph, deutonymph, and adult. Protonymphs, deutonymphs, and adults can bite humans for a blood meal.⁵ Bird mites range from 0.3 to 1 mm in length and have nonsegmented, egg-shaped bodies with 4 pairs of legs. Before taking a blood meal, bird mites generally are a translucent brown color, and appear red when engorged with blood.² Their small size makes them barely visible to the unaided eye. Of note, D gallinae and O sylviarum can be distinguished from each other based on subtle differences in morphology; for instance, the posterior genitoventral shield of O sylviarum is narrowly rounded, whereas it is broadly rounded in D gallinae. The dorsal shield of O sylviarum abruptly narrows posteriorly but is more smoothly narrowed in D gallinae.⁶ Additionally, O sylviarum tends to cause more irritating dermatitis in humans than D gallinae.³

Although they can be found worldwide, D gallinae and O sylviarum undergo optimal development at 20°C to 25°C and 70% humidity.^3,5,7 Bird mites generally develop over the course of 5 to 12 days; thus, the population of bird mites in a single nest may grow to the tens of thousands before young birds permanently leave. Dermanyssus gallinae can survive for months in abandoned nests without a blood meal, while O sylviarum can survive for several weeks.⁸ It is important to note that humans are not ideal hosts for bird mites, as they are unable to survive for extended periods of time or reproduce on human hosts.⁹

When bird mites are no longer able to obtain blood meals from nesting birds, they begin their nocturnal migration to find suitable hosts. Bird nests generally are abandoned in late spring; thus, most patients with bird mite dermatitis present to clinics with bird mite dermatitis in late spring and early summer.¹⁰ Mites often travel through cracks in doors, floors, walls, and ceilings but also can gain access to living areas through ventilation ducts and air conditioning units.¹ The mite’s bite and crawling on the skin is sometimes noticed by the patient. In general, however, intense itching is not observed until about 1 to 3 days after the mite makes contact with the skin. Patients often report that pruritus is worst at night.⁹ Papules and vesicles (bite reactions) may accompany the pruritus, and physicians commonly find bloody crust and excoriations in particularly pruritic areas.⁵ Urticarial plaques and diffuse erythema occasionally also may be present.⁹ Bird mites sometimes can be scraped from the skin and observed under light microscopy.¹¹ Blood eosinophilia is not found in bird mite dermatitis. On histologic examination, perivascular eosinophilic infiltration can be seen in the upper part of the dermis.¹²

The differential diagnosis in patients with pruritic dermatitis of unknown origin generally includes scabies, pediculosis, and dermatitis caused by other types of infestation. However, unlike scabies, bird mites do not cause burrows to form on the skin.⁹ The presence of a bird’s nest near the area where the patient lives places bird mite dermatitis higher in the differential.

Dermanyssus gallinae is a known vector of bacteria (eg, Salmonella, Shigella, Staphylococcus, Spirochaete, Rickettsia, Pasteurella, Chlamydia psittaci, Erysipelothrix rhusiopathiae) as well as the viruses that cause Eastern and Western equine encephalitis and St. Louis encephalitis. Transmission of these bacteria and viruses is known in birds, but transmission to humans has not been reported.^2,5,9,13

The management of bird mite dermatitis is straightforward. Usually mites can be successfully removed from the skin simply by bathing. Symptomatic treatment for bites with antihistamines and topical corticosteroids is sometimes but not always necessary.² Unlike scabies or lice, there is no need for treatment with lindane.¹ In terms of the prevention of additional bites, any bird nests located near living areas should be removed. Because bird mites often retreat back to nests between blood meals, insecticide sprays generally are unnecessary in interior spaces. Synthetic pyrethroids (eg, bifenthrin, cyfluthrin, cypermethrin, deltamethrin, cyhalothrin) can be used outside and in attics where nests may be located.^2,14,15 However, the ability of bird mites to develop resistance to repeated chemical control could become a future concern.¹⁶

Research regarding the true incidence of bird mite dermatitis is lacking. Some researchers believe that the condition is underreported, possibly due to its uncommon environmental origin.³ Reports of bird mite dermatitis in the literature also are scarce. Our case demonstrates the importance of taking a thorough patient history to rule out exposure to bird mites. All patients with pruritic dermatitis of unknown origin should be questioned about possible contact or proximity to bird nests. These simple questions can lead to the correct diagnosis and a treatment plan that will quickly and effectively resolve the pruritic skin eruption.

To the Editor:

A 34-year-old woman presented for evaluation of dry mouth and painless peeling of the oral mucosa of 2 months’ duration. She denied any other skin eruptions, dry eyes, vulvar or vaginal pain, or recent hair loss. A recent antinuclear antibodies test was negative. The patient’s medical history was otherwise unremarkable and her current medications included multivitamins only.

Oral examination revealed peeling gray-white tissue on the buccal mucosa and mouth floor (Figure 1). After the tissue was manually removed with a tongue blade, the mucosal base was normal in color and texture. The patient denied bruxism, biting of the mucosa or other oral trauma, or use of tobacco or nonsteroidal anti-inflammatory drugs.

Biopsies from the buccal mucosa were performed to rule out erosive lichen planus and autoimmune blistering disorders. Microscopy revealed parakeratosis and intracellular edema of the mucosa. An intraepithelial cleft at the parakeratotic surface also was present (Figure 2). Minimal inflammation was noted. Fungal staining and direct immunofluorescence were negative.

The gray-white clinical appearance of the oral mucosa resembled leukoedema, but the peeling phenomenon was uncharacteristic. Histologically, leukoedema typically has a parakeratotic and acanthotic epithelium with marked intracellular edema of the spinous layer.^1,2 Our patient demonstrated intracellular edema with the additional finding of a superficial intraepithelial cleft. These features were consistent with the observed mucosal sloughing and normal tissue base and led to our diagnosis of leukoedema with mucosal desquamation. This clinical and histologic picture was previously described in another report, but a causative agent could not be identified.²

Because leukoedema can be secondary to chemical or mechanical trauma,³ we hypothesized that the patient’s toothpaste may be the causative agent. After discontinuing use of her regular toothpaste and keeping the rest of her oral hygiene routine unchanged, the patient’s condition resolved within 2 days. The patient could not identify how long she had been using the toothpaste before symptoms began.

Our case as well as a report in the literature suggest that leukoedema with mucosal desquamation may be the result of contact mucositis to dental hygiene products.³ Reports in the dental literature suggest that a possible cause for oral mucosal desquamation is sensitivity to sodium lauryl sulfate (SLS),^1,4 an ingredient used in some toothpastes, including the one used by our patient. The patient has since switched to a non–SLS-containing toothpaste and has remained asymptomatic. She was unwilling to reintroduce an SLS-containing product for further evaluation.

Sodium lauryl sulfate is a strong anionic detergent that is commonly used as a foaming agent in dentifrices.⁴ In products with higher concentrations of SLS, the incidence of oral epithelial desquamation increases. Triclosan has been shown to protect against this irritant phenomenon.⁵ Interestingly, the SLS-containing toothpaste used by our patient did not contain triclosan.

Although leukoedema and mucosal desquamation induced by oral care products are well-described in the dental literature, it is important for dermatologists to be aware of this phenomenon, as the differential diagnosis includes autoimmune blistering disorders and erosive lichen planus, for which dermatology referral may be requested. Further studies of SLS and other toothpaste ingredients are needed to establish if sloughing of the oral mucosa is primarily caused by SLS or another ingredient.

To the Editor:

A 34-year-old woman presented for evaluation of dry mouth and painless peeling of the oral mucosa of 2 months’ duration. She denied any other skin eruptions, dry eyes, vulvar or vaginal pain, or recent hair loss. A recent antinuclear antibodies test was negative. The patient’s medical history was otherwise unremarkable and her current medications included multivitamins only.

Oral examination revealed peeling gray-white tissue on the buccal mucosa and mouth floor (Figure 1). After the tissue was manually removed with a tongue blade, the mucosal base was normal in color and texture. The patient denied bruxism, biting of the mucosa or other oral trauma, or use of tobacco or nonsteroidal anti-inflammatory drugs.

Biopsies from the buccal mucosa were performed to rule out erosive lichen planus and autoimmune blistering disorders. Microscopy revealed parakeratosis and intracellular edema of the mucosa. An intraepithelial cleft at the parakeratotic surface also was present (Figure 2). Minimal inflammation was noted. Fungal staining and direct immunofluorescence were negative.

The gray-white clinical appearance of the oral mucosa resembled leukoedema, but the peeling phenomenon was uncharacteristic. Histologically, leukoedema typically has a parakeratotic and acanthotic epithelium with marked intracellular edema of the spinous layer.^1,2 Our patient demonstrated intracellular edema with the additional finding of a superficial intraepithelial cleft. These features were consistent with the observed mucosal sloughing and normal tissue base and led to our diagnosis of leukoedema with mucosal desquamation. This clinical and histologic picture was previously described in another report, but a causative agent could not be identified.²

Because leukoedema can be secondary to chemical or mechanical trauma,³ we hypothesized that the patient’s toothpaste may be the causative agent. After discontinuing use of her regular toothpaste and keeping the rest of her oral hygiene routine unchanged, the patient’s condition resolved within 2 days. The patient could not identify how long she had been using the toothpaste before symptoms began.

Our case as well as a report in the literature suggest that leukoedema with mucosal desquamation may be the result of contact mucositis to dental hygiene products.³ Reports in the dental literature suggest that a possible cause for oral mucosal desquamation is sensitivity to sodium lauryl sulfate (SLS),^1,4 an ingredient used in some toothpastes, including the one used by our patient. The patient has since switched to a non–SLS-containing toothpaste and has remained asymptomatic. She was unwilling to reintroduce an SLS-containing product for further evaluation.

Sodium lauryl sulfate is a strong anionic detergent that is commonly used as a foaming agent in dentifrices.⁴ In products with higher concentrations of SLS, the incidence of oral epithelial desquamation increases. Triclosan has been shown to protect against this irritant phenomenon.⁵ Interestingly, the SLS-containing toothpaste used by our patient did not contain triclosan.

Although leukoedema and mucosal desquamation induced by oral care products are well-described in the dental literature, it is important for dermatologists to be aware of this phenomenon, as the differential diagnosis includes autoimmune blistering disorders and erosive lichen planus, for which dermatology referral may be requested. Further studies of SLS and other toothpaste ingredients are needed to establish if sloughing of the oral mucosa is primarily caused by SLS or another ingredient.

To the Editor:

A 34-year-old woman presented for evaluation of dry mouth and painless peeling of the oral mucosa of 2 months’ duration. She denied any other skin eruptions, dry eyes, vulvar or vaginal pain, or recent hair loss. A recent antinuclear antibodies test was negative. The patient’s medical history was otherwise unremarkable and her current medications included multivitamins only.

Oral examination revealed peeling gray-white tissue on the buccal mucosa and mouth floor (Figure 1). After the tissue was manually removed with a tongue blade, the mucosal base was normal in color and texture. The patient denied bruxism, biting of the mucosa or other oral trauma, or use of tobacco or nonsteroidal anti-inflammatory drugs.

Biopsies from the buccal mucosa were performed to rule out erosive lichen planus and autoimmune blistering disorders. Microscopy revealed parakeratosis and intracellular edema of the mucosa. An intraepithelial cleft at the parakeratotic surface also was present (Figure 2). Minimal inflammation was noted. Fungal staining and direct immunofluorescence were negative.

The gray-white clinical appearance of the oral mucosa resembled leukoedema, but the peeling phenomenon was uncharacteristic. Histologically, leukoedema typically has a parakeratotic and acanthotic epithelium with marked intracellular edema of the spinous layer.^1,2 Our patient demonstrated intracellular edema with the additional finding of a superficial intraepithelial cleft. These features were consistent with the observed mucosal sloughing and normal tissue base and led to our diagnosis of leukoedema with mucosal desquamation. This clinical and histologic picture was previously described in another report, but a causative agent could not be identified.²

Because leukoedema can be secondary to chemical or mechanical trauma,³ we hypothesized that the patient’s toothpaste may be the causative agent. After discontinuing use of her regular toothpaste and keeping the rest of her oral hygiene routine unchanged, the patient’s condition resolved within 2 days. The patient could not identify how long she had been using the toothpaste before symptoms began.

Our case as well as a report in the literature suggest that leukoedema with mucosal desquamation may be the result of contact mucositis to dental hygiene products.³ Reports in the dental literature suggest that a possible cause for oral mucosal desquamation is sensitivity to sodium lauryl sulfate (SLS),^1,4 an ingredient used in some toothpastes, including the one used by our patient. The patient has since switched to a non–SLS-containing toothpaste and has remained asymptomatic. She was unwilling to reintroduce an SLS-containing product for further evaluation.

Sodium lauryl sulfate is a strong anionic detergent that is commonly used as a foaming agent in dentifrices.⁴ In products with higher concentrations of SLS, the incidence of oral epithelial desquamation increases. Triclosan has been shown to protect against this irritant phenomenon.⁵ Interestingly, the SLS-containing toothpaste used by our patient did not contain triclosan.

Although leukoedema and mucosal desquamation induced by oral care products are well-described in the dental literature, it is important for dermatologists to be aware of this phenomenon, as the differential diagnosis includes autoimmune blistering disorders and erosive lichen planus, for which dermatology referral may be requested. Further studies of SLS and other toothpaste ingredients are needed to establish if sloughing of the oral mucosa is primarily caused by SLS or another ingredient.

To the Editor:

Hailey-Hailey disease, also known as familial benign pemphigus, is a chronic blistering skin disorder that typically presents as a recurrent vesicular or bullous dermatitis found predominantly in the intertriginous regions of the body. Because current treatment regimens for Hailey-Hailey disease are fairly limited, novel treatments may be explored in intractable cases.

A 71-year-old woman presented with well-demarcated erythematous plaques with erosions and white verrucous regions in the perivulvar, vaginal, and perianal areas of 1 month’s duration (Figure 1). The lesions were excruciatingly pruritic and excoriated. The patient reported no personal or family history of similar lesions.

Histopathologic examination of multiple biopsies from the periphery of the plaques showed acantholysis of the epidermis and surface necrosis with negative direct immunofluorescence. A diagnosis of Hailey-Hailey disease was made. Over several months following the initial presentation, the patient was treated with regimens of corticosteroids, antibiotics, antifungals, acitretin, and topical tacrolimus (which showed minimal response), but the condition continued to progress and thus warranted a more aggressive approach. After a 4-week course of oral cyclosporine 1.25 mg/kg twice daily, some healthy granulation tissue had formed, but new erosions continued to develop on the vulva, labia, and intergluteal cleft (Figure 2). Subsequently, a 2-month course of methotrexate yielded similar results with minimal healing and new necrotic areas (Figure 3).

Following methotrexate therapy, treatment with several other oral agents was considered such as azathioprine, mycophenolate mofetil, and oral tacrolimus. Since the patient had previously shown minimal response to topical tacrolimus, a course of oral treatment (0.05 mg/kg twice daily) was initiated. At 4 weeks’ follow-up, extensive healing of the lesions was noted (Figure 4) and the patient reported that the painful pruritus had improved.

After 6 weeks of treatment, there still were a few small lesions in the intergluteal cleft, which were treated with botulinum toxin type A (100 U diluted with 5 cc of bacteriostatic saline per cm²). After 3 separate injections with botulinum toxin type A and oral tacrolimus for 9 months, complete resolution of the lesions was obtained (Figure 5). After more than 6 months of remission, oral tacrolimus slowly was decreased by 1 mg every 6 weeks until treatment was stopped completely. She has remained in remission without oral treatment. After tapering the tacrolimus, botulinum toxin A injections were continued every 6 months for maintenance with the use of topical tacrolimus 3 to 4 times weekly (Figure 6).

The inheritance of Hailey-Hailey disease is autosomal dominant with incomplete penetrance, although spontaneous mutations are implicated in up to 30% of patients.^1,2 The pathogenesis of Hailey-Hailey disease involves a mutation in the ATPase, Ca++ transporting, type 2C, member 1 gene (ATP2C1), which encodes for the hSPCA1 protein.^1-2 The malfunction of this ATPase leads to inadequacy of the keratinocyte adhesive barrier resulting in acantholysis and intraepidermal vesicle formation. Macerated plaques also may be found instead of intact vesicles.³

Initial presentation of lesions in Hailey-Hailey disease typically occurs in the third or fourth decades of life but may present at any age.⁴ Areas exposed to increased amounts of friction (eg, axillae, groin, neck, perineum) commonly are involved.⁵ Lesions may occur in a relapsing and remitting course and usually are more prominent in summer months because they are exacerbated by sunburn and frictional trauma. Secondary bacterial or fungal infections are common and antibiotics and antifungals often are necessary to prevent progression of the lesions.^5,6

Various treatment regimens for Hailey-Hailey disease include topical and oral corticosteroids and antibiotics.⁵ Topical and oral retinoids, calcitriol, topical tacrolimus, cyclosporin, methotrexate, and even botulinum toxin A have been reported to be effective for refractory cases.^7-12 Our case describes a novel regimen of oral tacrolimus in conjunction with botulinum toxin A used in the successful treatment of recalcitrant Hailey-Hailey disease.

Tacrolimus binds to the immunophilin FK506 binding protein, which inhibits calcineurin. Calcineurin, a protein phosphatase, is necessary for T-cell activation through the nuclear factor of activated T cells.This inhibition of calcineurin blocks the expression of several cytokines.¹³ The efficacy of oral tacrolimus demonstrates that cellular immunity could play a role in the pathogenic mechanism of Hailey-Hailey disease.

Contraindications to oral tacrolimus therapy include renal or hepatic impairment, breast-feeding, pregnancy, and certain neoplastic diseases. There also is an increased risk of patients developing malignancies such as lymphoma or skin cancer due to immunosuppression. Use of oral tacrolimus also requires routine laboratory monitoring of renal and hepatic function, potassium, and blood glucose levels.¹³

Botulinum toxin A injections augmented the therapeutic approach in our patient possibly by controlling secretions of sweat and mucous, which may cause maceration and lead to exacerbation of Hailey-Hailey disease. Control of secretions may help in creating an environment that is less prone to exacerbation of lesions and secondary infection.¹⁴ The combination of oral tacrolimus and botulinum toxin A injections provided a safe therapeutic option for recalcitrant Hailey-Hailey disease in our patient.

To the Editor:

Hailey-Hailey disease, also known as familial benign pemphigus, is a chronic blistering skin disorder that typically presents as a recurrent vesicular or bullous dermatitis found predominantly in the intertriginous regions of the body. Because current treatment regimens for Hailey-Hailey disease are fairly limited, novel treatments may be explored in intractable cases.

A 71-year-old woman presented with well-demarcated erythematous plaques with erosions and white verrucous regions in the perivulvar, vaginal, and perianal areas of 1 month’s duration (Figure 1). The lesions were excruciatingly pruritic and excoriated. The patient reported no personal or family history of similar lesions.

Histopathologic examination of multiple biopsies from the periphery of the plaques showed acantholysis of the epidermis and surface necrosis with negative direct immunofluorescence. A diagnosis of Hailey-Hailey disease was made. Over several months following the initial presentation, the patient was treated with regimens of corticosteroids, antibiotics, antifungals, acitretin, and topical tacrolimus (which showed minimal response), but the condition continued to progress and thus warranted a more aggressive approach. After a 4-week course of oral cyclosporine 1.25 mg/kg twice daily, some healthy granulation tissue had formed, but new erosions continued to develop on the vulva, labia, and intergluteal cleft (Figure 2). Subsequently, a 2-month course of methotrexate yielded similar results with minimal healing and new necrotic areas (Figure 3).

Following methotrexate therapy, treatment with several other oral agents was considered such as azathioprine, mycophenolate mofetil, and oral tacrolimus. Since the patient had previously shown minimal response to topical tacrolimus, a course of oral treatment (0.05 mg/kg twice daily) was initiated. At 4 weeks’ follow-up, extensive healing of the lesions was noted (Figure 4) and the patient reported that the painful pruritus had improved.

After 6 weeks of treatment, there still were a few small lesions in the intergluteal cleft, which were treated with botulinum toxin type A (100 U diluted with 5 cc of bacteriostatic saline per cm²). After 3 separate injections with botulinum toxin type A and oral tacrolimus for 9 months, complete resolution of the lesions was obtained (Figure 5). After more than 6 months of remission, oral tacrolimus slowly was decreased by 1 mg every 6 weeks until treatment was stopped completely. She has remained in remission without oral treatment. After tapering the tacrolimus, botulinum toxin A injections were continued every 6 months for maintenance with the use of topical tacrolimus 3 to 4 times weekly (Figure 6).

The inheritance of Hailey-Hailey disease is autosomal dominant with incomplete penetrance, although spontaneous mutations are implicated in up to 30% of patients.^1,2 The pathogenesis of Hailey-Hailey disease involves a mutation in the ATPase, Ca++ transporting, type 2C, member 1 gene (ATP2C1), which encodes for the hSPCA1 protein.^1-2 The malfunction of this ATPase leads to inadequacy of the keratinocyte adhesive barrier resulting in acantholysis and intraepidermal vesicle formation. Macerated plaques also may be found instead of intact vesicles.³

Initial presentation of lesions in Hailey-Hailey disease typically occurs in the third or fourth decades of life but may present at any age.⁴ Areas exposed to increased amounts of friction (eg, axillae, groin, neck, perineum) commonly are involved.⁵ Lesions may occur in a relapsing and remitting course and usually are more prominent in summer months because they are exacerbated by sunburn and frictional trauma. Secondary bacterial or fungal infections are common and antibiotics and antifungals often are necessary to prevent progression of the lesions.^5,6

Various treatment regimens for Hailey-Hailey disease include topical and oral corticosteroids and antibiotics.⁵ Topical and oral retinoids, calcitriol, topical tacrolimus, cyclosporin, methotrexate, and even botulinum toxin A have been reported to be effective for refractory cases.^7-12 Our case describes a novel regimen of oral tacrolimus in conjunction with botulinum toxin A used in the successful treatment of recalcitrant Hailey-Hailey disease.

Tacrolimus binds to the immunophilin FK506 binding protein, which inhibits calcineurin. Calcineurin, a protein phosphatase, is necessary for T-cell activation through the nuclear factor of activated T cells.This inhibition of calcineurin blocks the expression of several cytokines.¹³ The efficacy of oral tacrolimus demonstrates that cellular immunity could play a role in the pathogenic mechanism of Hailey-Hailey disease.

Contraindications to oral tacrolimus therapy include renal or hepatic impairment, breast-feeding, pregnancy, and certain neoplastic diseases. There also is an increased risk of patients developing malignancies such as lymphoma or skin cancer due to immunosuppression. Use of oral tacrolimus also requires routine laboratory monitoring of renal and hepatic function, potassium, and blood glucose levels.¹³

Botulinum toxin A injections augmented the therapeutic approach in our patient possibly by controlling secretions of sweat and mucous, which may cause maceration and lead to exacerbation of Hailey-Hailey disease. Control of secretions may help in creating an environment that is less prone to exacerbation of lesions and secondary infection.¹⁴ The combination of oral tacrolimus and botulinum toxin A injections provided a safe therapeutic option for recalcitrant Hailey-Hailey disease in our patient.

To the Editor:

Hailey-Hailey disease, also known as familial benign pemphigus, is a chronic blistering skin disorder that typically presents as a recurrent vesicular or bullous dermatitis found predominantly in the intertriginous regions of the body. Because current treatment regimens for Hailey-Hailey disease are fairly limited, novel treatments may be explored in intractable cases.

A 71-year-old woman presented with well-demarcated erythematous plaques with erosions and white verrucous regions in the perivulvar, vaginal, and perianal areas of 1 month’s duration (Figure 1). The lesions were excruciatingly pruritic and excoriated. The patient reported no personal or family history of similar lesions.

Histopathologic examination of multiple biopsies from the periphery of the plaques showed acantholysis of the epidermis and surface necrosis with negative direct immunofluorescence. A diagnosis of Hailey-Hailey disease was made. Over several months following the initial presentation, the patient was treated with regimens of corticosteroids, antibiotics, antifungals, acitretin, and topical tacrolimus (which showed minimal response), but the condition continued to progress and thus warranted a more aggressive approach. After a 4-week course of oral cyclosporine 1.25 mg/kg twice daily, some healthy granulation tissue had formed, but new erosions continued to develop on the vulva, labia, and intergluteal cleft (Figure 2). Subsequently, a 2-month course of methotrexate yielded similar results with minimal healing and new necrotic areas (Figure 3).

Following methotrexate therapy, treatment with several other oral agents was considered such as azathioprine, mycophenolate mofetil, and oral tacrolimus. Since the patient had previously shown minimal response to topical tacrolimus, a course of oral treatment (0.05 mg/kg twice daily) was initiated. At 4 weeks’ follow-up, extensive healing of the lesions was noted (Figure 4) and the patient reported that the painful pruritus had improved.

After 6 weeks of treatment, there still were a few small lesions in the intergluteal cleft, which were treated with botulinum toxin type A (100 U diluted with 5 cc of bacteriostatic saline per cm²). After 3 separate injections with botulinum toxin type A and oral tacrolimus for 9 months, complete resolution of the lesions was obtained (Figure 5). After more than 6 months of remission, oral tacrolimus slowly was decreased by 1 mg every 6 weeks until treatment was stopped completely. She has remained in remission without oral treatment. After tapering the tacrolimus, botulinum toxin A injections were continued every 6 months for maintenance with the use of topical tacrolimus 3 to 4 times weekly (Figure 6).

The inheritance of Hailey-Hailey disease is autosomal dominant with incomplete penetrance, although spontaneous mutations are implicated in up to 30% of patients.^1,2 The pathogenesis of Hailey-Hailey disease involves a mutation in the ATPase, Ca++ transporting, type 2C, member 1 gene (ATP2C1), which encodes for the hSPCA1 protein.^1-2 The malfunction of this ATPase leads to inadequacy of the keratinocyte adhesive barrier resulting in acantholysis and intraepidermal vesicle formation. Macerated plaques also may be found instead of intact vesicles.³

Initial presentation of lesions in Hailey-Hailey disease typically occurs in the third or fourth decades of life but may present at any age.⁴ Areas exposed to increased amounts of friction (eg, axillae, groin, neck, perineum) commonly are involved.⁵ Lesions may occur in a relapsing and remitting course and usually are more prominent in summer months because they are exacerbated by sunburn and frictional trauma. Secondary bacterial or fungal infections are common and antibiotics and antifungals often are necessary to prevent progression of the lesions.^5,6

Various treatment regimens for Hailey-Hailey disease include topical and oral corticosteroids and antibiotics.⁵ Topical and oral retinoids, calcitriol, topical tacrolimus, cyclosporin, methotrexate, and even botulinum toxin A have been reported to be effective for refractory cases.^7-12 Our case describes a novel regimen of oral tacrolimus in conjunction with botulinum toxin A used in the successful treatment of recalcitrant Hailey-Hailey disease.

Tacrolimus binds to the immunophilin FK506 binding protein, which inhibits calcineurin. Calcineurin, a protein phosphatase, is necessary for T-cell activation through the nuclear factor of activated T cells.This inhibition of calcineurin blocks the expression of several cytokines.¹³ The efficacy of oral tacrolimus demonstrates that cellular immunity could play a role in the pathogenic mechanism of Hailey-Hailey disease.

Contraindications to oral tacrolimus therapy include renal or hepatic impairment, breast-feeding, pregnancy, and certain neoplastic diseases. There also is an increased risk of patients developing malignancies such as lymphoma or skin cancer due to immunosuppression. Use of oral tacrolimus also requires routine laboratory monitoring of renal and hepatic function, potassium, and blood glucose levels.¹³

Botulinum toxin A injections augmented the therapeutic approach in our patient possibly by controlling secretions of sweat and mucous, which may cause maceration and lead to exacerbation of Hailey-Hailey disease. Control of secretions may help in creating an environment that is less prone to exacerbation of lesions and secondary infection.¹⁴ The combination of oral tacrolimus and botulinum toxin A injections provided a safe therapeutic option for recalcitrant Hailey-Hailey disease in our patient.

To the Editor:

Sebaceous nevus (SN) is a relatively common hamartoma that presents most often as a single congenital hairless plaque on the scalp. After puberty, histologic features characteristically include papillomatous hyperplasia of the epidermis, a large number of mature or nearly mature sebaceous glands, and a lack of terminally differentiated hair follicles; however, histologic findings can be misleading during childhood when sebaceous glands are still underdeveloped. Bright yellow dots, which are thought to indicate the presence of sebaceous glands, may be seen on dermoscopy and can be useful in differentiating SN from aplasia cutis congenita in newborns.

We report a case of an SN in an 18-year-old woman and discuss how the histology findings correlated with features seen on dermoscopy.

An 18-year-old woman presented to our dermatology clinic with an asymptomatic, hairless plaque on the right parietal scalp that had been present since birth. The patient noted that the plaque had recently become larger in size. On physical examination, an 8×3-cm plaque with a smooth, flesh-colored surface was noted with central comedolike structures and an erythematous, verrucous periphery (Figure 1).

Dermoscopy (handheld dermoscope using polarized light) revealed 3 distinct types of round structures within the lesion: (1) comedolike openings (similar to those seen in seborrheic keratosis) that appeared as brownish-yellow, sharply circumscribed structures; (2) milialike cysts (also found in acanthotic seborrheic keratosis), which appeared as bright yellow structures; and (3) multiple whitish structures that were irregular in shape and size and covered the surface of the lesion where there were no other dermoscopic findings (Figure 2). The affected skin was pale to red in color and the verrucous aspect of the surface was better visualized at the edge of the lesion.

Two 4-mm punch biopsies were performed following dermoscopy: one for horizontal sectioning and one for vertical sectioning. Histologic analysis showed an acanthotic epidermis with an anastomosing network of elongated rete ridges in the superficial dermis. Numerous hyperplasic sebaceous glands were found in the mid dermis, with some also located above this level. Immature hair follicles were present and sebaceous gland ducts communicated directly with the epidermis through dilated hyperkeratinized pathways. Eccrine glands were normal, but no apocrine glands were present. A lymphocytic infiltrate was noted around the sebaceous glands and immature hair follicles and also around dilated capillaries in the superficial dermis. Moderate spongiosis and lymphocytic exocytosis were noted in the glandular epithelium and in the basal layer of the hair follicles and the epidermis. Superficial slides of horizontal sections of the biopsy specimen showed a correlation between the histology findings and dermoscopy images: multiple normal-appearing papilla surrounded by a network of anastomosing rete ridges correlated with multiple whitish structures, keratotic cysts with compact keratin corresponded to bright yellow dots, and larger conglomerates of loose lamelar keratin correlated with comedolike openings. Due to the presence of eczematous changes (eg, epithelial spongiosis, inflammatory cells) observed on histology, a diagnosis of an irritated sebaceous nevus was made, which explained the recent enlargement of the congenital lesion.

Sebaceous nevus is a benign, epidermal appendageal tumor with differentiation towards sebaceous glands that is composed of mature or nearly mature skin structures. Histologically, it is classified as a hamartoma.¹ It commonly arises on the scalp as a yellowish or flesh-colored, hairless plaque of variable size. At birth, its surface is smooth and the differential diagnoses include aplasia cutis congenita, congenital triangular alopecia, and alopecia areata.² As the patient ages, hormones stimulate the proliferation of sebaceous glands and the epidermis, and the lesion gradually acquires a verrucous, waxy surface.³ Benign appendageal tumors often develop inside SN. Basal cell epitheliomas are rarely found.⁴ Surgical excision is recommended for aesthetic purposes or to prevent the development of tumors.

Histology also varies with the patient’s age and can be misleading in childhood because the sebaceous glands are underdeveloped.^5,6 After adrenarche, histology becomes more diagnostic, showing a dermis almost completely filled with sebaceous glands with varying degrees of maturity.² The presence of incompletely differentiated follicles without hair shafts can be found in newborns and children and may be helpful for the correct histological diagnosis before puberty.^1,5 The epidermis presents no abnormalities at birth but develops acanthosis and papillomatosis as the patient ages. Ectopic dilated apocrine glands sometimes can be found deeper in the dermis in the late stage of the lesion.⁵

In a report by Neri et al,⁷ multiple bright yellow dots were noted on dermoscopy in 2 children with SN. The investigators concluded that this characteristic feature, which was thought to represent the sebaceous glands, can be useful in differentiating SN from aplasia cutis congenita in early infancy, but no histologic analyses were performed.⁷ In our patient, we identified 3 different dermoscopic features that correlated with histologic findings. Comedolike openings correlated with the accumulated keratin (ie, keratotic plugs) inside dilated sebaceous gland ducts directly connected to the epidermis. The brownish-yellow color of these openings observed on dermoscopy may be due to the oxidation of kerat-inous material, such as those in seborrheic keratosis lesions (Figure 3). We also noted bright yellow dots similar to those reported by Neri et al⁷; however, histologic analysis in our patient showed these dots more closely correlated with keratotic cysts similar to milialike structures seen in acanthotic seborrheic keratosis. The material remained lightly colored because no oxidation process had occurred (Figure 4). The third structure found on dermoscopy in our patient was multiple whitish structures that were irregular in shape and size. According to our comparison of superficial horizontal histology slides with dermoscopy images, we hypothesized this finding was the result of epidermal papillomatosis over a dermis filled with enlarged sebaceous glands (Figure 5). This finding was likely absent in the cases previously reported by Neri et al⁷ because epidermal and glandular changes occur later in the evolution of SN and the patients in these cases were younger than 4 months old.

Our correlation of dermoscopic features with histology findings in an 18-year-old woman with an irritated SN highlights the need for more studies needed in order to establish the prevalence of certain dermoscopic findings in this setting, particularly considering the important morphological changes that occur in these lesions as patients age as well as the histological variation among different hamartomas. Over the last decade, dermoscopy has proven to be a useful tool in the diagnosis of various hair and scalp diseases.⁸ Histologic correlation of dermoscopy findings is essential for more precise understanding of this new imaging technique and should be conducted whenever possible.

To the Editor:

Sebaceous nevus (SN) is a relatively common hamartoma that presents most often as a single congenital hairless plaque on the scalp. After puberty, histologic features characteristically include papillomatous hyperplasia of the epidermis, a large number of mature or nearly mature sebaceous glands, and a lack of terminally differentiated hair follicles; however, histologic findings can be misleading during childhood when sebaceous glands are still underdeveloped. Bright yellow dots, which are thought to indicate the presence of sebaceous glands, may be seen on dermoscopy and can be useful in differentiating SN from aplasia cutis congenita in newborns.

We report a case of an SN in an 18-year-old woman and discuss how the histology findings correlated with features seen on dermoscopy.

An 18-year-old woman presented to our dermatology clinic with an asymptomatic, hairless plaque on the right parietal scalp that had been present since birth. The patient noted that the plaque had recently become larger in size. On physical examination, an 8×3-cm plaque with a smooth, flesh-colored surface was noted with central comedolike structures and an erythematous, verrucous periphery (Figure 1).

Dermoscopy (handheld dermoscope using polarized light) revealed 3 distinct types of round structures within the lesion: (1) comedolike openings (similar to those seen in seborrheic keratosis) that appeared as brownish-yellow, sharply circumscribed structures; (2) milialike cysts (also found in acanthotic seborrheic keratosis), which appeared as bright yellow structures; and (3) multiple whitish structures that were irregular in shape and size and covered the surface of the lesion where there were no other dermoscopic findings (Figure 2). The affected skin was pale to red in color and the verrucous aspect of the surface was better visualized at the edge of the lesion.

Two 4-mm punch biopsies were performed following dermoscopy: one for horizontal sectioning and one for vertical sectioning. Histologic analysis showed an acanthotic epidermis with an anastomosing network of elongated rete ridges in the superficial dermis. Numerous hyperplasic sebaceous glands were found in the mid dermis, with some also located above this level. Immature hair follicles were present and sebaceous gland ducts communicated directly with the epidermis through dilated hyperkeratinized pathways. Eccrine glands were normal, but no apocrine glands were present. A lymphocytic infiltrate was noted around the sebaceous glands and immature hair follicles and also around dilated capillaries in the superficial dermis. Moderate spongiosis and lymphocytic exocytosis were noted in the glandular epithelium and in the basal layer of the hair follicles and the epidermis. Superficial slides of horizontal sections of the biopsy specimen showed a correlation between the histology findings and dermoscopy images: multiple normal-appearing papilla surrounded by a network of anastomosing rete ridges correlated with multiple whitish structures, keratotic cysts with compact keratin corresponded to bright yellow dots, and larger conglomerates of loose lamelar keratin correlated with comedolike openings. Due to the presence of eczematous changes (eg, epithelial spongiosis, inflammatory cells) observed on histology, a diagnosis of an irritated sebaceous nevus was made, which explained the recent enlargement of the congenital lesion.

Sebaceous nevus is a benign, epidermal appendageal tumor with differentiation towards sebaceous glands that is composed of mature or nearly mature skin structures. Histologically, it is classified as a hamartoma.¹ It commonly arises on the scalp as a yellowish or flesh-colored, hairless plaque of variable size. At birth, its surface is smooth and the differential diagnoses include aplasia cutis congenita, congenital triangular alopecia, and alopecia areata.² As the patient ages, hormones stimulate the proliferation of sebaceous glands and the epidermis, and the lesion gradually acquires a verrucous, waxy surface.³ Benign appendageal tumors often develop inside SN. Basal cell epitheliomas are rarely found.⁴ Surgical excision is recommended for aesthetic purposes or to prevent the development of tumors.

Histology also varies with the patient’s age and can be misleading in childhood because the sebaceous glands are underdeveloped.^5,6 After adrenarche, histology becomes more diagnostic, showing a dermis almost completely filled with sebaceous glands with varying degrees of maturity.² The presence of incompletely differentiated follicles without hair shafts can be found in newborns and children and may be helpful for the correct histological diagnosis before puberty.^1,5 The epidermis presents no abnormalities at birth but develops acanthosis and papillomatosis as the patient ages. Ectopic dilated apocrine glands sometimes can be found deeper in the dermis in the late stage of the lesion.⁵

In a report by Neri et al,⁷ multiple bright yellow dots were noted on dermoscopy in 2 children with SN. The investigators concluded that this characteristic feature, which was thought to represent the sebaceous glands, can be useful in differentiating SN from aplasia cutis congenita in early infancy, but no histologic analyses were performed.⁷ In our patient, we identified 3 different dermoscopic features that correlated with histologic findings. Comedolike openings correlated with the accumulated keratin (ie, keratotic plugs) inside dilated sebaceous gland ducts directly connected to the epidermis. The brownish-yellow color of these openings observed on dermoscopy may be due to the oxidation of kerat-inous material, such as those in seborrheic keratosis lesions (Figure 3). We also noted bright yellow dots similar to those reported by Neri et al⁷; however, histologic analysis in our patient showed these dots more closely correlated with keratotic cysts similar to milialike structures seen in acanthotic seborrheic keratosis. The material remained lightly colored because no oxidation process had occurred (Figure 4). The third structure found on dermoscopy in our patient was multiple whitish structures that were irregular in shape and size. According to our comparison of superficial horizontal histology slides with dermoscopy images, we hypothesized this finding was the result of epidermal papillomatosis over a dermis filled with enlarged sebaceous glands (Figure 5). This finding was likely absent in the cases previously reported by Neri et al⁷ because epidermal and glandular changes occur later in the evolution of SN and the patients in these cases were younger than 4 months old.

Our correlation of dermoscopic features with histology findings in an 18-year-old woman with an irritated SN highlights the need for more studies needed in order to establish the prevalence of certain dermoscopic findings in this setting, particularly considering the important morphological changes that occur in these lesions as patients age as well as the histological variation among different hamartomas. Over the last decade, dermoscopy has proven to be a useful tool in the diagnosis of various hair and scalp diseases.⁸ Histologic correlation of dermoscopy findings is essential for more precise understanding of this new imaging technique and should be conducted whenever possible.

To the Editor:

Sebaceous nevus (SN) is a relatively common hamartoma that presents most often as a single congenital hairless plaque on the scalp. After puberty, histologic features characteristically include papillomatous hyperplasia of the epidermis, a large number of mature or nearly mature sebaceous glands, and a lack of terminally differentiated hair follicles; however, histologic findings can be misleading during childhood when sebaceous glands are still underdeveloped. Bright yellow dots, which are thought to indicate the presence of sebaceous glands, may be seen on dermoscopy and can be useful in differentiating SN from aplasia cutis congenita in newborns.

We report a case of an SN in an 18-year-old woman and discuss how the histology findings correlated with features seen on dermoscopy.

An 18-year-old woman presented to our dermatology clinic with an asymptomatic, hairless plaque on the right parietal scalp that had been present since birth. The patient noted that the plaque had recently become larger in size. On physical examination, an 8×3-cm plaque with a smooth, flesh-colored surface was noted with central comedolike structures and an erythematous, verrucous periphery (Figure 1).

Dermoscopy (handheld dermoscope using polarized light) revealed 3 distinct types of round structures within the lesion: (1) comedolike openings (similar to those seen in seborrheic keratosis) that appeared as brownish-yellow, sharply circumscribed structures; (2) milialike cysts (also found in acanthotic seborrheic keratosis), which appeared as bright yellow structures; and (3) multiple whitish structures that were irregular in shape and size and covered the surface of the lesion where there were no other dermoscopic findings (Figure 2). The affected skin was pale to red in color and the verrucous aspect of the surface was better visualized at the edge of the lesion.

Two 4-mm punch biopsies were performed following dermoscopy: one for horizontal sectioning and one for vertical sectioning. Histologic analysis showed an acanthotic epidermis with an anastomosing network of elongated rete ridges in the superficial dermis. Numerous hyperplasic sebaceous glands were found in the mid dermis, with some also located above this level. Immature hair follicles were present and sebaceous gland ducts communicated directly with the epidermis through dilated hyperkeratinized pathways. Eccrine glands were normal, but no apocrine glands were present. A lymphocytic infiltrate was noted around the sebaceous glands and immature hair follicles and also around dilated capillaries in the superficial dermis. Moderate spongiosis and lymphocytic exocytosis were noted in the glandular epithelium and in the basal layer of the hair follicles and the epidermis. Superficial slides of horizontal sections of the biopsy specimen showed a correlation between the histology findings and dermoscopy images: multiple normal-appearing papilla surrounded by a network of anastomosing rete ridges correlated with multiple whitish structures, keratotic cysts with compact keratin corresponded to bright yellow dots, and larger conglomerates of loose lamelar keratin correlated with comedolike openings. Due to the presence of eczematous changes (eg, epithelial spongiosis, inflammatory cells) observed on histology, a diagnosis of an irritated sebaceous nevus was made, which explained the recent enlargement of the congenital lesion.

Sebaceous nevus is a benign, epidermal appendageal tumor with differentiation towards sebaceous glands that is composed of mature or nearly mature skin structures. Histologically, it is classified as a hamartoma.¹ It commonly arises on the scalp as a yellowish or flesh-colored, hairless plaque of variable size. At birth, its surface is smooth and the differential diagnoses include aplasia cutis congenita, congenital triangular alopecia, and alopecia areata.² As the patient ages, hormones stimulate the proliferation of sebaceous glands and the epidermis, and the lesion gradually acquires a verrucous, waxy surface.³ Benign appendageal tumors often develop inside SN. Basal cell epitheliomas are rarely found.⁴ Surgical excision is recommended for aesthetic purposes or to prevent the development of tumors.

Histology also varies with the patient’s age and can be misleading in childhood because the sebaceous glands are underdeveloped.^5,6 After adrenarche, histology becomes more diagnostic, showing a dermis almost completely filled with sebaceous glands with varying degrees of maturity.² The presence of incompletely differentiated follicles without hair shafts can be found in newborns and children and may be helpful for the correct histological diagnosis before puberty.^1,5 The epidermis presents no abnormalities at birth but develops acanthosis and papillomatosis as the patient ages. Ectopic dilated apocrine glands sometimes can be found deeper in the dermis in the late stage of the lesion.⁵

In a report by Neri et al,⁷ multiple bright yellow dots were noted on dermoscopy in 2 children with SN. The investigators concluded that this characteristic feature, which was thought to represent the sebaceous glands, can be useful in differentiating SN from aplasia cutis congenita in early infancy, but no histologic analyses were performed.⁷ In our patient, we identified 3 different dermoscopic features that correlated with histologic findings. Comedolike openings correlated with the accumulated keratin (ie, keratotic plugs) inside dilated sebaceous gland ducts directly connected to the epidermis. The brownish-yellow color of these openings observed on dermoscopy may be due to the oxidation of kerat-inous material, such as those in seborrheic keratosis lesions (Figure 3). We also noted bright yellow dots similar to those reported by Neri et al⁷; however, histologic analysis in our patient showed these dots more closely correlated with keratotic cysts similar to milialike structures seen in acanthotic seborrheic keratosis. The material remained lightly colored because no oxidation process had occurred (Figure 4). The third structure found on dermoscopy in our patient was multiple whitish structures that were irregular in shape and size. According to our comparison of superficial horizontal histology slides with dermoscopy images, we hypothesized this finding was the result of epidermal papillomatosis over a dermis filled with enlarged sebaceous glands (Figure 5). This finding was likely absent in the cases previously reported by Neri et al⁷ because epidermal and glandular changes occur later in the evolution of SN and the patients in these cases were younger than 4 months old.

Our correlation of dermoscopic features with histology findings in an 18-year-old woman with an irritated SN highlights the need for more studies needed in order to establish the prevalence of certain dermoscopic findings in this setting, particularly considering the important morphological changes that occur in these lesions as patients age as well as the histological variation among different hamartomas. Over the last decade, dermoscopy has proven to be a useful tool in the diagnosis of various hair and scalp diseases.⁸ Histologic correlation of dermoscopy findings is essential for more precise understanding of this new imaging technique and should be conducted whenever possible.

To the Editor:

Purpura fulminans is a severe and rapidly fatal thrombotic disorder that can occur in association with either hereditary or acquired deficiencies of the natural anticoagulants protein C and protein S.¹ It most commonly results from the acute inflammatory response and subsequent disseminated intravascular coagulation (DIC) seen in severe bacterial septicemia. Excessive bleeding, retiform purpura, and skin necrosis may develop as a result of the coagulopathies of typical DIC.¹Neisseria meningitidis, Streptococcus, and Staphylococcus frequently are implicated as pathogens, but Escherichia coli–associated purpura fulminans in adults is rare.^2,3 We report a case of purpura fulminans in the setting of E coli septicemia.

A 62-year-old woman with a history of end-stage liver disease secondary to alcoholic liver cirrhosis diagnosed 13 years prior complicated by ascites and esophageal varices presented to a primary care clinic for evaluation of a recent-onset nontender lesion on the left buttock. She was hypotensive with a blood pressure of 62/48 mmHg. The patient was prescribed ciprofloxacin 250 mg twice daily and hydrocodone/acetominophen 5 mg/325 mg twice daily as needed for pain management and was discharged. Six hours later, the patient presented to the emergency department with new onset symptoms of confusion and dark-colored spots on the abdomen and lower legs, which her family members noted had developed shortly after the patient took ciprofloxacin. In the emergency department, the patient was noted to be hypotensive and febrile with a severe metabolic acidosis. She was intubated for respiratory failure and received intravenous fluid resuscitation, broad-spectrum antibiotics, and vasopressors. Blood cultures were obtained, and the dermatology department was consulted.

On physical examination, extensive purpuric, reticulated, and stellate plaques with central necrosis and hemorrhagic bullae were noted on the abdomen (Figure, A) and bilateral lower legs (Figure, B) extending onto the thighs. The patient was coagulopathic with persistent sanguineous oozing at intravenous sites and bilateral nares. A small erythematous ulcer with overlying black eschar was noted on the left medial buttock.

Laboratory test results showed new-onset thrombocytopenia, prolonged prothrombin time/international normalized ratio and partial thromboplastin time, and low fibrinogen levels, which confirmed a diagnosis of acute DIC. Blood cultures were positive for gram-negative rods in 4 out of 4 bottles within 12 hours of being drawn. Further testing identified the microorganism as E coli, and antibiotic susceptibility testing revealed it was sensitive to most antibiotics.

The patient was clinically diagnosed with purpura fulminans secondary to severe E coli septicemia and DIC. This life-threatening disorder is considered a medical emergency with a high mortality rate. Laboratory findings supporting DIC include the presence of schistocytes on a peripheral blood smear, thrombocytopenia, positive plasma protamine paracoagulation test, low fibrinogen levels, and positive fibrin degradation products. Reported cases of purpura fulminans in the setting of E coli septicemia are rare, and meningococcemia is the most common presentation.^2,3 Bacterial components (eg, lipopolysaccharides found in the cell walls of gram-negative bacteria) may contribute to the progression of septicemia. Increased levels of endotoxin lipopolysaccharide can lead to septic shock and organ dysfunction.⁴ However, the release of lipooligosaccharides is associated with the development of meningococcal septicemia, and the lipopolysaccharide levels are directly correlated with prognosis in patients without meningitis.^5-7

Human activated protein C concentrate (and its precursor, protein C concentrate) replacement therapy has been shown to improve outcomes in patients with meningococcemia-associated–purpura fulminans and severe sepsis, respectively.⁸ Heparin may be considered in the treatment of patients with purpura fulminans in addition to the replacement of any missing clotting factors or blood products.⁹ The international guidelines for the management of severe sepsis and septic shock include early quantitative resuscitation of the patient during the first 6 hours after recognition of sepsis, performing blood cultures before antibiotic therapy, and administering broad-spectrum antimicrobial therapy within 1 hour of recognition of septic shock.¹⁰ The elapsed time from triage to the actual administration of appropriate antimicrobials are primary determinants of patient mortality.¹¹ Therefore, physicians must act quickly to stabilize the patient.

Gram-positive bacteria and gram-negative diplococci are common infectious agents implicated in purpura fulminans. Escherichia coli rarely has been identified as the inciting agent for purpura fulminans in adults. The increasing frequency of E coli strains that produce extended-spectrum β-lactamases—enzymes that mediate resistance to extended-spectrum (third generation) cephalosporins (eg, ceftazidime, cefotaxime, ceftriaxone) and monobactams (eg, aztreonam)—complicates matters further when deciding on appropriate antibiotics. Patients who have infections from extended-spectrum β-lactamase strains will require more potent carbapenems (eg, meropenem, imipenem) for treatment of infections. Despite undergoing treatment for septicemia, our patient went into cardiac arrest within 24 hours of presentation to the emergency department and died a few hours later. Physicians should consider E coli as an inciting agent of purpura fulminans and consider appropriate empiric antibiotics with gram-negative coverage to include E coli.

To the Editor:

Purpura fulminans is a severe and rapidly fatal thrombotic disorder that can occur in association with either hereditary or acquired deficiencies of the natural anticoagulants protein C and protein S.¹ It most commonly results from the acute inflammatory response and subsequent disseminated intravascular coagulation (DIC) seen in severe bacterial septicemia. Excessive bleeding, retiform purpura, and skin necrosis may develop as a result of the coagulopathies of typical DIC.¹Neisseria meningitidis, Streptococcus, and Staphylococcus frequently are implicated as pathogens, but Escherichia coli–associated purpura fulminans in adults is rare.^2,3 We report a case of purpura fulminans in the setting of E coli septicemia.

A 62-year-old woman with a history of end-stage liver disease secondary to alcoholic liver cirrhosis diagnosed 13 years prior complicated by ascites and esophageal varices presented to a primary care clinic for evaluation of a recent-onset nontender lesion on the left buttock. She was hypotensive with a blood pressure of 62/48 mmHg. The patient was prescribed ciprofloxacin 250 mg twice daily and hydrocodone/acetominophen 5 mg/325 mg twice daily as needed for pain management and was discharged. Six hours later, the patient presented to the emergency department with new onset symptoms of confusion and dark-colored spots on the abdomen and lower legs, which her family members noted had developed shortly after the patient took ciprofloxacin. In the emergency department, the patient was noted to be hypotensive and febrile with a severe metabolic acidosis. She was intubated for respiratory failure and received intravenous fluid resuscitation, broad-spectrum antibiotics, and vasopressors. Blood cultures were obtained, and the dermatology department was consulted.

On physical examination, extensive purpuric, reticulated, and stellate plaques with central necrosis and hemorrhagic bullae were noted on the abdomen (Figure, A) and bilateral lower legs (Figure, B) extending onto the thighs. The patient was coagulopathic with persistent sanguineous oozing at intravenous sites and bilateral nares. A small erythematous ulcer with overlying black eschar was noted on the left medial buttock.

Laboratory test results showed new-onset thrombocytopenia, prolonged prothrombin time/international normalized ratio and partial thromboplastin time, and low fibrinogen levels, which confirmed a diagnosis of acute DIC. Blood cultures were positive for gram-negative rods in 4 out of 4 bottles within 12 hours of being drawn. Further testing identified the microorganism as E coli, and antibiotic susceptibility testing revealed it was sensitive to most antibiotics.

The patient was clinically diagnosed with purpura fulminans secondary to severe E coli septicemia and DIC. This life-threatening disorder is considered a medical emergency with a high mortality rate. Laboratory findings supporting DIC include the presence of schistocytes on a peripheral blood smear, thrombocytopenia, positive plasma protamine paracoagulation test, low fibrinogen levels, and positive fibrin degradation products. Reported cases of purpura fulminans in the setting of E coli septicemia are rare, and meningococcemia is the most common presentation.^2,3 Bacterial components (eg, lipopolysaccharides found in the cell walls of gram-negative bacteria) may contribute to the progression of septicemia. Increased levels of endotoxin lipopolysaccharide can lead to septic shock and organ dysfunction.⁴ However, the release of lipooligosaccharides is associated with the development of meningococcal septicemia, and the lipopolysaccharide levels are directly correlated with prognosis in patients without meningitis.^5-7

Human activated protein C concentrate (and its precursor, protein C concentrate) replacement therapy has been shown to improve outcomes in patients with meningococcemia-associated–purpura fulminans and severe sepsis, respectively.⁸ Heparin may be considered in the treatment of patients with purpura fulminans in addition to the replacement of any missing clotting factors or blood products.⁹ The international guidelines for the management of severe sepsis and septic shock include early quantitative resuscitation of the patient during the first 6 hours after recognition of sepsis, performing blood cultures before antibiotic therapy, and administering broad-spectrum antimicrobial therapy within 1 hour of recognition of septic shock.¹⁰ The elapsed time from triage to the actual administration of appropriate antimicrobials are primary determinants of patient mortality.¹¹ Therefore, physicians must act quickly to stabilize the patient.

Gram-positive bacteria and gram-negative diplococci are common infectious agents implicated in purpura fulminans. Escherichia coli rarely has been identified as the inciting agent for purpura fulminans in adults. The increasing frequency of E coli strains that produce extended-spectrum β-lactamases—enzymes that mediate resistance to extended-spectrum (third generation) cephalosporins (eg, ceftazidime, cefotaxime, ceftriaxone) and monobactams (eg, aztreonam)—complicates matters further when deciding on appropriate antibiotics. Patients who have infections from extended-spectrum β-lactamase strains will require more potent carbapenems (eg, meropenem, imipenem) for treatment of infections. Despite undergoing treatment for septicemia, our patient went into cardiac arrest within 24 hours of presentation to the emergency department and died a few hours later. Physicians should consider E coli as an inciting agent of purpura fulminans and consider appropriate empiric antibiotics with gram-negative coverage to include E coli.

To the Editor:

Purpura fulminans is a severe and rapidly fatal thrombotic disorder that can occur in association with either hereditary or acquired deficiencies of the natural anticoagulants protein C and protein S.¹ It most commonly results from the acute inflammatory response and subsequent disseminated intravascular coagulation (DIC) seen in severe bacterial septicemia. Excessive bleeding, retiform purpura, and skin necrosis may develop as a result of the coagulopathies of typical DIC.¹Neisseria meningitidis, Streptococcus, and Staphylococcus frequently are implicated as pathogens, but Escherichia coli–associated purpura fulminans in adults is rare.^2,3 We report a case of purpura fulminans in the setting of E coli septicemia.

A 62-year-old woman with a history of end-stage liver disease secondary to alcoholic liver cirrhosis diagnosed 13 years prior complicated by ascites and esophageal varices presented to a primary care clinic for evaluation of a recent-onset nontender lesion on the left buttock. She was hypotensive with a blood pressure of 62/48 mmHg. The patient was prescribed ciprofloxacin 250 mg twice daily and hydrocodone/acetominophen 5 mg/325 mg twice daily as needed for pain management and was discharged. Six hours later, the patient presented to the emergency department with new onset symptoms of confusion and dark-colored spots on the abdomen and lower legs, which her family members noted had developed shortly after the patient took ciprofloxacin. In the emergency department, the patient was noted to be hypotensive and febrile with a severe metabolic acidosis. She was intubated for respiratory failure and received intravenous fluid resuscitation, broad-spectrum antibiotics, and vasopressors. Blood cultures were obtained, and the dermatology department was consulted.

On physical examination, extensive purpuric, reticulated, and stellate plaques with central necrosis and hemorrhagic bullae were noted on the abdomen (Figure, A) and bilateral lower legs (Figure, B) extending onto the thighs. The patient was coagulopathic with persistent sanguineous oozing at intravenous sites and bilateral nares. A small erythematous ulcer with overlying black eschar was noted on the left medial buttock.

Laboratory test results showed new-onset thrombocytopenia, prolonged prothrombin time/international normalized ratio and partial thromboplastin time, and low fibrinogen levels, which confirmed a diagnosis of acute DIC. Blood cultures were positive for gram-negative rods in 4 out of 4 bottles within 12 hours of being drawn. Further testing identified the microorganism as E coli, and antibiotic susceptibility testing revealed it was sensitive to most antibiotics.

The patient was clinically diagnosed with purpura fulminans secondary to severe E coli septicemia and DIC. This life-threatening disorder is considered a medical emergency with a high mortality rate. Laboratory findings supporting DIC include the presence of schistocytes on a peripheral blood smear, thrombocytopenia, positive plasma protamine paracoagulation test, low fibrinogen levels, and positive fibrin degradation products. Reported cases of purpura fulminans in the setting of E coli septicemia are rare, and meningococcemia is the most common presentation.^2,3 Bacterial components (eg, lipopolysaccharides found in the cell walls of gram-negative bacteria) may contribute to the progression of septicemia. Increased levels of endotoxin lipopolysaccharide can lead to septic shock and organ dysfunction.⁴ However, the release of lipooligosaccharides is associated with the development of meningococcal septicemia, and the lipopolysaccharide levels are directly correlated with prognosis in patients without meningitis.^5-7

Human activated protein C concentrate (and its precursor, protein C concentrate) replacement therapy has been shown to improve outcomes in patients with meningococcemia-associated–purpura fulminans and severe sepsis, respectively.⁸ Heparin may be considered in the treatment of patients with purpura fulminans in addition to the replacement of any missing clotting factors or blood products.⁹ The international guidelines for the management of severe sepsis and septic shock include early quantitative resuscitation of the patient during the first 6 hours after recognition of sepsis, performing blood cultures before antibiotic therapy, and administering broad-spectrum antimicrobial therapy within 1 hour of recognition of septic shock.¹⁰ The elapsed time from triage to the actual administration of appropriate antimicrobials are primary determinants of patient mortality.¹¹ Therefore, physicians must act quickly to stabilize the patient.

Gram-positive bacteria and gram-negative diplococci are common infectious agents implicated in purpura fulminans. Escherichia coli rarely has been identified as the inciting agent for purpura fulminans in adults. The increasing frequency of E coli strains that produce extended-spectrum β-lactamases—enzymes that mediate resistance to extended-spectrum (third generation) cephalosporins (eg, ceftazidime, cefotaxime, ceftriaxone) and monobactams (eg, aztreonam)—complicates matters further when deciding on appropriate antibiotics. Patients who have infections from extended-spectrum β-lactamase strains will require more potent carbapenems (eg, meropenem, imipenem) for treatment of infections. Despite undergoing treatment for septicemia, our patient went into cardiac arrest within 24 hours of presentation to the emergency department and died a few hours later. Physicians should consider E coli as an inciting agent of purpura fulminans and consider appropriate empiric antibiotics with gram-negative coverage to include E coli.

To the Editor:

Missed appointments are a major issue in every discipline of medicine¹ and can be detrimental for dermatologists,^2,3 whose clinics often have long wait times for referred patients and can lose up to $200 for each missed appointment.⁴ The purpose of this study was to quantify the rate of missed appointments at an academic dermatology clinic and identify factors associated with patient nonattendance.

After approval by an institutional review board, appointment data was collected from the electronic medical record at the dermatology clinic at Wake Forest Baptist Health, Winston-Salem, North Carolina, for the period from May 1, 2013, to April 30, 2014. Variables that were evaluated included age, race, sex, primary language, employment status, zip code, appointment time, insurance coverage, scheduled provider, patient status (new vs returning), and the nature of the visit (cosmetic vs noncosmetic visits and procedural vs nonprocedural visits). Zip codes served as a representation of distance traveled and were stratified into 4 concentric zones: zone 1 represented the region corresponding to the clinic’s zip code; zone 2 represented regions with zip codes adjacent to zone 1; and the remaining zones were determined by regions with zip codes adjacent to the prior zone. Primary language spoken was categorized as English or non-English. Insurance coverage was categorized as private, Medicaid, Medicare, self-pay, and other. Using stepwise selection, both a univariate model and a multivariable logistic regression model were created (variable inclusion, P≤.10; variable exclusion, P>.05). Of the 28,772 appointments scheduled during the study period, 5584 (19.4%) were missed. Univariate and multivariable analyses of the factors associated with missed appointments are shown in Table 1.

A telephone survey also was conducted to evaluate patient-reported factors associated with missed dermatology appointments. A list of patients who missed appointments during the period from January 1, 2014, to April 30, 2014, was extracted and every fourth patient was called within 6 weeks of the appointment to minimize recall bias. Patients were excluded from the study if they could not be reached after 3 attempts. Of the 799 patients contacted, 300 (38%) responded to the survey; 98 (12%) had phone numbers on record that were incorrect or were no longer in service; and 401 (50%) could not be reached after 3 attempts. The results of the telephone survey are provided in Table 2.

The demographic data suggested that characteristics associated with higher rates of missed appointments tended to reflect physical or financial barriers, such as dependency on others for transportation (eg, pediatric patients), longer distance traveled to the clinic, and lack of insurance coverage; however, only 4% and 8% of the survey respondents reported that they missed their appointment due to financial reasons or that they were unable to obtain transportation, respectively. Of the patients surveyed, 35% cited that the reason they missed their appointment was that they forgot about the appointment; additionally, 24% of respondents reported that they had not been reminded of the appointment.

Although physicians cannot directly address physical or financial barriers to attendance, we can introduce more effective methods of communication for patient reminders. Of the 799 patients who were called for the telephone survey, 12.3% had phone numbers on record that were either incorrect or no longer in service. As these patients’ phone numbers were listed in the electronic medical record for contact purposes, they likely did not receive telephone calls reminding them about their appointments. Although it was not formally evaluated in this study, many respondents expressed that they had other preferred methods of receiving appointment reminders (eg, e-mail, text message) than those that are currently considered commonplace (ie, telephone calls, voicemails).

This study was limited in that the appointment data came from a single academic dermatology clinic. There also were limitations in the data set for subgroup analysis; for example, to appropriately assess socioeconomic barriers to attendance of dermatology appointments, it would be valuable to stratify income within established factors of socioeconomic barriers (eg, race, employment status) to avoid research bias. Although many variables assessed were statistically significant (P<.05), the odds ratios often were close to 1, suggesting that they may not be clinically or practically relevant.

By identifying factors associated with missed dermatology appointments, interventions can be instituted to target high-risk groups and alter patient reminder protocols. If possible, identifying patients’ preferred contact methods (eg, telephone call, text message, etc) and verifying contact information may be cost-effective ways to reduce missed appointments in dermatology offices.

To the Editor:

Missed appointments are a major issue in every discipline of medicine¹ and can be detrimental for dermatologists,^2,3 whose clinics often have long wait times for referred patients and can lose up to $200 for each missed appointment.⁴ The purpose of this study was to quantify the rate of missed appointments at an academic dermatology clinic and identify factors associated with patient nonattendance.

After approval by an institutional review board, appointment data was collected from the electronic medical record at the dermatology clinic at Wake Forest Baptist Health, Winston-Salem, North Carolina, for the period from May 1, 2013, to April 30, 2014. Variables that were evaluated included age, race, sex, primary language, employment status, zip code, appointment time, insurance coverage, scheduled provider, patient status (new vs returning), and the nature of the visit (cosmetic vs noncosmetic visits and procedural vs nonprocedural visits). Zip codes served as a representation of distance traveled and were stratified into 4 concentric zones: zone 1 represented the region corresponding to the clinic’s zip code; zone 2 represented regions with zip codes adjacent to zone 1; and the remaining zones were determined by regions with zip codes adjacent to the prior zone. Primary language spoken was categorized as English or non-English. Insurance coverage was categorized as private, Medicaid, Medicare, self-pay, and other. Using stepwise selection, both a univariate model and a multivariable logistic regression model were created (variable inclusion, P≤.10; variable exclusion, P>.05). Of the 28,772 appointments scheduled during the study period, 5584 (19.4%) were missed. Univariate and multivariable analyses of the factors associated with missed appointments are shown in Table 1.

A telephone survey also was conducted to evaluate patient-reported factors associated with missed dermatology appointments. A list of patients who missed appointments during the period from January 1, 2014, to April 30, 2014, was extracted and every fourth patient was called within 6 weeks of the appointment to minimize recall bias. Patients were excluded from the study if they could not be reached after 3 attempts. Of the 799 patients contacted, 300 (38%) responded to the survey; 98 (12%) had phone numbers on record that were incorrect or were no longer in service; and 401 (50%) could not be reached after 3 attempts. The results of the telephone survey are provided in Table 2.

The demographic data suggested that characteristics associated with higher rates of missed appointments tended to reflect physical or financial barriers, such as dependency on others for transportation (eg, pediatric patients), longer distance traveled to the clinic, and lack of insurance coverage; however, only 4% and 8% of the survey respondents reported that they missed their appointment due to financial reasons or that they were unable to obtain transportation, respectively. Of the patients surveyed, 35% cited that the reason they missed their appointment was that they forgot about the appointment; additionally, 24% of respondents reported that they had not been reminded of the appointment.

Although physicians cannot directly address physical or financial barriers to attendance, we can introduce more effective methods of communication for patient reminders. Of the 799 patients who were called for the telephone survey, 12.3% had phone numbers on record that were either incorrect or no longer in service. As these patients’ phone numbers were listed in the electronic medical record for contact purposes, they likely did not receive telephone calls reminding them about their appointments. Although it was not formally evaluated in this study, many respondents expressed that they had other preferred methods of receiving appointment reminders (eg, e-mail, text message) than those that are currently considered commonplace (ie, telephone calls, voicemails).

This study was limited in that the appointment data came from a single academic dermatology clinic. There also were limitations in the data set for subgroup analysis; for example, to appropriately assess socioeconomic barriers to attendance of dermatology appointments, it would be valuable to stratify income within established factors of socioeconomic barriers (eg, race, employment status) to avoid research bias. Although many variables assessed were statistically significant (P<.05), the odds ratios often were close to 1, suggesting that they may not be clinically or practically relevant.

By identifying factors associated with missed dermatology appointments, interventions can be instituted to target high-risk groups and alter patient reminder protocols. If possible, identifying patients’ preferred contact methods (eg, telephone call, text message, etc) and verifying contact information may be cost-effective ways to reduce missed appointments in dermatology offices.

To the Editor:

Missed appointments are a major issue in every discipline of medicine¹ and can be detrimental for dermatologists,^2,3 whose clinics often have long wait times for referred patients and can lose up to $200 for each missed appointment.⁴ The purpose of this study was to quantify the rate of missed appointments at an academic dermatology clinic and identify factors associated with patient nonattendance.

After approval by an institutional review board, appointment data was collected from the electronic medical record at the dermatology clinic at Wake Forest Baptist Health, Winston-Salem, North Carolina, for the period from May 1, 2013, to April 30, 2014. Variables that were evaluated included age, race, sex, primary language, employment status, zip code, appointment time, insurance coverage, scheduled provider, patient status (new vs returning), and the nature of the visit (cosmetic vs noncosmetic visits and procedural vs nonprocedural visits). Zip codes served as a representation of distance traveled and were stratified into 4 concentric zones: zone 1 represented the region corresponding to the clinic’s zip code; zone 2 represented regions with zip codes adjacent to zone 1; and the remaining zones were determined by regions with zip codes adjacent to the prior zone. Primary language spoken was categorized as English or non-English. Insurance coverage was categorized as private, Medicaid, Medicare, self-pay, and other. Using stepwise selection, both a univariate model and a multivariable logistic regression model were created (variable inclusion, P≤.10; variable exclusion, P>.05). Of the 28,772 appointments scheduled during the study period, 5584 (19.4%) were missed. Univariate and multivariable analyses of the factors associated with missed appointments are shown in Table 1.

A telephone survey also was conducted to evaluate patient-reported factors associated with missed dermatology appointments. A list of patients who missed appointments during the period from January 1, 2014, to April 30, 2014, was extracted and every fourth patient was called within 6 weeks of the appointment to minimize recall bias. Patients were excluded from the study if they could not be reached after 3 attempts. Of the 799 patients contacted, 300 (38%) responded to the survey; 98 (12%) had phone numbers on record that were incorrect or were no longer in service; and 401 (50%) could not be reached after 3 attempts. The results of the telephone survey are provided in Table 2.

The demographic data suggested that characteristics associated with higher rates of missed appointments tended to reflect physical or financial barriers, such as dependency on others for transportation (eg, pediatric patients), longer distance traveled to the clinic, and lack of insurance coverage; however, only 4% and 8% of the survey respondents reported that they missed their appointment due to financial reasons or that they were unable to obtain transportation, respectively. Of the patients surveyed, 35% cited that the reason they missed their appointment was that they forgot about the appointment; additionally, 24% of respondents reported that they had not been reminded of the appointment.

Although physicians cannot directly address physical or financial barriers to attendance, we can introduce more effective methods of communication for patient reminders. Of the 799 patients who were called for the telephone survey, 12.3% had phone numbers on record that were either incorrect or no longer in service. As these patients’ phone numbers were listed in the electronic medical record for contact purposes, they likely did not receive telephone calls reminding them about their appointments. Although it was not formally evaluated in this study, many respondents expressed that they had other preferred methods of receiving appointment reminders (eg, e-mail, text message) than those that are currently considered commonplace (ie, telephone calls, voicemails).

This study was limited in that the appointment data came from a single academic dermatology clinic. There also were limitations in the data set for subgroup analysis; for example, to appropriately assess socioeconomic barriers to attendance of dermatology appointments, it would be valuable to stratify income within established factors of socioeconomic barriers (eg, race, employment status) to avoid research bias. Although many variables assessed were statistically significant (P<.05), the odds ratios often were close to 1, suggesting that they may not be clinically or practically relevant.

By identifying factors associated with missed dermatology appointments, interventions can be instituted to target high-risk groups and alter patient reminder protocols. If possible, identifying patients’ preferred contact methods (eg, telephone call, text message, etc) and verifying contact information may be cost-effective ways to reduce missed appointments in dermatology offices.

To the Editor:

Transient reactive papulotranslucent acrokeratoderma (TRPA) is a rare disorder that also has been described using the terms aquagenic syringeal acrokeratoderma, aquagenic palmoplantar keratoderma, aquagenic acrokeratoderma, aquagenic papulotranslucent acrokeratoderma, and aquagenic wrinkling of the palms.¹ It was initially described in 1996 by English and McCollough,² and since then fewer than 100 cases have been reported.^1-12

A 38-year-old man presented with prominent palmar hyperhidrosis with whitish papules on the palms of 10 days’ duration. The lesions were exacerbated following exposure to water but were asymptomatic aside from their unsightly cosmetic appearance. Dermatologic examination revealed translucent, whitish, pebbly papules confined to the central palmar creases (Figure 1) that were intensified following a 5-minute water immersion test.

Histopathologic examination of a punch biopsy specimen from the right palm revealed orthokeratotic hyperkeratosis and slight hypergranulosis in the epidermis (Figure 2). Subtle eccrine glandular hyperplasia was evident in the dermis (Figure 3). Periodic acid–Schiff staining was negative. Based on the clinical findings and results of the water immersion test, a diagnosis of TRPA was made. A therapeutic trial of calcipotriene ointment 0.005% twice daily was initiated and resulted in dramatic clearance of the lesions within 2 weeks (Figure 4). At 1-month follow-up, the patient was virtually free of all symptoms and no disease recurrence was noted at 5-year follow-up.

Figure 1. Whitish, pebbly papules confined to the central palmar creases in a 38-year-old man.			Figure 2. Orthokeratotic hyperkeratosis and mild hypergranulosis was noted in the epidermis (H&E, original magnification ×100).
Figure 3. Luminal dilatation in the eccrine glands with a prominence of glandular epithelial cells, which displayed abundant cytoplasm with a granular appearance (H&E, original magnification ×100).			Figure 4. Remarkable response to calcipotriene ointment 0.005%. The white punctuate scar indicates the previous punch biopsy site.

A 25-year-old woman presented with whitish plaques on the palms of 7 days’ duration. She reported frequent use of household cleansers in the month prior to presentation. The lesions were associated with prominent hyperhidrosis, pruritus, and a tingling sensation in the palms. Dermatologic examination revealed confluent, macerated, white, pavement stone–like papules with prominent puncta around the palmar flexures on both palms. Lesions were exacerbated after a 5-minute water immersion test (Figure 5).

The patient refused skin biopsy, and conservative treatment with a barrier cream and limited water exposure were of no benefit. Based on the clinical findings and results of the water immersion test, a diagnosis of TRPA was made. Due to the excellent outcome experienced in treating the previous patient, a trial of calcipotriene ointment 0.005% twice daily was initiated, and the patient reported complete resolution of signs and symptoms within the initial 2 weeks of treatment. Treatment was terminated at 1-month follow-up.

A 6-year-old boy presented with swollen, itchy palms of 2 months’ duration that the patient described as “wet” and “white.” Due to a recent epidemic of bird flu, the patient’s mother had advised him to use liquid cleansers and antiseptic gels on the hands for the past 2 months, which is when the symptoms on the palms started to develop. On dermatologic examination, whitish, cobblestonelike papules were noted near the palmar creases in association with profuse hyperhidrosis (Figure 6). Based on the clinical findings, a diagnosis of TRPA was made. Biopsy was not attempted and the patient was treated with calcipotriene ointment 0.005% twice daily. At 1-month follow-up, complete clearance of the lesions was noted.

Transient reactive papulotranslucent acrokeratoderma is an acquired and sporadic disorder that can occur in both sexes.^2,4,6,8-11 Onset generally occurs during adolescence or young adulthood.^1,3,8,9 Clinically, TRPA is characterized by edema and wrinkling of the palms following 5 to 10 minutes of contact with water that typically resolves within 1 hour after cessation of exposure.^2,3,6-8,10 The “hand-in-the-bucket” sign refers to accentuation of physical findings upon immersion of the hand in water.^6,10,11 Patients frequently report itching, burning, or tingling sensations in the affected areas.^2,4,6,7,9,11 Transient reactive papulotranslucent acrokeratoderma usually affects the palms in a diffuse, bilateral, and symmetrical pattern,^2,4,6-10 but cases showing involvement of the soles,^6,7 marginal distribution of lesions,³ unilateral involvement,¹ and prominence on the dorsal fingers⁵ also have been reported. The natural disease course involves reactive episodes and quiescent intervals.^2,7,9 Spontaneous resolution of TRPA has been reported.^4,6,8

The histological characteristics described in previous reports involve compact orthohyperkeratosis with dilated acrosyringia,^2-6,9,11 hyperkeratosis and hypergranulosis in the epidermis,^4,8,12 and eccrine glandular hyperplasia.^5,12 Alternatively, the skin may appear completely normal on histology.^1,7

Originally, it was proposed that TRPA is a variant of punctate keratoderma or hereditary papulotranslucent acrokeratoderma.^2,3 However, its position within the keratoderma spectrum is unclear and the etiopathogenesis has not been fully elucidated. Some investigators believe that transient structural and functional alterations in the epidermal milieu prompt epidermal swelling and compensatory dilation of eccrine ducts.^3,4,7,8,10 Other reports implicate the inherent structural weakness of eccrine duct walls^3,4,11 or aberrations in eccrine glands.^5,12 Whether the fundamental pathology lies within the epidermis, eccrine ducts, or the eccrine glands remains to be determined. Nevertheless, reports of TRPA in the setting of cystic fibrosis and its carrier state^3,11 as well as the presence of hyperhidrosis in most affected patients and the accumulation of lesions along the palmar creases may implicate oversaturation of the epidermis (due to salt retention or abnormal water absorption by the stratum corneum) as the pivotal event in TRPA pathogenesis.^1,10 Once the disease is expressed in susceptible individuals, episodes might be provoked by external factors such as friction, occlusion, sweating, liquid cleansers, antiseptic gels, gloves, topical preparations, and oral medications (eg, salicylic acid, cyclooxygenase 2 inhibitors).^1,4

Treatment alternatives such as hydrophilic petrolatum and glycerin, ammonium lactate, salicylic acid (with or without urea), aluminum chloride hexahydrate, and topical corticosteroids are limited by unsuccessful or temporary outcomes.^1,4,6,8-10 Botulinum toxin injections were effective in a patient with TRPA associated with hyperhidrosis.⁷ In the cases reported here, topical calcipotriene accomplished dramatic clearance of the lesions within the initial weeks of therapy. Spontaneous resolution was unlikely in these cases, as conservative therapies had not alleviated the signs and symptoms in any of the patients. However, we cannot exclude the possibility that improvement of the skin barrier function associated with other ingredients in the calcipotriene ointment (eg, petrolatum, mineral oil, α-tocopherol) may have led to the resolution of the lesions.

Calcipotriene has demonstrated efficacy in treating cutaneous disorders characterized by epidermal hyperproliferation and impaired terminal differentiation. Immunohistochemical and molecular biological evidence has indicated that topical calcipotriene exerts more pronounced inhibitory effects on epidermal proliferation than on dermal inflammation. It has been proposed that the bioavailability of calcipotriene in the dermal compartment may be markedly reduced compared to its availability in the epidermal compartment¹³; therefore it can be deduced that its penetration into the dermis is low in the thick skin of palms and its effect on eccrine sweat glands is negligible. Based on these factors, the clinical benefit of calcipotriene in TRPA could be ascribed directly to its antiproliferative and prodifferentiating effects on epidermal keratinocytes. We believe the primary pathology of TRPA lies in the epidermis and that changes in eccrine ducts and glands are secondary to the epidermal changes.

It is difficult to conduct large-scale studies of TRPA due to its rare presentation. Based on our encouraging preliminary observations in 3 patients, we recommend further therapeutic trials of topical calcipotriene in the treatment of TRPA.

To the Editor:

Transient reactive papulotranslucent acrokeratoderma (TRPA) is a rare disorder that also has been described using the terms aquagenic syringeal acrokeratoderma, aquagenic palmoplantar keratoderma, aquagenic acrokeratoderma, aquagenic papulotranslucent acrokeratoderma, and aquagenic wrinkling of the palms.¹ It was initially described in 1996 by English and McCollough,² and since then fewer than 100 cases have been reported.^1-12

A 38-year-old man presented with prominent palmar hyperhidrosis with whitish papules on the palms of 10 days’ duration. The lesions were exacerbated following exposure to water but were asymptomatic aside from their unsightly cosmetic appearance. Dermatologic examination revealed translucent, whitish, pebbly papules confined to the central palmar creases (Figure 1) that were intensified following a 5-minute water immersion test.

Histopathologic examination of a punch biopsy specimen from the right palm revealed orthokeratotic hyperkeratosis and slight hypergranulosis in the epidermis (Figure 2). Subtle eccrine glandular hyperplasia was evident in the dermis (Figure 3). Periodic acid–Schiff staining was negative. Based on the clinical findings and results of the water immersion test, a diagnosis of TRPA was made. A therapeutic trial of calcipotriene ointment 0.005% twice daily was initiated and resulted in dramatic clearance of the lesions within 2 weeks (Figure 4). At 1-month follow-up, the patient was virtually free of all symptoms and no disease recurrence was noted at 5-year follow-up.

Figure 1. Whitish, pebbly papules confined to the central palmar creases in a 38-year-old man.			Figure 2. Orthokeratotic hyperkeratosis and mild hypergranulosis was noted in the epidermis (H&E, original magnification ×100).
Figure 3. Luminal dilatation in the eccrine glands with a prominence of glandular epithelial cells, which displayed abundant cytoplasm with a granular appearance (H&E, original magnification ×100).			Figure 4. Remarkable response to calcipotriene ointment 0.005%. The white punctuate scar indicates the previous punch biopsy site.

A 25-year-old woman presented with whitish plaques on the palms of 7 days’ duration. She reported frequent use of household cleansers in the month prior to presentation. The lesions were associated with prominent hyperhidrosis, pruritus, and a tingling sensation in the palms. Dermatologic examination revealed confluent, macerated, white, pavement stone–like papules with prominent puncta around the palmar flexures on both palms. Lesions were exacerbated after a 5-minute water immersion test (Figure 5).

The patient refused skin biopsy, and conservative treatment with a barrier cream and limited water exposure were of no benefit. Based on the clinical findings and results of the water immersion test, a diagnosis of TRPA was made. Due to the excellent outcome experienced in treating the previous patient, a trial of calcipotriene ointment 0.005% twice daily was initiated, and the patient reported complete resolution of signs and symptoms within the initial 2 weeks of treatment. Treatment was terminated at 1-month follow-up.

A 6-year-old boy presented with swollen, itchy palms of 2 months’ duration that the patient described as “wet” and “white.” Due to a recent epidemic of bird flu, the patient’s mother had advised him to use liquid cleansers and antiseptic gels on the hands for the past 2 months, which is when the symptoms on the palms started to develop. On dermatologic examination, whitish, cobblestonelike papules were noted near the palmar creases in association with profuse hyperhidrosis (Figure 6). Based on the clinical findings, a diagnosis of TRPA was made. Biopsy was not attempted and the patient was treated with calcipotriene ointment 0.005% twice daily. At 1-month follow-up, complete clearance of the lesions was noted.

Transient reactive papulotranslucent acrokeratoderma is an acquired and sporadic disorder that can occur in both sexes.^2,4,6,8-11 Onset generally occurs during adolescence or young adulthood.^1,3,8,9 Clinically, TRPA is characterized by edema and wrinkling of the palms following 5 to 10 minutes of contact with water that typically resolves within 1 hour after cessation of exposure.^2,3,6-8,10 The “hand-in-the-bucket” sign refers to accentuation of physical findings upon immersion of the hand in water.^6,10,11 Patients frequently report itching, burning, or tingling sensations in the affected areas.^2,4,6,7,9,11 Transient reactive papulotranslucent acrokeratoderma usually affects the palms in a diffuse, bilateral, and symmetrical pattern,^2,4,6-10 but cases showing involvement of the soles,^6,7 marginal distribution of lesions,³ unilateral involvement,¹ and prominence on the dorsal fingers⁵ also have been reported. The natural disease course involves reactive episodes and quiescent intervals.^2,7,9 Spontaneous resolution of TRPA has been reported.^4,6,8

The histological characteristics described in previous reports involve compact orthohyperkeratosis with dilated acrosyringia,^2-6,9,11 hyperkeratosis and hypergranulosis in the epidermis,^4,8,12 and eccrine glandular hyperplasia.^5,12 Alternatively, the skin may appear completely normal on histology.^1,7

Originally, it was proposed that TRPA is a variant of punctate keratoderma or hereditary papulotranslucent acrokeratoderma.^2,3 However, its position within the keratoderma spectrum is unclear and the etiopathogenesis has not been fully elucidated. Some investigators believe that transient structural and functional alterations in the epidermal milieu prompt epidermal swelling and compensatory dilation of eccrine ducts.^3,4,7,8,10 Other reports implicate the inherent structural weakness of eccrine duct walls^3,4,11 or aberrations in eccrine glands.^5,12 Whether the fundamental pathology lies within the epidermis, eccrine ducts, or the eccrine glands remains to be determined. Nevertheless, reports of TRPA in the setting of cystic fibrosis and its carrier state^3,11 as well as the presence of hyperhidrosis in most affected patients and the accumulation of lesions along the palmar creases may implicate oversaturation of the epidermis (due to salt retention or abnormal water absorption by the stratum corneum) as the pivotal event in TRPA pathogenesis.^1,10 Once the disease is expressed in susceptible individuals, episodes might be provoked by external factors such as friction, occlusion, sweating, liquid cleansers, antiseptic gels, gloves, topical preparations, and oral medications (eg, salicylic acid, cyclooxygenase 2 inhibitors).^1,4

Treatment alternatives such as hydrophilic petrolatum and glycerin, ammonium lactate, salicylic acid (with or without urea), aluminum chloride hexahydrate, and topical corticosteroids are limited by unsuccessful or temporary outcomes.^1,4,6,8-10 Botulinum toxin injections were effective in a patient with TRPA associated with hyperhidrosis.⁷ In the cases reported here, topical calcipotriene accomplished dramatic clearance of the lesions within the initial weeks of therapy. Spontaneous resolution was unlikely in these cases, as conservative therapies had not alleviated the signs and symptoms in any of the patients. However, we cannot exclude the possibility that improvement of the skin barrier function associated with other ingredients in the calcipotriene ointment (eg, petrolatum, mineral oil, α-tocopherol) may have led to the resolution of the lesions.

Calcipotriene has demonstrated efficacy in treating cutaneous disorders characterized by epidermal hyperproliferation and impaired terminal differentiation. Immunohistochemical and molecular biological evidence has indicated that topical calcipotriene exerts more pronounced inhibitory effects on epidermal proliferation than on dermal inflammation. It has been proposed that the bioavailability of calcipotriene in the dermal compartment may be markedly reduced compared to its availability in the epidermal compartment¹³; therefore it can be deduced that its penetration into the dermis is low in the thick skin of palms and its effect on eccrine sweat glands is negligible. Based on these factors, the clinical benefit of calcipotriene in TRPA could be ascribed directly to its antiproliferative and prodifferentiating effects on epidermal keratinocytes. We believe the primary pathology of TRPA lies in the epidermis and that changes in eccrine ducts and glands are secondary to the epidermal changes.

It is difficult to conduct large-scale studies of TRPA due to its rare presentation. Based on our encouraging preliminary observations in 3 patients, we recommend further therapeutic trials of topical calcipotriene in the treatment of TRPA.

To the Editor:

Transient reactive papulotranslucent acrokeratoderma (TRPA) is a rare disorder that also has been described using the terms aquagenic syringeal acrokeratoderma, aquagenic palmoplantar keratoderma, aquagenic acrokeratoderma, aquagenic papulotranslucent acrokeratoderma, and aquagenic wrinkling of the palms.¹ It was initially described in 1996 by English and McCollough,² and since then fewer than 100 cases have been reported.^1-12

A 38-year-old man presented with prominent palmar hyperhidrosis with whitish papules on the palms of 10 days’ duration. The lesions were exacerbated following exposure to water but were asymptomatic aside from their unsightly cosmetic appearance. Dermatologic examination revealed translucent, whitish, pebbly papules confined to the central palmar creases (Figure 1) that were intensified following a 5-minute water immersion test.

Histopathologic examination of a punch biopsy specimen from the right palm revealed orthokeratotic hyperkeratosis and slight hypergranulosis in the epidermis (Figure 2). Subtle eccrine glandular hyperplasia was evident in the dermis (Figure 3). Periodic acid–Schiff staining was negative. Based on the clinical findings and results of the water immersion test, a diagnosis of TRPA was made. A therapeutic trial of calcipotriene ointment 0.005% twice daily was initiated and resulted in dramatic clearance of the lesions within 2 weeks (Figure 4). At 1-month follow-up, the patient was virtually free of all symptoms and no disease recurrence was noted at 5-year follow-up.

Figure 1. Whitish, pebbly papules confined to the central palmar creases in a 38-year-old man.			Figure 2. Orthokeratotic hyperkeratosis and mild hypergranulosis was noted in the epidermis (H&E, original magnification ×100).
Figure 3. Luminal dilatation in the eccrine glands with a prominence of glandular epithelial cells, which displayed abundant cytoplasm with a granular appearance (H&E, original magnification ×100).			Figure 4. Remarkable response to calcipotriene ointment 0.005%. The white punctuate scar indicates the previous punch biopsy site.

A 25-year-old woman presented with whitish plaques on the palms of 7 days’ duration. She reported frequent use of household cleansers in the month prior to presentation. The lesions were associated with prominent hyperhidrosis, pruritus, and a tingling sensation in the palms. Dermatologic examination revealed confluent, macerated, white, pavement stone–like papules with prominent puncta around the palmar flexures on both palms. Lesions were exacerbated after a 5-minute water immersion test (Figure 5).

The patient refused skin biopsy, and conservative treatment with a barrier cream and limited water exposure were of no benefit. Based on the clinical findings and results of the water immersion test, a diagnosis of TRPA was made. Due to the excellent outcome experienced in treating the previous patient, a trial of calcipotriene ointment 0.005% twice daily was initiated, and the patient reported complete resolution of signs and symptoms within the initial 2 weeks of treatment. Treatment was terminated at 1-month follow-up.

A 6-year-old boy presented with swollen, itchy palms of 2 months’ duration that the patient described as “wet” and “white.” Due to a recent epidemic of bird flu, the patient’s mother had advised him to use liquid cleansers and antiseptic gels on the hands for the past 2 months, which is when the symptoms on the palms started to develop. On dermatologic examination, whitish, cobblestonelike papules were noted near the palmar creases in association with profuse hyperhidrosis (Figure 6). Based on the clinical findings, a diagnosis of TRPA was made. Biopsy was not attempted and the patient was treated with calcipotriene ointment 0.005% twice daily. At 1-month follow-up, complete clearance of the lesions was noted.

Transient reactive papulotranslucent acrokeratoderma is an acquired and sporadic disorder that can occur in both sexes.^2,4,6,8-11 Onset generally occurs during adolescence or young adulthood.^1,3,8,9 Clinically, TRPA is characterized by edema and wrinkling of the palms following 5 to 10 minutes of contact with water that typically resolves within 1 hour after cessation of exposure.^2,3,6-8,10 The “hand-in-the-bucket” sign refers to accentuation of physical findings upon immersion of the hand in water.^6,10,11 Patients frequently report itching, burning, or tingling sensations in the affected areas.^2,4,6,7,9,11 Transient reactive papulotranslucent acrokeratoderma usually affects the palms in a diffuse, bilateral, and symmetrical pattern,^2,4,6-10 but cases showing involvement of the soles,^6,7 marginal distribution of lesions,³ unilateral involvement,¹ and prominence on the dorsal fingers⁵ also have been reported. The natural disease course involves reactive episodes and quiescent intervals.^2,7,9 Spontaneous resolution of TRPA has been reported.^4,6,8

The histological characteristics described in previous reports involve compact orthohyperkeratosis with dilated acrosyringia,^2-6,9,11 hyperkeratosis and hypergranulosis in the epidermis,^4,8,12 and eccrine glandular hyperplasia.^5,12 Alternatively, the skin may appear completely normal on histology.^1,7

Originally, it was proposed that TRPA is a variant of punctate keratoderma or hereditary papulotranslucent acrokeratoderma.^2,3 However, its position within the keratoderma spectrum is unclear and the etiopathogenesis has not been fully elucidated. Some investigators believe that transient structural and functional alterations in the epidermal milieu prompt epidermal swelling and compensatory dilation of eccrine ducts.^3,4,7,8,10 Other reports implicate the inherent structural weakness of eccrine duct walls^3,4,11 or aberrations in eccrine glands.^5,12 Whether the fundamental pathology lies within the epidermis, eccrine ducts, or the eccrine glands remains to be determined. Nevertheless, reports of TRPA in the setting of cystic fibrosis and its carrier state^3,11 as well as the presence of hyperhidrosis in most affected patients and the accumulation of lesions along the palmar creases may implicate oversaturation of the epidermis (due to salt retention or abnormal water absorption by the stratum corneum) as the pivotal event in TRPA pathogenesis.^1,10 Once the disease is expressed in susceptible individuals, episodes might be provoked by external factors such as friction, occlusion, sweating, liquid cleansers, antiseptic gels, gloves, topical preparations, and oral medications (eg, salicylic acid, cyclooxygenase 2 inhibitors).^1,4

Treatment alternatives such as hydrophilic petrolatum and glycerin, ammonium lactate, salicylic acid (with or without urea), aluminum chloride hexahydrate, and topical corticosteroids are limited by unsuccessful or temporary outcomes.^1,4,6,8-10 Botulinum toxin injections were effective in a patient with TRPA associated with hyperhidrosis.⁷ In the cases reported here, topical calcipotriene accomplished dramatic clearance of the lesions within the initial weeks of therapy. Spontaneous resolution was unlikely in these cases, as conservative therapies had not alleviated the signs and symptoms in any of the patients. However, we cannot exclude the possibility that improvement of the skin barrier function associated with other ingredients in the calcipotriene ointment (eg, petrolatum, mineral oil, α-tocopherol) may have led to the resolution of the lesions.

Calcipotriene has demonstrated efficacy in treating cutaneous disorders characterized by epidermal hyperproliferation and impaired terminal differentiation. Immunohistochemical and molecular biological evidence has indicated that topical calcipotriene exerts more pronounced inhibitory effects on epidermal proliferation than on dermal inflammation. It has been proposed that the bioavailability of calcipotriene in the dermal compartment may be markedly reduced compared to its availability in the epidermal compartment¹³; therefore it can be deduced that its penetration into the dermis is low in the thick skin of palms and its effect on eccrine sweat glands is negligible. Based on these factors, the clinical benefit of calcipotriene in TRPA could be ascribed directly to its antiproliferative and prodifferentiating effects on epidermal keratinocytes. We believe the primary pathology of TRPA lies in the epidermis and that changes in eccrine ducts and glands are secondary to the epidermal changes.

It is difficult to conduct large-scale studies of TRPA due to its rare presentation. Based on our encouraging preliminary observations in 3 patients, we recommend further therapeutic trials of topical calcipotriene in the treatment of TRPA.

To the Editor:

We read with great interest the article, 
“Omphalith-Associated Relapsing Umbilical Cellulitis: Recurrent Omphalitis Secondary to a 
Hair-Containing Belly Button Bezoar” (Cutis. 2010;86:199-202), which introduced the terms omphalotrich and tricomphalith to describe the pilar composition of a hair-containing umbilical foreign body in an 18-year-old man. We report a similar case.

A 38-year-old man presented with a 10-year history of an unusual odor in the umbilical region with recurrent discharge. He diligently maintained proper hygiene of the umbilicus using cotton swabs and had received recurrent cycles of oral antibiotics prescribed by his general practitioner with temporary improvement of the odor and amount of discharge. Physical examination revealed a normal umbilicus with a deep and tight umbilical cleft that required the use of curved mosquito forceps for further examination (Figure 1). A bezoar comprised of a compact collection of terminal hair shafts was noted deep in the umbilicus (Figure 2). A considerable amount of terminal hairs also were noted on the skin of the abdominal area. Following removal of the bezoar, no umbilical fistula was observed, and the presence of embryologic abnormalities (eg, omphalomesenteric duct remnants) was ruled out on magnetic resonance imaging. A diagnosis of recurrent omphalitis secondary to a hair-containing bezoar was made. Following extraction of the bezoar, the odor and discharge promptly resolved, thereby avoiding the need for oral antibiotics; however, a smaller bezoar comprised of a collection of terminal hair shafts was removed 
4 months later.

Figure 1. Deep and narrow umbilical cleft with serous exudate in the umbilicus after removal of the foreign body.		Figure 2. A section of the umbilical foreign body composed of a collection of terminal hair shafts.

An omphalith is an umbilical foreign body that results from the accumulation of keratinous and amorphous sebaceous material.² Several predisposing factors have been proposed for its pathogenesis, such as the anatomical disposition of the umbilicus and the patient’s hygiene. We hypothesize that a deep umbilicus and a large amount of terminal hairs in the abdominal area were predisposing factors in our patient. Cohen et al¹ proposed the terms omphalotrich and trichomphalith to describe the pilar composition of a hair-containing umbilical foreign body that did not have the characteristic stonelike presentation of a traditional omphalith. The authors also referred to the umbilical foreign body in their patient as a trichobezoar, a term used to describe exogenous foreign bodies composed of ingested hair in the gastrointestinal tract, given the embryologic origin of the umbilicus and epithelium of the 
gastrointestinal tract. We agree that the terms omphalotrich and trichomphalith appropriately describe the current presentation; we also propose the terms omphalitrichia or thricomphalia to describe the findings seen in our patient, which should always be ruled 
out in patients with recurrent omphalitis that is unresponsive to antibiotics.

To the Editor:

We read with great interest the article, 
“Omphalith-Associated Relapsing Umbilical Cellulitis: Recurrent Omphalitis Secondary to a 
Hair-Containing Belly Button Bezoar” (Cutis. 2010;86:199-202), which introduced the terms omphalotrich and tricomphalith to describe the pilar composition of a hair-containing umbilical foreign body in an 18-year-old man. We report a similar case.

A 38-year-old man presented with a 10-year history of an unusual odor in the umbilical region with recurrent discharge. He diligently maintained proper hygiene of the umbilicus using cotton swabs and had received recurrent cycles of oral antibiotics prescribed by his general practitioner with temporary improvement of the odor and amount of discharge. Physical examination revealed a normal umbilicus with a deep and tight umbilical cleft that required the use of curved mosquito forceps for further examination (Figure 1). A bezoar comprised of a compact collection of terminal hair shafts was noted deep in the umbilicus (Figure 2). A considerable amount of terminal hairs also were noted on the skin of the abdominal area. Following removal of the bezoar, no umbilical fistula was observed, and the presence of embryologic abnormalities (eg, omphalomesenteric duct remnants) was ruled out on magnetic resonance imaging. A diagnosis of recurrent omphalitis secondary to a hair-containing bezoar was made. Following extraction of the bezoar, the odor and discharge promptly resolved, thereby avoiding the need for oral antibiotics; however, a smaller bezoar comprised of a collection of terminal hair shafts was removed 
4 months later.

Figure 1. Deep and narrow umbilical cleft with serous exudate in the umbilicus after removal of the foreign body.		Figure 2. A section of the umbilical foreign body composed of a collection of terminal hair shafts.

An omphalith is an umbilical foreign body that results from the accumulation of keratinous and amorphous sebaceous material.² Several predisposing factors have been proposed for its pathogenesis, such as the anatomical disposition of the umbilicus and the patient’s hygiene. We hypothesize that a deep umbilicus and a large amount of terminal hairs in the abdominal area were predisposing factors in our patient. Cohen et al¹ proposed the terms omphalotrich and trichomphalith to describe the pilar composition of a hair-containing umbilical foreign body that did not have the characteristic stonelike presentation of a traditional omphalith. The authors also referred to the umbilical foreign body in their patient as a trichobezoar, a term used to describe exogenous foreign bodies composed of ingested hair in the gastrointestinal tract, given the embryologic origin of the umbilicus and epithelium of the 
gastrointestinal tract. We agree that the terms omphalotrich and trichomphalith appropriately describe the current presentation; we also propose the terms omphalitrichia or thricomphalia to describe the findings seen in our patient, which should always be ruled 
out in patients with recurrent omphalitis that is unresponsive to antibiotics.

To the Editor:

We read with great interest the article, 
“Omphalith-Associated Relapsing Umbilical Cellulitis: Recurrent Omphalitis Secondary to a 
Hair-Containing Belly Button Bezoar” (Cutis. 2010;86:199-202), which introduced the terms omphalotrich and tricomphalith to describe the pilar composition of a hair-containing umbilical foreign body in an 18-year-old man. We report a similar case.

A 38-year-old man presented with a 10-year history of an unusual odor in the umbilical region with recurrent discharge. He diligently maintained proper hygiene of the umbilicus using cotton swabs and had received recurrent cycles of oral antibiotics prescribed by his general practitioner with temporary improvement of the odor and amount of discharge. Physical examination revealed a normal umbilicus with a deep and tight umbilical cleft that required the use of curved mosquito forceps for further examination (Figure 1). A bezoar comprised of a compact collection of terminal hair shafts was noted deep in the umbilicus (Figure 2). A considerable amount of terminal hairs also were noted on the skin of the abdominal area. Following removal of the bezoar, no umbilical fistula was observed, and the presence of embryologic abnormalities (eg, omphalomesenteric duct remnants) was ruled out on magnetic resonance imaging. A diagnosis of recurrent omphalitis secondary to a hair-containing bezoar was made. Following extraction of the bezoar, the odor and discharge promptly resolved, thereby avoiding the need for oral antibiotics; however, a smaller bezoar comprised of a collection of terminal hair shafts was removed 
4 months later.

Figure 1. Deep and narrow umbilical cleft with serous exudate in the umbilicus after removal of the foreign body.		Figure 2. A section of the umbilical foreign body composed of a collection of terminal hair shafts.

An omphalith is an umbilical foreign body that results from the accumulation of keratinous and amorphous sebaceous material.² Several predisposing factors have been proposed for its pathogenesis, such as the anatomical disposition of the umbilicus and the patient’s hygiene. We hypothesize that a deep umbilicus and a large amount of terminal hairs in the abdominal area were predisposing factors in our patient. Cohen et al¹ proposed the terms omphalotrich and trichomphalith to describe the pilar composition of a hair-containing umbilical foreign body that did not have the characteristic stonelike presentation of a traditional omphalith. The authors also referred to the umbilical foreign body in their patient as a trichobezoar, a term used to describe exogenous foreign bodies composed of ingested hair in the gastrointestinal tract, given the embryologic origin of the umbilicus and epithelium of the 
gastrointestinal tract. We agree that the terms omphalotrich and trichomphalith appropriately describe the current presentation; we also propose the terms omphalitrichia or thricomphalia to describe the findings seen in our patient, which should always be ruled 
out in patients with recurrent omphalitis that is unresponsive to antibiotics.

To the Editor:

Staphylococcal scalded skin syndrome (SSSS) is a superficial blistering disorder mediated by Staphylococcus aureus exfoliative toxins (ETs).¹ It is rare in adults, but when diagnosed, it is often associated with renal failure, immunodeficiency, or overwhelming staphylococcal infection.² We present a unique case of a pregnant woman with chronic atopic dermatitis (AD) who developed SSSS.

A 21-year-old gravida 3, para 2, aborta 0pregnant woman (29 weeks’ gestation) with a history of chronic AD who was hospitalized with facial edema, purulent ocular discharge, and substantial worsening of AD presented for a dermatology consultation. Her AD was previously managed with topical steroids but had been complicated by multiple methicillin-resistant Staphylococcus aureus (MRSA) infections. On physical examination, she had substantial periorbital edema with purulent discharge from both eyes (Figure 1A), perioral crust with radial fissures (Figure 2A), and mild generalized facial swelling and desquamation (Figure 3). However, the oral cavity was not involved. She had diffuse desquamation in addition to chronic lichenified plaques of the arms, legs, and trunk and SSSS was clinically diagnosed. Cultures of conjunctival discharge were positive for MRSA. The patient was treated with intravenous vancomycin and had a full recovery (Figures 1B and 2B). She delivered a healthy newborn with Apgar scores of 9 and 9 at 1 and 5 minutes, respectively, at 36 weeks and 6 days’ gestation by cesarean delivery; however, her postoperative care was complicated by preeclampsia, which was treated with magnesium sulfate. The newborn showed no evidence of infection or blistering at birth or during the hospital stay.

Figure 1. Periorbital edema with purulent ocular discharge before (A) and after (B) treatment.			Figure 2. Perioral desquamation and radial fissuring before (A) and after (B) treatment.

Staphylococcal scalded skin syndrome is a superficial blistering disorder that ranges in severity from localized blisters to generalized exfoliation.¹ Exfoliative toxin is the major virulence factor responsible for SSSS. Exfoliative toxin is a serine protease that targets desmoglein 1, resulting in intraepidermal separation of keratinocytes.³ Two serologically distinct exfoliative toxins—ETA and ETB—have been associated with human disease.⁴ Although ETA is encoded on a phage genome, ETB is encoded on a large plasmid.³ Initially it was thought that only strains of S aureus carrying lytic group II phages were responsible for ET production; however, it is now accepted that all phage groups are capable of producing ET and causing SSSS.¹

Staphylococcal scalded skin syndrome is most common in infants and children and rare in adults. Although it has been occasionally described in otherwise healthy adults,⁵ it is most often diagnosed in patients with renal failure (decreased toxin excretion), immunodeficiency (lack of antibodies against toxins), and overwhelming staphylococcal infection (excessive toxin).² Mortality in treated children is low, but it can reach almost 60% in adults¹; therefore, defining risk factors that may aid in early diagnosis are exceedingly important.

We believe that both our patient’s history of 
AD and her pregnancy contributed to the development of SSSS. The patient had a history of multiple MRSA infections prior to this hospitalization, suggesting MRSA colonization, which is a common complication of AD with more than 75% of 
AD patients colonized with S aureus.⁶ Additionally, 
S aureus superantigen stimulation can result in the loss of regulatory T cells’ natural immunosuppression. Regulatory T cells are remarkably increased in patients with AD; therefore, the inflammatory response to S aureus is likely amplified in an atopic patient, as there is more native immunosuppressive capacity to be affected.⁴ Furthermore, we believe that pregnancy and its associated immunomodulation is a risk for SSSS. Immune changes in pregnancy are still not well understood; however, it is known that there are alterations to allow symbiosis between the mother and fetus. Anti-ET IgG antibodies are thought to play an important role in protecting against SSSS. Historically, studies on serum immunoglobulin levels during pregnancy have had conflicting findings. They have shown that IgG is either unchanged or decreased, while IgA, IgE, and IgM can be increased, decreased, or unchanged.⁷ In a study of immunoglobulins in pregnancy, Bahna et al⁷ showed that IgE is unchanged over the course of pregnancy, but their analysis did not address IgG levels. If IgG levels in fact decrease during pregnancy, the mother could be at risk for SSSS due to her inability to neutralize toxins. Even if total IgG levels remain unchanged, it is possible that specific antitoxin antibodies are decreased. Additionally, there is a documented suppression and alteration in T-cell response to prevent fetal rejection during pregnancy.⁸ Adult SSSS has been documented several times in human immunodeficiency virus–positive patients, suggesting there may be some association between T-cell suppression and SSSS susceptibility.⁹ Interestingly, pregnancy, similar to AD, results in an increase in immunosuppressive T cells,¹⁰ which, if deactivated by superantigens, could potentially contribute to an increased inflammatory response. All of these immune system alterations likely leave the mother vulnerable to toxin-mediated events such as SSSS.

We believe this case highlights the importance of considering SSSS in both atopic and pregnant patients with desquamating eruptions. In the case of pregnant patients, it is important to consider the risks and benefits of any medical treatments for both the mother and infant. Vancomycin is a pregnancy category B drug and was chosen for its known effectiveness and safety in pregnancy. One study compared 10 babies with mothers who were treated with vancomycin during the second and third trimesters for MRSA to 20 babies with mothers who did not receive vancomycin and did not find an increased risk for sensorineural hearing loss or nephrotoxicity.¹¹ There is no known increased risk for preeclampsia with vancomycin, but some studies have suggested that maternal infection independently increases the risk for preeclampsia.¹² Other treatment options were not as safe as vancomycin in this case: doxycycline is contraindicated (pregnancy category D) due to the potential for staining of deciduous teeth and skeletal growth impairment, trimethoprim-sulfamethoxazole is a pregnancy category D drug during the third trimester due to the risk of kernicterus, and linezolid is a pregnancy category C drug.¹³

To the Editor:

Staphylococcal scalded skin syndrome (SSSS) is a superficial blistering disorder mediated by Staphylococcus aureus exfoliative toxins (ETs).¹ It is rare in adults, but when diagnosed, it is often associated with renal failure, immunodeficiency, or overwhelming staphylococcal infection.² We present a unique case of a pregnant woman with chronic atopic dermatitis (AD) who developed SSSS.

A 21-year-old gravida 3, para 2, aborta 0pregnant woman (29 weeks’ gestation) with a history of chronic AD who was hospitalized with facial edema, purulent ocular discharge, and substantial worsening of AD presented for a dermatology consultation. Her AD was previously managed with topical steroids but had been complicated by multiple methicillin-resistant Staphylococcus aureus (MRSA) infections. On physical examination, she had substantial periorbital edema with purulent discharge from both eyes (Figure 1A), perioral crust with radial fissures (Figure 2A), and mild generalized facial swelling and desquamation (Figure 3). However, the oral cavity was not involved. She had diffuse desquamation in addition to chronic lichenified plaques of the arms, legs, and trunk and SSSS was clinically diagnosed. Cultures of conjunctival discharge were positive for MRSA. The patient was treated with intravenous vancomycin and had a full recovery (Figures 1B and 2B). She delivered a healthy newborn with Apgar scores of 9 and 9 at 1 and 5 minutes, respectively, at 36 weeks and 6 days’ gestation by cesarean delivery; however, her postoperative care was complicated by preeclampsia, which was treated with magnesium sulfate. The newborn showed no evidence of infection or blistering at birth or during the hospital stay.

Figure 1. Periorbital edema with purulent ocular discharge before (A) and after (B) treatment.			Figure 2. Perioral desquamation and radial fissuring before (A) and after (B) treatment.

Staphylococcal scalded skin syndrome is a superficial blistering disorder that ranges in severity from localized blisters to generalized exfoliation.¹ Exfoliative toxin is the major virulence factor responsible for SSSS. Exfoliative toxin is a serine protease that targets desmoglein 1, resulting in intraepidermal separation of keratinocytes.³ Two serologically distinct exfoliative toxins—ETA and ETB—have been associated with human disease.⁴ Although ETA is encoded on a phage genome, ETB is encoded on a large plasmid.³ Initially it was thought that only strains of S aureus carrying lytic group II phages were responsible for ET production; however, it is now accepted that all phage groups are capable of producing ET and causing SSSS.¹

Staphylococcal scalded skin syndrome is most common in infants and children and rare in adults. Although it has been occasionally described in otherwise healthy adults,⁵ it is most often diagnosed in patients with renal failure (decreased toxin excretion), immunodeficiency (lack of antibodies against toxins), and overwhelming staphylococcal infection (excessive toxin).² Mortality in treated children is low, but it can reach almost 60% in adults¹; therefore, defining risk factors that may aid in early diagnosis are exceedingly important.

We believe that both our patient’s history of 
AD and her pregnancy contributed to the development of SSSS. The patient had a history of multiple MRSA infections prior to this hospitalization, suggesting MRSA colonization, which is a common complication of AD with more than 75% of 
AD patients colonized with S aureus.⁶ Additionally, 
S aureus superantigen stimulation can result in the loss of regulatory T cells’ natural immunosuppression. Regulatory T cells are remarkably increased in patients with AD; therefore, the inflammatory response to S aureus is likely amplified in an atopic patient, as there is more native immunosuppressive capacity to be affected.⁴ Furthermore, we believe that pregnancy and its associated immunomodulation is a risk for SSSS. Immune changes in pregnancy are still not well understood; however, it is known that there are alterations to allow symbiosis between the mother and fetus. Anti-ET IgG antibodies are thought to play an important role in protecting against SSSS. Historically, studies on serum immunoglobulin levels during pregnancy have had conflicting findings. They have shown that IgG is either unchanged or decreased, while IgA, IgE, and IgM can be increased, decreased, or unchanged.⁷ In a study of immunoglobulins in pregnancy, Bahna et al⁷ showed that IgE is unchanged over the course of pregnancy, but their analysis did not address IgG levels. If IgG levels in fact decrease during pregnancy, the mother could be at risk for SSSS due to her inability to neutralize toxins. Even if total IgG levels remain unchanged, it is possible that specific antitoxin antibodies are decreased. Additionally, there is a documented suppression and alteration in T-cell response to prevent fetal rejection during pregnancy.⁸ Adult SSSS has been documented several times in human immunodeficiency virus–positive patients, suggesting there may be some association between T-cell suppression and SSSS susceptibility.⁹ Interestingly, pregnancy, similar to AD, results in an increase in immunosuppressive T cells,¹⁰ which, if deactivated by superantigens, could potentially contribute to an increased inflammatory response. All of these immune system alterations likely leave the mother vulnerable to toxin-mediated events such as SSSS.

We believe this case highlights the importance of considering SSSS in both atopic and pregnant patients with desquamating eruptions. In the case of pregnant patients, it is important to consider the risks and benefits of any medical treatments for both the mother and infant. Vancomycin is a pregnancy category B drug and was chosen for its known effectiveness and safety in pregnancy. One study compared 10 babies with mothers who were treated with vancomycin during the second and third trimesters for MRSA to 20 babies with mothers who did not receive vancomycin and did not find an increased risk for sensorineural hearing loss or nephrotoxicity.¹¹ There is no known increased risk for preeclampsia with vancomycin, but some studies have suggested that maternal infection independently increases the risk for preeclampsia.¹² Other treatment options were not as safe as vancomycin in this case: doxycycline is contraindicated (pregnancy category D) due to the potential for staining of deciduous teeth and skeletal growth impairment, trimethoprim-sulfamethoxazole is a pregnancy category D drug during the third trimester due to the risk of kernicterus, and linezolid is a pregnancy category C drug.¹³

To the Editor:

Staphylococcal scalded skin syndrome (SSSS) is a superficial blistering disorder mediated by Staphylococcus aureus exfoliative toxins (ETs).¹ It is rare in adults, but when diagnosed, it is often associated with renal failure, immunodeficiency, or overwhelming staphylococcal infection.² We present a unique case of a pregnant woman with chronic atopic dermatitis (AD) who developed SSSS.

A 21-year-old gravida 3, para 2, aborta 0pregnant woman (29 weeks’ gestation) with a history of chronic AD who was hospitalized with facial edema, purulent ocular discharge, and substantial worsening of AD presented for a dermatology consultation. Her AD was previously managed with topical steroids but had been complicated by multiple methicillin-resistant Staphylococcus aureus (MRSA) infections. On physical examination, she had substantial periorbital edema with purulent discharge from both eyes (Figure 1A), perioral crust with radial fissures (Figure 2A), and mild generalized facial swelling and desquamation (Figure 3). However, the oral cavity was not involved. She had diffuse desquamation in addition to chronic lichenified plaques of the arms, legs, and trunk and SSSS was clinically diagnosed. Cultures of conjunctival discharge were positive for MRSA. The patient was treated with intravenous vancomycin and had a full recovery (Figures 1B and 2B). She delivered a healthy newborn with Apgar scores of 9 and 9 at 1 and 5 minutes, respectively, at 36 weeks and 6 days’ gestation by cesarean delivery; however, her postoperative care was complicated by preeclampsia, which was treated with magnesium sulfate. The newborn showed no evidence of infection or blistering at birth or during the hospital stay.

Figure 1. Periorbital edema with purulent ocular discharge before (A) and after (B) treatment.			Figure 2. Perioral desquamation and radial fissuring before (A) and after (B) treatment.

Staphylococcal scalded skin syndrome is a superficial blistering disorder that ranges in severity from localized blisters to generalized exfoliation.¹ Exfoliative toxin is the major virulence factor responsible for SSSS. Exfoliative toxin is a serine protease that targets desmoglein 1, resulting in intraepidermal separation of keratinocytes.³ Two serologically distinct exfoliative toxins—ETA and ETB—have been associated with human disease.⁴ Although ETA is encoded on a phage genome, ETB is encoded on a large plasmid.³ Initially it was thought that only strains of S aureus carrying lytic group II phages were responsible for ET production; however, it is now accepted that all phage groups are capable of producing ET and causing SSSS.¹

Staphylococcal scalded skin syndrome is most common in infants and children and rare in adults. Although it has been occasionally described in otherwise healthy adults,⁵ it is most often diagnosed in patients with renal failure (decreased toxin excretion), immunodeficiency (lack of antibodies against toxins), and overwhelming staphylococcal infection (excessive toxin).² Mortality in treated children is low, but it can reach almost 60% in adults¹; therefore, defining risk factors that may aid in early diagnosis are exceedingly important.

We believe that both our patient’s history of 
AD and her pregnancy contributed to the development of SSSS. The patient had a history of multiple MRSA infections prior to this hospitalization, suggesting MRSA colonization, which is a common complication of AD with more than 75% of 
AD patients colonized with S aureus.⁶ Additionally, 
S aureus superantigen stimulation can result in the loss of regulatory T cells’ natural immunosuppression. Regulatory T cells are remarkably increased in patients with AD; therefore, the inflammatory response to S aureus is likely amplified in an atopic patient, as there is more native immunosuppressive capacity to be affected.⁴ Furthermore, we believe that pregnancy and its associated immunomodulation is a risk for SSSS. Immune changes in pregnancy are still not well understood; however, it is known that there are alterations to allow symbiosis between the mother and fetus. Anti-ET IgG antibodies are thought to play an important role in protecting against SSSS. Historically, studies on serum immunoglobulin levels during pregnancy have had conflicting findings. They have shown that IgG is either unchanged or decreased, while IgA, IgE, and IgM can be increased, decreased, or unchanged.⁷ In a study of immunoglobulins in pregnancy, Bahna et al⁷ showed that IgE is unchanged over the course of pregnancy, but their analysis did not address IgG levels. If IgG levels in fact decrease during pregnancy, the mother could be at risk for SSSS due to her inability to neutralize toxins. Even if total IgG levels remain unchanged, it is possible that specific antitoxin antibodies are decreased. Additionally, there is a documented suppression and alteration in T-cell response to prevent fetal rejection during pregnancy.⁸ Adult SSSS has been documented several times in human immunodeficiency virus–positive patients, suggesting there may be some association between T-cell suppression and SSSS susceptibility.⁹ Interestingly, pregnancy, similar to AD, results in an increase in immunosuppressive T cells,¹⁰ which, if deactivated by superantigens, could potentially contribute to an increased inflammatory response. All of these immune system alterations likely leave the mother vulnerable to toxin-mediated events such as SSSS.

We believe this case highlights the importance of considering SSSS in both atopic and pregnant patients with desquamating eruptions. In the case of pregnant patients, it is important to consider the risks and benefits of any medical treatments for both the mother and infant. Vancomycin is a pregnancy category B drug and was chosen for its known effectiveness and safety in pregnancy. One study compared 10 babies with mothers who were treated with vancomycin during the second and third trimesters for MRSA to 20 babies with mothers who did not receive vancomycin and did not find an increased risk for sensorineural hearing loss or nephrotoxicity.¹¹ There is no known increased risk for preeclampsia with vancomycin, but some studies have suggested that maternal infection independently increases the risk for preeclampsia.¹² Other treatment options were not as safe as vancomycin in this case: doxycycline is contraindicated (pregnancy category D) due to the potential for staining of deciduous teeth and skeletal growth impairment, trimethoprim-sulfamethoxazole is a pregnancy category D drug during the third trimester due to the risk of kernicterus, and linezolid is a pregnancy category C drug.¹³