Contact Dermatitis

Lichen striatus (LS) is a relatively rare and self-limited linear dermatosis of unknown etiology. Lichen striatus primarily affects children, with more than 50% of cases occurring in patients aged 5 to 15 years.^1,2 It presents clinically as a single unilateral linear band consisting of scaly, 1- to 3-mm papules that coalesce to form long streaks.^3,4 The diagnosis usually is made clinically based on the characteristic appearance of skin lesions and a pattern of distribution that follows the lines of Blaschko.^5,6 The papules usually are asymptomatic; however, if the patient is symptomatic, pruritus is the most common concern. Lichen striatus may resolve with postinflammatory hyperpigmentation or hypopigmentation that may last for several months to years.

Nail involvement is uncommon in LS; a review of the literature has shown that 30 cases have been reported in the world literature since 1941.⁷ Nail changes may present before, after, or concurrently with the skin lesions.^4,8 On rare occasions, nail involvement may be the only area of involvement without the presence of typical skin lesions.⁸ The involved nails may show longitudinal ridging, splitting, hyperkeratosis of the nail beds, thinning or thickening of the nail plate, nail pitting, and overcurvature of the nail plate, and rarely the nails may fall off completely.^8-10

We report the case of a boy who was diagnosed with isolated LS at 2 years of age. The lesions spontaneously resolved within 6 months. Three years later the patient presented with a rare manifestation of LS in the form of bilateral onychodystrophy.

Case Report

An otherwise healthy 2-year-old boy presented for evaluation of a nonpruritic linear rash on the right lower side of the abdomen of 3 weeks’ duration. A review of systems was negative for any other constitutional signs or symptoms. No sick contacts were reported at the patient’s home, and his immunizations were up-to-date. His medical history was remarkable for a burn on the left hand from contact with a hot object at 11 months of age that required skin grafting.

Dermatologic examination revealed a linear band of small, 1- to 3-mm, flesh-colored lichenoid papules. Many of the papules had a scaly appearance and some had a vesicular component or were flat topped. The band ranged from 2- to 3-cm wide and was 25 cm in length, extending from the right anterolateral part of the lower abdomen to the right upper lateral part of the buttocks (Figure 1). No abnormalities were noted on the rest of the skin. A diagnosis of LS was made.

Figure 1. A linear band of small, 1- to 3-mm, flesh-colored, lichenoid, scaly papules, some with a vesicular component. The band was 2- to 3-cm wide and 25-cm long, extending over the right side of the lower abdomen. Figure 2. Longitudinal ridging, splitting, and thinning of the proximal nail folds on the regrown nails. Figure 3. Bilateral pitting, thinning, and overcurvature of the nail plates of the toenails with more involvement of the toenails on the left foot.

At 5 years of age, the patient returned for evaluation of bluish discoloration and thinning of the nails of the left middle and ring fingers of several months duration. The patient was afebrile and appeared to be healthy. There was no lymphadenopathy or hepatomegaly and the rest of the physical examination by a pediatrician was unremarkable. The nails of the 2 affected fingers had fallen off 2 months prior to presentation and had started to regrow. On dermatologic examination, it was noted that the regrown nails showed some residual longitudinal ridging, thinning, and dark discoloration of the proximal nail folds (Figure 2). On examination of the other toenails and fingernails there was evidence of bilateral pitting, ridging, and discoloration (Figure 3). The left great toenail was predominantly affected. The patient’s guardians were not aware of the toenail changes and denied any history of trauma to the fingers. When asked about the course of the prior abdominal linear rash, they reported that the lesions had completely resolved within 6 months. The rare diagnosis of isolated onychodystrophy as a late manifestation of the prior LS was made.

Comment

The etiology of LS remains unknown, but there have been several hypotheses suggesting environmental triggers such as trauma¹¹ or infection.¹² Others have suggested a possible autoimmune response¹³ or genetic components.⁶ Reports of simultaneous occurrences of LS in siblings as well as in a mother and her son^14,15; outbreaks of LS among children who are not biologically related but in a shared living environment; and a possible seasonal variation suggest an environmental infectious agent (eg, a virus) as the possible triggering factor. However, laboratory testing for viral etiology in LS has not been helpful.

Many of the reported cases of LS have described a pattern of distribution along the lines of Blaschko.^5,6,16,17 Lines of Blaschko are thought to be embryologic in origin and caused by the segmental growth of clones of cutaneous cells or the mutation-induced mosaicism of cutaneous cells, which led to the theory that mosaicism is involved in LS. Lichen striatus needs to be differentiated from other conditions with similar cutaneous appearances (eg, lichen nitidus, linear lichen planus of the digits, linear psoriasis, linear keratosis follicularis, linear epidermal nevus).

Skin biopsy to confirm the diagnosis rarely is necessary, as LS is a self-limited disorder and generally no treatment is recommended. Topical and intralesional steroids do not routinely impact the resolution of LS; however, emollients and topical steroids may be used to treat associated dryness and pruritus, if present.¹⁸ Immunomodulators such as tacrolimus and pimecrolimus have been successfully used in treating persistent and pruritic LS lesions on the face and extremities.^19,20 Tacrolimus also has been successfully used to treat nail abnormalities in LS.²¹

Guardians and family members should be reassured that LS is a benign condition that generally resolves spontaneously within 3 to 12 months. Also, guardians should be counseled regarding the possibility of postinflammatory hyperpigmentation or hypopigmentation, which may last for several months to years, particularly in children with darker skin types. Lichen striatus of the nails may have a more protracted course, lasting from 6 months to 5 years,²² but usually resolves spontaneously and without deformity.

Our patient developed a rare case of isolated LS at 2 years of age. Reports have suggested later onset of the condition, with more than 50% of all LS cases occurring in children aged 5 to 15 years.^1,2 Despite the earlier onset in our case, the patient still presented with the classic nonpruritic single linear band of papules that is characteristic of LS.

The nail involvement in our case is quite intriguing because of its rarity, timing, and extent of involvement. Nail involvement is generally uncommon in LS, with approximately 30 cases reported worldwide since 1941.⁷ The nail changes in our patient were unique in their timing, with the isolated onychodystrophy developing 3 years after the initial skin lesion. This subtle timing may pose a diagnostic challenge in patients with LS if treating physicians are unable to link the presenting onychodystrophy to the earlier cutaneous component of the condition. Two reports have shown that nail changes in association with LS may occur at any time before, after, or concurrently with the skin lesions,^4,8 suggesting that on rare occasions, as in our case, nail involvement may be the only area of involvement without the presence of typical LS skin lesions.⁸

The nail involvement in our patient also showed a greater severity than prior reports,^8,9 as he lost 2 fingernails completely before regrowth. Also, the bilateral distribution of onychodystrophy in our patient involving both the fingernails and toenails appeared to be consistent with a report by Al-Niaimi and Cox.²²

Nail involvement in cases of LS may be underreported when, as in our case, nail dystrophy presents as the only area of involvement without the presence of the typical skin lesions characteristic of LS. It is reasonable to recommend that clinicians facing similar presentations of isolated onychodystrophy should include the possibility of LS in the differential diagnosis before committing patients to a more common diagnosis (eg, onychomycosis). Clinicians should inquire about any history of cutaneous LS and counsel patients to return for treatment should skin lesions develop that are suggestive of LS.

Lichen striatus (LS) is a relatively rare and self-limited linear dermatosis of unknown etiology. Lichen striatus primarily affects children, with more than 50% of cases occurring in patients aged 5 to 15 years.^1,2 It presents clinically as a single unilateral linear band consisting of scaly, 1- to 3-mm papules that coalesce to form long streaks.^3,4 The diagnosis usually is made clinically based on the characteristic appearance of skin lesions and a pattern of distribution that follows the lines of Blaschko.^5,6 The papules usually are asymptomatic; however, if the patient is symptomatic, pruritus is the most common concern. Lichen striatus may resolve with postinflammatory hyperpigmentation or hypopigmentation that may last for several months to years.

Nail involvement is uncommon in LS; a review of the literature has shown that 30 cases have been reported in the world literature since 1941.⁷ Nail changes may present before, after, or concurrently with the skin lesions.^4,8 On rare occasions, nail involvement may be the only area of involvement without the presence of typical skin lesions.⁸ The involved nails may show longitudinal ridging, splitting, hyperkeratosis of the nail beds, thinning or thickening of the nail plate, nail pitting, and overcurvature of the nail plate, and rarely the nails may fall off completely.^8-10

We report the case of a boy who was diagnosed with isolated LS at 2 years of age. The lesions spontaneously resolved within 6 months. Three years later the patient presented with a rare manifestation of LS in the form of bilateral onychodystrophy.

Case Report

An otherwise healthy 2-year-old boy presented for evaluation of a nonpruritic linear rash on the right lower side of the abdomen of 3 weeks’ duration. A review of systems was negative for any other constitutional signs or symptoms. No sick contacts were reported at the patient’s home, and his immunizations were up-to-date. His medical history was remarkable for a burn on the left hand from contact with a hot object at 11 months of age that required skin grafting.

Dermatologic examination revealed a linear band of small, 1- to 3-mm, flesh-colored lichenoid papules. Many of the papules had a scaly appearance and some had a vesicular component or were flat topped. The band ranged from 2- to 3-cm wide and was 25 cm in length, extending from the right anterolateral part of the lower abdomen to the right upper lateral part of the buttocks (Figure 1). No abnormalities were noted on the rest of the skin. A diagnosis of LS was made.

Figure 1. A linear band of small, 1- to 3-mm, flesh-colored, lichenoid, scaly papules, some with a vesicular component. The band was 2- to 3-cm wide and 25-cm long, extending over the right side of the lower abdomen. Figure 2. Longitudinal ridging, splitting, and thinning of the proximal nail folds on the regrown nails. Figure 3. Bilateral pitting, thinning, and overcurvature of the nail plates of the toenails with more involvement of the toenails on the left foot.

At 5 years of age, the patient returned for evaluation of bluish discoloration and thinning of the nails of the left middle and ring fingers of several months duration. The patient was afebrile and appeared to be healthy. There was no lymphadenopathy or hepatomegaly and the rest of the physical examination by a pediatrician was unremarkable. The nails of the 2 affected fingers had fallen off 2 months prior to presentation and had started to regrow. On dermatologic examination, it was noted that the regrown nails showed some residual longitudinal ridging, thinning, and dark discoloration of the proximal nail folds (Figure 2). On examination of the other toenails and fingernails there was evidence of bilateral pitting, ridging, and discoloration (Figure 3). The left great toenail was predominantly affected. The patient’s guardians were not aware of the toenail changes and denied any history of trauma to the fingers. When asked about the course of the prior abdominal linear rash, they reported that the lesions had completely resolved within 6 months. The rare diagnosis of isolated onychodystrophy as a late manifestation of the prior LS was made.

Comment

The etiology of LS remains unknown, but there have been several hypotheses suggesting environmental triggers such as trauma¹¹ or infection.¹² Others have suggested a possible autoimmune response¹³ or genetic components.⁶ Reports of simultaneous occurrences of LS in siblings as well as in a mother and her son^14,15; outbreaks of LS among children who are not biologically related but in a shared living environment; and a possible seasonal variation suggest an environmental infectious agent (eg, a virus) as the possible triggering factor. However, laboratory testing for viral etiology in LS has not been helpful.

Many of the reported cases of LS have described a pattern of distribution along the lines of Blaschko.^5,6,16,17 Lines of Blaschko are thought to be embryologic in origin and caused by the segmental growth of clones of cutaneous cells or the mutation-induced mosaicism of cutaneous cells, which led to the theory that mosaicism is involved in LS. Lichen striatus needs to be differentiated from other conditions with similar cutaneous appearances (eg, lichen nitidus, linear lichen planus of the digits, linear psoriasis, linear keratosis follicularis, linear epidermal nevus).

Skin biopsy to confirm the diagnosis rarely is necessary, as LS is a self-limited disorder and generally no treatment is recommended. Topical and intralesional steroids do not routinely impact the resolution of LS; however, emollients and topical steroids may be used to treat associated dryness and pruritus, if present.¹⁸ Immunomodulators such as tacrolimus and pimecrolimus have been successfully used in treating persistent and pruritic LS lesions on the face and extremities.^19,20 Tacrolimus also has been successfully used to treat nail abnormalities in LS.²¹

Guardians and family members should be reassured that LS is a benign condition that generally resolves spontaneously within 3 to 12 months. Also, guardians should be counseled regarding the possibility of postinflammatory hyperpigmentation or hypopigmentation, which may last for several months to years, particularly in children with darker skin types. Lichen striatus of the nails may have a more protracted course, lasting from 6 months to 5 years,²² but usually resolves spontaneously and without deformity.

Our patient developed a rare case of isolated LS at 2 years of age. Reports have suggested later onset of the condition, with more than 50% of all LS cases occurring in children aged 5 to 15 years.^1,2 Despite the earlier onset in our case, the patient still presented with the classic nonpruritic single linear band of papules that is characteristic of LS.

The nail involvement in our case is quite intriguing because of its rarity, timing, and extent of involvement. Nail involvement is generally uncommon in LS, with approximately 30 cases reported worldwide since 1941.⁷ The nail changes in our patient were unique in their timing, with the isolated onychodystrophy developing 3 years after the initial skin lesion. This subtle timing may pose a diagnostic challenge in patients with LS if treating physicians are unable to link the presenting onychodystrophy to the earlier cutaneous component of the condition. Two reports have shown that nail changes in association with LS may occur at any time before, after, or concurrently with the skin lesions,^4,8 suggesting that on rare occasions, as in our case, nail involvement may be the only area of involvement without the presence of typical LS skin lesions.⁸

The nail involvement in our patient also showed a greater severity than prior reports,^8,9 as he lost 2 fingernails completely before regrowth. Also, the bilateral distribution of onychodystrophy in our patient involving both the fingernails and toenails appeared to be consistent with a report by Al-Niaimi and Cox.²²

Nail involvement in cases of LS may be underreported when, as in our case, nail dystrophy presents as the only area of involvement without the presence of the typical skin lesions characteristic of LS. It is reasonable to recommend that clinicians facing similar presentations of isolated onychodystrophy should include the possibility of LS in the differential diagnosis before committing patients to a more common diagnosis (eg, onychomycosis). Clinicians should inquire about any history of cutaneous LS and counsel patients to return for treatment should skin lesions develop that are suggestive of LS.

Lichen striatus (LS) is a relatively rare and self-limited linear dermatosis of unknown etiology. Lichen striatus primarily affects children, with more than 50% of cases occurring in patients aged 5 to 15 years.^1,2 It presents clinically as a single unilateral linear band consisting of scaly, 1- to 3-mm papules that coalesce to form long streaks.^3,4 The diagnosis usually is made clinically based on the characteristic appearance of skin lesions and a pattern of distribution that follows the lines of Blaschko.^5,6 The papules usually are asymptomatic; however, if the patient is symptomatic, pruritus is the most common concern. Lichen striatus may resolve with postinflammatory hyperpigmentation or hypopigmentation that may last for several months to years.

Nail involvement is uncommon in LS; a review of the literature has shown that 30 cases have been reported in the world literature since 1941.⁷ Nail changes may present before, after, or concurrently with the skin lesions.^4,8 On rare occasions, nail involvement may be the only area of involvement without the presence of typical skin lesions.⁸ The involved nails may show longitudinal ridging, splitting, hyperkeratosis of the nail beds, thinning or thickening of the nail plate, nail pitting, and overcurvature of the nail plate, and rarely the nails may fall off completely.^8-10

We report the case of a boy who was diagnosed with isolated LS at 2 years of age. The lesions spontaneously resolved within 6 months. Three years later the patient presented with a rare manifestation of LS in the form of bilateral onychodystrophy.

Case Report

An otherwise healthy 2-year-old boy presented for evaluation of a nonpruritic linear rash on the right lower side of the abdomen of 3 weeks’ duration. A review of systems was negative for any other constitutional signs or symptoms. No sick contacts were reported at the patient’s home, and his immunizations were up-to-date. His medical history was remarkable for a burn on the left hand from contact with a hot object at 11 months of age that required skin grafting.

Dermatologic examination revealed a linear band of small, 1- to 3-mm, flesh-colored lichenoid papules. Many of the papules had a scaly appearance and some had a vesicular component or were flat topped. The band ranged from 2- to 3-cm wide and was 25 cm in length, extending from the right anterolateral part of the lower abdomen to the right upper lateral part of the buttocks (Figure 1). No abnormalities were noted on the rest of the skin. A diagnosis of LS was made.

Figure 1. A linear band of small, 1- to 3-mm, flesh-colored, lichenoid, scaly papules, some with a vesicular component. The band was 2- to 3-cm wide and 25-cm long, extending over the right side of the lower abdomen. Figure 2. Longitudinal ridging, splitting, and thinning of the proximal nail folds on the regrown nails. Figure 3. Bilateral pitting, thinning, and overcurvature of the nail plates of the toenails with more involvement of the toenails on the left foot.

At 5 years of age, the patient returned for evaluation of bluish discoloration and thinning of the nails of the left middle and ring fingers of several months duration. The patient was afebrile and appeared to be healthy. There was no lymphadenopathy or hepatomegaly and the rest of the physical examination by a pediatrician was unremarkable. The nails of the 2 affected fingers had fallen off 2 months prior to presentation and had started to regrow. On dermatologic examination, it was noted that the regrown nails showed some residual longitudinal ridging, thinning, and dark discoloration of the proximal nail folds (Figure 2). On examination of the other toenails and fingernails there was evidence of bilateral pitting, ridging, and discoloration (Figure 3). The left great toenail was predominantly affected. The patient’s guardians were not aware of the toenail changes and denied any history of trauma to the fingers. When asked about the course of the prior abdominal linear rash, they reported that the lesions had completely resolved within 6 months. The rare diagnosis of isolated onychodystrophy as a late manifestation of the prior LS was made.

Comment

The etiology of LS remains unknown, but there have been several hypotheses suggesting environmental triggers such as trauma¹¹ or infection.¹² Others have suggested a possible autoimmune response¹³ or genetic components.⁶ Reports of simultaneous occurrences of LS in siblings as well as in a mother and her son^14,15; outbreaks of LS among children who are not biologically related but in a shared living environment; and a possible seasonal variation suggest an environmental infectious agent (eg, a virus) as the possible triggering factor. However, laboratory testing for viral etiology in LS has not been helpful.

Many of the reported cases of LS have described a pattern of distribution along the lines of Blaschko.^5,6,16,17 Lines of Blaschko are thought to be embryologic in origin and caused by the segmental growth of clones of cutaneous cells or the mutation-induced mosaicism of cutaneous cells, which led to the theory that mosaicism is involved in LS. Lichen striatus needs to be differentiated from other conditions with similar cutaneous appearances (eg, lichen nitidus, linear lichen planus of the digits, linear psoriasis, linear keratosis follicularis, linear epidermal nevus).

Skin biopsy to confirm the diagnosis rarely is necessary, as LS is a self-limited disorder and generally no treatment is recommended. Topical and intralesional steroids do not routinely impact the resolution of LS; however, emollients and topical steroids may be used to treat associated dryness and pruritus, if present.¹⁸ Immunomodulators such as tacrolimus and pimecrolimus have been successfully used in treating persistent and pruritic LS lesions on the face and extremities.^19,20 Tacrolimus also has been successfully used to treat nail abnormalities in LS.²¹

Guardians and family members should be reassured that LS is a benign condition that generally resolves spontaneously within 3 to 12 months. Also, guardians should be counseled regarding the possibility of postinflammatory hyperpigmentation or hypopigmentation, which may last for several months to years, particularly in children with darker skin types. Lichen striatus of the nails may have a more protracted course, lasting from 6 months to 5 years,²² but usually resolves spontaneously and without deformity.

Our patient developed a rare case of isolated LS at 2 years of age. Reports have suggested later onset of the condition, with more than 50% of all LS cases occurring in children aged 5 to 15 years.^1,2 Despite the earlier onset in our case, the patient still presented with the classic nonpruritic single linear band of papules that is characteristic of LS.

The nail involvement in our case is quite intriguing because of its rarity, timing, and extent of involvement. Nail involvement is generally uncommon in LS, with approximately 30 cases reported worldwide since 1941.⁷ The nail changes in our patient were unique in their timing, with the isolated onychodystrophy developing 3 years after the initial skin lesion. This subtle timing may pose a diagnostic challenge in patients with LS if treating physicians are unable to link the presenting onychodystrophy to the earlier cutaneous component of the condition. Two reports have shown that nail changes in association with LS may occur at any time before, after, or concurrently with the skin lesions,^4,8 suggesting that on rare occasions, as in our case, nail involvement may be the only area of involvement without the presence of typical LS skin lesions.⁸

The nail involvement in our patient also showed a greater severity than prior reports,^8,9 as he lost 2 fingernails completely before regrowth. Also, the bilateral distribution of onychodystrophy in our patient involving both the fingernails and toenails appeared to be consistent with a report by Al-Niaimi and Cox.²²

Nail involvement in cases of LS may be underreported when, as in our case, nail dystrophy presents as the only area of involvement without the presence of the typical skin lesions characteristic of LS. It is reasonable to recommend that clinicians facing similar presentations of isolated onychodystrophy should include the possibility of LS in the differential diagnosis before committing patients to a more common diagnosis (eg, onychomycosis). Clinicians should inquire about any history of cutaneous LS and counsel patients to return for treatment should skin lesions develop that are suggestive of LS.

To the Editor:
A 61-year-old woman with a history of atrial fibrillation, type 2 diabetes mellitus, and hyperlipidemia presented with an erythematous, edematous, pruritic eruption on the chest, neck, and arms of 2 weeks’ duration. The patient had no history of considerable sun exposure or reports of photosensitivity. One month prior to presentation she had started taking dronedarone for improved control of atrial fibrillation. She had no known history of drug allergies. Other medications included valsartan, digoxin, pioglitazone, simvastatin, aspirin, hydrocodone, and zolpidem, all of which were unchanged for years. There were no changes in topical products used.

Physical examination revealed confluent, well-demarcated, erythematous and edematous papules and plaques over the anterior aspect of the neck, bilateral forearms, and dorsal aspect of the hands, with a v-shaped distribution on the chest (Figure). There was notable sparing of the submental region, upper arms, abdomen, back, and legs. Dronedarone was discontinued and she was started on fluocinonide ointment 0.05% and oral hydroxyzine for pruritus. Her rash resolved within the following few weeks.

Confluent, well-demarcated, erythematous and edematous papules and plaques in a v-shaped distribution on the chest (A) and dorsal aspect of the hands (B).

Dronedarone is a noniodinated benzofuran derivative. It is structurally similar to and shares the antiarrhythmic properties of amiodarone,¹ and thus it is used in the treatment of atrial fibrillation and atrial flutter. However, the pulmonary and thyroid toxicities sometimes associated with amiodarone have not been observed with dronedarone. The primary side effect of dronedarone is gastrointestinal distress, specifically nausea, vomiting, and diarrhea. Dronedarone has been associated with severe liver injury and hepatic failure.² Cutaneous reactions appear to be an uncommon side effect of dronedarone therapy. Across 5 clinical studies (N=6285), adverse events involving skin and subcutaneous tissue including eczema, allergic dermatitis, pruritus, and nonspecific rash occurred in 5% of dronedarone and 3% of placebo patients. Photosensitivity reactions occurred in less than 1% of dronedarone recipients.³

Although the lack of a biopsy leaves the possibility of a contact or photocontact dermatitis, our patient demonstrated the potential for dronedarone to cause a photodistributed drug eruption that resolved after cessation of the medication.

To the Editor:
A 61-year-old woman with a history of atrial fibrillation, type 2 diabetes mellitus, and hyperlipidemia presented with an erythematous, edematous, pruritic eruption on the chest, neck, and arms of 2 weeks’ duration. The patient had no history of considerable sun exposure or reports of photosensitivity. One month prior to presentation she had started taking dronedarone for improved control of atrial fibrillation. She had no known history of drug allergies. Other medications included valsartan, digoxin, pioglitazone, simvastatin, aspirin, hydrocodone, and zolpidem, all of which were unchanged for years. There were no changes in topical products used.

Physical examination revealed confluent, well-demarcated, erythematous and edematous papules and plaques over the anterior aspect of the neck, bilateral forearms, and dorsal aspect of the hands, with a v-shaped distribution on the chest (Figure). There was notable sparing of the submental region, upper arms, abdomen, back, and legs. Dronedarone was discontinued and she was started on fluocinonide ointment 0.05% and oral hydroxyzine for pruritus. Her rash resolved within the following few weeks.

Confluent, well-demarcated, erythematous and edematous papules and plaques in a v-shaped distribution on the chest (A) and dorsal aspect of the hands (B).

Dronedarone is a noniodinated benzofuran derivative. It is structurally similar to and shares the antiarrhythmic properties of amiodarone,¹ and thus it is used in the treatment of atrial fibrillation and atrial flutter. However, the pulmonary and thyroid toxicities sometimes associated with amiodarone have not been observed with dronedarone. The primary side effect of dronedarone is gastrointestinal distress, specifically nausea, vomiting, and diarrhea. Dronedarone has been associated with severe liver injury and hepatic failure.² Cutaneous reactions appear to be an uncommon side effect of dronedarone therapy. Across 5 clinical studies (N=6285), adverse events involving skin and subcutaneous tissue including eczema, allergic dermatitis, pruritus, and nonspecific rash occurred in 5% of dronedarone and 3% of placebo patients. Photosensitivity reactions occurred in less than 1% of dronedarone recipients.³

Although the lack of a biopsy leaves the possibility of a contact or photocontact dermatitis, our patient demonstrated the potential for dronedarone to cause a photodistributed drug eruption that resolved after cessation of the medication.

To the Editor:
A 61-year-old woman with a history of atrial fibrillation, type 2 diabetes mellitus, and hyperlipidemia presented with an erythematous, edematous, pruritic eruption on the chest, neck, and arms of 2 weeks’ duration. The patient had no history of considerable sun exposure or reports of photosensitivity. One month prior to presentation she had started taking dronedarone for improved control of atrial fibrillation. She had no known history of drug allergies. Other medications included valsartan, digoxin, pioglitazone, simvastatin, aspirin, hydrocodone, and zolpidem, all of which were unchanged for years. There were no changes in topical products used.

Physical examination revealed confluent, well-demarcated, erythematous and edematous papules and plaques over the anterior aspect of the neck, bilateral forearms, and dorsal aspect of the hands, with a v-shaped distribution on the chest (Figure). There was notable sparing of the submental region, upper arms, abdomen, back, and legs. Dronedarone was discontinued and she was started on fluocinonide ointment 0.05% and oral hydroxyzine for pruritus. Her rash resolved within the following few weeks.

Confluent, well-demarcated, erythematous and edematous papules and plaques in a v-shaped distribution on the chest (A) and dorsal aspect of the hands (B).

Dronedarone is a noniodinated benzofuran derivative. It is structurally similar to and shares the antiarrhythmic properties of amiodarone,¹ and thus it is used in the treatment of atrial fibrillation and atrial flutter. However, the pulmonary and thyroid toxicities sometimes associated with amiodarone have not been observed with dronedarone. The primary side effect of dronedarone is gastrointestinal distress, specifically nausea, vomiting, and diarrhea. Dronedarone has been associated with severe liver injury and hepatic failure.² Cutaneous reactions appear to be an uncommon side effect of dronedarone therapy. Across 5 clinical studies (N=6285), adverse events involving skin and subcutaneous tissue including eczema, allergic dermatitis, pruritus, and nonspecific rash occurred in 5% of dronedarone and 3% of placebo patients. Photosensitivity reactions occurred in less than 1% of dronedarone recipients.³

Although the lack of a biopsy leaves the possibility of a contact or photocontact dermatitis, our patient demonstrated the potential for dronedarone to cause a photodistributed drug eruption that resolved after cessation of the medication.

1. The risk for subsequently developing squamous cell carcinoma in situ of the vulva is most strongly associated with:

a. candidiasis

b. cicatricial pemphigoid

c. lichen planus

d. lichen sclerosus

e. recurrent Trichomonas infections

2. Vitamin D supplements and topical antibiotics commonly are used to treat:

a. desquamative inflammatory vaginitis

b. dysesthetic vulvodynia

c. human papillomavirus–related severe squamous dysplasia of the vulva and vagina

d. lichen sclerosus

e. psoriasis

3. A 28-year-old diabetic woman presented to your clinic with well-developed vulvar pruritus. She was known to have an implanted copper intrauterine device. A Papanicolaou test would most likely reveal:

a. bacteria

b. herpetic virocytes

c. high-grade dysplastic squamous cells

d. koilocytic squamous cells

e. pseudohyphae

4. A 54-year-old woman with Sjögren syndrome and atrophic gastritis presented to your clinic with vulvar pruritus. Atrophy of the skin and mucosa with fissures was clinically suggestive of:

a. candidiasis

b. dysesthetic vulvodynia

c. lichen sclerosus

d. lichen simplex chronicus

e. psoriasis

5. A 48-year-old woman was referred to your clinic for evaluation of persistent burning vulvar pain of 3 months’ duration. She said she felt tired most of the time. On physical examination the vulva looked normal. Commonly this condition is associated with:

a. diabetes mellitus

b. fibromyalgia

c. hypothyroidism

d. iron deficiency anemia

e. psoriasis

1. The risk for subsequently developing squamous cell carcinoma in situ of the vulva is most strongly associated with:

a. candidiasis

b. cicatricial pemphigoid

c. lichen planus

d. lichen sclerosus

e. recurrent Trichomonas infections

2. Vitamin D supplements and topical antibiotics commonly are used to treat:

a. desquamative inflammatory vaginitis

b. dysesthetic vulvodynia

c. human papillomavirus–related severe squamous dysplasia of the vulva and vagina

d. lichen sclerosus

e. psoriasis

3. A 28-year-old diabetic woman presented to your clinic with well-developed vulvar pruritus. She was known to have an implanted copper intrauterine device. A Papanicolaou test would most likely reveal:

a. bacteria

b. herpetic virocytes

c. high-grade dysplastic squamous cells

d. koilocytic squamous cells

e. pseudohyphae

4. A 54-year-old woman with Sjögren syndrome and atrophic gastritis presented to your clinic with vulvar pruritus. Atrophy of the skin and mucosa with fissures was clinically suggestive of:

a. candidiasis

b. dysesthetic vulvodynia

c. lichen sclerosus

d. lichen simplex chronicus

e. psoriasis

5. A 48-year-old woman was referred to your clinic for evaluation of persistent burning vulvar pain of 3 months’ duration. She said she felt tired most of the time. On physical examination the vulva looked normal. Commonly this condition is associated with:

a. diabetes mellitus

b. fibromyalgia

c. hypothyroidism

d. iron deficiency anemia

e. psoriasis

1. The risk for subsequently developing squamous cell carcinoma in situ of the vulva is most strongly associated with:

a. candidiasis

b. cicatricial pemphigoid

c. lichen planus

d. lichen sclerosus

e. recurrent Trichomonas infections

2. Vitamin D supplements and topical antibiotics commonly are used to treat:

a. desquamative inflammatory vaginitis

b. dysesthetic vulvodynia

c. human papillomavirus–related severe squamous dysplasia of the vulva and vagina

d. lichen sclerosus

e. psoriasis

3. A 28-year-old diabetic woman presented to your clinic with well-developed vulvar pruritus. She was known to have an implanted copper intrauterine device. A Papanicolaou test would most likely reveal:

a. bacteria

b. herpetic virocytes

c. high-grade dysplastic squamous cells

d. koilocytic squamous cells

e. pseudohyphae

4. A 54-year-old woman with Sjögren syndrome and atrophic gastritis presented to your clinic with vulvar pruritus. Atrophy of the skin and mucosa with fissures was clinically suggestive of:

a. candidiasis

b. dysesthetic vulvodynia

c. lichen sclerosus

d. lichen simplex chronicus

e. psoriasis

5. A 48-year-old woman was referred to your clinic for evaluation of persistent burning vulvar pain of 3 months’ duration. She said she felt tired most of the time. On physical examination the vulva looked normal. Commonly this condition is associated with:

a. diabetes mellitus

b. fibromyalgia

c. hypothyroidism

d. iron deficiency anemia

e. psoriasis

Pemphigus vulgaris (PV) is a rare autoimmune bullous dermatosis that has not shown a predilection toward a particular race or sex.¹ Autoantibodies for desmoglein 1 and desmoglein 3, members of the cadherin family that are involved in cellular adhesion, have been linked to the pathogenesis of PV.² These autoantibodies play a role in the loss of cell-to-cell adhesion in the basal and suprabasal layers of the deep epidermis while cellular adhesion in the superficial epidermis remains intact, leading to the clinical presentation of epidermal blistering and ulcerations most commonly found on the scalp, face, groin, and axillae. Diagnosis typically is made based on skin biopsy and confirmed by direct immunofluorescence. Histologically, PV displays acantholysis and suprabasal cleft formation. Immunofluorescence may show IgG antibodies against the PV antigen in the epidermis.³ Once a diagnosis has been made, treatment typically consists of systemic steroids, as the use of steroids has had great effect in preventing infections, sepsis, and fatality that were once associated with PV.⁴ Mortality rates associated with PV have decreased to 10% to 15% with systemic steroids from a mortality rate as high as 70% in the presteroid era.^1,5 Treatment of PV during pregnancy, as in our patient, requires obstetric and pediatric consultations before therapy is initiated. Use of corticosteroids during pregnancy can be potentially dangerous to the fetus, particularly if high doses are necessary to control maternal disease.^6,7

Case Report

A 34-year-old pregnant woman at 6 weeks’ gestation presented with widespread blistering dermatitis and associated burning and pruritus. Her obstetrical history was gravida 3, para 2. The patient reported a “rash” on the scalp that had developed 9 months prior. She had been treated as an outpatient at an outside institution with topical antibiotics and antifungal medications, yet the dermatitis progressed. Three weeks prior to hospitalization, the rash was present on the skin and mucosal surfaces, including the groin, chest, face, hard palate, buccal mucosa, lips (Figure 1), and back (Figure 2). Nontender bullae ruptured after 3 days, releasing clear, yellow, serous fluid with associated burning and pruritus. The bullae were hemorrhagic and erythematous at the base.

Figure 1. Facial involvement with bullae, crusted hemorrhagic lesions, and eschar in a 34-year-old pregnant woman.

Figure 2. Involvement of the back with bullae in various stages. Some bullae were intact while others newly erupted.

Figure 3. Superinfected and flaking scalp.

Figure 4. Biopsy revealed suprabasal acantholysis with a tombstone effect of residual basal cells (H&E, original magnification ×200).

At the current presentation, the patient had several excoriated 1- to 2-cm oval denudations; some were crusted with eschar. Nikolsky sign was negative. Multiple confluent bullous lesions had erupted on the entire scalp with a thick, impetiginous, yellow crust. She had a wet, boggy, foul-smelling, superinfected scalp that was mildly tender to touch with flaking tissue debris (Figure 3). A white blood cell count was 13.2×109/L (reference range, 4.5–11.0×109/L) with 5% eosinophils (reference range, 2.7%). The differential diagnosis included bullous impetigo, pemphigoid, Stevens-Johnson syndrome, dermatitis herpetiformis, and pemphigus vulgaris.

Biopsies of the scalp and back were taken and showed suprabasal acantholysis with a tombstone effect of residual basal cells standing up on the basement membrane without the characteristic acantholysis into skin appendages (Figure 4). The acantholytic cells in the bullous chamber did not round up as in Hailey-Hailey disease nor was there the dyskeratosis of Grover disease. Direct immunofluorescence on an elbow punch biopsy found diffuse 1+ intercellular IgG in the epidermis and diffuse 1+ basal intercellular C3, and was negative for IgA, IgM, and C1q, thus confirming a diagnosis of PV.

The patient was started on prednisone 20 mg once daily. An increase to prednisone 60 mg led to initial improvement of symptoms, but there was a relapse after several days, which is typical of PV in pregnancy,⁷ prompting the dose to be increased to 120 mg. Following alleviation of symptoms, the dose was later tapered back to 60 mg. No lesions were present at discharge or for 2.5 months thereafter, as the prednisone was tapered from 60 to 45 mg daily after discharge.

On follow-up, the patient’s PV was well controlled, but the prednisone dose was back up to 60 mg daily because of 2 new skin lesions that had developed since her last visit 2.5 months prior. Ultrasonography showed no fetal abnormalities as the pregnancy progressed to 28 weeks’ gestation. The patient developed hypertension and went into premature labor due to placenta previa. The neonate showed no skin lesions or anomalies while in the neonatal intensive care unit. The mother’s prednisone dose was tapered from 60 to 20 mg daily while the white blood cell count was 7.1×10⁹/L with 2% eosinophils and a new scalp lesion appeared. Seven months after her initial discharge from the hospital for the dermatologic condition, she was no longer nursing and azathioprine was added to prednisone 60 mg daily.

Comment

Pemphigus vulgaris is associated with infertility in its active phase; therefore, PV during pregnancy is rare.⁸ Pregnancy may exacerbate PV, which has been a similar finding in other well-documented autoimmune diseases.⁷ One review of PV in pregnancy reported that 11 of 49 patients (22%) experienced an exacerbation of the disease.⁸ This finding pre-sents 2 problems: (1) severe active disease during pregnancy with high antibody titers has been shown to heighten risk for morbidity and mortality for the fetus, and (2) a patient with active PV during pregnancy may require systemic therapy with doses high enough to subdue the disease. The presence of PV was a challenge throughout our patient’s pregnancy. Transient skin lesions may occasionally appear in the neonate and seem to have an increased association with severe active PV in the mother; however, neonatal PV also has been present in mild cases in the mother.⁷ These lesions are secondary to passive transplacental transfer of PV antibodies but do not have long-lasting clinical implications because of an antibody’s brief half-life.⁹ The lesions either spontaneously resolve or can be treated with a topical corticosteroid.

Treatment with high-dose systemic corticosteroids or immunosuppressants can be problematic because of the risks posed to the fetus, especially if the mother must be treated when the embryo is particularly susceptible (eg, during organogenesis).¹⁰ If a woman with known PV is planning to become pregnant, it is recommended to first control and suppress the disease so that therapy can be minimal during the pregnancy. It also is recommended to use aggressive topical therapy if possible to control PV in a pregnant woman.⁸ This option would not have been efficacious in our patient because of her severe widespread disease.

Prednisone is considered one of the first-line treatments of PV and has been historically successful as a treatment for pregnant patients with PV if maintained at a low dosage. Prednisone, similar to other corticosteroids, can cross the placental barrier and can increase the chance of premature birth, infection, and mortality in high doses.⁷ Similar to prednisone, azathioprine is not recommended during pregnancy, but if use is necessary, it is suggested to keep the dose low to prevent fetal harm.¹¹ Inadequate treatment and control of PV can be life threatening to the patient because of the severe infection that may ensue; thus it is necessary for the health of the patient and fetus to suppress the PV. One alternative to treatment with steroids and immunosuppressants is plasma exchange, which has been successful in the clinical context of pregnancy.¹² The cons of plasma exchange are repeat procedures, the need to give the patient more immunosuppressants to prevent a rejection, and the return of the autoantibody.⁷

Several studies have evaluated the safety and efficacy of rituximab in the treatment of refractory PV. Multiple case reports state that both 1 and 2 courses of intravenous rituximab therapy at a dosage of 375 mg per square meter of body surface area affected once weekly for 4 weeks proved to be useful in clinical improvement for patients with refractory disease.^13,14 Studies are currently underway to look at the effects of rituximab on pregnancy and the fetus. Preliminary findings show neonates may have B-cell abnormalities initially yet recover fully without infectious complications or sequelae.¹⁵ Rituximab currently is a pregnancy category C drug, and women are counseled to avoid pregnancy for at least 12 months after rituximab exposure and use contraception while actively taking the drug.¹⁶

Conclusion

Contrary to traditional thinking, PV itself may be associated with poor neonatal outcome, including prematurity and fetal death. These complications seem to be restricted to pregnancies with clinically severe PV.⁷ Our patient decided to progress with her pregnancy despite the potential risk to the fetus from the disease and treatment. Ultimately, the infant was delivered prematurely but was free of disease.

Pemphigus vulgaris (PV) is a rare autoimmune bullous dermatosis that has not shown a predilection toward a particular race or sex.¹ Autoantibodies for desmoglein 1 and desmoglein 3, members of the cadherin family that are involved in cellular adhesion, have been linked to the pathogenesis of PV.² These autoantibodies play a role in the loss of cell-to-cell adhesion in the basal and suprabasal layers of the deep epidermis while cellular adhesion in the superficial epidermis remains intact, leading to the clinical presentation of epidermal blistering and ulcerations most commonly found on the scalp, face, groin, and axillae. Diagnosis typically is made based on skin biopsy and confirmed by direct immunofluorescence. Histologically, PV displays acantholysis and suprabasal cleft formation. Immunofluorescence may show IgG antibodies against the PV antigen in the epidermis.³ Once a diagnosis has been made, treatment typically consists of systemic steroids, as the use of steroids has had great effect in preventing infections, sepsis, and fatality that were once associated with PV.⁴ Mortality rates associated with PV have decreased to 10% to 15% with systemic steroids from a mortality rate as high as 70% in the presteroid era.^1,5 Treatment of PV during pregnancy, as in our patient, requires obstetric and pediatric consultations before therapy is initiated. Use of corticosteroids during pregnancy can be potentially dangerous to the fetus, particularly if high doses are necessary to control maternal disease.^6,7

Case Report

A 34-year-old pregnant woman at 6 weeks’ gestation presented with widespread blistering dermatitis and associated burning and pruritus. Her obstetrical history was gravida 3, para 2. The patient reported a “rash” on the scalp that had developed 9 months prior. She had been treated as an outpatient at an outside institution with topical antibiotics and antifungal medications, yet the dermatitis progressed. Three weeks prior to hospitalization, the rash was present on the skin and mucosal surfaces, including the groin, chest, face, hard palate, buccal mucosa, lips (Figure 1), and back (Figure 2). Nontender bullae ruptured after 3 days, releasing clear, yellow, serous fluid with associated burning and pruritus. The bullae were hemorrhagic and erythematous at the base.

Figure 1. Facial involvement with bullae, crusted hemorrhagic lesions, and eschar in a 34-year-old pregnant woman.

Figure 2. Involvement of the back with bullae in various stages. Some bullae were intact while others newly erupted.

Figure 3. Superinfected and flaking scalp.

Figure 4. Biopsy revealed suprabasal acantholysis with a tombstone effect of residual basal cells (H&E, original magnification ×200).

At the current presentation, the patient had several excoriated 1- to 2-cm oval denudations; some were crusted with eschar. Nikolsky sign was negative. Multiple confluent bullous lesions had erupted on the entire scalp with a thick, impetiginous, yellow crust. She had a wet, boggy, foul-smelling, superinfected scalp that was mildly tender to touch with flaking tissue debris (Figure 3). A white blood cell count was 13.2×109/L (reference range, 4.5–11.0×109/L) with 5% eosinophils (reference range, 2.7%). The differential diagnosis included bullous impetigo, pemphigoid, Stevens-Johnson syndrome, dermatitis herpetiformis, and pemphigus vulgaris.

Biopsies of the scalp and back were taken and showed suprabasal acantholysis with a tombstone effect of residual basal cells standing up on the basement membrane without the characteristic acantholysis into skin appendages (Figure 4). The acantholytic cells in the bullous chamber did not round up as in Hailey-Hailey disease nor was there the dyskeratosis of Grover disease. Direct immunofluorescence on an elbow punch biopsy found diffuse 1+ intercellular IgG in the epidermis and diffuse 1+ basal intercellular C3, and was negative for IgA, IgM, and C1q, thus confirming a diagnosis of PV.

The patient was started on prednisone 20 mg once daily. An increase to prednisone 60 mg led to initial improvement of symptoms, but there was a relapse after several days, which is typical of PV in pregnancy,⁷ prompting the dose to be increased to 120 mg. Following alleviation of symptoms, the dose was later tapered back to 60 mg. No lesions were present at discharge or for 2.5 months thereafter, as the prednisone was tapered from 60 to 45 mg daily after discharge.

On follow-up, the patient’s PV was well controlled, but the prednisone dose was back up to 60 mg daily because of 2 new skin lesions that had developed since her last visit 2.5 months prior. Ultrasonography showed no fetal abnormalities as the pregnancy progressed to 28 weeks’ gestation. The patient developed hypertension and went into premature labor due to placenta previa. The neonate showed no skin lesions or anomalies while in the neonatal intensive care unit. The mother’s prednisone dose was tapered from 60 to 20 mg daily while the white blood cell count was 7.1×10⁹/L with 2% eosinophils and a new scalp lesion appeared. Seven months after her initial discharge from the hospital for the dermatologic condition, she was no longer nursing and azathioprine was added to prednisone 60 mg daily.

Comment

Pemphigus vulgaris is associated with infertility in its active phase; therefore, PV during pregnancy is rare.⁸ Pregnancy may exacerbate PV, which has been a similar finding in other well-documented autoimmune diseases.⁷ One review of PV in pregnancy reported that 11 of 49 patients (22%) experienced an exacerbation of the disease.⁸ This finding pre-sents 2 problems: (1) severe active disease during pregnancy with high antibody titers has been shown to heighten risk for morbidity and mortality for the fetus, and (2) a patient with active PV during pregnancy may require systemic therapy with doses high enough to subdue the disease. The presence of PV was a challenge throughout our patient’s pregnancy. Transient skin lesions may occasionally appear in the neonate and seem to have an increased association with severe active PV in the mother; however, neonatal PV also has been present in mild cases in the mother.⁷ These lesions are secondary to passive transplacental transfer of PV antibodies but do not have long-lasting clinical implications because of an antibody’s brief half-life.⁹ The lesions either spontaneously resolve or can be treated with a topical corticosteroid.

Treatment with high-dose systemic corticosteroids or immunosuppressants can be problematic because of the risks posed to the fetus, especially if the mother must be treated when the embryo is particularly susceptible (eg, during organogenesis).¹⁰ If a woman with known PV is planning to become pregnant, it is recommended to first control and suppress the disease so that therapy can be minimal during the pregnancy. It also is recommended to use aggressive topical therapy if possible to control PV in a pregnant woman.⁸ This option would not have been efficacious in our patient because of her severe widespread disease.

Prednisone is considered one of the first-line treatments of PV and has been historically successful as a treatment for pregnant patients with PV if maintained at a low dosage. Prednisone, similar to other corticosteroids, can cross the placental barrier and can increase the chance of premature birth, infection, and mortality in high doses.⁷ Similar to prednisone, azathioprine is not recommended during pregnancy, but if use is necessary, it is suggested to keep the dose low to prevent fetal harm.¹¹ Inadequate treatment and control of PV can be life threatening to the patient because of the severe infection that may ensue; thus it is necessary for the health of the patient and fetus to suppress the PV. One alternative to treatment with steroids and immunosuppressants is plasma exchange, which has been successful in the clinical context of pregnancy.¹² The cons of plasma exchange are repeat procedures, the need to give the patient more immunosuppressants to prevent a rejection, and the return of the autoantibody.⁷

Several studies have evaluated the safety and efficacy of rituximab in the treatment of refractory PV. Multiple case reports state that both 1 and 2 courses of intravenous rituximab therapy at a dosage of 375 mg per square meter of body surface area affected once weekly for 4 weeks proved to be useful in clinical improvement for patients with refractory disease.^13,14 Studies are currently underway to look at the effects of rituximab on pregnancy and the fetus. Preliminary findings show neonates may have B-cell abnormalities initially yet recover fully without infectious complications or sequelae.¹⁵ Rituximab currently is a pregnancy category C drug, and women are counseled to avoid pregnancy for at least 12 months after rituximab exposure and use contraception while actively taking the drug.¹⁶

Conclusion

Contrary to traditional thinking, PV itself may be associated with poor neonatal outcome, including prematurity and fetal death. These complications seem to be restricted to pregnancies with clinically severe PV.⁷ Our patient decided to progress with her pregnancy despite the potential risk to the fetus from the disease and treatment. Ultimately, the infant was delivered prematurely but was free of disease.

Pemphigus vulgaris (PV) is a rare autoimmune bullous dermatosis that has not shown a predilection toward a particular race or sex.¹ Autoantibodies for desmoglein 1 and desmoglein 3, members of the cadherin family that are involved in cellular adhesion, have been linked to the pathogenesis of PV.² These autoantibodies play a role in the loss of cell-to-cell adhesion in the basal and suprabasal layers of the deep epidermis while cellular adhesion in the superficial epidermis remains intact, leading to the clinical presentation of epidermal blistering and ulcerations most commonly found on the scalp, face, groin, and axillae. Diagnosis typically is made based on skin biopsy and confirmed by direct immunofluorescence. Histologically, PV displays acantholysis and suprabasal cleft formation. Immunofluorescence may show IgG antibodies against the PV antigen in the epidermis.³ Once a diagnosis has been made, treatment typically consists of systemic steroids, as the use of steroids has had great effect in preventing infections, sepsis, and fatality that were once associated with PV.⁴ Mortality rates associated with PV have decreased to 10% to 15% with systemic steroids from a mortality rate as high as 70% in the presteroid era.^1,5 Treatment of PV during pregnancy, as in our patient, requires obstetric and pediatric consultations before therapy is initiated. Use of corticosteroids during pregnancy can be potentially dangerous to the fetus, particularly if high doses are necessary to control maternal disease.^6,7

Case Report

A 34-year-old pregnant woman at 6 weeks’ gestation presented with widespread blistering dermatitis and associated burning and pruritus. Her obstetrical history was gravida 3, para 2. The patient reported a “rash” on the scalp that had developed 9 months prior. She had been treated as an outpatient at an outside institution with topical antibiotics and antifungal medications, yet the dermatitis progressed. Three weeks prior to hospitalization, the rash was present on the skin and mucosal surfaces, including the groin, chest, face, hard palate, buccal mucosa, lips (Figure 1), and back (Figure 2). Nontender bullae ruptured after 3 days, releasing clear, yellow, serous fluid with associated burning and pruritus. The bullae were hemorrhagic and erythematous at the base.

Figure 1. Facial involvement with bullae, crusted hemorrhagic lesions, and eschar in a 34-year-old pregnant woman.

Figure 2. Involvement of the back with bullae in various stages. Some bullae were intact while others newly erupted.

Figure 3. Superinfected and flaking scalp.

Figure 4. Biopsy revealed suprabasal acantholysis with a tombstone effect of residual basal cells (H&E, original magnification ×200).

At the current presentation, the patient had several excoriated 1- to 2-cm oval denudations; some were crusted with eschar. Nikolsky sign was negative. Multiple confluent bullous lesions had erupted on the entire scalp with a thick, impetiginous, yellow crust. She had a wet, boggy, foul-smelling, superinfected scalp that was mildly tender to touch with flaking tissue debris (Figure 3). A white blood cell count was 13.2×109/L (reference range, 4.5–11.0×109/L) with 5% eosinophils (reference range, 2.7%). The differential diagnosis included bullous impetigo, pemphigoid, Stevens-Johnson syndrome, dermatitis herpetiformis, and pemphigus vulgaris.

Biopsies of the scalp and back were taken and showed suprabasal acantholysis with a tombstone effect of residual basal cells standing up on the basement membrane without the characteristic acantholysis into skin appendages (Figure 4). The acantholytic cells in the bullous chamber did not round up as in Hailey-Hailey disease nor was there the dyskeratosis of Grover disease. Direct immunofluorescence on an elbow punch biopsy found diffuse 1+ intercellular IgG in the epidermis and diffuse 1+ basal intercellular C3, and was negative for IgA, IgM, and C1q, thus confirming a diagnosis of PV.

The patient was started on prednisone 20 mg once daily. An increase to prednisone 60 mg led to initial improvement of symptoms, but there was a relapse after several days, which is typical of PV in pregnancy,⁷ prompting the dose to be increased to 120 mg. Following alleviation of symptoms, the dose was later tapered back to 60 mg. No lesions were present at discharge or for 2.5 months thereafter, as the prednisone was tapered from 60 to 45 mg daily after discharge.

On follow-up, the patient’s PV was well controlled, but the prednisone dose was back up to 60 mg daily because of 2 new skin lesions that had developed since her last visit 2.5 months prior. Ultrasonography showed no fetal abnormalities as the pregnancy progressed to 28 weeks’ gestation. The patient developed hypertension and went into premature labor due to placenta previa. The neonate showed no skin lesions or anomalies while in the neonatal intensive care unit. The mother’s prednisone dose was tapered from 60 to 20 mg daily while the white blood cell count was 7.1×10⁹/L with 2% eosinophils and a new scalp lesion appeared. Seven months after her initial discharge from the hospital for the dermatologic condition, she was no longer nursing and azathioprine was added to prednisone 60 mg daily.

Comment

Pemphigus vulgaris is associated with infertility in its active phase; therefore, PV during pregnancy is rare.⁸ Pregnancy may exacerbate PV, which has been a similar finding in other well-documented autoimmune diseases.⁷ One review of PV in pregnancy reported that 11 of 49 patients (22%) experienced an exacerbation of the disease.⁸ This finding pre-sents 2 problems: (1) severe active disease during pregnancy with high antibody titers has been shown to heighten risk for morbidity and mortality for the fetus, and (2) a patient with active PV during pregnancy may require systemic therapy with doses high enough to subdue the disease. The presence of PV was a challenge throughout our patient’s pregnancy. Transient skin lesions may occasionally appear in the neonate and seem to have an increased association with severe active PV in the mother; however, neonatal PV also has been present in mild cases in the mother.⁷ These lesions are secondary to passive transplacental transfer of PV antibodies but do not have long-lasting clinical implications because of an antibody’s brief half-life.⁹ The lesions either spontaneously resolve or can be treated with a topical corticosteroid.

Treatment with high-dose systemic corticosteroids or immunosuppressants can be problematic because of the risks posed to the fetus, especially if the mother must be treated when the embryo is particularly susceptible (eg, during organogenesis).¹⁰ If a woman with known PV is planning to become pregnant, it is recommended to first control and suppress the disease so that therapy can be minimal during the pregnancy. It also is recommended to use aggressive topical therapy if possible to control PV in a pregnant woman.⁸ This option would not have been efficacious in our patient because of her severe widespread disease.

Prednisone is considered one of the first-line treatments of PV and has been historically successful as a treatment for pregnant patients with PV if maintained at a low dosage. Prednisone, similar to other corticosteroids, can cross the placental barrier and can increase the chance of premature birth, infection, and mortality in high doses.⁷ Similar to prednisone, azathioprine is not recommended during pregnancy, but if use is necessary, it is suggested to keep the dose low to prevent fetal harm.¹¹ Inadequate treatment and control of PV can be life threatening to the patient because of the severe infection that may ensue; thus it is necessary for the health of the patient and fetus to suppress the PV. One alternative to treatment with steroids and immunosuppressants is plasma exchange, which has been successful in the clinical context of pregnancy.¹² The cons of plasma exchange are repeat procedures, the need to give the patient more immunosuppressants to prevent a rejection, and the return of the autoantibody.⁷

Several studies have evaluated the safety and efficacy of rituximab in the treatment of refractory PV. Multiple case reports state that both 1 and 2 courses of intravenous rituximab therapy at a dosage of 375 mg per square meter of body surface area affected once weekly for 4 weeks proved to be useful in clinical improvement for patients with refractory disease.^13,14 Studies are currently underway to look at the effects of rituximab on pregnancy and the fetus. Preliminary findings show neonates may have B-cell abnormalities initially yet recover fully without infectious complications or sequelae.¹⁵ Rituximab currently is a pregnancy category C drug, and women are counseled to avoid pregnancy for at least 12 months after rituximab exposure and use contraception while actively taking the drug.¹⁶

Conclusion

Contrary to traditional thinking, PV itself may be associated with poor neonatal outcome, including prematurity and fetal death. These complications seem to be restricted to pregnancies with clinically severe PV.⁷ Our patient decided to progress with her pregnancy despite the potential risk to the fetus from the disease and treatment. Ultimately, the infant was delivered prematurely but was free of disease.

To the Editor:
Dermal melanocytosis is thought to be the result of a defect in melanoblast migration during embryogenesis and is characterized by the presence of functional fusiform and dendritic melanocytes in the dermis. Congenital dermal melanocytosis is classified into various subtypes based on the distribution, morphology, natural history of lesions, and distinctive histologic findings. We present an unusual case of congenital dermal melanocytosis that might fit the rare entity of dermal melanocyte hamartoma (DMH).

Figure 1. Uniform grayish blue patches over the torso with sharp demarcation lines that followed a dermatomal distribution.

Figure 2. Three conspicuous darker blue macules (arrows) within a bluish patch.

Figure 3. Intradermal dendritic pigmented melanocytes localized in the upper dermis and arranged parallel to the skin surface (H&E, original magnification ×100 [inset, original magnification ×400]).

A 4-month-old girl presented with bilateral bluish patches over the trunk and upper extremities. The lesions were present since birth, and remained entirely unchanged during a follow-up period of 18 months. Mental and physical development was normal. There was no family history of pigmentary disorders. On physical examination uniform grayish blue patches were seen over the torso and upper extremities. The patches seemed to follow a dermatomal distribution along the trunk and extremities (Figure 1). Several well-circumscribed, much darker blue macules were scattered within the bluish patches (Figure 2). The rest of the physical examination was unremarkable. Complete blood cell count and blood chemistry values were within reference range. Skin biopsy specimens from both the grayish blue patches and the conspicuous darker blue macules showed a fair amount of dermal bipolar dendritic pigmented melanocytes arranged parallel to the skin surface with no apparent disturbance of collagen bundles (Figure 3). No melanophages were seen. The clinical, histologic, and laboratory findings were consistent with a diagnosis of congenital dermal melanocytosis. An underlying lysosomal storage disease was ruled out through metabolic screening that included liver function tests, abdominal sonography, and neurologic and ophthalmologic examinations.

The clinical spectrum of congenital dermal melanocytosis includes several clinical entities such as mongolian spots, Ota nevus, Ito nevus, blue nevi, and DMH.¹ The differentiation between these different types of dermal melanocytosis can be challenging, especially when the process of melanocytosis is extensive. Among the several types of congenital dermal melanocytosis, Ota or Ito nevi can be ruled out in our patient based on the clinical presentation.

The term dermal melanocyte hamartoma was introduced by Burkhart and Gohara.² It is characterized by congenital dermal melanocytosis that follows a dermatomal pattern. The original case report included speckled, darker blue macules with a background of grayish blue patches similar to our patient.² Melanocytes in DMH typically are located in the upper half of the reticular dermis, as opposed to extensive mongolian spots in which ectopic melanocytes usually are found in the lower half of the dermis. The pigmentation in our patient did not change during 22 months of follow-up, which is more consistent with the diagnosis of DMH versus extensive mongolian spots. Our patient did not present with any systemic anomalies. However, a case of congenital melanocytosis and neuroectodermal malformation has been described in the literature.³

Little is known about the etiology of dermal melanocytosis. Mutations in the guanine nucleotide binding protein q polypeptide gene, GNAQ, or guanine nucleotide binding protein alpha 11 gene, GNA11, were found to cause dermal melanocytosis in mice.⁴ Also, GNAQ mutations have been demonstrated in humans with dermal melanocytosis as well as uveal melanoma.⁵ Progress in our understanding of the pathogenesis of dermal melanocytosis is expected to lead to a more accurate classification of dermal pigmentation disorders.

To the Editor:
Dermal melanocytosis is thought to be the result of a defect in melanoblast migration during embryogenesis and is characterized by the presence of functional fusiform and dendritic melanocytes in the dermis. Congenital dermal melanocytosis is classified into various subtypes based on the distribution, morphology, natural history of lesions, and distinctive histologic findings. We present an unusual case of congenital dermal melanocytosis that might fit the rare entity of dermal melanocyte hamartoma (DMH).

Figure 1. Uniform grayish blue patches over the torso with sharp demarcation lines that followed a dermatomal distribution.

Figure 2. Three conspicuous darker blue macules (arrows) within a bluish patch.

Figure 3. Intradermal dendritic pigmented melanocytes localized in the upper dermis and arranged parallel to the skin surface (H&E, original magnification ×100 [inset, original magnification ×400]).

A 4-month-old girl presented with bilateral bluish patches over the trunk and upper extremities. The lesions were present since birth, and remained entirely unchanged during a follow-up period of 18 months. Mental and physical development was normal. There was no family history of pigmentary disorders. On physical examination uniform grayish blue patches were seen over the torso and upper extremities. The patches seemed to follow a dermatomal distribution along the trunk and extremities (Figure 1). Several well-circumscribed, much darker blue macules were scattered within the bluish patches (Figure 2). The rest of the physical examination was unremarkable. Complete blood cell count and blood chemistry values were within reference range. Skin biopsy specimens from both the grayish blue patches and the conspicuous darker blue macules showed a fair amount of dermal bipolar dendritic pigmented melanocytes arranged parallel to the skin surface with no apparent disturbance of collagen bundles (Figure 3). No melanophages were seen. The clinical, histologic, and laboratory findings were consistent with a diagnosis of congenital dermal melanocytosis. An underlying lysosomal storage disease was ruled out through metabolic screening that included liver function tests, abdominal sonography, and neurologic and ophthalmologic examinations.

The clinical spectrum of congenital dermal melanocytosis includes several clinical entities such as mongolian spots, Ota nevus, Ito nevus, blue nevi, and DMH.¹ The differentiation between these different types of dermal melanocytosis can be challenging, especially when the process of melanocytosis is extensive. Among the several types of congenital dermal melanocytosis, Ota or Ito nevi can be ruled out in our patient based on the clinical presentation.

The term dermal melanocyte hamartoma was introduced by Burkhart and Gohara.² It is characterized by congenital dermal melanocytosis that follows a dermatomal pattern. The original case report included speckled, darker blue macules with a background of grayish blue patches similar to our patient.² Melanocytes in DMH typically are located in the upper half of the reticular dermis, as opposed to extensive mongolian spots in which ectopic melanocytes usually are found in the lower half of the dermis. The pigmentation in our patient did not change during 22 months of follow-up, which is more consistent with the diagnosis of DMH versus extensive mongolian spots. Our patient did not present with any systemic anomalies. However, a case of congenital melanocytosis and neuroectodermal malformation has been described in the literature.³

Little is known about the etiology of dermal melanocytosis. Mutations in the guanine nucleotide binding protein q polypeptide gene, GNAQ, or guanine nucleotide binding protein alpha 11 gene, GNA11, were found to cause dermal melanocytosis in mice.⁴ Also, GNAQ mutations have been demonstrated in humans with dermal melanocytosis as well as uveal melanoma.⁵ Progress in our understanding of the pathogenesis of dermal melanocytosis is expected to lead to a more accurate classification of dermal pigmentation disorders.

To the Editor:
Dermal melanocytosis is thought to be the result of a defect in melanoblast migration during embryogenesis and is characterized by the presence of functional fusiform and dendritic melanocytes in the dermis. Congenital dermal melanocytosis is classified into various subtypes based on the distribution, morphology, natural history of lesions, and distinctive histologic findings. We present an unusual case of congenital dermal melanocytosis that might fit the rare entity of dermal melanocyte hamartoma (DMH).

Figure 1. Uniform grayish blue patches over the torso with sharp demarcation lines that followed a dermatomal distribution.

Figure 2. Three conspicuous darker blue macules (arrows) within a bluish patch.

Figure 3. Intradermal dendritic pigmented melanocytes localized in the upper dermis and arranged parallel to the skin surface (H&E, original magnification ×100 [inset, original magnification ×400]).

A 4-month-old girl presented with bilateral bluish patches over the trunk and upper extremities. The lesions were present since birth, and remained entirely unchanged during a follow-up period of 18 months. Mental and physical development was normal. There was no family history of pigmentary disorders. On physical examination uniform grayish blue patches were seen over the torso and upper extremities. The patches seemed to follow a dermatomal distribution along the trunk and extremities (Figure 1). Several well-circumscribed, much darker blue macules were scattered within the bluish patches (Figure 2). The rest of the physical examination was unremarkable. Complete blood cell count and blood chemistry values were within reference range. Skin biopsy specimens from both the grayish blue patches and the conspicuous darker blue macules showed a fair amount of dermal bipolar dendritic pigmented melanocytes arranged parallel to the skin surface with no apparent disturbance of collagen bundles (Figure 3). No melanophages were seen. The clinical, histologic, and laboratory findings were consistent with a diagnosis of congenital dermal melanocytosis. An underlying lysosomal storage disease was ruled out through metabolic screening that included liver function tests, abdominal sonography, and neurologic and ophthalmologic examinations.

The clinical spectrum of congenital dermal melanocytosis includes several clinical entities such as mongolian spots, Ota nevus, Ito nevus, blue nevi, and DMH.¹ The differentiation between these different types of dermal melanocytosis can be challenging, especially when the process of melanocytosis is extensive. Among the several types of congenital dermal melanocytosis, Ota or Ito nevi can be ruled out in our patient based on the clinical presentation.

The term dermal melanocyte hamartoma was introduced by Burkhart and Gohara.² It is characterized by congenital dermal melanocytosis that follows a dermatomal pattern. The original case report included speckled, darker blue macules with a background of grayish blue patches similar to our patient.² Melanocytes in DMH typically are located in the upper half of the reticular dermis, as opposed to extensive mongolian spots in which ectopic melanocytes usually are found in the lower half of the dermis. The pigmentation in our patient did not change during 22 months of follow-up, which is more consistent with the diagnosis of DMH versus extensive mongolian spots. Our patient did not present with any systemic anomalies. However, a case of congenital melanocytosis and neuroectodermal malformation has been described in the literature.³

Little is known about the etiology of dermal melanocytosis. Mutations in the guanine nucleotide binding protein q polypeptide gene, GNAQ, or guanine nucleotide binding protein alpha 11 gene, GNA11, were found to cause dermal melanocytosis in mice.⁴ Also, GNAQ mutations have been demonstrated in humans with dermal melanocytosis as well as uveal melanoma.⁵ Progress in our understanding of the pathogenesis of dermal melanocytosis is expected to lead to a more accurate classification of dermal pigmentation disorders.

Patch testing is one of the major diagnostic tools in the evaluation of allergic contact dermatitis. One limitation of patch testing is the use of steroids prior to testing. Because steroids may suppress a positive test reaction, the use of topical steroids on the test site or oral steroids should be discontinued for at least 2 weeks prior to testing. Therefore, it is interesting to consider the effect of biologics on the reliability of patch testing.

Kim et al (Dermatitis. 2014;25:182-190) evaluated the prevalence of positive patch tests in psoriasis patients receiving biologics and whether these results differed from those of psoriasis patients who were not receiving biologics. An institutional review board–approved retrospective chart review was performed for individuals with psoriasis who were patch tested from January 2002 to 2012 at Tufts Medical Center in Boston, Massachusetts. Patients were selected if they had a history of psoriasis, psoriatic arthritis, and patch testing as identified by International Classification of Diseases, Ninth Revision, codes 696.1, 696.0, and 95044, respectively, in their medical records. Patients were patch tested using a modified North American Contact Dermatitis Group standard and cosmetics series. Readings were performed at 48 hours and 72 to 96 hours. The North American Contact Dermatitis Group grading system was used to grade reactions. 

The chart review included 15 psoriasis patients who were on biologics (cases) and 16 psoriasis patients who were not on biologics (control subjects). The biologics used were ustekinumab (n=7), etanercept (n=4), adalimumab (n=3), and infliximab (n=1). The authors determined that 80% (12/15) of cases had at least 1 positive reaction compared with 81% (13/16) of control subjects, 67% (10/15) of cases had 2+ positive reactions compared with 63% (10/16) of control subjects, and 27% (4/15) of cases had 3+ positive reactions compared with 38% (6/16) of control subjects. These differences were not statistically significant.

Given the limitation of the small number of patients evaluated, the authors concluded that biologics do not appear to influence the abilities of patients with psoriasis to mount a positive patch test.

What’s the issue?

This study is small, but the findings do give an indication that the biologic agents utilized for psoriasis do not suppress patch test reactions. These data are not typically what we collect in this population, but it is nice to know. What has been your experience in patch testing patients on biologic therapy?

We want to know your views! Tell us what you think.

Patch testing is one of the major diagnostic tools in the evaluation of allergic contact dermatitis. One limitation of patch testing is the use of steroids prior to testing. Because steroids may suppress a positive test reaction, the use of topical steroids on the test site or oral steroids should be discontinued for at least 2 weeks prior to testing. Therefore, it is interesting to consider the effect of biologics on the reliability of patch testing.

Kim et al (Dermatitis. 2014;25:182-190) evaluated the prevalence of positive patch tests in psoriasis patients receiving biologics and whether these results differed from those of psoriasis patients who were not receiving biologics. An institutional review board–approved retrospective chart review was performed for individuals with psoriasis who were patch tested from January 2002 to 2012 at Tufts Medical Center in Boston, Massachusetts. Patients were selected if they had a history of psoriasis, psoriatic arthritis, and patch testing as identified by International Classification of Diseases, Ninth Revision, codes 696.1, 696.0, and 95044, respectively, in their medical records. Patients were patch tested using a modified North American Contact Dermatitis Group standard and cosmetics series. Readings were performed at 48 hours and 72 to 96 hours. The North American Contact Dermatitis Group grading system was used to grade reactions. 

The chart review included 15 psoriasis patients who were on biologics (cases) and 16 psoriasis patients who were not on biologics (control subjects). The biologics used were ustekinumab (n=7), etanercept (n=4), adalimumab (n=3), and infliximab (n=1). The authors determined that 80% (12/15) of cases had at least 1 positive reaction compared with 81% (13/16) of control subjects, 67% (10/15) of cases had 2+ positive reactions compared with 63% (10/16) of control subjects, and 27% (4/15) of cases had 3+ positive reactions compared with 38% (6/16) of control subjects. These differences were not statistically significant.

Given the limitation of the small number of patients evaluated, the authors concluded that biologics do not appear to influence the abilities of patients with psoriasis to mount a positive patch test.

What’s the issue?

This study is small, but the findings do give an indication that the biologic agents utilized for psoriasis do not suppress patch test reactions. These data are not typically what we collect in this population, but it is nice to know. What has been your experience in patch testing patients on biologic therapy?

We want to know your views! Tell us what you think.

Patch testing is one of the major diagnostic tools in the evaluation of allergic contact dermatitis. One limitation of patch testing is the use of steroids prior to testing. Because steroids may suppress a positive test reaction, the use of topical steroids on the test site or oral steroids should be discontinued for at least 2 weeks prior to testing. Therefore, it is interesting to consider the effect of biologics on the reliability of patch testing.

Kim et al (Dermatitis. 2014;25:182-190) evaluated the prevalence of positive patch tests in psoriasis patients receiving biologics and whether these results differed from those of psoriasis patients who were not receiving biologics. An institutional review board–approved retrospective chart review was performed for individuals with psoriasis who were patch tested from January 2002 to 2012 at Tufts Medical Center in Boston, Massachusetts. Patients were selected if they had a history of psoriasis, psoriatic arthritis, and patch testing as identified by International Classification of Diseases, Ninth Revision, codes 696.1, 696.0, and 95044, respectively, in their medical records. Patients were patch tested using a modified North American Contact Dermatitis Group standard and cosmetics series. Readings were performed at 48 hours and 72 to 96 hours. The North American Contact Dermatitis Group grading system was used to grade reactions. 

The chart review included 15 psoriasis patients who were on biologics (cases) and 16 psoriasis patients who were not on biologics (control subjects). The biologics used were ustekinumab (n=7), etanercept (n=4), adalimumab (n=3), and infliximab (n=1). The authors determined that 80% (12/15) of cases had at least 1 positive reaction compared with 81% (13/16) of control subjects, 67% (10/15) of cases had 2+ positive reactions compared with 63% (10/16) of control subjects, and 27% (4/15) of cases had 3+ positive reactions compared with 38% (6/16) of control subjects. These differences were not statistically significant.

Given the limitation of the small number of patients evaluated, the authors concluded that biologics do not appear to influence the abilities of patients with psoriasis to mount a positive patch test.

What’s the issue?

This study is small, but the findings do give an indication that the biologic agents utilized for psoriasis do not suppress patch test reactions. These data are not typically what we collect in this population, but it is nice to know. What has been your experience in patch testing patients on biologic therapy?

We want to know your views! Tell us what you think.