Janjua SA

Piebaldism is a rare autosomal dominant disorder characterized by congenital poliosis and leukoderma. We present a case of a 10-year-old girl with a typical clinical presentation, followed by a concise review of the literature discussing the etiology, clinical features, diagnosis, and management of the condition.

Case Report
A 10-year-old girl presented for evaluation of a white forelock and multiple white patches of skin on the trunk and extremities (Figure). The white forelock was present at birth and a few white patches appeared on the chest at 3 months of age. During the subsequent 4 years, the white patches gradually progressed to involve the central forehead, abdomen, and extremities. Multiple frecklelike macules also appeared within the patches and the surrounding healthy skin.

Physical examination revealed a healthy girl with a prominent, large, diamond-shaped, depigmented patch on the central forehead that was associated with a white forelock. The hairs of the medial eyebrows and the eyelashes also were depigmented. Large, irregularly shaped, depigmented patches were present on the trunk and anterior extremities. There were multiple hyperpigmented macules overlying both the depigmented patches and the adjacent normally pigmented skin. The rest of the physical examination and the results of routine blood tests and urinalysis were unremarkable. The patient's mother and 4 siblings also were born with a white forelock. Similar depigmented patches on the trunk and extremities with a similar pattern and distribution were noted in all of them. Neither the patient nor her mother and siblings had midfacial anomalies, deafness, or heterochromia irides.

Comment
Piebaldism is a rare autosomal dominant disorder of melanocyte development resulting from mutations of the c-kit protooncogene.1,2 The disorder is characterized clinically by congenital poliosis and leukoderma. A white forelock is present at birth and may be the only manifestation in most affected individuals.3 The white forelock may have a triangular or diamond shape, and the underlying skin of the scalp also is amelanotic. Typical piebald lesions are typified by well-circumscribed, irregular, chalk white patches, often with hyperpigmented frecklelike macules noted on both depigmented and unaffected adjacent skin.4 The lesions often exhibit a classic distribution, involving the central forehead and anterior trunk, with extension to the flanks and anterior midarms, midknees, and midlegs. The medial third of the eyebrows and eyelashes also may be affected in severe cases.4 Characteristically, there is sparing of the dorsal midline, hands, feet, and periorificial areas. Piebaldism generally is a static disorder of pigmentation, though contraction of the affected areas with time or the appearance of new hyperpigmented macular lesions has been described.5 Progression of the depigmented patches has been reported in isolated cases with a novel Val620Ala mutation in Kit.6 Piebaldism rarely is associated with other disorders such as Hirschsprung disease, neurofibromatosis type 1, congenital dyserythropoietic anemia type II, Diamond-Blackfan anemia, and Grover disease.7-11 Individual case reports with associated deafness also have been described.12 Histopathologic evaluation of the depigmented lesions reveals absent or considerably reduced melanocytes. The hyperpigmented macules have a normal number of melanocytes and an increased number of melanosomes in the melanocytes and keratinocytes.4 The molecular basis of piebaldism was traced by Giebel and Spritz1 and Fleischman et al13 to mutations of the c-kit protooncogene. To date, 14 point mutations, 9 deletion mutations, 2 nucleotide splicing mutations, and 3 insertions of Kit have been described.6,14 c-kit Mutations are found in about 75% of patients with piebaldism.14 Mutations in the slug gene, which is a zinc-finger neural crest transcription factor, have been reported in piebaldism that lacked mutations in Kit.15 The human kit gene encodes the tyrosine kinase transmembrane cellular receptor for mast/stem cell growth factor, which is a critical factor for melanoblast migration, proliferation, differentiation, and survival.6 It would be pertinent to note here that the severity of the phenotype in piebaldism correlates with the site of the mutation within the kit gene. The most severe phenotypes are caused by mutations involving the intracellular tyrosine kinase domain, whereas the mildest phenotypes result from mutations involving the amino-terminal extracellular ligand-binding domain.6 The differential diagnosis of piebaldism includes any condition that may present with a depigmented lesion. Vitiligo is characterized by acquired depigmentation, typically in an acral and periorificial distribution. Piebaldism generally is distinguished from vitiligo by the presence of lesions from birth, hyperpigmented macules within and at the border of depigmented areas, and its static course. Moreover, piebaldism spares the dorsal midline, hands, feet, and periorificial areas. Waardenburg syndrome is an autosomal dominant disorder characterized by a congenital white forelock, lateral displacement of the medial canthi, a hypertrophic nasal root, heterochromia irides, and sensorineural hearing loss.16 At least 4 types of Waardenburg syndrome have been described based on the clinical and genetic criteria. The presence of hyperpigmented patches within the islands of depigmentation and on healthy skin; the absence of midfacial lesions, heterochromia irides, and deafness; and the location of depigmented patches on the trunk and extremities help to distinguish piebaldism from the various forms of Waardenburg syndrome.16 Ziprkowski-Margolis syndrome is a rare X-linked recessive syndrome characterized by deaf-mutism, heterochromic irides, piebaldlike hypomelanosis, and hyperpigmented macules, with a geographic appearance developing mainly on the trunk and extremities.17 Woolf syndrome is an autosomal recessive disorder consisting of piebaldism and deafness. Audiometry is crucial to exclude this diagnosis.18 Depending on its presentation, other conditions to consider include Addison disease, albinism, and systemic sclerosis, as well as use of depigmenting agents. Piebaldism is considered a relatively benign disorder, but it may have psychological impact because it is socially disabling, which presents a therapeutic challenge. Depigmented skin in piebaldism generally is considered unresponsive to medical or light therapy. Of note, the diagnosis of piebaldism should alert the clinician to the possibility of Waardenburg syndrome as determined by the results of ocular and auditory examinations. Sunscreens are recommended to avoid sunburns and to reduce the carcinogenic potential. To camouflage the exposed areas, makeup or temporary pigmenting agents such as the tanning product dihydroxyacetone may be used.19 The lesions of piebaldism do not respond to the topical agents used to treat vitiligo. Different surgical techniques have been tried, with variable success, including thin split-thickness grafts, minigrafting, transplant of autologous cultured melanocytes, and a combination of dermabrasion and grafting of the pigmented skin into the depigmented areas.20,21 Guerra et al22 reported achromic epidermis removed with the erbium:YAG laser and autologous cultured epidermal grafts were applied to the recipient bed in 6 patients. Autologous cultured epidermis, bearing a controlled number of melanocytes, induced repigmentation of all piebald lesions. The mean percentage repigmentation was 95.45%.22

Piebaldism is a rare autosomal dominant disorder characterized by congenital poliosis and leukoderma. We present a case of a 10-year-old girl with a typical clinical presentation, followed by a concise review of the literature discussing the etiology, clinical features, diagnosis, and management of the condition.

Case Report
A 10-year-old girl presented for evaluation of a white forelock and multiple white patches of skin on the trunk and extremities (Figure). The white forelock was present at birth and a few white patches appeared on the chest at 3 months of age. During the subsequent 4 years, the white patches gradually progressed to involve the central forehead, abdomen, and extremities. Multiple frecklelike macules also appeared within the patches and the surrounding healthy skin.

Physical examination revealed a healthy girl with a prominent, large, diamond-shaped, depigmented patch on the central forehead that was associated with a white forelock. The hairs of the medial eyebrows and the eyelashes also were depigmented. Large, irregularly shaped, depigmented patches were present on the trunk and anterior extremities. There were multiple hyperpigmented macules overlying both the depigmented patches and the adjacent normally pigmented skin. The rest of the physical examination and the results of routine blood tests and urinalysis were unremarkable. The patient's mother and 4 siblings also were born with a white forelock. Similar depigmented patches on the trunk and extremities with a similar pattern and distribution were noted in all of them. Neither the patient nor her mother and siblings had midfacial anomalies, deafness, or heterochromia irides.

Comment
Piebaldism is a rare autosomal dominant disorder of melanocyte development resulting from mutations of the c-kit protooncogene.1,2 The disorder is characterized clinically by congenital poliosis and leukoderma. A white forelock is present at birth and may be the only manifestation in most affected individuals.3 The white forelock may have a triangular or diamond shape, and the underlying skin of the scalp also is amelanotic. Typical piebald lesions are typified by well-circumscribed, irregular, chalk white patches, often with hyperpigmented frecklelike macules noted on both depigmented and unaffected adjacent skin.4 The lesions often exhibit a classic distribution, involving the central forehead and anterior trunk, with extension to the flanks and anterior midarms, midknees, and midlegs. The medial third of the eyebrows and eyelashes also may be affected in severe cases.4 Characteristically, there is sparing of the dorsal midline, hands, feet, and periorificial areas. Piebaldism generally is a static disorder of pigmentation, though contraction of the affected areas with time or the appearance of new hyperpigmented macular lesions has been described.5 Progression of the depigmented patches has been reported in isolated cases with a novel Val620Ala mutation in Kit.6 Piebaldism rarely is associated with other disorders such as Hirschsprung disease, neurofibromatosis type 1, congenital dyserythropoietic anemia type II, Diamond-Blackfan anemia, and Grover disease.7-11 Individual case reports with associated deafness also have been described.12 Histopathologic evaluation of the depigmented lesions reveals absent or considerably reduced melanocytes. The hyperpigmented macules have a normal number of melanocytes and an increased number of melanosomes in the melanocytes and keratinocytes.4 The molecular basis of piebaldism was traced by Giebel and Spritz1 and Fleischman et al13 to mutations of the c-kit protooncogene. To date, 14 point mutations, 9 deletion mutations, 2 nucleotide splicing mutations, and 3 insertions of Kit have been described.6,14 c-kit Mutations are found in about 75% of patients with piebaldism.14 Mutations in the slug gene, which is a zinc-finger neural crest transcription factor, have been reported in piebaldism that lacked mutations in Kit.15 The human kit gene encodes the tyrosine kinase transmembrane cellular receptor for mast/stem cell growth factor, which is a critical factor for melanoblast migration, proliferation, differentiation, and survival.6 It would be pertinent to note here that the severity of the phenotype in piebaldism correlates with the site of the mutation within the kit gene. The most severe phenotypes are caused by mutations involving the intracellular tyrosine kinase domain, whereas the mildest phenotypes result from mutations involving the amino-terminal extracellular ligand-binding domain.6 The differential diagnosis of piebaldism includes any condition that may present with a depigmented lesion. Vitiligo is characterized by acquired depigmentation, typically in an acral and periorificial distribution. Piebaldism generally is distinguished from vitiligo by the presence of lesions from birth, hyperpigmented macules within and at the border of depigmented areas, and its static course. Moreover, piebaldism spares the dorsal midline, hands, feet, and periorificial areas. Waardenburg syndrome is an autosomal dominant disorder characterized by a congenital white forelock, lateral displacement of the medial canthi, a hypertrophic nasal root, heterochromia irides, and sensorineural hearing loss.16 At least 4 types of Waardenburg syndrome have been described based on the clinical and genetic criteria. The presence of hyperpigmented patches within the islands of depigmentation and on healthy skin; the absence of midfacial lesions, heterochromia irides, and deafness; and the location of depigmented patches on the trunk and extremities help to distinguish piebaldism from the various forms of Waardenburg syndrome.16 Ziprkowski-Margolis syndrome is a rare X-linked recessive syndrome characterized by deaf-mutism, heterochromic irides, piebaldlike hypomelanosis, and hyperpigmented macules, with a geographic appearance developing mainly on the trunk and extremities.17 Woolf syndrome is an autosomal recessive disorder consisting of piebaldism and deafness. Audiometry is crucial to exclude this diagnosis.18 Depending on its presentation, other conditions to consider include Addison disease, albinism, and systemic sclerosis, as well as use of depigmenting agents. Piebaldism is considered a relatively benign disorder, but it may have psychological impact because it is socially disabling, which presents a therapeutic challenge. Depigmented skin in piebaldism generally is considered unresponsive to medical or light therapy. Of note, the diagnosis of piebaldism should alert the clinician to the possibility of Waardenburg syndrome as determined by the results of ocular and auditory examinations. Sunscreens are recommended to avoid sunburns and to reduce the carcinogenic potential. To camouflage the exposed areas, makeup or temporary pigmenting agents such as the tanning product dihydroxyacetone may be used.19 The lesions of piebaldism do not respond to the topical agents used to treat vitiligo. Different surgical techniques have been tried, with variable success, including thin split-thickness grafts, minigrafting, transplant of autologous cultured melanocytes, and a combination of dermabrasion and grafting of the pigmented skin into the depigmented areas.20,21 Guerra et al22 reported achromic epidermis removed with the erbium:YAG laser and autologous cultured epidermal grafts were applied to the recipient bed in 6 patients. Autologous cultured epidermis, bearing a controlled number of melanocytes, induced repigmentation of all piebald lesions. The mean percentage repigmentation was 95.45%.22

Piebaldism is a rare autosomal dominant disorder characterized by congenital poliosis and leukoderma. We present a case of a 10-year-old girl with a typical clinical presentation, followed by a concise review of the literature discussing the etiology, clinical features, diagnosis, and management of the condition.

Case Report
A 10-year-old girl presented for evaluation of a white forelock and multiple white patches of skin on the trunk and extremities (Figure). The white forelock was present at birth and a few white patches appeared on the chest at 3 months of age. During the subsequent 4 years, the white patches gradually progressed to involve the central forehead, abdomen, and extremities. Multiple frecklelike macules also appeared within the patches and the surrounding healthy skin.

Physical examination revealed a healthy girl with a prominent, large, diamond-shaped, depigmented patch on the central forehead that was associated with a white forelock. The hairs of the medial eyebrows and the eyelashes also were depigmented. Large, irregularly shaped, depigmented patches were present on the trunk and anterior extremities. There were multiple hyperpigmented macules overlying both the depigmented patches and the adjacent normally pigmented skin. The rest of the physical examination and the results of routine blood tests and urinalysis were unremarkable. The patient's mother and 4 siblings also were born with a white forelock. Similar depigmented patches on the trunk and extremities with a similar pattern and distribution were noted in all of them. Neither the patient nor her mother and siblings had midfacial anomalies, deafness, or heterochromia irides.

Comment
Piebaldism is a rare autosomal dominant disorder of melanocyte development resulting from mutations of the c-kit protooncogene.1,2 The disorder is characterized clinically by congenital poliosis and leukoderma. A white forelock is present at birth and may be the only manifestation in most affected individuals.3 The white forelock may have a triangular or diamond shape, and the underlying skin of the scalp also is amelanotic. Typical piebald lesions are typified by well-circumscribed, irregular, chalk white patches, often with hyperpigmented frecklelike macules noted on both depigmented and unaffected adjacent skin.4 The lesions often exhibit a classic distribution, involving the central forehead and anterior trunk, with extension to the flanks and anterior midarms, midknees, and midlegs. The medial third of the eyebrows and eyelashes also may be affected in severe cases.4 Characteristically, there is sparing of the dorsal midline, hands, feet, and periorificial areas. Piebaldism generally is a static disorder of pigmentation, though contraction of the affected areas with time or the appearance of new hyperpigmented macular lesions has been described.5 Progression of the depigmented patches has been reported in isolated cases with a novel Val620Ala mutation in Kit.6 Piebaldism rarely is associated with other disorders such as Hirschsprung disease, neurofibromatosis type 1, congenital dyserythropoietic anemia type II, Diamond-Blackfan anemia, and Grover disease.7-11 Individual case reports with associated deafness also have been described.12 Histopathologic evaluation of the depigmented lesions reveals absent or considerably reduced melanocytes. The hyperpigmented macules have a normal number of melanocytes and an increased number of melanosomes in the melanocytes and keratinocytes.4 The molecular basis of piebaldism was traced by Giebel and Spritz1 and Fleischman et al13 to mutations of the c-kit protooncogene. To date, 14 point mutations, 9 deletion mutations, 2 nucleotide splicing mutations, and 3 insertions of Kit have been described.6,14 c-kit Mutations are found in about 75% of patients with piebaldism.14 Mutations in the slug gene, which is a zinc-finger neural crest transcription factor, have been reported in piebaldism that lacked mutations in Kit.15 The human kit gene encodes the tyrosine kinase transmembrane cellular receptor for mast/stem cell growth factor, which is a critical factor for melanoblast migration, proliferation, differentiation, and survival.6 It would be pertinent to note here that the severity of the phenotype in piebaldism correlates with the site of the mutation within the kit gene. The most severe phenotypes are caused by mutations involving the intracellular tyrosine kinase domain, whereas the mildest phenotypes result from mutations involving the amino-terminal extracellular ligand-binding domain.6 The differential diagnosis of piebaldism includes any condition that may present with a depigmented lesion. Vitiligo is characterized by acquired depigmentation, typically in an acral and periorificial distribution. Piebaldism generally is distinguished from vitiligo by the presence of lesions from birth, hyperpigmented macules within and at the border of depigmented areas, and its static course. Moreover, piebaldism spares the dorsal midline, hands, feet, and periorificial areas. Waardenburg syndrome is an autosomal dominant disorder characterized by a congenital white forelock, lateral displacement of the medial canthi, a hypertrophic nasal root, heterochromia irides, and sensorineural hearing loss.16 At least 4 types of Waardenburg syndrome have been described based on the clinical and genetic criteria. The presence of hyperpigmented patches within the islands of depigmentation and on healthy skin; the absence of midfacial lesions, heterochromia irides, and deafness; and the location of depigmented patches on the trunk and extremities help to distinguish piebaldism from the various forms of Waardenburg syndrome.16 Ziprkowski-Margolis syndrome is a rare X-linked recessive syndrome characterized by deaf-mutism, heterochromic irides, piebaldlike hypomelanosis, and hyperpigmented macules, with a geographic appearance developing mainly on the trunk and extremities.17 Woolf syndrome is an autosomal recessive disorder consisting of piebaldism and deafness. Audiometry is crucial to exclude this diagnosis.18 Depending on its presentation, other conditions to consider include Addison disease, albinism, and systemic sclerosis, as well as use of depigmenting agents. Piebaldism is considered a relatively benign disorder, but it may have psychological impact because it is socially disabling, which presents a therapeutic challenge. Depigmented skin in piebaldism generally is considered unresponsive to medical or light therapy. Of note, the diagnosis of piebaldism should alert the clinician to the possibility of Waardenburg syndrome as determined by the results of ocular and auditory examinations. Sunscreens are recommended to avoid sunburns and to reduce the carcinogenic potential. To camouflage the exposed areas, makeup or temporary pigmenting agents such as the tanning product dihydroxyacetone may be used.19 The lesions of piebaldism do not respond to the topical agents used to treat vitiligo. Different surgical techniques have been tried, with variable success, including thin split-thickness grafts, minigrafting, transplant of autologous cultured melanocytes, and a combination of dermabrasion and grafting of the pigmented skin into the depigmented areas.20,21 Guerra et al22 reported achromic epidermis removed with the erbium:YAG laser and autologous cultured epidermal grafts were applied to the recipient bed in 6 patients. Autologous cultured epidermis, bearing a controlled number of melanocytes, induced repigmentation of all piebald lesions. The mean percentage repigmentation was 95.45%.22

Tuberculosis verrucosa cutis (TVC) is a form of cutaneous tuberculosis that results from accidental inoculation of Mycobacterium tuberculosis in a previously infected or sensitized individual with a moderate to high degree of slowly evolving cell-mediated immunity. TVC usually begins as a solitary papulonodule following a trivial injury or trauma on one of the extremities that soon acquires a scaly and verrucous surface. The lesion, which is usually persistent, expands slowly over several months or years with or without central clearing and atrophy. We report a case of TVC in a 15-year-old girl that was undiagnosed for 10 years. The diagnosis was confirmed by a positive mycobacterial culture and characteristic histopathologic findings of the biopsy specimens. The patient responded well to antituberculous therapy (ATT), and the lesion resolved with residual scarring.

Case Report
A 15-year-old girl presented with a 10-year history of a slowly enlarging asymptomatic warty plaque over the right knee. The lesion started as a small asymptomatic red papule following a trivial injury and slowly progressed over several months to form a large warty plaque covered with a thick scale. The patient and her mother reported that the lesion also would get tender, intermittently discharging yellowish exudate. The lesion initially was treated with home remedies and later with topical steroids and oral antibiotics prescribed by local physicians, but the lesion continued expanding slowly to involve a large area of the right knee and upper leg. There was neither a family history of nor any known contacts with tuberculosis. Results of a physical examination revealed a 4X7-cm, large, well-defined, verrucous, thick, scaly, linear plaque situated over the right knee with involvement of the lower aspect of the anterior thigh and the right anterior upper aspect of the leg. Central clearing with atrophy gave the lesion a somewhat annular shape (Figure 1). Diascopy results did not show an apple jelly—brown color. Regional lymph nodes were not palpable.

The remainder of the physical examination showed unremarkable findings. A bacillus Calmette-Guérin vaccination scar could be identified on the left deltoid. Routine blood and urinalyses results were within reference range. Purified protein derivative test results were strongly positive (>15 mm of induration after 72 hours). Findings from a chest x-ray revealed no evidence of pulmonary disease. Histopathologic examination results of a biopsy specimen taken from the lesion revealed marked epidermal hyperkeratosis, acanthosis, pseudoepitheliomatous hyperplasia, and multiple well-formed tuberculous granulomas in the dermis (Figure 2). Each of the granulomas consisted of large numbers of lymphocytes, neutrophils, histiocytes, and Langhans giant cells (Figure 3). However, caseation necrosis was not present, and acid-fast bacilli could not be found. Mycobacterium tuberculosis was cultured from the biopsy specimen.

Daily oral antituberculous therapy (ATT) (rifampicin 450 mg/d, isoniazid 300 mg, and pyrazinamide 1200 mg) was recommended for 3 months (Figure 4). The patient responded well to the treatment and there was perceptible regression of the skin lesion. Treatment was continued with rifampicin 450 mg/d and isoniazid 300 mg/d for another 6 months, resulting in complete regression of the lesion with residual scarring.

Comment
Tuberculosis is a serious public health concern in developing countries due to lower socioeconomic status, malnutrition, and overcrowding; additionally, the morbidity and mortality rates of the disease are increasing rapidly in these countries. The incidence of tuberculosis also is on the rise in developed countries, including the United States and United Kingdom, both of which were previously considered free of this disease.1,2 Systemic tuberculosis was well-documented in ancient medical scriptures, but its first intelligent description, phthisis (to waste away), was given by Hippocrates (circa 460—376 BC).3 Cutaneous tuberculosis makes up only a small proportion of the cases of extrapulmonary tuberculosis. Children and immunocompromised adults are at increased risk of developing this form of the disease.3 Cutaneous tuberculosis may present in a number of diverse clinical forms (Table). The 4 major categories of cutaneous tuberculosis that have been described in the literature include: (1) inoculation from an exogenous source (ie, tuberculous chancre, tuberculosis verrucosa cutis [TVC]); (2) endogenous cutaneous spread either contiguous or by autoinoculation (ie, tuberculosis cutis orificialis, scrofuloderma); (3) hematogenous spread (ie, lupus vulgaris, acute miliary tuberculosis, tuberculosis ulcer/gumma/abscess); and (4) tuberculids (ie, erythema induratum [Bazin disease], papulonecrotic tuberculids, lichen scrofulosorum).4,5

TVC is a form of cutaneous tuberculosis that results from accidental inoculation of M tuberculosis into the skin through open wounds or abrasions in previously infected or sensitized individuals with a moderate to high degree of immunity,6 as opposed to tuberculosis chancre, which occurs in uninfected or unsensitized individuals. Individuals vaccinated with the bacillus Calmette-Guérin vaccine have been sensitized and carry a higher risk of developing TVC.7 In low socioeconomic environments, children can be infected by playing on ground contaminated with tuberculous sputum.8 Autoinoculation of a wound with a patient's own tuberculous sputum rarely causes TVC.7 The sites of predilection for inoculation tuberculosis in children are the lower extremities (ie, knees, thighs, and buttocks) because these areas are most likely to be traumatized. In adults, fingers and hands frequently are involved. The historically well-known "prosector's wart" is considered a prototype of TVC and is caused by accidental inoculation during autopsy.4 The diagnosis of TVC should be based on history and evolution of the disease, cardinal morphologic features, histopathologic characteristics, and mycobacterial culture of the biopsy specimen. The lesions of TVC typically are asymptomatic and start as small papules that slowly progress to verrucous or hyperkeratotic plaques over several months to years.9 Superficial scaling and fissuring with subsequent intermittent purulent discharge may occur. There may be central clearing with scarring and atrophy, as seen in this case. The disease usually runs a prolonged course with persistent verrucous lesions, especially if left untreated.9 Regional lymph nodes commonly are not enlarged unless there is superadded bacterial infection.10 Other organs, including the lungs, bone, and kidneys, do not appear to be affected in TVC, which differs from other forms of cutaneous tuberculosis.11 TVC is only locally invasive and usually does not cause any deformity or functional impairment of the affected extremity, but exceptions can occur.9 Differentiation from infection with atypical mycobacteria may prove to be difficult and usually requires culture of the causative organism.4,12 Other unusual infections such as North American blastomycosis, chromoblastomycosis, Majocchi granuloma, and fixed sporotrichosis may need to be differentiated from TVC by histopathology. Inflammatory dermatoses, including psoriasis, lichen simplex chronicus, hypertrophic discoid lupus erythematosus, and hypertrophic lichen planus, also may mimic TVC but are differentiated on the basis of characteristic clinical findings and histopathology.4,12 The histopathologic features of TVC include a pseudoepitheliomatous epidermal hyperplasia with hyperkeratosis and a dense dermal infiltrate of neutrophils, lymphocytes, and giant cells arranged in multiple well-formed tuberculous granulomas.13,14 Acid-fast bacilli rarely are seen and typical tuberculous foci with caseation necrosis are uncommon. Case reports in the literature indicate the usefulness of polymerase chain reaction for the detection of M tuberculosis in cutaneous tuberculosis.13,14 Polymerase chain reaction has not been found to be very helpful in the paucibacillary forms of cutaneous tuberculosis such as TVC.14 In cases for which the clinician has strong suspicion but negative laboratory test results, it might be possible to use the dramatic response to ATT as a diagnostic criterion.15,16 A study of patients with equivocal laboratory results noted 100% clinical improvement in all patients taking ATT for 20 days, and it has been proposed that response to treatment in 4 weeks can be used to support the diagnosis.11 Standard multidrug ATT is the treatment of choice and most lesions resolve after 4 to 5 months.17 An intensive phase of ATT consists of rifampicin, isoniazid, and pyrazinamide used for 2 months, with rifampicin and isoniazid continued for an additional 4 to 10 months. In cases of isoniazid resistance, ethambutol may be added to the regimen.15 The intensive-phase treatment should result in perceptible regression of the lesion, prompting the treating physician to continue the treatment through the continuation phase. Surgical excision of the isolated lesion also is useful.4 Our case of cutaneous tuberculosis remained undiagnosed for an unusually long period of 10 years. Although cutaneous tuberculosis may be regarded as a rare finding in the United States and other developed countries, it is not uncommon in countries with endemic tuberculosis. Delay in referral may lead to long-standing extensive lesions, as in this case. Physician awareness and education of early diagnosis and management of cutaneous tuberculosis are key to reducing the number of cases similar to ours. Acknowledgment—The authors wish to thank Elizabeth Davis, MFA, at the Wellman Center for Photomedicine, Boston, Massachusetts, for her editorial assistance.

Tuberculosis verrucosa cutis (TVC) is a form of cutaneous tuberculosis that results from accidental inoculation of Mycobacterium tuberculosis in a previously infected or sensitized individual with a moderate to high degree of slowly evolving cell-mediated immunity. TVC usually begins as a solitary papulonodule following a trivial injury or trauma on one of the extremities that soon acquires a scaly and verrucous surface. The lesion, which is usually persistent, expands slowly over several months or years with or without central clearing and atrophy. We report a case of TVC in a 15-year-old girl that was undiagnosed for 10 years. The diagnosis was confirmed by a positive mycobacterial culture and characteristic histopathologic findings of the biopsy specimens. The patient responded well to antituberculous therapy (ATT), and the lesion resolved with residual scarring.

Case Report
A 15-year-old girl presented with a 10-year history of a slowly enlarging asymptomatic warty plaque over the right knee. The lesion started as a small asymptomatic red papule following a trivial injury and slowly progressed over several months to form a large warty plaque covered with a thick scale. The patient and her mother reported that the lesion also would get tender, intermittently discharging yellowish exudate. The lesion initially was treated with home remedies and later with topical steroids and oral antibiotics prescribed by local physicians, but the lesion continued expanding slowly to involve a large area of the right knee and upper leg. There was neither a family history of nor any known contacts with tuberculosis. Results of a physical examination revealed a 4X7-cm, large, well-defined, verrucous, thick, scaly, linear plaque situated over the right knee with involvement of the lower aspect of the anterior thigh and the right anterior upper aspect of the leg. Central clearing with atrophy gave the lesion a somewhat annular shape (Figure 1). Diascopy results did not show an apple jelly—brown color. Regional lymph nodes were not palpable.

The remainder of the physical examination showed unremarkable findings. A bacillus Calmette-Guérin vaccination scar could be identified on the left deltoid. Routine blood and urinalyses results were within reference range. Purified protein derivative test results were strongly positive (>15 mm of induration after 72 hours). Findings from a chest x-ray revealed no evidence of pulmonary disease. Histopathologic examination results of a biopsy specimen taken from the lesion revealed marked epidermal hyperkeratosis, acanthosis, pseudoepitheliomatous hyperplasia, and multiple well-formed tuberculous granulomas in the dermis (Figure 2). Each of the granulomas consisted of large numbers of lymphocytes, neutrophils, histiocytes, and Langhans giant cells (Figure 3). However, caseation necrosis was not present, and acid-fast bacilli could not be found. Mycobacterium tuberculosis was cultured from the biopsy specimen.

Daily oral antituberculous therapy (ATT) (rifampicin 450 mg/d, isoniazid 300 mg, and pyrazinamide 1200 mg) was recommended for 3 months (Figure 4). The patient responded well to the treatment and there was perceptible regression of the skin lesion. Treatment was continued with rifampicin 450 mg/d and isoniazid 300 mg/d for another 6 months, resulting in complete regression of the lesion with residual scarring.

Comment
Tuberculosis is a serious public health concern in developing countries due to lower socioeconomic status, malnutrition, and overcrowding; additionally, the morbidity and mortality rates of the disease are increasing rapidly in these countries. The incidence of tuberculosis also is on the rise in developed countries, including the United States and United Kingdom, both of which were previously considered free of this disease.1,2 Systemic tuberculosis was well-documented in ancient medical scriptures, but its first intelligent description, phthisis (to waste away), was given by Hippocrates (circa 460—376 BC).3 Cutaneous tuberculosis makes up only a small proportion of the cases of extrapulmonary tuberculosis. Children and immunocompromised adults are at increased risk of developing this form of the disease.3 Cutaneous tuberculosis may present in a number of diverse clinical forms (Table). The 4 major categories of cutaneous tuberculosis that have been described in the literature include: (1) inoculation from an exogenous source (ie, tuberculous chancre, tuberculosis verrucosa cutis [TVC]); (2) endogenous cutaneous spread either contiguous or by autoinoculation (ie, tuberculosis cutis orificialis, scrofuloderma); (3) hematogenous spread (ie, lupus vulgaris, acute miliary tuberculosis, tuberculosis ulcer/gumma/abscess); and (4) tuberculids (ie, erythema induratum [Bazin disease], papulonecrotic tuberculids, lichen scrofulosorum).4,5

TVC is a form of cutaneous tuberculosis that results from accidental inoculation of M tuberculosis into the skin through open wounds or abrasions in previously infected or sensitized individuals with a moderate to high degree of immunity,6 as opposed to tuberculosis chancre, which occurs in uninfected or unsensitized individuals. Individuals vaccinated with the bacillus Calmette-Guérin vaccine have been sensitized and carry a higher risk of developing TVC.7 In low socioeconomic environments, children can be infected by playing on ground contaminated with tuberculous sputum.8 Autoinoculation of a wound with a patient's own tuberculous sputum rarely causes TVC.7 The sites of predilection for inoculation tuberculosis in children are the lower extremities (ie, knees, thighs, and buttocks) because these areas are most likely to be traumatized. In adults, fingers and hands frequently are involved. The historically well-known "prosector's wart" is considered a prototype of TVC and is caused by accidental inoculation during autopsy.4 The diagnosis of TVC should be based on history and evolution of the disease, cardinal morphologic features, histopathologic characteristics, and mycobacterial culture of the biopsy specimen. The lesions of TVC typically are asymptomatic and start as small papules that slowly progress to verrucous or hyperkeratotic plaques over several months to years.9 Superficial scaling and fissuring with subsequent intermittent purulent discharge may occur. There may be central clearing with scarring and atrophy, as seen in this case. The disease usually runs a prolonged course with persistent verrucous lesions, especially if left untreated.9 Regional lymph nodes commonly are not enlarged unless there is superadded bacterial infection.10 Other organs, including the lungs, bone, and kidneys, do not appear to be affected in TVC, which differs from other forms of cutaneous tuberculosis.11 TVC is only locally invasive and usually does not cause any deformity or functional impairment of the affected extremity, but exceptions can occur.9 Differentiation from infection with atypical mycobacteria may prove to be difficult and usually requires culture of the causative organism.4,12 Other unusual infections such as North American blastomycosis, chromoblastomycosis, Majocchi granuloma, and fixed sporotrichosis may need to be differentiated from TVC by histopathology. Inflammatory dermatoses, including psoriasis, lichen simplex chronicus, hypertrophic discoid lupus erythematosus, and hypertrophic lichen planus, also may mimic TVC but are differentiated on the basis of characteristic clinical findings and histopathology.4,12 The histopathologic features of TVC include a pseudoepitheliomatous epidermal hyperplasia with hyperkeratosis and a dense dermal infiltrate of neutrophils, lymphocytes, and giant cells arranged in multiple well-formed tuberculous granulomas.13,14 Acid-fast bacilli rarely are seen and typical tuberculous foci with caseation necrosis are uncommon. Case reports in the literature indicate the usefulness of polymerase chain reaction for the detection of M tuberculosis in cutaneous tuberculosis.13,14 Polymerase chain reaction has not been found to be very helpful in the paucibacillary forms of cutaneous tuberculosis such as TVC.14 In cases for which the clinician has strong suspicion but negative laboratory test results, it might be possible to use the dramatic response to ATT as a diagnostic criterion.15,16 A study of patients with equivocal laboratory results noted 100% clinical improvement in all patients taking ATT for 20 days, and it has been proposed that response to treatment in 4 weeks can be used to support the diagnosis.11 Standard multidrug ATT is the treatment of choice and most lesions resolve after 4 to 5 months.17 An intensive phase of ATT consists of rifampicin, isoniazid, and pyrazinamide used for 2 months, with rifampicin and isoniazid continued for an additional 4 to 10 months. In cases of isoniazid resistance, ethambutol may be added to the regimen.15 The intensive-phase treatment should result in perceptible regression of the lesion, prompting the treating physician to continue the treatment through the continuation phase. Surgical excision of the isolated lesion also is useful.4 Our case of cutaneous tuberculosis remained undiagnosed for an unusually long period of 10 years. Although cutaneous tuberculosis may be regarded as a rare finding in the United States and other developed countries, it is not uncommon in countries with endemic tuberculosis. Delay in referral may lead to long-standing extensive lesions, as in this case. Physician awareness and education of early diagnosis and management of cutaneous tuberculosis are key to reducing the number of cases similar to ours. Acknowledgment—The authors wish to thank Elizabeth Davis, MFA, at the Wellman Center for Photomedicine, Boston, Massachusetts, for her editorial assistance.

Tuberculosis verrucosa cutis (TVC) is a form of cutaneous tuberculosis that results from accidental inoculation of Mycobacterium tuberculosis in a previously infected or sensitized individual with a moderate to high degree of slowly evolving cell-mediated immunity. TVC usually begins as a solitary papulonodule following a trivial injury or trauma on one of the extremities that soon acquires a scaly and verrucous surface. The lesion, which is usually persistent, expands slowly over several months or years with or without central clearing and atrophy. We report a case of TVC in a 15-year-old girl that was undiagnosed for 10 years. The diagnosis was confirmed by a positive mycobacterial culture and characteristic histopathologic findings of the biopsy specimens. The patient responded well to antituberculous therapy (ATT), and the lesion resolved with residual scarring.

Case Report
A 15-year-old girl presented with a 10-year history of a slowly enlarging asymptomatic warty plaque over the right knee. The lesion started as a small asymptomatic red papule following a trivial injury and slowly progressed over several months to form a large warty plaque covered with a thick scale. The patient and her mother reported that the lesion also would get tender, intermittently discharging yellowish exudate. The lesion initially was treated with home remedies and later with topical steroids and oral antibiotics prescribed by local physicians, but the lesion continued expanding slowly to involve a large area of the right knee and upper leg. There was neither a family history of nor any known contacts with tuberculosis. Results of a physical examination revealed a 4X7-cm, large, well-defined, verrucous, thick, scaly, linear plaque situated over the right knee with involvement of the lower aspect of the anterior thigh and the right anterior upper aspect of the leg. Central clearing with atrophy gave the lesion a somewhat annular shape (Figure 1). Diascopy results did not show an apple jelly—brown color. Regional lymph nodes were not palpable.

The remainder of the physical examination showed unremarkable findings. A bacillus Calmette-Guérin vaccination scar could be identified on the left deltoid. Routine blood and urinalyses results were within reference range. Purified protein derivative test results were strongly positive (>15 mm of induration after 72 hours). Findings from a chest x-ray revealed no evidence of pulmonary disease. Histopathologic examination results of a biopsy specimen taken from the lesion revealed marked epidermal hyperkeratosis, acanthosis, pseudoepitheliomatous hyperplasia, and multiple well-formed tuberculous granulomas in the dermis (Figure 2). Each of the granulomas consisted of large numbers of lymphocytes, neutrophils, histiocytes, and Langhans giant cells (Figure 3). However, caseation necrosis was not present, and acid-fast bacilli could not be found. Mycobacterium tuberculosis was cultured from the biopsy specimen.

Daily oral antituberculous therapy (ATT) (rifampicin 450 mg/d, isoniazid 300 mg, and pyrazinamide 1200 mg) was recommended for 3 months (Figure 4). The patient responded well to the treatment and there was perceptible regression of the skin lesion. Treatment was continued with rifampicin 450 mg/d and isoniazid 300 mg/d for another 6 months, resulting in complete regression of the lesion with residual scarring.

Comment
Tuberculosis is a serious public health concern in developing countries due to lower socioeconomic status, malnutrition, and overcrowding; additionally, the morbidity and mortality rates of the disease are increasing rapidly in these countries. The incidence of tuberculosis also is on the rise in developed countries, including the United States and United Kingdom, both of which were previously considered free of this disease.1,2 Systemic tuberculosis was well-documented in ancient medical scriptures, but its first intelligent description, phthisis (to waste away), was given by Hippocrates (circa 460—376 BC).3 Cutaneous tuberculosis makes up only a small proportion of the cases of extrapulmonary tuberculosis. Children and immunocompromised adults are at increased risk of developing this form of the disease.3 Cutaneous tuberculosis may present in a number of diverse clinical forms (Table). The 4 major categories of cutaneous tuberculosis that have been described in the literature include: (1) inoculation from an exogenous source (ie, tuberculous chancre, tuberculosis verrucosa cutis [TVC]); (2) endogenous cutaneous spread either contiguous or by autoinoculation (ie, tuberculosis cutis orificialis, scrofuloderma); (3) hematogenous spread (ie, lupus vulgaris, acute miliary tuberculosis, tuberculosis ulcer/gumma/abscess); and (4) tuberculids (ie, erythema induratum [Bazin disease], papulonecrotic tuberculids, lichen scrofulosorum).4,5

TVC is a form of cutaneous tuberculosis that results from accidental inoculation of M tuberculosis into the skin through open wounds or abrasions in previously infected or sensitized individuals with a moderate to high degree of immunity,6 as opposed to tuberculosis chancre, which occurs in uninfected or unsensitized individuals. Individuals vaccinated with the bacillus Calmette-Guérin vaccine have been sensitized and carry a higher risk of developing TVC.7 In low socioeconomic environments, children can be infected by playing on ground contaminated with tuberculous sputum.8 Autoinoculation of a wound with a patient's own tuberculous sputum rarely causes TVC.7 The sites of predilection for inoculation tuberculosis in children are the lower extremities (ie, knees, thighs, and buttocks) because these areas are most likely to be traumatized. In adults, fingers and hands frequently are involved. The historically well-known "prosector's wart" is considered a prototype of TVC and is caused by accidental inoculation during autopsy.4 The diagnosis of TVC should be based on history and evolution of the disease, cardinal morphologic features, histopathologic characteristics, and mycobacterial culture of the biopsy specimen. The lesions of TVC typically are asymptomatic and start as small papules that slowly progress to verrucous or hyperkeratotic plaques over several months to years.9 Superficial scaling and fissuring with subsequent intermittent purulent discharge may occur. There may be central clearing with scarring and atrophy, as seen in this case. The disease usually runs a prolonged course with persistent verrucous lesions, especially if left untreated.9 Regional lymph nodes commonly are not enlarged unless there is superadded bacterial infection.10 Other organs, including the lungs, bone, and kidneys, do not appear to be affected in TVC, which differs from other forms of cutaneous tuberculosis.11 TVC is only locally invasive and usually does not cause any deformity or functional impairment of the affected extremity, but exceptions can occur.9 Differentiation from infection with atypical mycobacteria may prove to be difficult and usually requires culture of the causative organism.4,12 Other unusual infections such as North American blastomycosis, chromoblastomycosis, Majocchi granuloma, and fixed sporotrichosis may need to be differentiated from TVC by histopathology. Inflammatory dermatoses, including psoriasis, lichen simplex chronicus, hypertrophic discoid lupus erythematosus, and hypertrophic lichen planus, also may mimic TVC but are differentiated on the basis of characteristic clinical findings and histopathology.4,12 The histopathologic features of TVC include a pseudoepitheliomatous epidermal hyperplasia with hyperkeratosis and a dense dermal infiltrate of neutrophils, lymphocytes, and giant cells arranged in multiple well-formed tuberculous granulomas.13,14 Acid-fast bacilli rarely are seen and typical tuberculous foci with caseation necrosis are uncommon. Case reports in the literature indicate the usefulness of polymerase chain reaction for the detection of M tuberculosis in cutaneous tuberculosis.13,14 Polymerase chain reaction has not been found to be very helpful in the paucibacillary forms of cutaneous tuberculosis such as TVC.14 In cases for which the clinician has strong suspicion but negative laboratory test results, it might be possible to use the dramatic response to ATT as a diagnostic criterion.15,16 A study of patients with equivocal laboratory results noted 100% clinical improvement in all patients taking ATT for 20 days, and it has been proposed that response to treatment in 4 weeks can be used to support the diagnosis.11 Standard multidrug ATT is the treatment of choice and most lesions resolve after 4 to 5 months.17 An intensive phase of ATT consists of rifampicin, isoniazid, and pyrazinamide used for 2 months, with rifampicin and isoniazid continued for an additional 4 to 10 months. In cases of isoniazid resistance, ethambutol may be added to the regimen.15 The intensive-phase treatment should result in perceptible regression of the lesion, prompting the treating physician to continue the treatment through the continuation phase. Surgical excision of the isolated lesion also is useful.4 Our case of cutaneous tuberculosis remained undiagnosed for an unusually long period of 10 years. Although cutaneous tuberculosis may be regarded as a rare finding in the United States and other developed countries, it is not uncommon in countries with endemic tuberculosis. Delay in referral may lead to long-standing extensive lesions, as in this case. Physician awareness and education of early diagnosis and management of cutaneous tuberculosis are key to reducing the number of cases similar to ours. Acknowledgment—The authors wish to thank Elizabeth Davis, MFA, at the Wellman Center for Photomedicine, Boston, Massachusetts, for her editorial assistance.

Inflammatory linear verrucous epidermal nevus (ILVEN) is a unilateral, persistent, linear, pruritic eruption that usually appears on an extremity in infancy or childhood. We present a case of ILVEN in a 4-year-old boy and provide a short review of the literature, with emphasis on our current understanding of the etiology, clinical presentation, diagnosis, and management of ILVEN.

Case Report
A 4-year-old boy presented for evaluation of an extremely pruritic linear plaque involving his right groin and right thigh since the age of one year (Figure 1). The plaque first appeared on the right buttock (Figure 2) and slowly enlarged, extending down spirally to involve the right inguinal region and upper inner thigh. There was no family history of similar dermatoses.

Results of a physical examination revealed multiple erythematous warty scaling papules coalesced to form a linear, verrucous, hyperpigmented plaque. The plaque extended from the right buttock and inguinal region to the right upper medial thigh following the lines of Blaschko. The rest of the physical examination results were unremarkable, and no associated physical anomaly was found. The eruption and the associated pruritus did not respond to either oral antihistamines or topical high potency steroids. Results of a biopsy specimen taken from the lesion revealed hyperkeratosis, parakeratosis, acanthosis, and a decreased granular layer. A perivascular infiltrate of lymphocytes also was evident in the upper dermis. A diagnosis of inflammatory linear verrucous epidermal nevus (ILVEN) was made based on clinical and histopathologic grounds.

Comment
The condition later known as ILVEN was first described by Unna in 1896.1 However, it was not until 1971 that the disorder was described and clearly defined as a distinct entity by Altman and Mehregan2 in a case series of 25 patients. The authors clearly delineated ILVEN as a clinical and histopathologic variety of linear verrucous nevus that clinically appears inflammatory and histopathologically appears psoriasiform. The etiology of ILVEN remains unknown. It is considered a variant of keratinocytic epidermal nevus. Most cases are sporadic, but a familial case, with the condition occurring in a mother and her daughter, has been described.3 Because ILVEN bears some histologic resemblance to psoriasis, some authors believe that the 2 conditions share a common pathogenesis, possibly mediated by cytokines.4 There is some evidence that interleukins 1 and 6, tumor necrosis factor α, and intercellular adhesion molecule-1 are upregulated in ILVEN, similar to psoriasis.4 It also has been proposed that activation of an autosomal-dominant lethal mutation that survives by mosaicism may be the cause. The mutated cells might survive in the vicinity of the normal cells.5 ILVEN usually appears in infancy or early childhood but may be present at birth; the condition is very rarely present in adulthood.6 ILVEN occurs predominantly in females (female-male ratio, 4:1), and no racial predominance has been noted. About 6% of patients with epidermal nevi had ILVEN.6 ILVEN typically presents with multiple, discrete, erythematous, slightly warty and scaly papules that tend to coalesce into linear plaques. In a retrospective study of 23 patients with ILVEN, Lee and Rogers7 documented a predilection for the buttock and legs, and most cases were unilateral. Onset usually was within the first 6 months of life, most patients (16 patients) were male, and extension beyond the original margins occurred in 6 patients (26%).7 Altman and Mehregan² described 6 characteristic features of ILVEN: (1) early age of onset, (2) predominance in females (4:1 female-male ratio), (3) frequent involvement of the left leg, (4) pruritus, (5) marked refractoriness to therapy, and (6) a distinctive psoriasiform and inflammatory histologic appearance. In a few children, ILVEN has been found to occur in association with musculoskeletal or other abnormalities, including supernumerary digits and strabismus,8 congenital bony anomalies of the ipsilateral extremities,9 congenital dislocation of the ipsilateral hip and Fallot tetralogy of the heart,10 autoimmune thyroiditis,11 lichen amyloidosis,12 nevus depigmentosus,13 arthritis14 and melanodontia.15 More recently, ILVEN was associated with ipsilateral undescended testicle.16 However, this finding was disputed by Happle,17 who interpreted the case as an epidermal nevus of the epidermolytic type and stated that the ipsilateral cryptorchidism should be considered as a coincidental finding. The histopathologic presentation of ILVEN is very similar to psoriasis. Results of a histologic examination reveal psoriasiform hyperplasia of the epidermis, alternating parakeratosis without a granular layer, and orthokeratosis with a thickened granular layer.18 The authors of a recent study19 looked at advanced immunohistochemical methods to differentiate ILVEN from psoriasis. The investigators found that the number of Ki-67—positive nuclei tends to be lower, and the number of keratin-10—positive cells and HLA-DR expression tend to be higher in patients with ILVEN. The density of CD8+, CD45RO+, CD2+, CD94, and CD161 also showed a marked difference between ILVEN and psoriasis. In addition, the number of T cells relevant in the pathogenesis of psoriasis was markedly reduced in ILVEN.19 Other dermatoses that need to be differentiated from ILVEN are summarized in the Table. Nevoid psoriasis in a Blaschko distribution closely mimics ILVEN, but the former usually is asymptomatic and responds well to antipsoriatic treatment. Psoriasis also may become superimposed on an epidermal nevus because of Köbnerization.20

Epidermal nevi may occur almost anywhere on the head, neck, legs, or trunk.6 Nevus verrucosus is a term for the localized lesions of epidermal nevi.21 Linear verrucous epidermal nevi are linear hamartomas of epidermal structures that usually appear at birth or during infancy. Linear verrucous epidermal nevi usually are found on the lower extremities and have resistance to treatment and risk of recurrence. The nevi rarely are seen on the face and very rarely involve the oral mucosa.21 Clinically, there is no erythema or pruritus. Immunohistochemical studies further help differentiate ILVEN from other noninflammatory linear epidermal nevi. The CHILD syndrome (congenital hemidysplasia with ichthyosiform erythroderma and limb defects) is characterized by segmentally distributed asymptomatic erythematous verrucous areas, associated with ipsilateral extremity defects, ranging from digital hypoplasia to agenesis of the extremity.22 Hence, ILVEN reported in association with severe extremity defects is most likely CHILD syndrome.23 An alternative acronym that has been used to describe this association is PENCIL (psoriasiform epidermal nevus with congenital ipsilateral limb defects).24 Lichen striatus usually is asymptomatic and resolves spontaneously. There also are histologic differences between ILVEN and lichen striatus.25 Linear lichen planus mainly affects children and is characterized by discrete pruritic, polygonal, violaceous papules arranged in a linear fashion, usually along an entire extremity; however, the papules also may be zosteriform.26 Linear porokeratosis also usually presents during childhood as ringlike, hypertrophic, verrucous plaques with a linear morphology, usually on a single extremity, but other parts of the body also may be involved.27 More recently, Jang et al28 reported a case of mycosis fungoides, presenting with a clinical picture of ILVEN. Nevoid basal cell carcinoma (BCC) syndrome is characterized by BCCs in both sun-exposed and nonexposed skin. The diameter of the lesions varies from 1 to 10 mm and commonly involves the face, back, and chest. Features such as odontogenic cysts, palmar and plantar pitting, and facial milia may be associated. Basaloid follicular hamartoma, also known as linear unilateral basal cell nevus with comedones, may present as a unilateral linear lesion.29 In its early stages, the lesion shows hypopigmented smooth or striaelike areas, which later may develop darker-pigmented papules and tumors with or without ulceration. Of note, it may be histologically indistinguishable from the infundibulocystic type of BCC.29 The most widely applied medical treatments for ILVEN have been intralesional corticosteroids or potent topical corticosteroids, the latter often with occlusion.30 However, the clinical appearance and associated intense pruritus usually are refractory to treatment. Topical calcipotriol has been reported to provide some relief in some patients,31 but it is not recommended in children because of limited clinical safety data. A recent case report noted improvement of pruritus in ILVEN with topical pimecrolimus cream.32 Dithranol has been used with success in one case report,33 but this has been interpreted as an antipsoriatic effect in ILVEN with superimposed psoriasis.34 Other therapeutic choices reported in the literature include topical tretinoin combined with 5-fluorouracil,35 and acitretin.36 Destructive therapies, such as the application of liquid nitrogen, electrodesiccation, ablative laser and dermabrasion, have all been equally disappointing.37 Of note, case reports have shown efficacy of CO238 and pulsed dye laser treatment.39 

Conclusion
ILVEN may be an isolated finding or may be associated with other abnormalities. Most patients pre-sent in infancy or early childhood. The diagnosis may sometimes be difficult and necessitate biopsy and advanced immunohistochemical analysis. Most lesions do not persist and spontaneously resolve by adulthood.40 The management usually is only symptomatic and often unsatisfactory. 

Inflammatory linear verrucous epidermal nevus (ILVEN) is a unilateral, persistent, linear, pruritic eruption that usually appears on an extremity in infancy or childhood. We present a case of ILVEN in a 4-year-old boy and provide a short review of the literature, with emphasis on our current understanding of the etiology, clinical presentation, diagnosis, and management of ILVEN.

Case Report
A 4-year-old boy presented for evaluation of an extremely pruritic linear plaque involving his right groin and right thigh since the age of one year (Figure 1). The plaque first appeared on the right buttock (Figure 2) and slowly enlarged, extending down spirally to involve the right inguinal region and upper inner thigh. There was no family history of similar dermatoses.

Results of a physical examination revealed multiple erythematous warty scaling papules coalesced to form a linear, verrucous, hyperpigmented plaque. The plaque extended from the right buttock and inguinal region to the right upper medial thigh following the lines of Blaschko. The rest of the physical examination results were unremarkable, and no associated physical anomaly was found. The eruption and the associated pruritus did not respond to either oral antihistamines or topical high potency steroids. Results of a biopsy specimen taken from the lesion revealed hyperkeratosis, parakeratosis, acanthosis, and a decreased granular layer. A perivascular infiltrate of lymphocytes also was evident in the upper dermis. A diagnosis of inflammatory linear verrucous epidermal nevus (ILVEN) was made based on clinical and histopathologic grounds.

Comment
The condition later known as ILVEN was first described by Unna in 1896.1 However, it was not until 1971 that the disorder was described and clearly defined as a distinct entity by Altman and Mehregan2 in a case series of 25 patients. The authors clearly delineated ILVEN as a clinical and histopathologic variety of linear verrucous nevus that clinically appears inflammatory and histopathologically appears psoriasiform. The etiology of ILVEN remains unknown. It is considered a variant of keratinocytic epidermal nevus. Most cases are sporadic, but a familial case, with the condition occurring in a mother and her daughter, has been described.3 Because ILVEN bears some histologic resemblance to psoriasis, some authors believe that the 2 conditions share a common pathogenesis, possibly mediated by cytokines.4 There is some evidence that interleukins 1 and 6, tumor necrosis factor α, and intercellular adhesion molecule-1 are upregulated in ILVEN, similar to psoriasis.4 It also has been proposed that activation of an autosomal-dominant lethal mutation that survives by mosaicism may be the cause. The mutated cells might survive in the vicinity of the normal cells.5 ILVEN usually appears in infancy or early childhood but may be present at birth; the condition is very rarely present in adulthood.6 ILVEN occurs predominantly in females (female-male ratio, 4:1), and no racial predominance has been noted. About 6% of patients with epidermal nevi had ILVEN.6 ILVEN typically presents with multiple, discrete, erythematous, slightly warty and scaly papules that tend to coalesce into linear plaques. In a retrospective study of 23 patients with ILVEN, Lee and Rogers7 documented a predilection for the buttock and legs, and most cases were unilateral. Onset usually was within the first 6 months of life, most patients (16 patients) were male, and extension beyond the original margins occurred in 6 patients (26%).7 Altman and Mehregan² described 6 characteristic features of ILVEN: (1) early age of onset, (2) predominance in females (4:1 female-male ratio), (3) frequent involvement of the left leg, (4) pruritus, (5) marked refractoriness to therapy, and (6) a distinctive psoriasiform and inflammatory histologic appearance. In a few children, ILVEN has been found to occur in association with musculoskeletal or other abnormalities, including supernumerary digits and strabismus,8 congenital bony anomalies of the ipsilateral extremities,9 congenital dislocation of the ipsilateral hip and Fallot tetralogy of the heart,10 autoimmune thyroiditis,11 lichen amyloidosis,12 nevus depigmentosus,13 arthritis14 and melanodontia.15 More recently, ILVEN was associated with ipsilateral undescended testicle.16 However, this finding was disputed by Happle,17 who interpreted the case as an epidermal nevus of the epidermolytic type and stated that the ipsilateral cryptorchidism should be considered as a coincidental finding. The histopathologic presentation of ILVEN is very similar to psoriasis. Results of a histologic examination reveal psoriasiform hyperplasia of the epidermis, alternating parakeratosis without a granular layer, and orthokeratosis with a thickened granular layer.18 The authors of a recent study19 looked at advanced immunohistochemical methods to differentiate ILVEN from psoriasis. The investigators found that the number of Ki-67—positive nuclei tends to be lower, and the number of keratin-10—positive cells and HLA-DR expression tend to be higher in patients with ILVEN. The density of CD8+, CD45RO+, CD2+, CD94, and CD161 also showed a marked difference between ILVEN and psoriasis. In addition, the number of T cells relevant in the pathogenesis of psoriasis was markedly reduced in ILVEN.19 Other dermatoses that need to be differentiated from ILVEN are summarized in the Table. Nevoid psoriasis in a Blaschko distribution closely mimics ILVEN, but the former usually is asymptomatic and responds well to antipsoriatic treatment. Psoriasis also may become superimposed on an epidermal nevus because of Köbnerization.20

Epidermal nevi may occur almost anywhere on the head, neck, legs, or trunk.6 Nevus verrucosus is a term for the localized lesions of epidermal nevi.21 Linear verrucous epidermal nevi are linear hamartomas of epidermal structures that usually appear at birth or during infancy. Linear verrucous epidermal nevi usually are found on the lower extremities and have resistance to treatment and risk of recurrence. The nevi rarely are seen on the face and very rarely involve the oral mucosa.21 Clinically, there is no erythema or pruritus. Immunohistochemical studies further help differentiate ILVEN from other noninflammatory linear epidermal nevi. The CHILD syndrome (congenital hemidysplasia with ichthyosiform erythroderma and limb defects) is characterized by segmentally distributed asymptomatic erythematous verrucous areas, associated with ipsilateral extremity defects, ranging from digital hypoplasia to agenesis of the extremity.22 Hence, ILVEN reported in association with severe extremity defects is most likely CHILD syndrome.23 An alternative acronym that has been used to describe this association is PENCIL (psoriasiform epidermal nevus with congenital ipsilateral limb defects).24 Lichen striatus usually is asymptomatic and resolves spontaneously. There also are histologic differences between ILVEN and lichen striatus.25 Linear lichen planus mainly affects children and is characterized by discrete pruritic, polygonal, violaceous papules arranged in a linear fashion, usually along an entire extremity; however, the papules also may be zosteriform.26 Linear porokeratosis also usually presents during childhood as ringlike, hypertrophic, verrucous plaques with a linear morphology, usually on a single extremity, but other parts of the body also may be involved.27 More recently, Jang et al28 reported a case of mycosis fungoides, presenting with a clinical picture of ILVEN. Nevoid basal cell carcinoma (BCC) syndrome is characterized by BCCs in both sun-exposed and nonexposed skin. The diameter of the lesions varies from 1 to 10 mm and commonly involves the face, back, and chest. Features such as odontogenic cysts, palmar and plantar pitting, and facial milia may be associated. Basaloid follicular hamartoma, also known as linear unilateral basal cell nevus with comedones, may present as a unilateral linear lesion.29 In its early stages, the lesion shows hypopigmented smooth or striaelike areas, which later may develop darker-pigmented papules and tumors with or without ulceration. Of note, it may be histologically indistinguishable from the infundibulocystic type of BCC.29 The most widely applied medical treatments for ILVEN have been intralesional corticosteroids or potent topical corticosteroids, the latter often with occlusion.30 However, the clinical appearance and associated intense pruritus usually are refractory to treatment. Topical calcipotriol has been reported to provide some relief in some patients,31 but it is not recommended in children because of limited clinical safety data. A recent case report noted improvement of pruritus in ILVEN with topical pimecrolimus cream.32 Dithranol has been used with success in one case report,33 but this has been interpreted as an antipsoriatic effect in ILVEN with superimposed psoriasis.34 Other therapeutic choices reported in the literature include topical tretinoin combined with 5-fluorouracil,35 and acitretin.36 Destructive therapies, such as the application of liquid nitrogen, electrodesiccation, ablative laser and dermabrasion, have all been equally disappointing.37 Of note, case reports have shown efficacy of CO238 and pulsed dye laser treatment.39 

Conclusion
ILVEN may be an isolated finding or may be associated with other abnormalities. Most patients pre-sent in infancy or early childhood. The diagnosis may sometimes be difficult and necessitate biopsy and advanced immunohistochemical analysis. Most lesions do not persist and spontaneously resolve by adulthood.40 The management usually is only symptomatic and often unsatisfactory. 

Inflammatory linear verrucous epidermal nevus (ILVEN) is a unilateral, persistent, linear, pruritic eruption that usually appears on an extremity in infancy or childhood. We present a case of ILVEN in a 4-year-old boy and provide a short review of the literature, with emphasis on our current understanding of the etiology, clinical presentation, diagnosis, and management of ILVEN.

Case Report
A 4-year-old boy presented for evaluation of an extremely pruritic linear plaque involving his right groin and right thigh since the age of one year (Figure 1). The plaque first appeared on the right buttock (Figure 2) and slowly enlarged, extending down spirally to involve the right inguinal region and upper inner thigh. There was no family history of similar dermatoses.

Results of a physical examination revealed multiple erythematous warty scaling papules coalesced to form a linear, verrucous, hyperpigmented plaque. The plaque extended from the right buttock and inguinal region to the right upper medial thigh following the lines of Blaschko. The rest of the physical examination results were unremarkable, and no associated physical anomaly was found. The eruption and the associated pruritus did not respond to either oral antihistamines or topical high potency steroids. Results of a biopsy specimen taken from the lesion revealed hyperkeratosis, parakeratosis, acanthosis, and a decreased granular layer. A perivascular infiltrate of lymphocytes also was evident in the upper dermis. A diagnosis of inflammatory linear verrucous epidermal nevus (ILVEN) was made based on clinical and histopathologic grounds.

Comment
The condition later known as ILVEN was first described by Unna in 1896.1 However, it was not until 1971 that the disorder was described and clearly defined as a distinct entity by Altman and Mehregan2 in a case series of 25 patients. The authors clearly delineated ILVEN as a clinical and histopathologic variety of linear verrucous nevus that clinically appears inflammatory and histopathologically appears psoriasiform. The etiology of ILVEN remains unknown. It is considered a variant of keratinocytic epidermal nevus. Most cases are sporadic, but a familial case, with the condition occurring in a mother and her daughter, has been described.3 Because ILVEN bears some histologic resemblance to psoriasis, some authors believe that the 2 conditions share a common pathogenesis, possibly mediated by cytokines.4 There is some evidence that interleukins 1 and 6, tumor necrosis factor α, and intercellular adhesion molecule-1 are upregulated in ILVEN, similar to psoriasis.4 It also has been proposed that activation of an autosomal-dominant lethal mutation that survives by mosaicism may be the cause. The mutated cells might survive in the vicinity of the normal cells.5 ILVEN usually appears in infancy or early childhood but may be present at birth; the condition is very rarely present in adulthood.6 ILVEN occurs predominantly in females (female-male ratio, 4:1), and no racial predominance has been noted. About 6% of patients with epidermal nevi had ILVEN.6 ILVEN typically presents with multiple, discrete, erythematous, slightly warty and scaly papules that tend to coalesce into linear plaques. In a retrospective study of 23 patients with ILVEN, Lee and Rogers7 documented a predilection for the buttock and legs, and most cases were unilateral. Onset usually was within the first 6 months of life, most patients (16 patients) were male, and extension beyond the original margins occurred in 6 patients (26%).7 Altman and Mehregan² described 6 characteristic features of ILVEN: (1) early age of onset, (2) predominance in females (4:1 female-male ratio), (3) frequent involvement of the left leg, (4) pruritus, (5) marked refractoriness to therapy, and (6) a distinctive psoriasiform and inflammatory histologic appearance. In a few children, ILVEN has been found to occur in association with musculoskeletal or other abnormalities, including supernumerary digits and strabismus,8 congenital bony anomalies of the ipsilateral extremities,9 congenital dislocation of the ipsilateral hip and Fallot tetralogy of the heart,10 autoimmune thyroiditis,11 lichen amyloidosis,12 nevus depigmentosus,13 arthritis14 and melanodontia.15 More recently, ILVEN was associated with ipsilateral undescended testicle.16 However, this finding was disputed by Happle,17 who interpreted the case as an epidermal nevus of the epidermolytic type and stated that the ipsilateral cryptorchidism should be considered as a coincidental finding. The histopathologic presentation of ILVEN is very similar to psoriasis. Results of a histologic examination reveal psoriasiform hyperplasia of the epidermis, alternating parakeratosis without a granular layer, and orthokeratosis with a thickened granular layer.18 The authors of a recent study19 looked at advanced immunohistochemical methods to differentiate ILVEN from psoriasis. The investigators found that the number of Ki-67—positive nuclei tends to be lower, and the number of keratin-10—positive cells and HLA-DR expression tend to be higher in patients with ILVEN. The density of CD8+, CD45RO+, CD2+, CD94, and CD161 also showed a marked difference between ILVEN and psoriasis. In addition, the number of T cells relevant in the pathogenesis of psoriasis was markedly reduced in ILVEN.19 Other dermatoses that need to be differentiated from ILVEN are summarized in the Table. Nevoid psoriasis in a Blaschko distribution closely mimics ILVEN, but the former usually is asymptomatic and responds well to antipsoriatic treatment. Psoriasis also may become superimposed on an epidermal nevus because of Köbnerization.20

Epidermal nevi may occur almost anywhere on the head, neck, legs, or trunk.6 Nevus verrucosus is a term for the localized lesions of epidermal nevi.21 Linear verrucous epidermal nevi are linear hamartomas of epidermal structures that usually appear at birth or during infancy. Linear verrucous epidermal nevi usually are found on the lower extremities and have resistance to treatment and risk of recurrence. The nevi rarely are seen on the face and very rarely involve the oral mucosa.21 Clinically, there is no erythema or pruritus. Immunohistochemical studies further help differentiate ILVEN from other noninflammatory linear epidermal nevi. The CHILD syndrome (congenital hemidysplasia with ichthyosiform erythroderma and limb defects) is characterized by segmentally distributed asymptomatic erythematous verrucous areas, associated with ipsilateral extremity defects, ranging from digital hypoplasia to agenesis of the extremity.22 Hence, ILVEN reported in association with severe extremity defects is most likely CHILD syndrome.23 An alternative acronym that has been used to describe this association is PENCIL (psoriasiform epidermal nevus with congenital ipsilateral limb defects).24 Lichen striatus usually is asymptomatic and resolves spontaneously. There also are histologic differences between ILVEN and lichen striatus.25 Linear lichen planus mainly affects children and is characterized by discrete pruritic, polygonal, violaceous papules arranged in a linear fashion, usually along an entire extremity; however, the papules also may be zosteriform.26 Linear porokeratosis also usually presents during childhood as ringlike, hypertrophic, verrucous plaques with a linear morphology, usually on a single extremity, but other parts of the body also may be involved.27 More recently, Jang et al28 reported a case of mycosis fungoides, presenting with a clinical picture of ILVEN. Nevoid basal cell carcinoma (BCC) syndrome is characterized by BCCs in both sun-exposed and nonexposed skin. The diameter of the lesions varies from 1 to 10 mm and commonly involves the face, back, and chest. Features such as odontogenic cysts, palmar and plantar pitting, and facial milia may be associated. Basaloid follicular hamartoma, also known as linear unilateral basal cell nevus with comedones, may present as a unilateral linear lesion.29 In its early stages, the lesion shows hypopigmented smooth or striaelike areas, which later may develop darker-pigmented papules and tumors with or without ulceration. Of note, it may be histologically indistinguishable from the infundibulocystic type of BCC.29 The most widely applied medical treatments for ILVEN have been intralesional corticosteroids or potent topical corticosteroids, the latter often with occlusion.30 However, the clinical appearance and associated intense pruritus usually are refractory to treatment. Topical calcipotriol has been reported to provide some relief in some patients,31 but it is not recommended in children because of limited clinical safety data. A recent case report noted improvement of pruritus in ILVEN with topical pimecrolimus cream.32 Dithranol has been used with success in one case report,33 but this has been interpreted as an antipsoriatic effect in ILVEN with superimposed psoriasis.34 Other therapeutic choices reported in the literature include topical tretinoin combined with 5-fluorouracil,35 and acitretin.36 Destructive therapies, such as the application of liquid nitrogen, electrodesiccation, ablative laser and dermabrasion, have all been equally disappointing.37 Of note, case reports have shown efficacy of CO238 and pulsed dye laser treatment.39 

Conclusion
ILVEN may be an isolated finding or may be associated with other abnormalities. Most patients pre-sent in infancy or early childhood. The diagnosis may sometimes be difficult and necessitate biopsy and advanced immunohistochemical analysis. Most lesions do not persist and spontaneously resolve by adulthood.40 The management usually is only symptomatic and often unsatisfactory.