Cutis

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. 

Nocardia species are Gram-positive filamentous saprophytes that are indigenous to the soil of a large part of the United States.¹ Although the genus harbors the potential to be pathogenic in humans, infections by this genus are uncommon, especially in immunocompetent hosts. Most nocardial infections in humans result from Nocardia asteroides,^1-4 an organism often associated with multifocal lesions affecting more than one organ system via hematogenous seeding. On the other hand, infection with Nocardia brasiliensis is more likely to have cutaneous manifestations.¹ There have been a few case reports of N brasiliensis in immunocompetent patients.^1,2,5,6 We present a case of lymphocutaneous N brasiliensis infection contracted from commercially treated lumber in an immunocompetent patient. To our knowledge, this is the first reported case of cutaneous nocardiosis from commercially treated raw materials.

Case Report

An otherwise-healthy 43-year-old man presented to our medical facility complaining of pain and swelling of his left hand. One week prior to presentation, the man's left ring finger was punctured by a large splinter from pressure-treated stained lumber. At the time of his injury, the man removed the wood from his hand; he treated himself further with soap, water, and hydrogen peroxide when he returned to his home. The patient was seen 3 days later at an outside clinic for increasing pain and redness over his left ring finger. A course of oral antibiotics (500-mg cephalexin twice daily) was initiated. The digit showed no improvement despite 4 days of oral antibiotics, and the man was referred to our institution for further care.

At presentation to our facility, the patient was afebrile but had a draining 1-cm lesion over the dorsoulnar side of his left ring finger, erythema extending over the extensor surface of the forearm, and tender subcutaneous nodules with epitrochlear lymphadenopathy (Figure). His laboratory values revealed a white blood cell count of 9700/µL, an erythrocyte sedimentation rate of 15 mm/h, and a C-reactive protein level of 2.39 mg/L. Incision and drainage with local debridement revealed a thick white purulence that was sent for culture and analysis with Gram stain. The patient was admitted to the hospital and placed on intravenous antibiotics (3.375 g of piperacillin-tazobactam 4 times daily) awaiting organism identification. No organisms were seen under a Gram stain.

PLEASE REFER TO THE PDF TO VIEW THE FIGURE

Over the next 3 days, the patient had no clinical improvement in either his pain or erythema, necessitating a repeat debridement. On this debridement, we did not notice a focal recollection of purulence or necrotic tissue. We also performed further testing to investigate the potential that our patient was immunocompromised. All tests for systemic disease that would cause immune compromise revealed negative results. Four days after the patient's original debridement, cultures revealed a partially acid-fast, Gram-positive rod identified as N brasiliensis. The patient was started on oral trimethoprim-sulfamethoxazole (160-mg trimethoprim and 800-mg sulfamethoxazole), one tablet twice daily. With the initiation of this oral regimen, there was a dramatic improvement in his clinical condition, leading to discharge from the hospital 4 days later. This oral regimen was maintained for 4 months. At the patient's 8-month follow-up appointment, he demonstrated complete healing, absence of any functional deficit, and no recurrence of disease.

Comment

Bacteria of the genus Nocardia have several known pathogenic species in humans: N asteroides, N brasiliensis, Nocardia caviae, Nocardia madurae, and Nocardia otitidiscaviarium.^1,7N asteroides is the most common pathogen and accounts for 90% of nocardial infections.⁸ While other species are more prone to systemic infections, N brasiliensis most often is a cutaneous disease that may occur as a superficial cellulitis, abscess, mycetoma, or lymphocutaneous infection.^6,7 Also unlike other species, N brasiliensis is more likely to cause a primary infection than to behave as an opportunistic invader.⁶ Worldwide, N brasiliensis is a fairly common pathogen and is responsible for more than 90% of mycetomas in countries such as Mexico.⁷

Primary lymphocutaneous infection with N brasiliensis is an uncommon diagnosis in the United States. Most reported US cases are from Texas, California, and the southeastern states.¹ When N brasiliensis is isolated as the infectious organism, it is often from hand injuries in otherwise-healthy individuals.⁸ Cutaneous manifestations may be underrecognized because of their resemblance to Sporothrix infection. When treated with potassium iodide, the common treatment for Sporothrix infections, Nocardia may begin to resolve.^9,10

Cutaneous lesions caused by Nocardia form tender subcutaneous nodules that spread up the extremity in a linear fashion. These lesions also may produce sulfurlike granules similar to sporotrichosis. It is not unusual to see secondary skip-type lesions more proximal in the affected extremity.^2,3,9,11

Nocardia is relatively easy to grow in culture from cutaneous lesions, but a few idiosyncrasies should be noted. A native to soil and decaying vegetation, N brasiliensis grows easily on common culture mediums in aerobic conditions, but supplementation with 10% CO₂ may promote colony growth.⁶ The colonies themselves will develop a velvety appearance on the agar because of its aerial hyphae. These colonies start very small and may be slow growing; therefore, there is a risk of plate overgrowth by contaminant bacteria.^2,6,11 Some laboratories will discard cultures after 3 to 7 days if there is no growth, which adds to the risk of delayed diagnosis. If N brasiliensis is considered in the differential diagnosis, the laboratory should be notified because the cultures may take several weeks to grow colonies large enough for identification.² Some authors recommend keeping Nocardia cultures for 6 weeks before discarding them as negative.¹⁰ More rapid diagnosis may be made by skin biopsy and microscopic evaluation of the lesion.¹¹

There is a tendency for local recurrence of the infection, which requires a longer course of oral antibiotics.^1,6 Treatment of chronic lesions may demand up to one year of oral antibiotics. Trimethoprim-sulfamethoxazole has a high therapeutic-to-toxic ratio and synergistically inhibits folate metabolism in Nocardia, effectively killing the organism.¹N brasiliensis also has demonstrated adequate sensitivity to minocycline, providing a viable second choice of therapy.⁶

Conclusion

N brasiliensis is an uncommon infectious agent. When infection does occur, it is often misdiagnosed, which prolongs the treatment course and increases the potential for chronicity. This organism should be considered in penetrating hand injuries contaminated by soil; cutaneous infections that worsen despite surgical debridement and standard antibiotics; recurrent cutaneous infections; and infections in which sporotrichosis is a possible etiology.⁶ In suspected cases of N brasiliensis infection, clinicians should notify the laboratory to prolong the duration of incubation. When the diagnosis of N brasiliensis infection is made, a prolonged course of oral antibiotics is recommended.

Nocardia species are Gram-positive filamentous saprophytes that are indigenous to the soil of a large part of the United States.¹ Although the genus harbors the potential to be pathogenic in humans, infections by this genus are uncommon, especially in immunocompetent hosts. Most nocardial infections in humans result from Nocardia asteroides,^1-4 an organism often associated with multifocal lesions affecting more than one organ system via hematogenous seeding. On the other hand, infection with Nocardia brasiliensis is more likely to have cutaneous manifestations.¹ There have been a few case reports of N brasiliensis in immunocompetent patients.^1,2,5,6 We present a case of lymphocutaneous N brasiliensis infection contracted from commercially treated lumber in an immunocompetent patient. To our knowledge, this is the first reported case of cutaneous nocardiosis from commercially treated raw materials.

Case Report

An otherwise-healthy 43-year-old man presented to our medical facility complaining of pain and swelling of his left hand. One week prior to presentation, the man's left ring finger was punctured by a large splinter from pressure-treated stained lumber. At the time of his injury, the man removed the wood from his hand; he treated himself further with soap, water, and hydrogen peroxide when he returned to his home. The patient was seen 3 days later at an outside clinic for increasing pain and redness over his left ring finger. A course of oral antibiotics (500-mg cephalexin twice daily) was initiated. The digit showed no improvement despite 4 days of oral antibiotics, and the man was referred to our institution for further care.

At presentation to our facility, the patient was afebrile but had a draining 1-cm lesion over the dorsoulnar side of his left ring finger, erythema extending over the extensor surface of the forearm, and tender subcutaneous nodules with epitrochlear lymphadenopathy (Figure). His laboratory values revealed a white blood cell count of 9700/µL, an erythrocyte sedimentation rate of 15 mm/h, and a C-reactive protein level of 2.39 mg/L. Incision and drainage with local debridement revealed a thick white purulence that was sent for culture and analysis with Gram stain. The patient was admitted to the hospital and placed on intravenous antibiotics (3.375 g of piperacillin-tazobactam 4 times daily) awaiting organism identification. No organisms were seen under a Gram stain.

PLEASE REFER TO THE PDF TO VIEW THE FIGURE

Over the next 3 days, the patient had no clinical improvement in either his pain or erythema, necessitating a repeat debridement. On this debridement, we did not notice a focal recollection of purulence or necrotic tissue. We also performed further testing to investigate the potential that our patient was immunocompromised. All tests for systemic disease that would cause immune compromise revealed negative results. Four days after the patient's original debridement, cultures revealed a partially acid-fast, Gram-positive rod identified as N brasiliensis. The patient was started on oral trimethoprim-sulfamethoxazole (160-mg trimethoprim and 800-mg sulfamethoxazole), one tablet twice daily. With the initiation of this oral regimen, there was a dramatic improvement in his clinical condition, leading to discharge from the hospital 4 days later. This oral regimen was maintained for 4 months. At the patient's 8-month follow-up appointment, he demonstrated complete healing, absence of any functional deficit, and no recurrence of disease.

Comment

Bacteria of the genus Nocardia have several known pathogenic species in humans: N asteroides, N brasiliensis, Nocardia caviae, Nocardia madurae, and Nocardia otitidiscaviarium.^1,7N asteroides is the most common pathogen and accounts for 90% of nocardial infections.⁸ While other species are more prone to systemic infections, N brasiliensis most often is a cutaneous disease that may occur as a superficial cellulitis, abscess, mycetoma, or lymphocutaneous infection.^6,7 Also unlike other species, N brasiliensis is more likely to cause a primary infection than to behave as an opportunistic invader.⁶ Worldwide, N brasiliensis is a fairly common pathogen and is responsible for more than 90% of mycetomas in countries such as Mexico.⁷

Primary lymphocutaneous infection with N brasiliensis is an uncommon diagnosis in the United States. Most reported US cases are from Texas, California, and the southeastern states.¹ When N brasiliensis is isolated as the infectious organism, it is often from hand injuries in otherwise-healthy individuals.⁸ Cutaneous manifestations may be underrecognized because of their resemblance to Sporothrix infection. When treated with potassium iodide, the common treatment for Sporothrix infections, Nocardia may begin to resolve.^9,10

Cutaneous lesions caused by Nocardia form tender subcutaneous nodules that spread up the extremity in a linear fashion. These lesions also may produce sulfurlike granules similar to sporotrichosis. It is not unusual to see secondary skip-type lesions more proximal in the affected extremity.^2,3,9,11

Nocardia is relatively easy to grow in culture from cutaneous lesions, but a few idiosyncrasies should be noted. A native to soil and decaying vegetation, N brasiliensis grows easily on common culture mediums in aerobic conditions, but supplementation with 10% CO₂ may promote colony growth.⁶ The colonies themselves will develop a velvety appearance on the agar because of its aerial hyphae. These colonies start very small and may be slow growing; therefore, there is a risk of plate overgrowth by contaminant bacteria.^2,6,11 Some laboratories will discard cultures after 3 to 7 days if there is no growth, which adds to the risk of delayed diagnosis. If N brasiliensis is considered in the differential diagnosis, the laboratory should be notified because the cultures may take several weeks to grow colonies large enough for identification.² Some authors recommend keeping Nocardia cultures for 6 weeks before discarding them as negative.¹⁰ More rapid diagnosis may be made by skin biopsy and microscopic evaluation of the lesion.¹¹

There is a tendency for local recurrence of the infection, which requires a longer course of oral antibiotics.^1,6 Treatment of chronic lesions may demand up to one year of oral antibiotics. Trimethoprim-sulfamethoxazole has a high therapeutic-to-toxic ratio and synergistically inhibits folate metabolism in Nocardia, effectively killing the organism.¹N brasiliensis also has demonstrated adequate sensitivity to minocycline, providing a viable second choice of therapy.⁶

Conclusion

N brasiliensis is an uncommon infectious agent. When infection does occur, it is often misdiagnosed, which prolongs the treatment course and increases the potential for chronicity. This organism should be considered in penetrating hand injuries contaminated by soil; cutaneous infections that worsen despite surgical debridement and standard antibiotics; recurrent cutaneous infections; and infections in which sporotrichosis is a possible etiology.⁶ In suspected cases of N brasiliensis infection, clinicians should notify the laboratory to prolong the duration of incubation. When the diagnosis of N brasiliensis infection is made, a prolonged course of oral antibiotics is recommended.

Nocardia species are Gram-positive filamentous saprophytes that are indigenous to the soil of a large part of the United States.¹ Although the genus harbors the potential to be pathogenic in humans, infections by this genus are uncommon, especially in immunocompetent hosts. Most nocardial infections in humans result from Nocardia asteroides,^1-4 an organism often associated with multifocal lesions affecting more than one organ system via hematogenous seeding. On the other hand, infection with Nocardia brasiliensis is more likely to have cutaneous manifestations.¹ There have been a few case reports of N brasiliensis in immunocompetent patients.^1,2,5,6 We present a case of lymphocutaneous N brasiliensis infection contracted from commercially treated lumber in an immunocompetent patient. To our knowledge, this is the first reported case of cutaneous nocardiosis from commercially treated raw materials.

Case Report

An otherwise-healthy 43-year-old man presented to our medical facility complaining of pain and swelling of his left hand. One week prior to presentation, the man's left ring finger was punctured by a large splinter from pressure-treated stained lumber. At the time of his injury, the man removed the wood from his hand; he treated himself further with soap, water, and hydrogen peroxide when he returned to his home. The patient was seen 3 days later at an outside clinic for increasing pain and redness over his left ring finger. A course of oral antibiotics (500-mg cephalexin twice daily) was initiated. The digit showed no improvement despite 4 days of oral antibiotics, and the man was referred to our institution for further care.

At presentation to our facility, the patient was afebrile but had a draining 1-cm lesion over the dorsoulnar side of his left ring finger, erythema extending over the extensor surface of the forearm, and tender subcutaneous nodules with epitrochlear lymphadenopathy (Figure). His laboratory values revealed a white blood cell count of 9700/µL, an erythrocyte sedimentation rate of 15 mm/h, and a C-reactive protein level of 2.39 mg/L. Incision and drainage with local debridement revealed a thick white purulence that was sent for culture and analysis with Gram stain. The patient was admitted to the hospital and placed on intravenous antibiotics (3.375 g of piperacillin-tazobactam 4 times daily) awaiting organism identification. No organisms were seen under a Gram stain.

PLEASE REFER TO THE PDF TO VIEW THE FIGURE

Over the next 3 days, the patient had no clinical improvement in either his pain or erythema, necessitating a repeat debridement. On this debridement, we did not notice a focal recollection of purulence or necrotic tissue. We also performed further testing to investigate the potential that our patient was immunocompromised. All tests for systemic disease that would cause immune compromise revealed negative results. Four days after the patient's original debridement, cultures revealed a partially acid-fast, Gram-positive rod identified as N brasiliensis. The patient was started on oral trimethoprim-sulfamethoxazole (160-mg trimethoprim and 800-mg sulfamethoxazole), one tablet twice daily. With the initiation of this oral regimen, there was a dramatic improvement in his clinical condition, leading to discharge from the hospital 4 days later. This oral regimen was maintained for 4 months. At the patient's 8-month follow-up appointment, he demonstrated complete healing, absence of any functional deficit, and no recurrence of disease.

Comment

Bacteria of the genus Nocardia have several known pathogenic species in humans: N asteroides, N brasiliensis, Nocardia caviae, Nocardia madurae, and Nocardia otitidiscaviarium.^1,7N asteroides is the most common pathogen and accounts for 90% of nocardial infections.⁸ While other species are more prone to systemic infections, N brasiliensis most often is a cutaneous disease that may occur as a superficial cellulitis, abscess, mycetoma, or lymphocutaneous infection.^6,7 Also unlike other species, N brasiliensis is more likely to cause a primary infection than to behave as an opportunistic invader.⁶ Worldwide, N brasiliensis is a fairly common pathogen and is responsible for more than 90% of mycetomas in countries such as Mexico.⁷

Primary lymphocutaneous infection with N brasiliensis is an uncommon diagnosis in the United States. Most reported US cases are from Texas, California, and the southeastern states.¹ When N brasiliensis is isolated as the infectious organism, it is often from hand injuries in otherwise-healthy individuals.⁸ Cutaneous manifestations may be underrecognized because of their resemblance to Sporothrix infection. When treated with potassium iodide, the common treatment for Sporothrix infections, Nocardia may begin to resolve.^9,10

Cutaneous lesions caused by Nocardia form tender subcutaneous nodules that spread up the extremity in a linear fashion. These lesions also may produce sulfurlike granules similar to sporotrichosis. It is not unusual to see secondary skip-type lesions more proximal in the affected extremity.^2,3,9,11

Nocardia is relatively easy to grow in culture from cutaneous lesions, but a few idiosyncrasies should be noted. A native to soil and decaying vegetation, N brasiliensis grows easily on common culture mediums in aerobic conditions, but supplementation with 10% CO₂ may promote colony growth.⁶ The colonies themselves will develop a velvety appearance on the agar because of its aerial hyphae. These colonies start very small and may be slow growing; therefore, there is a risk of plate overgrowth by contaminant bacteria.^2,6,11 Some laboratories will discard cultures after 3 to 7 days if there is no growth, which adds to the risk of delayed diagnosis. If N brasiliensis is considered in the differential diagnosis, the laboratory should be notified because the cultures may take several weeks to grow colonies large enough for identification.² Some authors recommend keeping Nocardia cultures for 6 weeks before discarding them as negative.¹⁰ More rapid diagnosis may be made by skin biopsy and microscopic evaluation of the lesion.¹¹

There is a tendency for local recurrence of the infection, which requires a longer course of oral antibiotics.^1,6 Treatment of chronic lesions may demand up to one year of oral antibiotics. Trimethoprim-sulfamethoxazole has a high therapeutic-to-toxic ratio and synergistically inhibits folate metabolism in Nocardia, effectively killing the organism.¹N brasiliensis also has demonstrated adequate sensitivity to minocycline, providing a viable second choice of therapy.⁶

Conclusion

N brasiliensis is an uncommon infectious agent. When infection does occur, it is often misdiagnosed, which prolongs the treatment course and increases the potential for chronicity. This organism should be considered in penetrating hand injuries contaminated by soil; cutaneous infections that worsen despite surgical debridement and standard antibiotics; recurrent cutaneous infections; and infections in which sporotrichosis is a possible etiology.⁶ In suspected cases of N brasiliensis infection, clinicians should notify the laboratory to prolong the duration of incubation. When the diagnosis of N brasiliensis infection is made, a prolonged course of oral antibiotics is recommended.