Pigmentation Disorders

The Diagnosis: Livedoid Vasculopathy

Livedoid vasculopathy (LV) is a rare cutaneous disorder that most commonly affects the lower legs. It has an estimated incidence of 1 case per 100,000 per year and predominantly affects women.¹ The disease pathogenesis is not fully understood but is thought to involve thrombosis and occlusion of dermal vessels resulting in tissue hypoxia.² Both inherited and acquired thrombophilic conditions frequently are seen in patients with LV.^3,4 Livedoid vasculopathy also has been described as idiopathic⁵ and is associated with immune complex deposition.⁶ However, the number of cases of idiopathic LV may be overestimated; as technological advancements to detect coagulation abnormalities improve, it is hypothesized that this entity will be identified less often.^2,4

Livedoid vasculopathy has been described in the literature using the term PPURPLE (painful purpuric ulcers with reticular pattern of lower extremities).⁷ The triad of livedo racemosa, recurrent painful ulcerations, and residual healing with atrophie blanche characterizes the clinical manifestations of LV; however, all 3 characteristics do not need to appear simultaneously for a diagnosis to be made. The condition has a chronic course with spontaneous remissions and exacerbations. Episodic ulcerations occur, especially in the summertime, and heal slowly, leaving behind atrophic, porcelain white, stellate-shaped scars called atrophie blanche. Livedo racemosa also may be seen in Sneddon syndrome; however, these patients experience neurologic symptoms secondary to cerebrovascular occlusion. In contrast to livedo racemosa, acquired livedo reticularis represents a physiologic hypoperfusion pattern that occurs in response to cold exposure.⁸ A localized sharp pain, known as angina cutis, typically precedes the clinical symptom of painful ulcerations.⁹ Atrophie blanche once was thought to be specific to LV but has been seen in other diseases such as systemic lupus erythematosus and chronic venous insufficiency.²

The diagnosis of LV is based on identification of characteristic clinical features and skin biopsy. In almost all biopsy specimens, histopathology reveals fibrinoid occlusion of vessels in the superficial and mid dermis.⁴ Other findings may include epidermal necrosis and vessel wall hyalinization and infarction² (Figure). Because LV is commonly misdiagnosed as vasculitis, the absence of hallmark features of vasculitis such as neutrophilic infiltrate of blood vessel walls and fibrinoid necrosis suggest the diagnosis. Extensive laboratory evaluation for inherited and acquired coagulation abnormalities should be performed.

Treatment of LV is difficult, as there is currently no consensus on optimal therapy. The mainstay of therapy is to reduce pain, prevent infection, and reduce ulceration and development of atrophie blanche. Underlying causes should be identified and appropriately treated. Because the primary pathogenesis of LV is considered to be a hypercoagulable state, first-line treatment often includes therapies to enhance blood flow and prevent thrombosis such as smoking cessation, antiplatelet therapy, and pentoxifylline. Vasodilating agents, anti-inflammatory agents, anticoagulation, and fibrinolytic therapy also have been used with varying degrees of success.⁷

The Diagnosis: Livedoid Vasculopathy

Livedoid vasculopathy (LV) is a rare cutaneous disorder that most commonly affects the lower legs. It has an estimated incidence of 1 case per 100,000 per year and predominantly affects women.¹ The disease pathogenesis is not fully understood but is thought to involve thrombosis and occlusion of dermal vessels resulting in tissue hypoxia.² Both inherited and acquired thrombophilic conditions frequently are seen in patients with LV.^3,4 Livedoid vasculopathy also has been described as idiopathic⁵ and is associated with immune complex deposition.⁶ However, the number of cases of idiopathic LV may be overestimated; as technological advancements to detect coagulation abnormalities improve, it is hypothesized that this entity will be identified less often.^2,4

Livedoid vasculopathy has been described in the literature using the term PPURPLE (painful purpuric ulcers with reticular pattern of lower extremities).⁷ The triad of livedo racemosa, recurrent painful ulcerations, and residual healing with atrophie blanche characterizes the clinical manifestations of LV; however, all 3 characteristics do not need to appear simultaneously for a diagnosis to be made. The condition has a chronic course with spontaneous remissions and exacerbations. Episodic ulcerations occur, especially in the summertime, and heal slowly, leaving behind atrophic, porcelain white, stellate-shaped scars called atrophie blanche. Livedo racemosa also may be seen in Sneddon syndrome; however, these patients experience neurologic symptoms secondary to cerebrovascular occlusion. In contrast to livedo racemosa, acquired livedo reticularis represents a physiologic hypoperfusion pattern that occurs in response to cold exposure.⁸ A localized sharp pain, known as angina cutis, typically precedes the clinical symptom of painful ulcerations.⁹ Atrophie blanche once was thought to be specific to LV but has been seen in other diseases such as systemic lupus erythematosus and chronic venous insufficiency.²

The diagnosis of LV is based on identification of characteristic clinical features and skin biopsy. In almost all biopsy specimens, histopathology reveals fibrinoid occlusion of vessels in the superficial and mid dermis.⁴ Other findings may include epidermal necrosis and vessel wall hyalinization and infarction² (Figure). Because LV is commonly misdiagnosed as vasculitis, the absence of hallmark features of vasculitis such as neutrophilic infiltrate of blood vessel walls and fibrinoid necrosis suggest the diagnosis. Extensive laboratory evaluation for inherited and acquired coagulation abnormalities should be performed.

Treatment of LV is difficult, as there is currently no consensus on optimal therapy. The mainstay of therapy is to reduce pain, prevent infection, and reduce ulceration and development of atrophie blanche. Underlying causes should be identified and appropriately treated. Because the primary pathogenesis of LV is considered to be a hypercoagulable state, first-line treatment often includes therapies to enhance blood flow and prevent thrombosis such as smoking cessation, antiplatelet therapy, and pentoxifylline. Vasodilating agents, anti-inflammatory agents, anticoagulation, and fibrinolytic therapy also have been used with varying degrees of success.⁷

The Diagnosis: Livedoid Vasculopathy

Livedoid vasculopathy (LV) is a rare cutaneous disorder that most commonly affects the lower legs. It has an estimated incidence of 1 case per 100,000 per year and predominantly affects women.¹ The disease pathogenesis is not fully understood but is thought to involve thrombosis and occlusion of dermal vessels resulting in tissue hypoxia.² Both inherited and acquired thrombophilic conditions frequently are seen in patients with LV.^3,4 Livedoid vasculopathy also has been described as idiopathic⁵ and is associated with immune complex deposition.⁶ However, the number of cases of idiopathic LV may be overestimated; as technological advancements to detect coagulation abnormalities improve, it is hypothesized that this entity will be identified less often.^2,4

Livedoid vasculopathy has been described in the literature using the term PPURPLE (painful purpuric ulcers with reticular pattern of lower extremities).⁷ The triad of livedo racemosa, recurrent painful ulcerations, and residual healing with atrophie blanche characterizes the clinical manifestations of LV; however, all 3 characteristics do not need to appear simultaneously for a diagnosis to be made. The condition has a chronic course with spontaneous remissions and exacerbations. Episodic ulcerations occur, especially in the summertime, and heal slowly, leaving behind atrophic, porcelain white, stellate-shaped scars called atrophie blanche. Livedo racemosa also may be seen in Sneddon syndrome; however, these patients experience neurologic symptoms secondary to cerebrovascular occlusion. In contrast to livedo racemosa, acquired livedo reticularis represents a physiologic hypoperfusion pattern that occurs in response to cold exposure.⁸ A localized sharp pain, known as angina cutis, typically precedes the clinical symptom of painful ulcerations.⁹ Atrophie blanche once was thought to be specific to LV but has been seen in other diseases such as systemic lupus erythematosus and chronic venous insufficiency.²

The diagnosis of LV is based on identification of characteristic clinical features and skin biopsy. In almost all biopsy specimens, histopathology reveals fibrinoid occlusion of vessels in the superficial and mid dermis.⁴ Other findings may include epidermal necrosis and vessel wall hyalinization and infarction² (Figure). Because LV is commonly misdiagnosed as vasculitis, the absence of hallmark features of vasculitis such as neutrophilic infiltrate of blood vessel walls and fibrinoid necrosis suggest the diagnosis. Extensive laboratory evaluation for inherited and acquired coagulation abnormalities should be performed.

Treatment of LV is difficult, as there is currently no consensus on optimal therapy. The mainstay of therapy is to reduce pain, prevent infection, and reduce ulceration and development of atrophie blanche. Underlying causes should be identified and appropriately treated. Because the primary pathogenesis of LV is considered to be a hypercoagulable state, first-line treatment often includes therapies to enhance blood flow and prevent thrombosis such as smoking cessation, antiplatelet therapy, and pentoxifylline. Vasodilating agents, anti-inflammatory agents, anticoagulation, and fibrinolytic therapy also have been used with varying degrees of success.⁷

Case Report

A 23-year-old woman presented with a horizontal split along the midline of the right great toenail associated with some tenderness of 2 to 3 months’ duration. Approximately 5 years prior, she noticed a bluish-colored area under the nail that had been steadily increasing in size. She denied a history of trauma, drainage, or bleeding. There was no history of other nail abnormalities. Her medications and personal, family, and social history were noncontributory.

Physical examination of the right great toenail revealed a horizontal split of the nail plate with a bluish hue visible under the nail plate (Figure 1A). The remaining toenails and fingernails were normal. A punch biopsy of the nail bed was performed with a presumptive clinical diagnosis of subungual melanoma versus melanocytic nevus versus cyst (Figure 1B). Nail plate avulsion revealed a blackened nail bed dotted with areas of bluish color and a red friable nodule present focally. Upon further inspection, extension was apparent into the distal matrix.

Histopathologic examination revealed a cystic structure with an epithelial lining mostly reminiscent of an isthmus catagen cyst admixed with the presence of both an intermittent focal granular layer and an eosinophilic cuticle surrounding pink laminated keratin, most consistent with a diagnosis of subungual onycholemmal cyst (SOC)(Figure 2). A reexcision was performed with removal of half of the nail bed, including a portion of the distal matrix extending inferiorly to the bone. Variably sized, epithelium-lined, keratin-filled cystic structures emanated from the nail bed epithelium. There were foci of hemorrhage and granulation tissue secondary to cyst rupture (Figure 3). The defect healed by secondary intention. No clinical evidence of recurrence was seen at 6-month follow-up.

Subungual onycholemmal cysts, also known as subungual epidermoid cysts or subungual epidermoid inclusions, are rare and distinctive nail abnormalities occurring in the dermis of the nail bed. We present a case of an SOC in a toenail mimicking subungual malignant melanoma.

Originally described by Samman¹ in 1959, SOCs were attributed to trauma to the nail with resultant implantation of the epidermis into the deeper tissue. Lewin^2,3 examined 90 postmortem fingernail and nail bed samples and found 8 subungual epidermoid cysts associated with clubbing of the fingernails. He postulated that the early pathogenesis of clubbing involved dermal fibroblast proliferation in the nail bed, leading to sequestration of nail bed epithelium into the dermis with resultant cyst formation. Microscopic subungual cysts also were identified in normal-appearing nails without evidence of trauma, thought to have arisen from the tips of the nail bed rete ridges by a process of bulbous proliferation rather than sequestration. These findings in normal nails suggest that SOCs may represent a more common entity than previously recognized.

It is imperative to recognize the presence of nail unit tumors early because of the risk for permanent nail plate dystrophy and the possibility of a malignant tumor.^4,5 Subungual onycholemmal cysts may present with a wide spectrum of clinical findings including marked subungual hyperkeratosis, onychodystrophy, ridging, nail bed pigmentation, clubbing, thickening, or less often a normal-appearing nail. Based on reported cases, several trends are evident. Although nail dystrophy is most often asymptomatic, pain is not uncommon.^5,6 It most commonly involves single digits, predominantly thumbs and great toenails.^7,8 This predilection suggests that trauma or other local factors may be involved in its pathogenesis. Of note, trauma to the nail may occur years before the development of the lesions or it may not be recalled at all.

Diagnosis requires a degree of clinical suspicion and a nail bed biopsy with partial or total nail plate avulsion to visualize the pathologic portion of the nail bed. Because surgical intervention may lead to the implantation of epithelium, recurrences after nail biopsy or excision may occur.

In contrast to epidermal inclusion cysts arising in the skin, most SOCs do not have a granular layer.⁹ Hair and nails represent analogous differentiation products of the ectoderm. The nail matrix is homologous to portions of the hair matrix, while the nail bed epithelium is comparable to the outer root sheath of the hair follicle.⁷ Subungual onycholemmal cysts originate from the nail bed epithelium, which keratinizes in the absence of a granular layer, similar to the follicular isthmus outer root sheath. Thus, SOCs are comparable to the outer root sheath–derived isthmus-catagen cysts because of their abrupt central keratinization.⁸

Subungual onycholemmal cysts also must be distinguished from slowly growing malignant tumors of the nail bed epithelium, referred to as onycholemmal carcinomas by Alessi et al.¹⁰ This entity characteristically presents in elderly patients as a slowly growing, circumscribed, subungual discoloration that may ulcerate, destroying the nail apparatus and penetrating the phalangeal bone. On histopathology, it is characterized by small cysts filled with eosinophilic keratin devoid of a granular layer and lined by atypical squamous epithelium accompanied by solid nests and strands of atypical keratinocytes within the dermis.¹¹ When a cystic component and clear cells predominate, the designation of malignant proliferating onycholemmal cyst has been applied. Its infiltrative growth pattern with destruction of the underlying bone makes it an important entity to exclude when considering the differential diagnosis of tumors of the nail bed.

Subungual melanomas comprise only 1% to 3% of malignant melanomas and 85% are initially misdiagnosed due to their rarity and nonspecific variable presentation. Aside from clinical evidence of Hutchinson sign in the early stages in almost all cases, accurate diagnosis of subungual melanoma and differentiation from SOCs relies on histopathology. A biopsy is necessary to make the diagnosis, but even microscopic findings may be nonspecific during the early stages.

Conclusion

We report a case of a 23-year-old woman with horizontal ridging and tenderness of the right great toenail associated with pigmentation of 5 years’ duration due to an SOC. The etiology of these subungual cysts, with or without nail abnormalities, still remains unclear. Its predilection for the thumbs and great toenails suggests that trauma or other local factors may be involved in its pathogenesis. Because of the rarity of this entity, there are no guidelines for surgical treatment. Subungual onycholemmal cysts may be an underrecognized and more common entity that must be considered when discussing tumors of the nail unit.

Case Report

A 23-year-old woman presented with a horizontal split along the midline of the right great toenail associated with some tenderness of 2 to 3 months’ duration. Approximately 5 years prior, she noticed a bluish-colored area under the nail that had been steadily increasing in size. She denied a history of trauma, drainage, or bleeding. There was no history of other nail abnormalities. Her medications and personal, family, and social history were noncontributory.

Physical examination of the right great toenail revealed a horizontal split of the nail plate with a bluish hue visible under the nail plate (Figure 1A). The remaining toenails and fingernails were normal. A punch biopsy of the nail bed was performed with a presumptive clinical diagnosis of subungual melanoma versus melanocytic nevus versus cyst (Figure 1B). Nail plate avulsion revealed a blackened nail bed dotted with areas of bluish color and a red friable nodule present focally. Upon further inspection, extension was apparent into the distal matrix.

Histopathologic examination revealed a cystic structure with an epithelial lining mostly reminiscent of an isthmus catagen cyst admixed with the presence of both an intermittent focal granular layer and an eosinophilic cuticle surrounding pink laminated keratin, most consistent with a diagnosis of subungual onycholemmal cyst (SOC)(Figure 2). A reexcision was performed with removal of half of the nail bed, including a portion of the distal matrix extending inferiorly to the bone. Variably sized, epithelium-lined, keratin-filled cystic structures emanated from the nail bed epithelium. There were foci of hemorrhage and granulation tissue secondary to cyst rupture (Figure 3). The defect healed by secondary intention. No clinical evidence of recurrence was seen at 6-month follow-up.

Subungual onycholemmal cysts, also known as subungual epidermoid cysts or subungual epidermoid inclusions, are rare and distinctive nail abnormalities occurring in the dermis of the nail bed. We present a case of an SOC in a toenail mimicking subungual malignant melanoma.

Originally described by Samman¹ in 1959, SOCs were attributed to trauma to the nail with resultant implantation of the epidermis into the deeper tissue. Lewin^2,3 examined 90 postmortem fingernail and nail bed samples and found 8 subungual epidermoid cysts associated with clubbing of the fingernails. He postulated that the early pathogenesis of clubbing involved dermal fibroblast proliferation in the nail bed, leading to sequestration of nail bed epithelium into the dermis with resultant cyst formation. Microscopic subungual cysts also were identified in normal-appearing nails without evidence of trauma, thought to have arisen from the tips of the nail bed rete ridges by a process of bulbous proliferation rather than sequestration. These findings in normal nails suggest that SOCs may represent a more common entity than previously recognized.

It is imperative to recognize the presence of nail unit tumors early because of the risk for permanent nail plate dystrophy and the possibility of a malignant tumor.^4,5 Subungual onycholemmal cysts may present with a wide spectrum of clinical findings including marked subungual hyperkeratosis, onychodystrophy, ridging, nail bed pigmentation, clubbing, thickening, or less often a normal-appearing nail. Based on reported cases, several trends are evident. Although nail dystrophy is most often asymptomatic, pain is not uncommon.^5,6 It most commonly involves single digits, predominantly thumbs and great toenails.^7,8 This predilection suggests that trauma or other local factors may be involved in its pathogenesis. Of note, trauma to the nail may occur years before the development of the lesions or it may not be recalled at all.

Diagnosis requires a degree of clinical suspicion and a nail bed biopsy with partial or total nail plate avulsion to visualize the pathologic portion of the nail bed. Because surgical intervention may lead to the implantation of epithelium, recurrences after nail biopsy or excision may occur.

In contrast to epidermal inclusion cysts arising in the skin, most SOCs do not have a granular layer.⁹ Hair and nails represent analogous differentiation products of the ectoderm. The nail matrix is homologous to portions of the hair matrix, while the nail bed epithelium is comparable to the outer root sheath of the hair follicle.⁷ Subungual onycholemmal cysts originate from the nail bed epithelium, which keratinizes in the absence of a granular layer, similar to the follicular isthmus outer root sheath. Thus, SOCs are comparable to the outer root sheath–derived isthmus-catagen cysts because of their abrupt central keratinization.⁸

Subungual onycholemmal cysts also must be distinguished from slowly growing malignant tumors of the nail bed epithelium, referred to as onycholemmal carcinomas by Alessi et al.¹⁰ This entity characteristically presents in elderly patients as a slowly growing, circumscribed, subungual discoloration that may ulcerate, destroying the nail apparatus and penetrating the phalangeal bone. On histopathology, it is characterized by small cysts filled with eosinophilic keratin devoid of a granular layer and lined by atypical squamous epithelium accompanied by solid nests and strands of atypical keratinocytes within the dermis.¹¹ When a cystic component and clear cells predominate, the designation of malignant proliferating onycholemmal cyst has been applied. Its infiltrative growth pattern with destruction of the underlying bone makes it an important entity to exclude when considering the differential diagnosis of tumors of the nail bed.

Subungual melanomas comprise only 1% to 3% of malignant melanomas and 85% are initially misdiagnosed due to their rarity and nonspecific variable presentation. Aside from clinical evidence of Hutchinson sign in the early stages in almost all cases, accurate diagnosis of subungual melanoma and differentiation from SOCs relies on histopathology. A biopsy is necessary to make the diagnosis, but even microscopic findings may be nonspecific during the early stages.

Conclusion

We report a case of a 23-year-old woman with horizontal ridging and tenderness of the right great toenail associated with pigmentation of 5 years’ duration due to an SOC. The etiology of these subungual cysts, with or without nail abnormalities, still remains unclear. Its predilection for the thumbs and great toenails suggests that trauma or other local factors may be involved in its pathogenesis. Because of the rarity of this entity, there are no guidelines for surgical treatment. Subungual onycholemmal cysts may be an underrecognized and more common entity that must be considered when discussing tumors of the nail unit.

Case Report

A 23-year-old woman presented with a horizontal split along the midline of the right great toenail associated with some tenderness of 2 to 3 months’ duration. Approximately 5 years prior, she noticed a bluish-colored area under the nail that had been steadily increasing in size. She denied a history of trauma, drainage, or bleeding. There was no history of other nail abnormalities. Her medications and personal, family, and social history were noncontributory.

Physical examination of the right great toenail revealed a horizontal split of the nail plate with a bluish hue visible under the nail plate (Figure 1A). The remaining toenails and fingernails were normal. A punch biopsy of the nail bed was performed with a presumptive clinical diagnosis of subungual melanoma versus melanocytic nevus versus cyst (Figure 1B). Nail plate avulsion revealed a blackened nail bed dotted with areas of bluish color and a red friable nodule present focally. Upon further inspection, extension was apparent into the distal matrix.

Histopathologic examination revealed a cystic structure with an epithelial lining mostly reminiscent of an isthmus catagen cyst admixed with the presence of both an intermittent focal granular layer and an eosinophilic cuticle surrounding pink laminated keratin, most consistent with a diagnosis of subungual onycholemmal cyst (SOC)(Figure 2). A reexcision was performed with removal of half of the nail bed, including a portion of the distal matrix extending inferiorly to the bone. Variably sized, epithelium-lined, keratin-filled cystic structures emanated from the nail bed epithelium. There were foci of hemorrhage and granulation tissue secondary to cyst rupture (Figure 3). The defect healed by secondary intention. No clinical evidence of recurrence was seen at 6-month follow-up.

Subungual onycholemmal cysts, also known as subungual epidermoid cysts or subungual epidermoid inclusions, are rare and distinctive nail abnormalities occurring in the dermis of the nail bed. We present a case of an SOC in a toenail mimicking subungual malignant melanoma.

Originally described by Samman¹ in 1959, SOCs were attributed to trauma to the nail with resultant implantation of the epidermis into the deeper tissue. Lewin^2,3 examined 90 postmortem fingernail and nail bed samples and found 8 subungual epidermoid cysts associated with clubbing of the fingernails. He postulated that the early pathogenesis of clubbing involved dermal fibroblast proliferation in the nail bed, leading to sequestration of nail bed epithelium into the dermis with resultant cyst formation. Microscopic subungual cysts also were identified in normal-appearing nails without evidence of trauma, thought to have arisen from the tips of the nail bed rete ridges by a process of bulbous proliferation rather than sequestration. These findings in normal nails suggest that SOCs may represent a more common entity than previously recognized.

It is imperative to recognize the presence of nail unit tumors early because of the risk for permanent nail plate dystrophy and the possibility of a malignant tumor.^4,5 Subungual onycholemmal cysts may present with a wide spectrum of clinical findings including marked subungual hyperkeratosis, onychodystrophy, ridging, nail bed pigmentation, clubbing, thickening, or less often a normal-appearing nail. Based on reported cases, several trends are evident. Although nail dystrophy is most often asymptomatic, pain is not uncommon.^5,6 It most commonly involves single digits, predominantly thumbs and great toenails.^7,8 This predilection suggests that trauma or other local factors may be involved in its pathogenesis. Of note, trauma to the nail may occur years before the development of the lesions or it may not be recalled at all.

Diagnosis requires a degree of clinical suspicion and a nail bed biopsy with partial or total nail plate avulsion to visualize the pathologic portion of the nail bed. Because surgical intervention may lead to the implantation of epithelium, recurrences after nail biopsy or excision may occur.

In contrast to epidermal inclusion cysts arising in the skin, most SOCs do not have a granular layer.⁹ Hair and nails represent analogous differentiation products of the ectoderm. The nail matrix is homologous to portions of the hair matrix, while the nail bed epithelium is comparable to the outer root sheath of the hair follicle.⁷ Subungual onycholemmal cysts originate from the nail bed epithelium, which keratinizes in the absence of a granular layer, similar to the follicular isthmus outer root sheath. Thus, SOCs are comparable to the outer root sheath–derived isthmus-catagen cysts because of their abrupt central keratinization.⁸

Subungual onycholemmal cysts also must be distinguished from slowly growing malignant tumors of the nail bed epithelium, referred to as onycholemmal carcinomas by Alessi et al.¹⁰ This entity characteristically presents in elderly patients as a slowly growing, circumscribed, subungual discoloration that may ulcerate, destroying the nail apparatus and penetrating the phalangeal bone. On histopathology, it is characterized by small cysts filled with eosinophilic keratin devoid of a granular layer and lined by atypical squamous epithelium accompanied by solid nests and strands of atypical keratinocytes within the dermis.¹¹ When a cystic component and clear cells predominate, the designation of malignant proliferating onycholemmal cyst has been applied. Its infiltrative growth pattern with destruction of the underlying bone makes it an important entity to exclude when considering the differential diagnosis of tumors of the nail bed.

Subungual melanomas comprise only 1% to 3% of malignant melanomas and 85% are initially misdiagnosed due to their rarity and nonspecific variable presentation. Aside from clinical evidence of Hutchinson sign in the early stages in almost all cases, accurate diagnosis of subungual melanoma and differentiation from SOCs relies on histopathology. A biopsy is necessary to make the diagnosis, but even microscopic findings may be nonspecific during the early stages.

Conclusion

We report a case of a 23-year-old woman with horizontal ridging and tenderness of the right great toenail associated with pigmentation of 5 years’ duration due to an SOC. The etiology of these subungual cysts, with or without nail abnormalities, still remains unclear. Its predilection for the thumbs and great toenails suggests that trauma or other local factors may be involved in its pathogenesis. Because of the rarity of this entity, there are no guidelines for surgical treatment. Subungual onycholemmal cysts may be an underrecognized and more common entity that must be considered when discussing tumors of the nail unit.

Linear Basal Cell Carcinoma

On examination, the lesion was suspected to be a nevocellular nevus, foreign body granuloma, or venous lake; however, a skin biopsy specimen from the lesion on the left wrist revealed a tumor mass of basaloid cells, peripheral palisading arrangement, and scattered pigment granules (Figure 1). Tumor cells were negative for S-100 protein staining. These findings were consistent with a diagnosis of linear basal cell carcinoma (BCC). The lesion was removed by simple excision with primary closure of the wound. The surgical margins were free of tumor cells. The lesion had not recurred at 6-month follow-up. The patient was subsequently lost to follow-up.

Basal cell carcinoma presents with diverse clinical features, and several morphologic and histologic variants have been reported.¹ Linear BCC was described as a distinct clinical entity in 1985 by Lewis² in a 73-year-old man with a 20-mm linear pigmented lesion on the left cheek. Linear BCC often is not recognized or categorized as such by clinicians, as some may think that linear BCC is not a distinct entity but rather is one of the diverse clinical features of BCC.³ Linear BCC is believed to have specific clinical and histologic features and can be regarded as a distinct entity.⁴ Mavrikakis et al⁵ objectively defined linear BCC as a lesion that appeared to extend preferentially in one direction, resulting in a lesion with relatively straight borders and a length much greater than the width (3:1 ratio). Our patient presented with a linearly curved lesion, which is a rare feature of BCC.

Linear BCC occurs in equal proportions in men and women aged 40 to 87 years. More than 92% of reported patients were older than 60 years.⁶ The most common site for linear BCC is the periocular area, with the majority of lesions occurring on the cheek or lower eyelid. The second most common site is the neck, followed by the trunk, lower face, and inguinal skin fold.^3,5

The mechanism of linearity has been speculated. The majority of the reported cases of linear BCC have no history of trauma.⁷ However, focal trauma has been assumed to be a risk factor for the development of linear BCC, so the possibility that the Köbner phenomenon may be related to its linear pattern has been proposed.⁸ The Köbner phenomenon can be implicated in our case, as there was a history of surgery, which resulted in a scar.

Menzies⁹ described dermoscopic features of pigmented BCC and stated that the diagnosis of pigmented BCC required the presence of 1 or more of the following 6 positive features: large blue-gray ovoid nests; multiple blue-gray globules; maple leaf–like areas; spoke wheel areas; ulceration; and arborizing treelike vessels. In our case, there were multiple blue-gray globules and a streak that resembled ginseng (Figure 2).

Linear BCC is an uncommon morphological variant that requires clinical recognition. Our case was unique because of the ginsenglike streak on dermoscopy and possible association with a prior trauma.

Linear Basal Cell Carcinoma

On examination, the lesion was suspected to be a nevocellular nevus, foreign body granuloma, or venous lake; however, a skin biopsy specimen from the lesion on the left wrist revealed a tumor mass of basaloid cells, peripheral palisading arrangement, and scattered pigment granules (Figure 1). Tumor cells were negative for S-100 protein staining. These findings were consistent with a diagnosis of linear basal cell carcinoma (BCC). The lesion was removed by simple excision with primary closure of the wound. The surgical margins were free of tumor cells. The lesion had not recurred at 6-month follow-up. The patient was subsequently lost to follow-up.

Basal cell carcinoma presents with diverse clinical features, and several morphologic and histologic variants have been reported.¹ Linear BCC was described as a distinct clinical entity in 1985 by Lewis² in a 73-year-old man with a 20-mm linear pigmented lesion on the left cheek. Linear BCC often is not recognized or categorized as such by clinicians, as some may think that linear BCC is not a distinct entity but rather is one of the diverse clinical features of BCC.³ Linear BCC is believed to have specific clinical and histologic features and can be regarded as a distinct entity.⁴ Mavrikakis et al⁵ objectively defined linear BCC as a lesion that appeared to extend preferentially in one direction, resulting in a lesion with relatively straight borders and a length much greater than the width (3:1 ratio). Our patient presented with a linearly curved lesion, which is a rare feature of BCC.

Linear BCC occurs in equal proportions in men and women aged 40 to 87 years. More than 92% of reported patients were older than 60 years.⁶ The most common site for linear BCC is the periocular area, with the majority of lesions occurring on the cheek or lower eyelid. The second most common site is the neck, followed by the trunk, lower face, and inguinal skin fold.^3,5

The mechanism of linearity has been speculated. The majority of the reported cases of linear BCC have no history of trauma.⁷ However, focal trauma has been assumed to be a risk factor for the development of linear BCC, so the possibility that the Köbner phenomenon may be related to its linear pattern has been proposed.⁸ The Köbner phenomenon can be implicated in our case, as there was a history of surgery, which resulted in a scar.

Menzies⁹ described dermoscopic features of pigmented BCC and stated that the diagnosis of pigmented BCC required the presence of 1 or more of the following 6 positive features: large blue-gray ovoid nests; multiple blue-gray globules; maple leaf–like areas; spoke wheel areas; ulceration; and arborizing treelike vessels. In our case, there were multiple blue-gray globules and a streak that resembled ginseng (Figure 2).

Linear BCC is an uncommon morphological variant that requires clinical recognition. Our case was unique because of the ginsenglike streak on dermoscopy and possible association with a prior trauma.

Linear Basal Cell Carcinoma

On examination, the lesion was suspected to be a nevocellular nevus, foreign body granuloma, or venous lake; however, a skin biopsy specimen from the lesion on the left wrist revealed a tumor mass of basaloid cells, peripheral palisading arrangement, and scattered pigment granules (Figure 1). Tumor cells were negative for S-100 protein staining. These findings were consistent with a diagnosis of linear basal cell carcinoma (BCC). The lesion was removed by simple excision with primary closure of the wound. The surgical margins were free of tumor cells. The lesion had not recurred at 6-month follow-up. The patient was subsequently lost to follow-up.

Basal cell carcinoma presents with diverse clinical features, and several morphologic and histologic variants have been reported.¹ Linear BCC was described as a distinct clinical entity in 1985 by Lewis² in a 73-year-old man with a 20-mm linear pigmented lesion on the left cheek. Linear BCC often is not recognized or categorized as such by clinicians, as some may think that linear BCC is not a distinct entity but rather is one of the diverse clinical features of BCC.³ Linear BCC is believed to have specific clinical and histologic features and can be regarded as a distinct entity.⁴ Mavrikakis et al⁵ objectively defined linear BCC as a lesion that appeared to extend preferentially in one direction, resulting in a lesion with relatively straight borders and a length much greater than the width (3:1 ratio). Our patient presented with a linearly curved lesion, which is a rare feature of BCC.

Linear BCC occurs in equal proportions in men and women aged 40 to 87 years. More than 92% of reported patients were older than 60 years.⁶ The most common site for linear BCC is the periocular area, with the majority of lesions occurring on the cheek or lower eyelid. The second most common site is the neck, followed by the trunk, lower face, and inguinal skin fold.^3,5

The mechanism of linearity has been speculated. The majority of the reported cases of linear BCC have no history of trauma.⁷ However, focal trauma has been assumed to be a risk factor for the development of linear BCC, so the possibility that the Köbner phenomenon may be related to its linear pattern has been proposed.⁸ The Köbner phenomenon can be implicated in our case, as there was a history of surgery, which resulted in a scar.

Menzies⁹ described dermoscopic features of pigmented BCC and stated that the diagnosis of pigmented BCC required the presence of 1 or more of the following 6 positive features: large blue-gray ovoid nests; multiple blue-gray globules; maple leaf–like areas; spoke wheel areas; ulceration; and arborizing treelike vessels. In our case, there were multiple blue-gray globules and a streak that resembled ginseng (Figure 2).

Linear BCC is an uncommon morphological variant that requires clinical recognition. Our case was unique because of the ginsenglike streak on dermoscopy and possible association with a prior trauma.

Silvery hair is characteristic of 3 rare autosomal-recessive disorders—Chédiak-Higashi syndrome (CHS), Elejalde syndrome (ES), and Griscelli syndrome (GS)—which are associated with mutations in various genes that encode several proteins involved in the intracellular processing and movement of melanosomes. We report the case of a 2-month-old male infant with transient silvery hair and generalized hypopigmentation of the skin and eyes who did not have any genetic mutations associated with the classic syndromes that usually are characterized by transient silvery hair.

Case Report

A 2-month-old male infant presented to the dermatology department for evaluation of silvery hair with generalized hypopigmentation of the skin and eyes (Figure 1) that had developed at 1 month of age. His parents were healthy, nonconsanguineous, and reported no family history of silvery hair. The patient was delivered by cesarean section at 35 weeks’ gestation. His medical history was remarkable for congenital hydrops fetalis with pleuropericardial effusion, ascites, soft-tissue edema, and hydrocele with no signs of any congenital infection. Both the patient and his mother were O Rh +.

Several studies were performed following delivery. A direct Coombs test was negative. Blood studies revealed hypothyroidism and hypoalbuminemia secondary to protein loss associated with fetal hydrops. Cerebral, abdominal, and renal ultrasound; echocardiogram; thoracic and abdominal computed tomography; and cerebral magnetic resonance imaging revealed no abnormalities.

Karyotype results showed 46,XY,add(2)(p23), and subsequent spectral karyotyping and fluorescence in situ hybridization tests identified a chromosomal abnormality (46,XY,add[2][p23].ish del[2][pter][2PTEL27‒], dup[4][qter][D4S2930++])(Figure 2). Parental karyotypes were normal.

After birth, the infant was admitted to the neonatal intensive care unit for 50 days and received pleural and peritoneal drainages, mechanical ventilation, vasoactive drugs, parenteral nutrition with resolution of the hypoalbuminemia, levothyroxine, and intravenous antibiotics for central venous catheter infection. No drugs known to be associated with hypopigmentation of the hair, skin, or eyes were administered.

Two weeks after discharge from the neonatal intensive care unit, the patient was referred to our department. Physical examination revealed silvery hair on the scalp, eyebrows, and eyelashes, along with generalized hypopigmentation of the skin and eyes. Abdominal, cardiovascular, respiratory, and neurologic examination revealed no abnormalities, and no hepatosplenomegaly, lymphadenopathy, nystagmus, or strabismus was noted.

Light microscopy of the hair revealed small and regular aggregates of melanin along the hair shaft, predominantly in the medulla (Figure 3). Light microscopy of a skin biopsy specimen showed normal pigmentation in the melanocytes and no giant melanosomes. The melanocyte count was within reference range. A peripheral blood smear showed no giant granules in the granulocytes. No treatment was administered and the patient was followed closely every month. When the patient returned for follow-up at 9 months of age, physical examination revealed brown hair on the head, eyebrows, and eyelashes, as well as normal pigmentation of the skin and eyes (Figure 4). Thyroid function was normal and no recurrent infections of any type were noted. At follow-up at the age of 4 years, he showed normal neurological and psychological development with brown hair, no recurrent infections, and normal thyroid function. Given that CHS, ES, and GS had been ruled out, the clinical presentation and the genetic mutation detected may indicate that this case represents a new entity characterized by transient silvery hair.

Comment

Silvery hair is a known feature of CHS, ES, and GS (Table). The characteristic hypopigmentation associated with these autosomal-recessive disorders is the result of impaired melanosome transport leading to failed transfer of melanin to keratinocytes. These disorders differ from oculocutaneous albinism in that melanin synthesis is unaffected.

Chédiak-Higashi syndrome is characterized by generalized hypopigmentation of the skin and eyes, silvery hair, neurologic and immune dysfunction, lymphoproliferative disorders, and large granules in granulocytes and other cell types.^1-3 A common complication of CHS is hemophagocytic lymphohistiocytosis, which is characterized by fever, jaundice, lymphadenopathy, hepatosplenomegaly, and pancytopenia.⁴ Pigmentary dilution of the irises also may be present, along with photophobia, strabismus, nystagmus, and impaired visual acuity. Chédiak-Higashi syndrome is the result of a genetic defect in the lysosomal trafficking regulator gene, also known as CHS1 (located on chromosome 1q42.1‒q42.2).⁵ Melanin in the hair shaft is distributed uniformly in multiple small aggregates. Light microscopy of the skin typically shows giant melanosomes in melanocytes and aberrant keratinocyte maturation.

Elejalde syndrome is characterized by silvery hair (eyelashes and eyebrows), neurologic defects, and normal immunologic function.^6,7 The underlying molecular basis remains unknown. It appears related to or allelic to GS type 1 and thus associated with mutations in MYO5A (myosin VA); however, the gene mutation responsible has yet to be defined.⁸ Light microscopy of the hair shaft usually shows an irregular distribution of large melanin aggregates, primarily in the medulla.^9,10 Skin biopsy generally shows irregular distribution and irregular size of melanin granules in the basal layer.¹¹ Leukocytes usually show no abnormal cytoplasmic granules. Ocular involvement is common and may present as nystagmus, diplopia, hypopigmented retinas, and/or papilledema.

In GS, hair microscopy generally reveals large aggregates of melanin pigment distributed irregularly along the hair shaft. Granulocytes typically show no giant granules. Light microscopy of the skin usually shows increased pigment in melanocytes with sparse pigment in keratinocytes. Griscelli syndrome is classified into 3 types.¹² In GS type 1, patients have silvery gray hair, light-colored skin, severe neurologic defects,¹³ and normal immune status. This variant is caused by a mutation in the MYO5A gene located on chromosome 15q21. In GS type 2, patients have silvery gray hair, pyogenic infections, an accelerated phase of hemophagocytic lymphohistiocytosis, and variable neurologic defects in the absence of primary neurologic disease.^14,15 This variant is caused by a mutation in the RAB27A (member RAS oncogene family) gene located on chromosome 15q21. In GS type 3, patients exhibit generalized hypopigmentation of the skin and hair with no abnormalities of the nervous or immune systems. There are 2 different mutations associated with GS type 3: the first is located on chromosome 2q37.3, causing a mutation in MLPH (melanophilin), and the second is caused by an F-exon deletion in the MYO5A gene.¹⁴

Our patient had silvery hair, generalized hypopigmentation of the skin and eyes, and normal central nervous system function with no other ocular involvement and no evidence of recurrent infections of any kind. Light microscopy showed small and regular melanin pigment aggregates in the hair shaft, which differs from the irregular pigment aggregates in GS and ES.

The regular melanin pigment aggregates observed along the hair shaft were consistent with CHS, but other manifestations of this syndrome were absent: ocular, neurologic, hematologic, and immunologic abnormalities with presence of giant intracytoplasmic granules in leukocytes, and giant melanosomes in melanocytes. In our patient, the absence of these features along with the spontaneous repigmentation of the silvery hair, improvement of thyroid function, reversal of hypoalbuminemia, and the chromosomopathy detected make a diagnosis of CHS highly improbable.

We concluded that the silvery hair noted in our patient resulted from the 46,XY,add(2)(p23) chromosomal abnormality. This mutation could affect some of the genes that control the trafficking of melanosomes or could induce hypothyroidism and hypoproteinemia associated with congenital hydrops fetalis (Figure 5).

Hydrops fetalis is a potentially fatal condition characterized by severe edema (swelling) in a fetus or neonate. There are 2 types of hydrops fetalis: immune and nonimmune. Immune hydrops fetalis may develop in an Rh+ fetus with an Rh– mother, as the mother’s immune cells begin to break down the red blood cells of the fetus, resulting in anemia in the fetus with subsequent fetal heart failure, leading to an accumulation of large amounts of fluid in the tissues and organs. Nonimmune hydrops fetalis can occur secondary to diseases that interfere with the fetus’s ability to manage fluid (eg, severe anemia; congenital infections; urinary, lymphatic, heart, or thoracic defects; inborn errors of metabolism; chromosomal abnormalities). Case studies have suggested that congenital hypothyroidism could be a cause of nonimmune hydrops fetalis.^16,17 Thyroid hormone deficiency reduces stimulation of adrenergic receptors in the lymphatic system and lungs, thereby decreasing lymph flow and protein efflux to the lymphatic system and decreasing clearance of liquid from the lungs. The final result is lymph vessel engorgement and subsequent leakage of lymphatic fluid to pleural spaces, causing hydrops fetalis and chylothorax.

The 46,XY,add(2)(p23) chromosomal abnormality has not been commonly associated with hypothyroidism and hydrops fetalis. The silvery hair in our patient was transient and spontaneously repigmented to brown over the course of follow-up in conjunction with improved physiologic changes. We concluded that the silvery hair in our patient was induced by his hypoproteinemic status secondary to hydrops fetalis and hypothyroidism.

Conclusion

In addition to CHS, ES, and GS, the differential diagnosis for silvery hair with abnormal skin pigmentation in children should include 46,XY,add(2)(p23) mutation, as was detected in our patient. Evaluation should include light microscopy of the hair shaft, skin biopsy, assessment of immune function, peripheral blood smear, and neurologic and eye examinations.

Silvery hair is characteristic of 3 rare autosomal-recessive disorders—Chédiak-Higashi syndrome (CHS), Elejalde syndrome (ES), and Griscelli syndrome (GS)—which are associated with mutations in various genes that encode several proteins involved in the intracellular processing and movement of melanosomes. We report the case of a 2-month-old male infant with transient silvery hair and generalized hypopigmentation of the skin and eyes who did not have any genetic mutations associated with the classic syndromes that usually are characterized by transient silvery hair.

Case Report

A 2-month-old male infant presented to the dermatology department for evaluation of silvery hair with generalized hypopigmentation of the skin and eyes (Figure 1) that had developed at 1 month of age. His parents were healthy, nonconsanguineous, and reported no family history of silvery hair. The patient was delivered by cesarean section at 35 weeks’ gestation. His medical history was remarkable for congenital hydrops fetalis with pleuropericardial effusion, ascites, soft-tissue edema, and hydrocele with no signs of any congenital infection. Both the patient and his mother were O Rh +.

Several studies were performed following delivery. A direct Coombs test was negative. Blood studies revealed hypothyroidism and hypoalbuminemia secondary to protein loss associated with fetal hydrops. Cerebral, abdominal, and renal ultrasound; echocardiogram; thoracic and abdominal computed tomography; and cerebral magnetic resonance imaging revealed no abnormalities.

Karyotype results showed 46,XY,add(2)(p23), and subsequent spectral karyotyping and fluorescence in situ hybridization tests identified a chromosomal abnormality (46,XY,add[2][p23].ish del[2][pter][2PTEL27‒], dup[4][qter][D4S2930++])(Figure 2). Parental karyotypes were normal.

After birth, the infant was admitted to the neonatal intensive care unit for 50 days and received pleural and peritoneal drainages, mechanical ventilation, vasoactive drugs, parenteral nutrition with resolution of the hypoalbuminemia, levothyroxine, and intravenous antibiotics for central venous catheter infection. No drugs known to be associated with hypopigmentation of the hair, skin, or eyes were administered.

Two weeks after discharge from the neonatal intensive care unit, the patient was referred to our department. Physical examination revealed silvery hair on the scalp, eyebrows, and eyelashes, along with generalized hypopigmentation of the skin and eyes. Abdominal, cardiovascular, respiratory, and neurologic examination revealed no abnormalities, and no hepatosplenomegaly, lymphadenopathy, nystagmus, or strabismus was noted.

Light microscopy of the hair revealed small and regular aggregates of melanin along the hair shaft, predominantly in the medulla (Figure 3). Light microscopy of a skin biopsy specimen showed normal pigmentation in the melanocytes and no giant melanosomes. The melanocyte count was within reference range. A peripheral blood smear showed no giant granules in the granulocytes. No treatment was administered and the patient was followed closely every month. When the patient returned for follow-up at 9 months of age, physical examination revealed brown hair on the head, eyebrows, and eyelashes, as well as normal pigmentation of the skin and eyes (Figure 4). Thyroid function was normal and no recurrent infections of any type were noted. At follow-up at the age of 4 years, he showed normal neurological and psychological development with brown hair, no recurrent infections, and normal thyroid function. Given that CHS, ES, and GS had been ruled out, the clinical presentation and the genetic mutation detected may indicate that this case represents a new entity characterized by transient silvery hair.

Comment

Silvery hair is a known feature of CHS, ES, and GS (Table). The characteristic hypopigmentation associated with these autosomal-recessive disorders is the result of impaired melanosome transport leading to failed transfer of melanin to keratinocytes. These disorders differ from oculocutaneous albinism in that melanin synthesis is unaffected.

Chédiak-Higashi syndrome is characterized by generalized hypopigmentation of the skin and eyes, silvery hair, neurologic and immune dysfunction, lymphoproliferative disorders, and large granules in granulocytes and other cell types.^1-3 A common complication of CHS is hemophagocytic lymphohistiocytosis, which is characterized by fever, jaundice, lymphadenopathy, hepatosplenomegaly, and pancytopenia.⁴ Pigmentary dilution of the irises also may be present, along with photophobia, strabismus, nystagmus, and impaired visual acuity. Chédiak-Higashi syndrome is the result of a genetic defect in the lysosomal trafficking regulator gene, also known as CHS1 (located on chromosome 1q42.1‒q42.2).⁵ Melanin in the hair shaft is distributed uniformly in multiple small aggregates. Light microscopy of the skin typically shows giant melanosomes in melanocytes and aberrant keratinocyte maturation.

Elejalde syndrome is characterized by silvery hair (eyelashes and eyebrows), neurologic defects, and normal immunologic function.^6,7 The underlying molecular basis remains unknown. It appears related to or allelic to GS type 1 and thus associated with mutations in MYO5A (myosin VA); however, the gene mutation responsible has yet to be defined.⁸ Light microscopy of the hair shaft usually shows an irregular distribution of large melanin aggregates, primarily in the medulla.^9,10 Skin biopsy generally shows irregular distribution and irregular size of melanin granules in the basal layer.¹¹ Leukocytes usually show no abnormal cytoplasmic granules. Ocular involvement is common and may present as nystagmus, diplopia, hypopigmented retinas, and/or papilledema.

In GS, hair microscopy generally reveals large aggregates of melanin pigment distributed irregularly along the hair shaft. Granulocytes typically show no giant granules. Light microscopy of the skin usually shows increased pigment in melanocytes with sparse pigment in keratinocytes. Griscelli syndrome is classified into 3 types.¹² In GS type 1, patients have silvery gray hair, light-colored skin, severe neurologic defects,¹³ and normal immune status. This variant is caused by a mutation in the MYO5A gene located on chromosome 15q21. In GS type 2, patients have silvery gray hair, pyogenic infections, an accelerated phase of hemophagocytic lymphohistiocytosis, and variable neurologic defects in the absence of primary neurologic disease.^14,15 This variant is caused by a mutation in the RAB27A (member RAS oncogene family) gene located on chromosome 15q21. In GS type 3, patients exhibit generalized hypopigmentation of the skin and hair with no abnormalities of the nervous or immune systems. There are 2 different mutations associated with GS type 3: the first is located on chromosome 2q37.3, causing a mutation in MLPH (melanophilin), and the second is caused by an F-exon deletion in the MYO5A gene.¹⁴

Our patient had silvery hair, generalized hypopigmentation of the skin and eyes, and normal central nervous system function with no other ocular involvement and no evidence of recurrent infections of any kind. Light microscopy showed small and regular melanin pigment aggregates in the hair shaft, which differs from the irregular pigment aggregates in GS and ES.

The regular melanin pigment aggregates observed along the hair shaft were consistent with CHS, but other manifestations of this syndrome were absent: ocular, neurologic, hematologic, and immunologic abnormalities with presence of giant intracytoplasmic granules in leukocytes, and giant melanosomes in melanocytes. In our patient, the absence of these features along with the spontaneous repigmentation of the silvery hair, improvement of thyroid function, reversal of hypoalbuminemia, and the chromosomopathy detected make a diagnosis of CHS highly improbable.

We concluded that the silvery hair noted in our patient resulted from the 46,XY,add(2)(p23) chromosomal abnormality. This mutation could affect some of the genes that control the trafficking of melanosomes or could induce hypothyroidism and hypoproteinemia associated with congenital hydrops fetalis (Figure 5).

Hydrops fetalis is a potentially fatal condition characterized by severe edema (swelling) in a fetus or neonate. There are 2 types of hydrops fetalis: immune and nonimmune. Immune hydrops fetalis may develop in an Rh+ fetus with an Rh– mother, as the mother’s immune cells begin to break down the red blood cells of the fetus, resulting in anemia in the fetus with subsequent fetal heart failure, leading to an accumulation of large amounts of fluid in the tissues and organs. Nonimmune hydrops fetalis can occur secondary to diseases that interfere with the fetus’s ability to manage fluid (eg, severe anemia; congenital infections; urinary, lymphatic, heart, or thoracic defects; inborn errors of metabolism; chromosomal abnormalities). Case studies have suggested that congenital hypothyroidism could be a cause of nonimmune hydrops fetalis.^16,17 Thyroid hormone deficiency reduces stimulation of adrenergic receptors in the lymphatic system and lungs, thereby decreasing lymph flow and protein efflux to the lymphatic system and decreasing clearance of liquid from the lungs. The final result is lymph vessel engorgement and subsequent leakage of lymphatic fluid to pleural spaces, causing hydrops fetalis and chylothorax.

The 46,XY,add(2)(p23) chromosomal abnormality has not been commonly associated with hypothyroidism and hydrops fetalis. The silvery hair in our patient was transient and spontaneously repigmented to brown over the course of follow-up in conjunction with improved physiologic changes. We concluded that the silvery hair in our patient was induced by his hypoproteinemic status secondary to hydrops fetalis and hypothyroidism.

Conclusion

In addition to CHS, ES, and GS, the differential diagnosis for silvery hair with abnormal skin pigmentation in children should include 46,XY,add(2)(p23) mutation, as was detected in our patient. Evaluation should include light microscopy of the hair shaft, skin biopsy, assessment of immune function, peripheral blood smear, and neurologic and eye examinations.

Silvery hair is characteristic of 3 rare autosomal-recessive disorders—Chédiak-Higashi syndrome (CHS), Elejalde syndrome (ES), and Griscelli syndrome (GS)—which are associated with mutations in various genes that encode several proteins involved in the intracellular processing and movement of melanosomes. We report the case of a 2-month-old male infant with transient silvery hair and generalized hypopigmentation of the skin and eyes who did not have any genetic mutations associated with the classic syndromes that usually are characterized by transient silvery hair.

Case Report

A 2-month-old male infant presented to the dermatology department for evaluation of silvery hair with generalized hypopigmentation of the skin and eyes (Figure 1) that had developed at 1 month of age. His parents were healthy, nonconsanguineous, and reported no family history of silvery hair. The patient was delivered by cesarean section at 35 weeks’ gestation. His medical history was remarkable for congenital hydrops fetalis with pleuropericardial effusion, ascites, soft-tissue edema, and hydrocele with no signs of any congenital infection. Both the patient and his mother were O Rh +.

Several studies were performed following delivery. A direct Coombs test was negative. Blood studies revealed hypothyroidism and hypoalbuminemia secondary to protein loss associated with fetal hydrops. Cerebral, abdominal, and renal ultrasound; echocardiogram; thoracic and abdominal computed tomography; and cerebral magnetic resonance imaging revealed no abnormalities.

Karyotype results showed 46,XY,add(2)(p23), and subsequent spectral karyotyping and fluorescence in situ hybridization tests identified a chromosomal abnormality (46,XY,add[2][p23].ish del[2][pter][2PTEL27‒], dup[4][qter][D4S2930++])(Figure 2). Parental karyotypes were normal.

After birth, the infant was admitted to the neonatal intensive care unit for 50 days and received pleural and peritoneal drainages, mechanical ventilation, vasoactive drugs, parenteral nutrition with resolution of the hypoalbuminemia, levothyroxine, and intravenous antibiotics for central venous catheter infection. No drugs known to be associated with hypopigmentation of the hair, skin, or eyes were administered.

Two weeks after discharge from the neonatal intensive care unit, the patient was referred to our department. Physical examination revealed silvery hair on the scalp, eyebrows, and eyelashes, along with generalized hypopigmentation of the skin and eyes. Abdominal, cardiovascular, respiratory, and neurologic examination revealed no abnormalities, and no hepatosplenomegaly, lymphadenopathy, nystagmus, or strabismus was noted.

Light microscopy of the hair revealed small and regular aggregates of melanin along the hair shaft, predominantly in the medulla (Figure 3). Light microscopy of a skin biopsy specimen showed normal pigmentation in the melanocytes and no giant melanosomes. The melanocyte count was within reference range. A peripheral blood smear showed no giant granules in the granulocytes. No treatment was administered and the patient was followed closely every month. When the patient returned for follow-up at 9 months of age, physical examination revealed brown hair on the head, eyebrows, and eyelashes, as well as normal pigmentation of the skin and eyes (Figure 4). Thyroid function was normal and no recurrent infections of any type were noted. At follow-up at the age of 4 years, he showed normal neurological and psychological development with brown hair, no recurrent infections, and normal thyroid function. Given that CHS, ES, and GS had been ruled out, the clinical presentation and the genetic mutation detected may indicate that this case represents a new entity characterized by transient silvery hair.

Comment

Silvery hair is a known feature of CHS, ES, and GS (Table). The characteristic hypopigmentation associated with these autosomal-recessive disorders is the result of impaired melanosome transport leading to failed transfer of melanin to keratinocytes. These disorders differ from oculocutaneous albinism in that melanin synthesis is unaffected.

Chédiak-Higashi syndrome is characterized by generalized hypopigmentation of the skin and eyes, silvery hair, neurologic and immune dysfunction, lymphoproliferative disorders, and large granules in granulocytes and other cell types.^1-3 A common complication of CHS is hemophagocytic lymphohistiocytosis, which is characterized by fever, jaundice, lymphadenopathy, hepatosplenomegaly, and pancytopenia.⁴ Pigmentary dilution of the irises also may be present, along with photophobia, strabismus, nystagmus, and impaired visual acuity. Chédiak-Higashi syndrome is the result of a genetic defect in the lysosomal trafficking regulator gene, also known as CHS1 (located on chromosome 1q42.1‒q42.2).⁵ Melanin in the hair shaft is distributed uniformly in multiple small aggregates. Light microscopy of the skin typically shows giant melanosomes in melanocytes and aberrant keratinocyte maturation.

Elejalde syndrome is characterized by silvery hair (eyelashes and eyebrows), neurologic defects, and normal immunologic function.^6,7 The underlying molecular basis remains unknown. It appears related to or allelic to GS type 1 and thus associated with mutations in MYO5A (myosin VA); however, the gene mutation responsible has yet to be defined.⁸ Light microscopy of the hair shaft usually shows an irregular distribution of large melanin aggregates, primarily in the medulla.^9,10 Skin biopsy generally shows irregular distribution and irregular size of melanin granules in the basal layer.¹¹ Leukocytes usually show no abnormal cytoplasmic granules. Ocular involvement is common and may present as nystagmus, diplopia, hypopigmented retinas, and/or papilledema.

In GS, hair microscopy generally reveals large aggregates of melanin pigment distributed irregularly along the hair shaft. Granulocytes typically show no giant granules. Light microscopy of the skin usually shows increased pigment in melanocytes with sparse pigment in keratinocytes. Griscelli syndrome is classified into 3 types.¹² In GS type 1, patients have silvery gray hair, light-colored skin, severe neurologic defects,¹³ and normal immune status. This variant is caused by a mutation in the MYO5A gene located on chromosome 15q21. In GS type 2, patients have silvery gray hair, pyogenic infections, an accelerated phase of hemophagocytic lymphohistiocytosis, and variable neurologic defects in the absence of primary neurologic disease.^14,15 This variant is caused by a mutation in the RAB27A (member RAS oncogene family) gene located on chromosome 15q21. In GS type 3, patients exhibit generalized hypopigmentation of the skin and hair with no abnormalities of the nervous or immune systems. There are 2 different mutations associated with GS type 3: the first is located on chromosome 2q37.3, causing a mutation in MLPH (melanophilin), and the second is caused by an F-exon deletion in the MYO5A gene.¹⁴

Our patient had silvery hair, generalized hypopigmentation of the skin and eyes, and normal central nervous system function with no other ocular involvement and no evidence of recurrent infections of any kind. Light microscopy showed small and regular melanin pigment aggregates in the hair shaft, which differs from the irregular pigment aggregates in GS and ES.

The regular melanin pigment aggregates observed along the hair shaft were consistent with CHS, but other manifestations of this syndrome were absent: ocular, neurologic, hematologic, and immunologic abnormalities with presence of giant intracytoplasmic granules in leukocytes, and giant melanosomes in melanocytes. In our patient, the absence of these features along with the spontaneous repigmentation of the silvery hair, improvement of thyroid function, reversal of hypoalbuminemia, and the chromosomopathy detected make a diagnosis of CHS highly improbable.

We concluded that the silvery hair noted in our patient resulted from the 46,XY,add(2)(p23) chromosomal abnormality. This mutation could affect some of the genes that control the trafficking of melanosomes or could induce hypothyroidism and hypoproteinemia associated with congenital hydrops fetalis (Figure 5).

Hydrops fetalis is a potentially fatal condition characterized by severe edema (swelling) in a fetus or neonate. There are 2 types of hydrops fetalis: immune and nonimmune. Immune hydrops fetalis may develop in an Rh+ fetus with an Rh– mother, as the mother’s immune cells begin to break down the red blood cells of the fetus, resulting in anemia in the fetus with subsequent fetal heart failure, leading to an accumulation of large amounts of fluid in the tissues and organs. Nonimmune hydrops fetalis can occur secondary to diseases that interfere with the fetus’s ability to manage fluid (eg, severe anemia; congenital infections; urinary, lymphatic, heart, or thoracic defects; inborn errors of metabolism; chromosomal abnormalities). Case studies have suggested that congenital hypothyroidism could be a cause of nonimmune hydrops fetalis.^16,17 Thyroid hormone deficiency reduces stimulation of adrenergic receptors in the lymphatic system and lungs, thereby decreasing lymph flow and protein efflux to the lymphatic system and decreasing clearance of liquid from the lungs. The final result is lymph vessel engorgement and subsequent leakage of lymphatic fluid to pleural spaces, causing hydrops fetalis and chylothorax.

The 46,XY,add(2)(p23) chromosomal abnormality has not been commonly associated with hypothyroidism and hydrops fetalis. The silvery hair in our patient was transient and spontaneously repigmented to brown over the course of follow-up in conjunction with improved physiologic changes. We concluded that the silvery hair in our patient was induced by his hypoproteinemic status secondary to hydrops fetalis and hypothyroidism.

Conclusion

In addition to CHS, ES, and GS, the differential diagnosis for silvery hair with abnormal skin pigmentation in children should include 46,XY,add(2)(p23) mutation, as was detected in our patient. Evaluation should include light microscopy of the hair shaft, skin biopsy, assessment of immune function, peripheral blood smear, and neurologic and eye examinations.

Vitiligo is a common, asymptomatic, acquired depigmentation disorder that is caused by an unknown etiology. Lesions appear as sharply demarcated, depigmented macules and patches that are scattered symmetrically or unsymmetrically over the body. The presentation can be delineated based on the segmental or nonsegmental nature of the disease. According to the revised classification/nomenclature of vitiligo,¹ the disorder can be classified as nonsegmental, segmental, mixed, or unclassified. The pathogenesis of the vitiligo disease process is due to multiple modalities that contribute to melanocyte loss. Theories for melanocyte destruction include but are not limited to autoimmunity, biochemicals, epidermal cytokines, increased hydrogen peroxide and free radicals, and humoral and cellular immune alteration.^2,3

Despite its long history, the most frustrating aspect of the vitiligo disease process remains its treatment due to limited efficacy, frequent application of topicals, and the need for high-potency steroids. Medical therapies usually are the first line of treatment and are most effective with few side effects for bilateral nonsegmental or evolving vitiligo.² Some of the primary therapies with the highest efficacies appear to be calcipotriene and psoralen plus UVA, psoralen plus UVA as monotherapy, excimer laser, narrowband UVB, oral steroids, 8-methoxypsoralen, tacrolimus, and topical steroids.⁴ The theory is that these treatments would be successful if the patient had active melanocytes in the external root sheath that would be able to repigment a patch of vitiligo.⁵ Hence, it would be more difficult to treat areas such as the dorsal aspect of the fingers and toes because they lack hair-bearing areas with melanocytes.⁶ The alternative approach to treating vitiligo patches would be surgical intervention techniques, as they provide melanocytic cells to a previously depigmented area.^3,5 The focus of this article is to evaluate the efficacy and appropriate use of some of the surgical procedures that can be used in the treatment of vitiligo patients.

Candidate Selection

First, vitiligo patients for whom first-line treatment with medical therapies has failed are candidates for surgical techniques. The second vital component is to clinically confirm the diagnosis of vitiligo as opposed to other genetic, infectious, or autoimmune causes of pigment loss. Lastly, the vitiligo patch should be stable. A stable vitiligo patch does not continue to progress and is no longer responsive to topical medications that are meant to repigment for a discernible period of time.⁷

Classification of Disease Stage

To classify the stage of vitiligo prior to surgical intervention, Gauthier⁸ created a basic grading system: grade I, with partial depletion of epidermal melanocytes in a vitiligo patch that responds to repigmentation in a follicular pattern evenly such as on the face and neck; grade II, with complete depletion of epidermal melanocytes with a usual follicular pattern of repigmentation; and grade III, indicating complete depletion of follicular melanocytes with no hope of response to medical therapy. According to Rusfianti and Wirohadidjodjo,² the surgical techniques that have developed over the years for treatment of grade III vitiligo patients include split-thickness skin grafting, suction blister grafting, miniature punch grafting, and cultured melanocyte transplantation.

Surgical Techniques

Split-thickness skin grafting is an older procedure that entails the use of a harvesting graft site with no pigment loss and dermabrasion of the recipient area to allow interaction with the wound bed.⁹ With proper care and minimal movement or wrinkling of the graft site, patients can have repigmentation without skip areas.

Suction blister grafting is another tried and tested surgical intervention. Hasegawa et al¹⁰ conducted a study of 15 patients (13 males, 2 females; age range, 16–38 years) diagnosed with segmental vitiligo who were treated using the suction blister grafting technique with CO₂ laser resurfacing. Patients were recruited 1 month prior to initiating therapy and no other treatments were used during the month or in conjunction with the surgical intervention. Suction blisters were harvested from the left thigh and transferred in saline to the recipient site, which was abraded with 1 pass of the short-pulse CO₂ laser system. The recipient sites were then closed with 7-0 nylon sutures and covered tightly with tie-over dressings for at least 1 week. Within 6 months of the procedure, a treatment response of 100% was seen in 15 patients, making it an effective method for treatment-resistant vitiligo patients.¹⁰

Miniature punch grafting is another possible treatment option for resistant cases of vitiligo. Mapar et al¹¹ conducted a study in 25 patients (21 women, 4 men; age range, 20–47 years) who had been diagnosed with stable vitiligo (ie, no progression in the last 2 years) and were treated with single hair follicle transplant versus miniature punch grafting. The theory behind the study was to use the melanocytic reservoir noted in the normal hair follicle to repigment the vitiligo patch. With follow-up of both methods of treatment, there was no statistical difference in treatment results.¹¹ A similar study was conducted by Malakar and Lahiri¹² in patients with lip leukoderma (a variant of vitiligo). One hundred eight patients (41 males, 67 females; age range, 14–62 years) who had been diagnosed with stable lip leukoderma (ie, stable vitiligo for at least 6 months) underwent treatment via autologous miniature punch grafting. Punch biopsies were performed in donor sites of the buttocks and upper thighs with 72% of patients noting complete repigmentation. Complications noted were herpes labialis–induced lip leukoderma, which ultimately led to rejection of the graft site.¹² Overall, however, miniature punch grafting is a viable surgical option in stable vitiligo patients.

Cultured melanocyte transplantation, or a noncultured epidermal suspension, was first initiated in 1992.¹³ Silpa-Archa et al¹⁴ conducted an open, split-comparison study of 6 vitiligo patients (5 women, 1 man; age range, 20–65 years) with stable lesions. Fifty percent of patients received autologous pigmented skin cellular suspension, which was applied to vitiligo-affected skin that was treated with a fractionated CO₂ laser, and 50% received dermabrasion. Composite dressing was placed overlying the site with dressing removal in 1 week. The degree of repigmentation was based on a modified vitiligo area scoring index scale of poor (0%–25%), fair (26%–50%), good (51%–75%), very good (76%–90%), or excellent (91%–100%). Overall repigmentation was very good to excellent in all 6 patients.¹⁴ Potentially, this method can far improve the surgical treatment options for future vitiligo patients.

Final Thoughts

Overall, when evaluating surgical interventions for the treatment of vitiligo, careful consideration of the patient’s disease progression, failed therapies, outcome expectations, and repigmentation is warranted prior to initiating any procedure. For appropriate candidates, a range of surgical methodologies has proven to be effective in treatment of stable vitiligo patients.

Vitiligo is a common, asymptomatic, acquired depigmentation disorder that is caused by an unknown etiology. Lesions appear as sharply demarcated, depigmented macules and patches that are scattered symmetrically or unsymmetrically over the body. The presentation can be delineated based on the segmental or nonsegmental nature of the disease. According to the revised classification/nomenclature of vitiligo,¹ the disorder can be classified as nonsegmental, segmental, mixed, or unclassified. The pathogenesis of the vitiligo disease process is due to multiple modalities that contribute to melanocyte loss. Theories for melanocyte destruction include but are not limited to autoimmunity, biochemicals, epidermal cytokines, increased hydrogen peroxide and free radicals, and humoral and cellular immune alteration.^2,3

Despite its long history, the most frustrating aspect of the vitiligo disease process remains its treatment due to limited efficacy, frequent application of topicals, and the need for high-potency steroids. Medical therapies usually are the first line of treatment and are most effective with few side effects for bilateral nonsegmental or evolving vitiligo.² Some of the primary therapies with the highest efficacies appear to be calcipotriene and psoralen plus UVA, psoralen plus UVA as monotherapy, excimer laser, narrowband UVB, oral steroids, 8-methoxypsoralen, tacrolimus, and topical steroids.⁴ The theory is that these treatments would be successful if the patient had active melanocytes in the external root sheath that would be able to repigment a patch of vitiligo.⁵ Hence, it would be more difficult to treat areas such as the dorsal aspect of the fingers and toes because they lack hair-bearing areas with melanocytes.⁶ The alternative approach to treating vitiligo patches would be surgical intervention techniques, as they provide melanocytic cells to a previously depigmented area.^3,5 The focus of this article is to evaluate the efficacy and appropriate use of some of the surgical procedures that can be used in the treatment of vitiligo patients.

Candidate Selection

First, vitiligo patients for whom first-line treatment with medical therapies has failed are candidates for surgical techniques. The second vital component is to clinically confirm the diagnosis of vitiligo as opposed to other genetic, infectious, or autoimmune causes of pigment loss. Lastly, the vitiligo patch should be stable. A stable vitiligo patch does not continue to progress and is no longer responsive to topical medications that are meant to repigment for a discernible period of time.⁷

Classification of Disease Stage

To classify the stage of vitiligo prior to surgical intervention, Gauthier⁸ created a basic grading system: grade I, with partial depletion of epidermal melanocytes in a vitiligo patch that responds to repigmentation in a follicular pattern evenly such as on the face and neck; grade II, with complete depletion of epidermal melanocytes with a usual follicular pattern of repigmentation; and grade III, indicating complete depletion of follicular melanocytes with no hope of response to medical therapy. According to Rusfianti and Wirohadidjodjo,² the surgical techniques that have developed over the years for treatment of grade III vitiligo patients include split-thickness skin grafting, suction blister grafting, miniature punch grafting, and cultured melanocyte transplantation.

Surgical Techniques

Split-thickness skin grafting is an older procedure that entails the use of a harvesting graft site with no pigment loss and dermabrasion of the recipient area to allow interaction with the wound bed.⁹ With proper care and minimal movement or wrinkling of the graft site, patients can have repigmentation without skip areas.

Suction blister grafting is another tried and tested surgical intervention. Hasegawa et al¹⁰ conducted a study of 15 patients (13 males, 2 females; age range, 16–38 years) diagnosed with segmental vitiligo who were treated using the suction blister grafting technique with CO₂ laser resurfacing. Patients were recruited 1 month prior to initiating therapy and no other treatments were used during the month or in conjunction with the surgical intervention. Suction blisters were harvested from the left thigh and transferred in saline to the recipient site, which was abraded with 1 pass of the short-pulse CO₂ laser system. The recipient sites were then closed with 7-0 nylon sutures and covered tightly with tie-over dressings for at least 1 week. Within 6 months of the procedure, a treatment response of 100% was seen in 15 patients, making it an effective method for treatment-resistant vitiligo patients.¹⁰

Miniature punch grafting is another possible treatment option for resistant cases of vitiligo. Mapar et al¹¹ conducted a study in 25 patients (21 women, 4 men; age range, 20–47 years) who had been diagnosed with stable vitiligo (ie, no progression in the last 2 years) and were treated with single hair follicle transplant versus miniature punch grafting. The theory behind the study was to use the melanocytic reservoir noted in the normal hair follicle to repigment the vitiligo patch. With follow-up of both methods of treatment, there was no statistical difference in treatment results.¹¹ A similar study was conducted by Malakar and Lahiri¹² in patients with lip leukoderma (a variant of vitiligo). One hundred eight patients (41 males, 67 females; age range, 14–62 years) who had been diagnosed with stable lip leukoderma (ie, stable vitiligo for at least 6 months) underwent treatment via autologous miniature punch grafting. Punch biopsies were performed in donor sites of the buttocks and upper thighs with 72% of patients noting complete repigmentation. Complications noted were herpes labialis–induced lip leukoderma, which ultimately led to rejection of the graft site.¹² Overall, however, miniature punch grafting is a viable surgical option in stable vitiligo patients.

Cultured melanocyte transplantation, or a noncultured epidermal suspension, was first initiated in 1992.¹³ Silpa-Archa et al¹⁴ conducted an open, split-comparison study of 6 vitiligo patients (5 women, 1 man; age range, 20–65 years) with stable lesions. Fifty percent of patients received autologous pigmented skin cellular suspension, which was applied to vitiligo-affected skin that was treated with a fractionated CO₂ laser, and 50% received dermabrasion. Composite dressing was placed overlying the site with dressing removal in 1 week. The degree of repigmentation was based on a modified vitiligo area scoring index scale of poor (0%–25%), fair (26%–50%), good (51%–75%), very good (76%–90%), or excellent (91%–100%). Overall repigmentation was very good to excellent in all 6 patients.¹⁴ Potentially, this method can far improve the surgical treatment options for future vitiligo patients.

Final Thoughts

Overall, when evaluating surgical interventions for the treatment of vitiligo, careful consideration of the patient’s disease progression, failed therapies, outcome expectations, and repigmentation is warranted prior to initiating any procedure. For appropriate candidates, a range of surgical methodologies has proven to be effective in treatment of stable vitiligo patients.

Vitiligo is a common, asymptomatic, acquired depigmentation disorder that is caused by an unknown etiology. Lesions appear as sharply demarcated, depigmented macules and patches that are scattered symmetrically or unsymmetrically over the body. The presentation can be delineated based on the segmental or nonsegmental nature of the disease. According to the revised classification/nomenclature of vitiligo,¹ the disorder can be classified as nonsegmental, segmental, mixed, or unclassified. The pathogenesis of the vitiligo disease process is due to multiple modalities that contribute to melanocyte loss. Theories for melanocyte destruction include but are not limited to autoimmunity, biochemicals, epidermal cytokines, increased hydrogen peroxide and free radicals, and humoral and cellular immune alteration.^2,3

Despite its long history, the most frustrating aspect of the vitiligo disease process remains its treatment due to limited efficacy, frequent application of topicals, and the need for high-potency steroids. Medical therapies usually are the first line of treatment and are most effective with few side effects for bilateral nonsegmental or evolving vitiligo.² Some of the primary therapies with the highest efficacies appear to be calcipotriene and psoralen plus UVA, psoralen plus UVA as monotherapy, excimer laser, narrowband UVB, oral steroids, 8-methoxypsoralen, tacrolimus, and topical steroids.⁴ The theory is that these treatments would be successful if the patient had active melanocytes in the external root sheath that would be able to repigment a patch of vitiligo.⁵ Hence, it would be more difficult to treat areas such as the dorsal aspect of the fingers and toes because they lack hair-bearing areas with melanocytes.⁶ The alternative approach to treating vitiligo patches would be surgical intervention techniques, as they provide melanocytic cells to a previously depigmented area.^3,5 The focus of this article is to evaluate the efficacy and appropriate use of some of the surgical procedures that can be used in the treatment of vitiligo patients.

Candidate Selection

First, vitiligo patients for whom first-line treatment with medical therapies has failed are candidates for surgical techniques. The second vital component is to clinically confirm the diagnosis of vitiligo as opposed to other genetic, infectious, or autoimmune causes of pigment loss. Lastly, the vitiligo patch should be stable. A stable vitiligo patch does not continue to progress and is no longer responsive to topical medications that are meant to repigment for a discernible period of time.⁷

Classification of Disease Stage

To classify the stage of vitiligo prior to surgical intervention, Gauthier⁸ created a basic grading system: grade I, with partial depletion of epidermal melanocytes in a vitiligo patch that responds to repigmentation in a follicular pattern evenly such as on the face and neck; grade II, with complete depletion of epidermal melanocytes with a usual follicular pattern of repigmentation; and grade III, indicating complete depletion of follicular melanocytes with no hope of response to medical therapy. According to Rusfianti and Wirohadidjodjo,² the surgical techniques that have developed over the years for treatment of grade III vitiligo patients include split-thickness skin grafting, suction blister grafting, miniature punch grafting, and cultured melanocyte transplantation.

Surgical Techniques

Split-thickness skin grafting is an older procedure that entails the use of a harvesting graft site with no pigment loss and dermabrasion of the recipient area to allow interaction with the wound bed.⁹ With proper care and minimal movement or wrinkling of the graft site, patients can have repigmentation without skip areas.

Suction blister grafting is another tried and tested surgical intervention. Hasegawa et al¹⁰ conducted a study of 15 patients (13 males, 2 females; age range, 16–38 years) diagnosed with segmental vitiligo who were treated using the suction blister grafting technique with CO₂ laser resurfacing. Patients were recruited 1 month prior to initiating therapy and no other treatments were used during the month or in conjunction with the surgical intervention. Suction blisters were harvested from the left thigh and transferred in saline to the recipient site, which was abraded with 1 pass of the short-pulse CO₂ laser system. The recipient sites were then closed with 7-0 nylon sutures and covered tightly with tie-over dressings for at least 1 week. Within 6 months of the procedure, a treatment response of 100% was seen in 15 patients, making it an effective method for treatment-resistant vitiligo patients.¹⁰

Miniature punch grafting is another possible treatment option for resistant cases of vitiligo. Mapar et al¹¹ conducted a study in 25 patients (21 women, 4 men; age range, 20–47 years) who had been diagnosed with stable vitiligo (ie, no progression in the last 2 years) and were treated with single hair follicle transplant versus miniature punch grafting. The theory behind the study was to use the melanocytic reservoir noted in the normal hair follicle to repigment the vitiligo patch. With follow-up of both methods of treatment, there was no statistical difference in treatment results.¹¹ A similar study was conducted by Malakar and Lahiri¹² in patients with lip leukoderma (a variant of vitiligo). One hundred eight patients (41 males, 67 females; age range, 14–62 years) who had been diagnosed with stable lip leukoderma (ie, stable vitiligo for at least 6 months) underwent treatment via autologous miniature punch grafting. Punch biopsies were performed in donor sites of the buttocks and upper thighs with 72% of patients noting complete repigmentation. Complications noted were herpes labialis–induced lip leukoderma, which ultimately led to rejection of the graft site.¹² Overall, however, miniature punch grafting is a viable surgical option in stable vitiligo patients.

Cultured melanocyte transplantation, or a noncultured epidermal suspension, was first initiated in 1992.¹³ Silpa-Archa et al¹⁴ conducted an open, split-comparison study of 6 vitiligo patients (5 women, 1 man; age range, 20–65 years) with stable lesions. Fifty percent of patients received autologous pigmented skin cellular suspension, which was applied to vitiligo-affected skin that was treated with a fractionated CO₂ laser, and 50% received dermabrasion. Composite dressing was placed overlying the site with dressing removal in 1 week. The degree of repigmentation was based on a modified vitiligo area scoring index scale of poor (0%–25%), fair (26%–50%), good (51%–75%), very good (76%–90%), or excellent (91%–100%). Overall repigmentation was very good to excellent in all 6 patients.¹⁴ Potentially, this method can far improve the surgical treatment options for future vitiligo patients.

Final Thoughts

Overall, when evaluating surgical interventions for the treatment of vitiligo, careful consideration of the patient’s disease progression, failed therapies, outcome expectations, and repigmentation is warranted prior to initiating any procedure. For appropriate candidates, a range of surgical methodologies has proven to be effective in treatment of stable vitiligo patients.

What does your patient need to know at the first visit? Does it apply to patients of all genders and ages?

Before performing laser procedures on patients with richly pigmented skin (Fitzpatrick skin types IV–VI), patients need to be informed of the higher risk for pigmentary alterations as potential complications of the procedure. Specifically, hyperpigmentation or hypopigmentation can occur postprocedure, depending on the type of device used, the treatment settings, the technique, the underlying skin disorder being treated, and the patient’s individual response to treatment. Fortunately, these pigment alterations are in most cases self-limited but can last for weeks to months depending on the severity and the nature of the dyspigmentation.

What are your go-to treatments? What are the side effects?

Notwithstanding the higher risks for pigmentary alterations, lasers can be extremely useful for the management of numerous dermatologic concerns in patients with Fitzpatrick skin types IV to VI including laser hair removal for pseudofolliculitis barbae or nonablative fractional laser resurfacing for acne scarring and pigmentary disorders. My go-to treatments include the following: long-pulsed 1064-nm Nd:YAG laser for hair removal in Fitzpatrick skin types V to VI, 808-nm diode laser with linear scanning of hair removal in Fitzpatrick skin type IV or less, 1550-nm erbium-doped nonablative fractional laser for acne scarring in Fitzpatrick skin types IV to VI, and low-power diode 1927-nm fractional laser for melasma and postinflammatory hyperpigmentation in Fitzpatrick skin types IV to VI.

All of these procedures are performed with conservative treatment settings such as low fluences and longer pulse durations for laser hair removal and low treatment densities for fractional laser procedures. Prior to laser resurfacing, I recommend hydroquinone cream 4% twice daily starting 2 weeks before the first session and for 4 weeks posttreatment. These recommendations are based on published evidence (see Suggested Readings) as well as anecdotal experience.

How do you keep patients compliant with treatment?

Emphasizing the need for broad-spectrum sunscreen and avoidance of intense sun exposure before and after laser treatments is important during the initial consultation and prior to each treatment. I warn my patients of the higher risk for hyperpigmentation if the skin is tanned or has recently had intense sun exposure.

What do you do if they refuse treatment?

If patients refuse laser treatment or recommended precautions, then I will consider nonlaser treatment options.

What resources do you recommend to patients for more information?

I recommend patients visit the Skin of Color Society website (www.skinofcolorsociety.org).

Suggested Readings

• Alexis AF. Fractional laser resurfacing of acne scarring in patients with Fitzpatrick skin types IV-VI. J Drugs Dermatol. 2011;10(12 suppl):s6-s7.
• Alexis AF. Lasers and light-based therapies in ethnic skin: treatment options and recommendations for Fitzpatrick skin types V and VI. Br J Dermatol. 2013;169(suppl 3):91-97.
• Alexis AF, Coley MK, Nijhawan RI, et al. Nonablative fractional laser resurfacing for acne scarring in patients with Fitzpatrick skin phototypes IV-VI. Dermatol Surg. 2016;42:392-402.
• Battle EF, Hobbs LM. Laser-assisted hair removal for darker skin types. Dermatol Ther. 2004;17:177-183.
• Clark CM, Silverberg JI, Alexis AF. A retrospective chart review to assess the safety of nonablative fractional laser resurfacing in Fitzpatrick skin types IV to VI. J Drugs Dermatol. 2013;12:428-431.
• Ross EV, Cooke LM, Timko AL, et al. Treatment of pseudofolliculitis barbae in skin types IV, V, and VI with a long-pulsed neodymium:yttrium aluminum garnet laser. J Am Acad Dermatol. 2002;47:263-270.

What does your patient need to know at the first visit? Does it apply to patients of all genders and ages?

Before performing laser procedures on patients with richly pigmented skin (Fitzpatrick skin types IV–VI), patients need to be informed of the higher risk for pigmentary alterations as potential complications of the procedure. Specifically, hyperpigmentation or hypopigmentation can occur postprocedure, depending on the type of device used, the treatment settings, the technique, the underlying skin disorder being treated, and the patient’s individual response to treatment. Fortunately, these pigment alterations are in most cases self-limited but can last for weeks to months depending on the severity and the nature of the dyspigmentation.

What are your go-to treatments? What are the side effects?

Notwithstanding the higher risks for pigmentary alterations, lasers can be extremely useful for the management of numerous dermatologic concerns in patients with Fitzpatrick skin types IV to VI including laser hair removal for pseudofolliculitis barbae or nonablative fractional laser resurfacing for acne scarring and pigmentary disorders. My go-to treatments include the following: long-pulsed 1064-nm Nd:YAG laser for hair removal in Fitzpatrick skin types V to VI, 808-nm diode laser with linear scanning of hair removal in Fitzpatrick skin type IV or less, 1550-nm erbium-doped nonablative fractional laser for acne scarring in Fitzpatrick skin types IV to VI, and low-power diode 1927-nm fractional laser for melasma and postinflammatory hyperpigmentation in Fitzpatrick skin types IV to VI.

All of these procedures are performed with conservative treatment settings such as low fluences and longer pulse durations for laser hair removal and low treatment densities for fractional laser procedures. Prior to laser resurfacing, I recommend hydroquinone cream 4% twice daily starting 2 weeks before the first session and for 4 weeks posttreatment. These recommendations are based on published evidence (see Suggested Readings) as well as anecdotal experience.

How do you keep patients compliant with treatment?

Emphasizing the need for broad-spectrum sunscreen and avoidance of intense sun exposure before and after laser treatments is important during the initial consultation and prior to each treatment. I warn my patients of the higher risk for hyperpigmentation if the skin is tanned or has recently had intense sun exposure.

What do you do if they refuse treatment?

If patients refuse laser treatment or recommended precautions, then I will consider nonlaser treatment options.

What resources do you recommend to patients for more information?

I recommend patients visit the Skin of Color Society website (www.skinofcolorsociety.org).

Suggested Readings

• Alexis AF. Fractional laser resurfacing of acne scarring in patients with Fitzpatrick skin types IV-VI. J Drugs Dermatol. 2011;10(12 suppl):s6-s7.
• Alexis AF. Lasers and light-based therapies in ethnic skin: treatment options and recommendations for Fitzpatrick skin types V and VI. Br J Dermatol. 2013;169(suppl 3):91-97.
• Alexis AF, Coley MK, Nijhawan RI, et al. Nonablative fractional laser resurfacing for acne scarring in patients with Fitzpatrick skin phototypes IV-VI. Dermatol Surg. 2016;42:392-402.
• Battle EF, Hobbs LM. Laser-assisted hair removal for darker skin types. Dermatol Ther. 2004;17:177-183.
• Clark CM, Silverberg JI, Alexis AF. A retrospective chart review to assess the safety of nonablative fractional laser resurfacing in Fitzpatrick skin types IV to VI. J Drugs Dermatol. 2013;12:428-431.
• Ross EV, Cooke LM, Timko AL, et al. Treatment of pseudofolliculitis barbae in skin types IV, V, and VI with a long-pulsed neodymium:yttrium aluminum garnet laser. J Am Acad Dermatol. 2002;47:263-270.

What does your patient need to know at the first visit? Does it apply to patients of all genders and ages?

Before performing laser procedures on patients with richly pigmented skin (Fitzpatrick skin types IV–VI), patients need to be informed of the higher risk for pigmentary alterations as potential complications of the procedure. Specifically, hyperpigmentation or hypopigmentation can occur postprocedure, depending on the type of device used, the treatment settings, the technique, the underlying skin disorder being treated, and the patient’s individual response to treatment. Fortunately, these pigment alterations are in most cases self-limited but can last for weeks to months depending on the severity and the nature of the dyspigmentation.

What are your go-to treatments? What are the side effects?

Notwithstanding the higher risks for pigmentary alterations, lasers can be extremely useful for the management of numerous dermatologic concerns in patients with Fitzpatrick skin types IV to VI including laser hair removal for pseudofolliculitis barbae or nonablative fractional laser resurfacing for acne scarring and pigmentary disorders. My go-to treatments include the following: long-pulsed 1064-nm Nd:YAG laser for hair removal in Fitzpatrick skin types V to VI, 808-nm diode laser with linear scanning of hair removal in Fitzpatrick skin type IV or less, 1550-nm erbium-doped nonablative fractional laser for acne scarring in Fitzpatrick skin types IV to VI, and low-power diode 1927-nm fractional laser for melasma and postinflammatory hyperpigmentation in Fitzpatrick skin types IV to VI.

All of these procedures are performed with conservative treatment settings such as low fluences and longer pulse durations for laser hair removal and low treatment densities for fractional laser procedures. Prior to laser resurfacing, I recommend hydroquinone cream 4% twice daily starting 2 weeks before the first session and for 4 weeks posttreatment. These recommendations are based on published evidence (see Suggested Readings) as well as anecdotal experience.

How do you keep patients compliant with treatment?

Emphasizing the need for broad-spectrum sunscreen and avoidance of intense sun exposure before and after laser treatments is important during the initial consultation and prior to each treatment. I warn my patients of the higher risk for hyperpigmentation if the skin is tanned or has recently had intense sun exposure.

What do you do if they refuse treatment?

If patients refuse laser treatment or recommended precautions, then I will consider nonlaser treatment options.

What resources do you recommend to patients for more information?

I recommend patients visit the Skin of Color Society website (www.skinofcolorsociety.org).

Suggested Readings

• Alexis AF. Fractional laser resurfacing of acne scarring in patients with Fitzpatrick skin types IV-VI. J Drugs Dermatol. 2011;10(12 suppl):s6-s7.
• Alexis AF. Lasers and light-based therapies in ethnic skin: treatment options and recommendations for Fitzpatrick skin types V and VI. Br J Dermatol. 2013;169(suppl 3):91-97.
• Alexis AF, Coley MK, Nijhawan RI, et al. Nonablative fractional laser resurfacing for acne scarring in patients with Fitzpatrick skin phototypes IV-VI. Dermatol Surg. 2016;42:392-402.
• Battle EF, Hobbs LM. Laser-assisted hair removal for darker skin types. Dermatol Ther. 2004;17:177-183.
• Clark CM, Silverberg JI, Alexis AF. A retrospective chart review to assess the safety of nonablative fractional laser resurfacing in Fitzpatrick skin types IV to VI. J Drugs Dermatol. 2013;12:428-431.
• Ross EV, Cooke LM, Timko AL, et al. Treatment of pseudofolliculitis barbae in skin types IV, V, and VI with a long-pulsed neodymium:yttrium aluminum garnet laser. J Am Acad Dermatol. 2002;47:263-270.

The Diagnosis: Primary Cutaneous Carcinosarcoma

A generous shave biopsy and debulking performed on the initial visit revealed an infiltrating tumor consisting of malignant epithelial and stromal components (Figure). The basaloid and squamoid epithelial cells were keratin positive. The stromal cells demonstrated positivity for CD10 but were keratin negative. The epithelial portion of the tumor was composed mostly of basaloid islands of cells with nuclear pleomorphism, scattered mitoses, and focal sebaceous differentiation. The mesenchymal portion of the tumor displayed florid pleomorphism and polymorphism, with many large atypical cells and proliferation. A diagnosis of primary cutaneous carcinosarcoma (PCC) was rendered. Head and neck computed tomography showed tumor penetration of less than 1 cm into scalp soft tissues with no involvement of the underlying bone. There was some evidence of swelling of the supragaleal soft tissues without indication of perineural spread. An 11-mm hyperlucent lower cervical lymph node on the left side that likely represented an incidental finding was noted. Surgical excision with margin evaluation was recommended, but the patient declined. He instead received radiation therapy to the left side of the posterior scalp with a total dose of 30 Gy at 6 Gy per fraction and 1 fraction daily. The patient was found to have a well-healed scar with no evidence of recurrence at 4-week follow-up and again at 5 months after radiation therapy.

A generous shave biopsy and debulking performed on the initial visit revealed an inflitrating tumor consisting on malignant epithelial and stromal components (A-C)(H&E; original magnifications ×10, ×20, and ×40, respectively).

Primary cutaneous carcinosarcoma is a rare biphasic neoplasm of unknown etiology that is characterized by the presence of both malignant epithelial and mesenchymal components.¹ Carcinosarcomas have been reported in both the male and female reproductive tracts, urinary tract, gastrointestinal tract, lungs, breasts, larynx, thymus, and thyroid but is uncommon as a primary neoplasm of the skin.² Epidermal PCC occurs with greater frequency in males than in females and typically presents in the eighth or ninth decades of life.³ These tumors tend to arise in sun-exposed regions, most commonly on the face and scalp.²

Morphologically, PCCs typically are exophytic growths that often feature surface ulceration and may or may not bleed upon palpation.⁴ Primary cutaneous carcinosarcomas may present as long-standing lesions that have undergone rapid transformation in the weeks preceding presentation.⁴ It is not uncommon for PCC lesions to carry the clinical diagnosis of squamous cell carcinoma, which suggests notable morphologic overlap between these entities. Histopathologically, PCC shows a basal cell carcinoma and/or a squamous cell carcinoma epithelial component intimately admixed with a sarcomatous component.⁵ The mesenchymal component of PCC typically resembles a superficial malignant fibrous histiocytoma characterized by pleomorphic nuclei and cytoplasm, necrosis, and an increased number of mitotic figures.² Immunohistochemistry can be beneficial in the diagnosis of PCC. A combination of p63 and AE1/AE3 stains can be used to confirm cells of epithelial origin. Staining with vimentin, CD10, or caldesmon can help to delineate the mesenchymal component of PCC.

Epidermal PCC most commonly affects elderly individuals with a history of extensive sun exposure. It has been suggested that p53 mutations due to UV damage are key in tumor formation for both epithelial and mesenchymal elements.⁵ Literature supports a monoclonal origin for the epithelial and mesenchymal components of this tumor; however, there is insufficient evidence.⁶ Surgical excision is the primary treatment modality for epidermal PCC, but adjuvant or substitutive radiotherapy has been used in some cases.⁴ The prognosis of PCC is notably better than its visceral counterpart due to early diagnosis and treatment of easily visible lesions. Epidermal PCC has a 70% 5-year disease-free survival rate, while adnexal PCC tends to occur in younger patients and has a 25% 5-year disease-free survival rate.³ Due to the rarity of reported cases and limited follow-up, the long-term prognosis for PCC remains unclear.

We report an unusual case of PCC on the scalp that was successfully treated with radiation therapy alone. This modality should be considered in patients with large tumors who refuse surgery or are not good surgical candidates.

The Diagnosis: Primary Cutaneous Carcinosarcoma

A generous shave biopsy and debulking performed on the initial visit revealed an infiltrating tumor consisting of malignant epithelial and stromal components (Figure). The basaloid and squamoid epithelial cells were keratin positive. The stromal cells demonstrated positivity for CD10 but were keratin negative. The epithelial portion of the tumor was composed mostly of basaloid islands of cells with nuclear pleomorphism, scattered mitoses, and focal sebaceous differentiation. The mesenchymal portion of the tumor displayed florid pleomorphism and polymorphism, with many large atypical cells and proliferation. A diagnosis of primary cutaneous carcinosarcoma (PCC) was rendered. Head and neck computed tomography showed tumor penetration of less than 1 cm into scalp soft tissues with no involvement of the underlying bone. There was some evidence of swelling of the supragaleal soft tissues without indication of perineural spread. An 11-mm hyperlucent lower cervical lymph node on the left side that likely represented an incidental finding was noted. Surgical excision with margin evaluation was recommended, but the patient declined. He instead received radiation therapy to the left side of the posterior scalp with a total dose of 30 Gy at 6 Gy per fraction and 1 fraction daily. The patient was found to have a well-healed scar with no evidence of recurrence at 4-week follow-up and again at 5 months after radiation therapy.

A generous shave biopsy and debulking performed on the initial visit revealed an inflitrating tumor consisting on malignant epithelial and stromal components (A-C)(H&E; original magnifications ×10, ×20, and ×40, respectively).

Primary cutaneous carcinosarcoma is a rare biphasic neoplasm of unknown etiology that is characterized by the presence of both malignant epithelial and mesenchymal components.¹ Carcinosarcomas have been reported in both the male and female reproductive tracts, urinary tract, gastrointestinal tract, lungs, breasts, larynx, thymus, and thyroid but is uncommon as a primary neoplasm of the skin.² Epidermal PCC occurs with greater frequency in males than in females and typically presents in the eighth or ninth decades of life.³ These tumors tend to arise in sun-exposed regions, most commonly on the face and scalp.²

Morphologically, PCCs typically are exophytic growths that often feature surface ulceration and may or may not bleed upon palpation.⁴ Primary cutaneous carcinosarcomas may present as long-standing lesions that have undergone rapid transformation in the weeks preceding presentation.⁴ It is not uncommon for PCC lesions to carry the clinical diagnosis of squamous cell carcinoma, which suggests notable morphologic overlap between these entities. Histopathologically, PCC shows a basal cell carcinoma and/or a squamous cell carcinoma epithelial component intimately admixed with a sarcomatous component.⁵ The mesenchymal component of PCC typically resembles a superficial malignant fibrous histiocytoma characterized by pleomorphic nuclei and cytoplasm, necrosis, and an increased number of mitotic figures.² Immunohistochemistry can be beneficial in the diagnosis of PCC. A combination of p63 and AE1/AE3 stains can be used to confirm cells of epithelial origin. Staining with vimentin, CD10, or caldesmon can help to delineate the mesenchymal component of PCC.

Epidermal PCC most commonly affects elderly individuals with a history of extensive sun exposure. It has been suggested that p53 mutations due to UV damage are key in tumor formation for both epithelial and mesenchymal elements.⁵ Literature supports a monoclonal origin for the epithelial and mesenchymal components of this tumor; however, there is insufficient evidence.⁶ Surgical excision is the primary treatment modality for epidermal PCC, but adjuvant or substitutive radiotherapy has been used in some cases.⁴ The prognosis of PCC is notably better than its visceral counterpart due to early diagnosis and treatment of easily visible lesions. Epidermal PCC has a 70% 5-year disease-free survival rate, while adnexal PCC tends to occur in younger patients and has a 25% 5-year disease-free survival rate.³ Due to the rarity of reported cases and limited follow-up, the long-term prognosis for PCC remains unclear.

We report an unusual case of PCC on the scalp that was successfully treated with radiation therapy alone. This modality should be considered in patients with large tumors who refuse surgery or are not good surgical candidates.

The Diagnosis: Primary Cutaneous Carcinosarcoma

A generous shave biopsy and debulking performed on the initial visit revealed an infiltrating tumor consisting of malignant epithelial and stromal components (Figure). The basaloid and squamoid epithelial cells were keratin positive. The stromal cells demonstrated positivity for CD10 but were keratin negative. The epithelial portion of the tumor was composed mostly of basaloid islands of cells with nuclear pleomorphism, scattered mitoses, and focal sebaceous differentiation. The mesenchymal portion of the tumor displayed florid pleomorphism and polymorphism, with many large atypical cells and proliferation. A diagnosis of primary cutaneous carcinosarcoma (PCC) was rendered. Head and neck computed tomography showed tumor penetration of less than 1 cm into scalp soft tissues with no involvement of the underlying bone. There was some evidence of swelling of the supragaleal soft tissues without indication of perineural spread. An 11-mm hyperlucent lower cervical lymph node on the left side that likely represented an incidental finding was noted. Surgical excision with margin evaluation was recommended, but the patient declined. He instead received radiation therapy to the left side of the posterior scalp with a total dose of 30 Gy at 6 Gy per fraction and 1 fraction daily. The patient was found to have a well-healed scar with no evidence of recurrence at 4-week follow-up and again at 5 months after radiation therapy.

A generous shave biopsy and debulking performed on the initial visit revealed an inflitrating tumor consisting on malignant epithelial and stromal components (A-C)(H&E; original magnifications ×10, ×20, and ×40, respectively).

Primary cutaneous carcinosarcoma is a rare biphasic neoplasm of unknown etiology that is characterized by the presence of both malignant epithelial and mesenchymal components.¹ Carcinosarcomas have been reported in both the male and female reproductive tracts, urinary tract, gastrointestinal tract, lungs, breasts, larynx, thymus, and thyroid but is uncommon as a primary neoplasm of the skin.² Epidermal PCC occurs with greater frequency in males than in females and typically presents in the eighth or ninth decades of life.³ These tumors tend to arise in sun-exposed regions, most commonly on the face and scalp.²

Morphologically, PCCs typically are exophytic growths that often feature surface ulceration and may or may not bleed upon palpation.⁴ Primary cutaneous carcinosarcomas may present as long-standing lesions that have undergone rapid transformation in the weeks preceding presentation.⁴ It is not uncommon for PCC lesions to carry the clinical diagnosis of squamous cell carcinoma, which suggests notable morphologic overlap between these entities. Histopathologically, PCC shows a basal cell carcinoma and/or a squamous cell carcinoma epithelial component intimately admixed with a sarcomatous component.⁵ The mesenchymal component of PCC typically resembles a superficial malignant fibrous histiocytoma characterized by pleomorphic nuclei and cytoplasm, necrosis, and an increased number of mitotic figures.² Immunohistochemistry can be beneficial in the diagnosis of PCC. A combination of p63 and AE1/AE3 stains can be used to confirm cells of epithelial origin. Staining with vimentin, CD10, or caldesmon can help to delineate the mesenchymal component of PCC.

Epidermal PCC most commonly affects elderly individuals with a history of extensive sun exposure. It has been suggested that p53 mutations due to UV damage are key in tumor formation for both epithelial and mesenchymal elements.⁵ Literature supports a monoclonal origin for the epithelial and mesenchymal components of this tumor; however, there is insufficient evidence.⁶ Surgical excision is the primary treatment modality for epidermal PCC, but adjuvant or substitutive radiotherapy has been used in some cases.⁴ The prognosis of PCC is notably better than its visceral counterpart due to early diagnosis and treatment of easily visible lesions. Epidermal PCC has a 70% 5-year disease-free survival rate, while adnexal PCC tends to occur in younger patients and has a 25% 5-year disease-free survival rate.³ Due to the rarity of reported cases and limited follow-up, the long-term prognosis for PCC remains unclear.

We report an unusual case of PCC on the scalp that was successfully treated with radiation therapy alone. This modality should be considered in patients with large tumors who refuse surgery or are not good surgical candidates.

Vitiligo is an acquired idiopathic disease of unknown etiology. Characterized by depigmented maculae and melanocytic destruction, it usually presents in childhood or young adulthood. The incidence of vitiligo ranges from 0.5% to 2% globally and there is no racial or gender predilection.¹

Patients with vitiligo may exhibit pigmentary abnormalities of the iris and retina.² Noninflammatory depigmented lesions of the ocular fundus observed in vitiligo indicate a local loss of melanocytes.¹ The fact that melanocytes are present not only in the skin and roots of the hair but also in the uvea and stria vascularis of the inner ear may explain the ophthalmologic disorders that accompany vitiligo.³ The term glaucoma refers to a large number of diseases that share a common feature: a distinctive and progressive optic neuropathy that may derive from various risks and is associated with a gradual loss of the visual field. If the disorder is not diagnosed and treated properly it could cause blindness.

Glaucoma is classified on the basis of the underlying abnormality that causes intraocular pressure (IOP) to rise. Glaucoma is first divided into open-angle and angle-closure glaucoma; glaucoma associated with developmental anomalies is then subdivided according to specific alterations.⁴

A PubMed search of articles indexed for MEDLINE using the terms vitiligo and glaucoma revealed only 1 study examining the incidence of glaucoma in patients with vitiligo.⁵ In the study reported here, we determined the presence of and possible risk factors for glaucoma in patients with vitiligo who had presented to the dermatology polyclinic.

Methods

We registered 49 patients diagnosed with vitiligo by clinical and Wood light examination and 20 age- and sex-matched healthy controls. Patients who were using topical corticosteroid treatments for vitiligo lesions located on the face were excluded from the study due to the glaucoma-inducing effects of corticosteroids. Similarly, patients who received drugs with sympathetic and parasympathetic action that can cause glaucoma were excluded.

The patients received a comprehensive ophthalmologic examination that included visual acuity testing, refraction, IOP measurement, gonioscopy, and fundus examination. All patients and controls underwent visual field tests and optic nerve head analyses using a confocal scanning laser ophthalmoscope. Glaucoma was diagnosed based on fundus examination, IOP measurement, field of vision evaluation, and optic nerve head analysis.

Informed consent was obtained from all participants. The research protocol was approved by the university hospital ethics committee.

Results

The study registered a total of 49 patients with vitiligo (28 female; 21 male) and 20 healthy controls (10 female; 10 male) with a variety of demographic and clinical characteristics (Table 1).

Mean (SD) IOP values were 13.83 (2.84) mm Hg for the right eye and 13.89 (2.60) mm Hg for the left eye in the vitiligo group. Values were 14.35 (2.56) mm Hg and 14.95 (2.92) mm Hg, respectively, in the control group. The IOP differences between the 2 groups were not statistically significant (P>.05).

Nine patients (18.4%) in the vitiligo group were found to have signs of normal-tension glaucoma (NTG). Optic nerve damage and vision loss occurs in the presence of normal IOP in NTG. There were no signs of NTG in the control group. Normal-tension glaucoma was diagnosed in the vitiligo group based on glaucomatous optic disc appearance, visual field defects, and structural analysis of the entire optic nerve head in confocal scanning laser ophthalmoscope. The NTG difference between the vitiligo and control groups was statistically significant (P=.04).

In the vitiligo group, of the 9 patients who had NTG, 6 had periorbital vitiligo lesions; the remaining 3 had none. Although patients who had periorbital lesions had a higher rate of glaucoma relative to the patients without periorbital lesions, the difference was not statistically significant (P>.05).

No statistically significant differences (P>.05) were found between patients with vitiligo with and without glaucoma in terms of age, sex, disease duration, family history of vitiligo, presence or absence of periorbital involvement, manner of involvement, percentage of the involved body areas, and IOP (Table 1).

Comment

Glaucoma is characterized by increased IOP, visual field loss, and changes in the optic nerve head. Although elevated IOP is common in ocular hypertension as well as in glaucoma, there is no glaucomatous visual field loss in ocular hypertension. In NTG, on the other hand, glaucomatous visual field loss and optic nerve head changes occur without an increase in IOP.⁶ Normal-tension glaucoma is a particular type of open-angle glaucoma. It is believed that NTG and high-tension glaucoma induce optic nerve head damage through different means.⁷ Alternative theories have been put forth to account for the glaucomatous damage to the optic nerve head that occurs in NTG, despite normal or close to normal IOP. These theories include vascular disorders (eg, ischemia, which interrupts the orthograde or retrograde axonal transport), excessive accumulation of free radicals, triggering of apoptosis, and low resistance of lamina cribrosa.⁸

Although there are various studies exploring ocular symptoms in patients with vitiligo,^9-15 only 1 study has examined the incidence of glaucoma in this group of patients.⁵ Biswas et al¹¹ examined ocular signs in 100 patients with vitiligo and found that 23% of patients had hypopigmented foci in the iris, 18% had pigmentation in the anterior chamber, 11% had chorioretinal degeneration, 9% had hypopigmentation of the retinal pigment epithelium, 5% had uveitis, and 34% were evaluated as normal. In this study, the authors concluded that there was a strong relationship between vitiligo and eye diseases.¹¹ When Gopal et al⁹ compared the eye examinations of 150 vitiligo patients and 100 healthy controls, they found uveitis, iris, and retinal pigmentary abnormalities in 16% of the vitiligo patients (P<.001).

Rogosić et al⁵ examined the incidence of glaucoma in 42 patients with vitiligo and found primary open-angle glaucoma in 24 (57%) patients. The patients had a mean age of 56 years, mean disease duration of 13 years, and mean IOP of 18 mm Hg for the right eye and 17.5 mm Hg for the left eye. The incidence of glaucoma was significantly higher in patients with vitiligo (P<.001) and increased with disease duration.⁵

Similar studies, however, have failed to show a relationship between vitiligo and glaucoma. In a study that evaluated the retinal pigment epithelium and the optic nerve in patients with vitiligo, Perossini et al¹⁰ found that the fundus examination of the patients was perfectly normal.

In our study, we detected NTG in 18.4% of patients with vitiligo. We did not find a significant statistical difference between patients with and without glaucoma (Table 2). Rogosić et al⁵ found a significant relationship between age and glaucoma incidence, but we did not find such a relationship, which we believe is because the mean age of our patients was lower than the prior study.

In vitiligo, melanocytes are destroyed through an unknown mechanism. Although the cellular and molecular mechanisms causing melanocytic destruction have not yet been determined, various hypotheses have been put forward to explain the etiopathogenesis of vitiligo. Among these, the most commonly held hypotheses are the neural, self-destruction, and autoimmune hypotheses.¹⁶

Based on the observation that stress and serious trauma could precipitate or trigger the onset of vitiligo,¹⁶ the neural hypothesis holds that neurochemical mediators released from the edges of the nerve endings exert toxic effects on melanocytes. The fact that both melanocytes and choroidal pigment cells originate from the mesenchyme and dermatomal spreading of segmental vitiligo are arguments propounded in favor of this hypothesis.¹⁷

The self-destruction hypothesis suggests that the intrinsic protective mechanisms that normally enable melanocytes to eliminate toxic intermediate products or metabolites on the melanogenesis path have been impaired in patients with vitiligo.^18,19 There is evidence of increased oxidative stress over the whole epidermis of patients with vitiligo.²⁰ Thus, free radicals affect melanin and cause membrane damage via lipid peroxidation reactions.²¹

The autoimmune hypothesis proposes a clinical relationship between vitiligo and several diseases believed to be autoimmune. Because the macrophage infiltration observed in vitiligo lesions is more pronounced on the perilesional skin, this hypothesis holds that macrophages may play a role in melanocyte removal.²¹ The Koebner phenomenon observed in vitiligo lends support to the critical role of trauma in the etiopathogenesis of the disease.

Although we could not explain the co-presence of vitiligo and glaucoma, we believe that it may result from the fact that both diseases are observed in tissues that have the same embryologic origin and etiology, perhaps vascular or neural disorders, excessive accumulation of free radicals, or the triggering of apoptosis. Dermatologists should be alert to the presence of glaucoma in patients with vitiligo because glaucoma is an eye disease that progresses slowly and may lead to vision loss.

Vitiligo is an acquired idiopathic disease of unknown etiology. Characterized by depigmented maculae and melanocytic destruction, it usually presents in childhood or young adulthood. The incidence of vitiligo ranges from 0.5% to 2% globally and there is no racial or gender predilection.¹

Patients with vitiligo may exhibit pigmentary abnormalities of the iris and retina.² Noninflammatory depigmented lesions of the ocular fundus observed in vitiligo indicate a local loss of melanocytes.¹ The fact that melanocytes are present not only in the skin and roots of the hair but also in the uvea and stria vascularis of the inner ear may explain the ophthalmologic disorders that accompany vitiligo.³ The term glaucoma refers to a large number of diseases that share a common feature: a distinctive and progressive optic neuropathy that may derive from various risks and is associated with a gradual loss of the visual field. If the disorder is not diagnosed and treated properly it could cause blindness.

Glaucoma is classified on the basis of the underlying abnormality that causes intraocular pressure (IOP) to rise. Glaucoma is first divided into open-angle and angle-closure glaucoma; glaucoma associated with developmental anomalies is then subdivided according to specific alterations.⁴

A PubMed search of articles indexed for MEDLINE using the terms vitiligo and glaucoma revealed only 1 study examining the incidence of glaucoma in patients with vitiligo.⁵ In the study reported here, we determined the presence of and possible risk factors for glaucoma in patients with vitiligo who had presented to the dermatology polyclinic.

Methods

We registered 49 patients diagnosed with vitiligo by clinical and Wood light examination and 20 age- and sex-matched healthy controls. Patients who were using topical corticosteroid treatments for vitiligo lesions located on the face were excluded from the study due to the glaucoma-inducing effects of corticosteroids. Similarly, patients who received drugs with sympathetic and parasympathetic action that can cause glaucoma were excluded.

The patients received a comprehensive ophthalmologic examination that included visual acuity testing, refraction, IOP measurement, gonioscopy, and fundus examination. All patients and controls underwent visual field tests and optic nerve head analyses using a confocal scanning laser ophthalmoscope. Glaucoma was diagnosed based on fundus examination, IOP measurement, field of vision evaluation, and optic nerve head analysis.

Informed consent was obtained from all participants. The research protocol was approved by the university hospital ethics committee.

Results

The study registered a total of 49 patients with vitiligo (28 female; 21 male) and 20 healthy controls (10 female; 10 male) with a variety of demographic and clinical characteristics (Table 1).

Mean (SD) IOP values were 13.83 (2.84) mm Hg for the right eye and 13.89 (2.60) mm Hg for the left eye in the vitiligo group. Values were 14.35 (2.56) mm Hg and 14.95 (2.92) mm Hg, respectively, in the control group. The IOP differences between the 2 groups were not statistically significant (P>.05).

Nine patients (18.4%) in the vitiligo group were found to have signs of normal-tension glaucoma (NTG). Optic nerve damage and vision loss occurs in the presence of normal IOP in NTG. There were no signs of NTG in the control group. Normal-tension glaucoma was diagnosed in the vitiligo group based on glaucomatous optic disc appearance, visual field defects, and structural analysis of the entire optic nerve head in confocal scanning laser ophthalmoscope. The NTG difference between the vitiligo and control groups was statistically significant (P=.04).

In the vitiligo group, of the 9 patients who had NTG, 6 had periorbital vitiligo lesions; the remaining 3 had none. Although patients who had periorbital lesions had a higher rate of glaucoma relative to the patients without periorbital lesions, the difference was not statistically significant (P>.05).

No statistically significant differences (P>.05) were found between patients with vitiligo with and without glaucoma in terms of age, sex, disease duration, family history of vitiligo, presence or absence of periorbital involvement, manner of involvement, percentage of the involved body areas, and IOP (Table 1).

Comment

Glaucoma is characterized by increased IOP, visual field loss, and changes in the optic nerve head. Although elevated IOP is common in ocular hypertension as well as in glaucoma, there is no glaucomatous visual field loss in ocular hypertension. In NTG, on the other hand, glaucomatous visual field loss and optic nerve head changes occur without an increase in IOP.⁶ Normal-tension glaucoma is a particular type of open-angle glaucoma. It is believed that NTG and high-tension glaucoma induce optic nerve head damage through different means.⁷ Alternative theories have been put forth to account for the glaucomatous damage to the optic nerve head that occurs in NTG, despite normal or close to normal IOP. These theories include vascular disorders (eg, ischemia, which interrupts the orthograde or retrograde axonal transport), excessive accumulation of free radicals, triggering of apoptosis, and low resistance of lamina cribrosa.⁸

Although there are various studies exploring ocular symptoms in patients with vitiligo,^9-15 only 1 study has examined the incidence of glaucoma in this group of patients.⁵ Biswas et al¹¹ examined ocular signs in 100 patients with vitiligo and found that 23% of patients had hypopigmented foci in the iris, 18% had pigmentation in the anterior chamber, 11% had chorioretinal degeneration, 9% had hypopigmentation of the retinal pigment epithelium, 5% had uveitis, and 34% were evaluated as normal. In this study, the authors concluded that there was a strong relationship between vitiligo and eye diseases.¹¹ When Gopal et al⁹ compared the eye examinations of 150 vitiligo patients and 100 healthy controls, they found uveitis, iris, and retinal pigmentary abnormalities in 16% of the vitiligo patients (P<.001).

Rogosić et al⁵ examined the incidence of glaucoma in 42 patients with vitiligo and found primary open-angle glaucoma in 24 (57%) patients. The patients had a mean age of 56 years, mean disease duration of 13 years, and mean IOP of 18 mm Hg for the right eye and 17.5 mm Hg for the left eye. The incidence of glaucoma was significantly higher in patients with vitiligo (P<.001) and increased with disease duration.⁵

Similar studies, however, have failed to show a relationship between vitiligo and glaucoma. In a study that evaluated the retinal pigment epithelium and the optic nerve in patients with vitiligo, Perossini et al¹⁰ found that the fundus examination of the patients was perfectly normal.

In our study, we detected NTG in 18.4% of patients with vitiligo. We did not find a significant statistical difference between patients with and without glaucoma (Table 2). Rogosić et al⁵ found a significant relationship between age and glaucoma incidence, but we did not find such a relationship, which we believe is because the mean age of our patients was lower than the prior study.

In vitiligo, melanocytes are destroyed through an unknown mechanism. Although the cellular and molecular mechanisms causing melanocytic destruction have not yet been determined, various hypotheses have been put forward to explain the etiopathogenesis of vitiligo. Among these, the most commonly held hypotheses are the neural, self-destruction, and autoimmune hypotheses.¹⁶

Based on the observation that stress and serious trauma could precipitate or trigger the onset of vitiligo,¹⁶ the neural hypothesis holds that neurochemical mediators released from the edges of the nerve endings exert toxic effects on melanocytes. The fact that both melanocytes and choroidal pigment cells originate from the mesenchyme and dermatomal spreading of segmental vitiligo are arguments propounded in favor of this hypothesis.¹⁷

The self-destruction hypothesis suggests that the intrinsic protective mechanisms that normally enable melanocytes to eliminate toxic intermediate products or metabolites on the melanogenesis path have been impaired in patients with vitiligo.^18,19 There is evidence of increased oxidative stress over the whole epidermis of patients with vitiligo.²⁰ Thus, free radicals affect melanin and cause membrane damage via lipid peroxidation reactions.²¹

The autoimmune hypothesis proposes a clinical relationship between vitiligo and several diseases believed to be autoimmune. Because the macrophage infiltration observed in vitiligo lesions is more pronounced on the perilesional skin, this hypothesis holds that macrophages may play a role in melanocyte removal.²¹ The Koebner phenomenon observed in vitiligo lends support to the critical role of trauma in the etiopathogenesis of the disease.

Although we could not explain the co-presence of vitiligo and glaucoma, we believe that it may result from the fact that both diseases are observed in tissues that have the same embryologic origin and etiology, perhaps vascular or neural disorders, excessive accumulation of free radicals, or the triggering of apoptosis. Dermatologists should be alert to the presence of glaucoma in patients with vitiligo because glaucoma is an eye disease that progresses slowly and may lead to vision loss.

Vitiligo is an acquired idiopathic disease of unknown etiology. Characterized by depigmented maculae and melanocytic destruction, it usually presents in childhood or young adulthood. The incidence of vitiligo ranges from 0.5% to 2% globally and there is no racial or gender predilection.¹

Patients with vitiligo may exhibit pigmentary abnormalities of the iris and retina.² Noninflammatory depigmented lesions of the ocular fundus observed in vitiligo indicate a local loss of melanocytes.¹ The fact that melanocytes are present not only in the skin and roots of the hair but also in the uvea and stria vascularis of the inner ear may explain the ophthalmologic disorders that accompany vitiligo.³ The term glaucoma refers to a large number of diseases that share a common feature: a distinctive and progressive optic neuropathy that may derive from various risks and is associated with a gradual loss of the visual field. If the disorder is not diagnosed and treated properly it could cause blindness.

Glaucoma is classified on the basis of the underlying abnormality that causes intraocular pressure (IOP) to rise. Glaucoma is first divided into open-angle and angle-closure glaucoma; glaucoma associated with developmental anomalies is then subdivided according to specific alterations.⁴

A PubMed search of articles indexed for MEDLINE using the terms vitiligo and glaucoma revealed only 1 study examining the incidence of glaucoma in patients with vitiligo.⁵ In the study reported here, we determined the presence of and possible risk factors for glaucoma in patients with vitiligo who had presented to the dermatology polyclinic.

Methods

We registered 49 patients diagnosed with vitiligo by clinical and Wood light examination and 20 age- and sex-matched healthy controls. Patients who were using topical corticosteroid treatments for vitiligo lesions located on the face were excluded from the study due to the glaucoma-inducing effects of corticosteroids. Similarly, patients who received drugs with sympathetic and parasympathetic action that can cause glaucoma were excluded.

The patients received a comprehensive ophthalmologic examination that included visual acuity testing, refraction, IOP measurement, gonioscopy, and fundus examination. All patients and controls underwent visual field tests and optic nerve head analyses using a confocal scanning laser ophthalmoscope. Glaucoma was diagnosed based on fundus examination, IOP measurement, field of vision evaluation, and optic nerve head analysis.

Informed consent was obtained from all participants. The research protocol was approved by the university hospital ethics committee.

Results

The study registered a total of 49 patients with vitiligo (28 female; 21 male) and 20 healthy controls (10 female; 10 male) with a variety of demographic and clinical characteristics (Table 1).

Mean (SD) IOP values were 13.83 (2.84) mm Hg for the right eye and 13.89 (2.60) mm Hg for the left eye in the vitiligo group. Values were 14.35 (2.56) mm Hg and 14.95 (2.92) mm Hg, respectively, in the control group. The IOP differences between the 2 groups were not statistically significant (P>.05).

Nine patients (18.4%) in the vitiligo group were found to have signs of normal-tension glaucoma (NTG). Optic nerve damage and vision loss occurs in the presence of normal IOP in NTG. There were no signs of NTG in the control group. Normal-tension glaucoma was diagnosed in the vitiligo group based on glaucomatous optic disc appearance, visual field defects, and structural analysis of the entire optic nerve head in confocal scanning laser ophthalmoscope. The NTG difference between the vitiligo and control groups was statistically significant (P=.04).

In the vitiligo group, of the 9 patients who had NTG, 6 had periorbital vitiligo lesions; the remaining 3 had none. Although patients who had periorbital lesions had a higher rate of glaucoma relative to the patients without periorbital lesions, the difference was not statistically significant (P>.05).

No statistically significant differences (P>.05) were found between patients with vitiligo with and without glaucoma in terms of age, sex, disease duration, family history of vitiligo, presence or absence of periorbital involvement, manner of involvement, percentage of the involved body areas, and IOP (Table 1).

Comment

Glaucoma is characterized by increased IOP, visual field loss, and changes in the optic nerve head. Although elevated IOP is common in ocular hypertension as well as in glaucoma, there is no glaucomatous visual field loss in ocular hypertension. In NTG, on the other hand, glaucomatous visual field loss and optic nerve head changes occur without an increase in IOP.⁶ Normal-tension glaucoma is a particular type of open-angle glaucoma. It is believed that NTG and high-tension glaucoma induce optic nerve head damage through different means.⁷ Alternative theories have been put forth to account for the glaucomatous damage to the optic nerve head that occurs in NTG, despite normal or close to normal IOP. These theories include vascular disorders (eg, ischemia, which interrupts the orthograde or retrograde axonal transport), excessive accumulation of free radicals, triggering of apoptosis, and low resistance of lamina cribrosa.⁸

Although there are various studies exploring ocular symptoms in patients with vitiligo,^9-15 only 1 study has examined the incidence of glaucoma in this group of patients.⁵ Biswas et al¹¹ examined ocular signs in 100 patients with vitiligo and found that 23% of patients had hypopigmented foci in the iris, 18% had pigmentation in the anterior chamber, 11% had chorioretinal degeneration, 9% had hypopigmentation of the retinal pigment epithelium, 5% had uveitis, and 34% were evaluated as normal. In this study, the authors concluded that there was a strong relationship between vitiligo and eye diseases.¹¹ When Gopal et al⁹ compared the eye examinations of 150 vitiligo patients and 100 healthy controls, they found uveitis, iris, and retinal pigmentary abnormalities in 16% of the vitiligo patients (P<.001).

Rogosić et al⁵ examined the incidence of glaucoma in 42 patients with vitiligo and found primary open-angle glaucoma in 24 (57%) patients. The patients had a mean age of 56 years, mean disease duration of 13 years, and mean IOP of 18 mm Hg for the right eye and 17.5 mm Hg for the left eye. The incidence of glaucoma was significantly higher in patients with vitiligo (P<.001) and increased with disease duration.⁵

Similar studies, however, have failed to show a relationship between vitiligo and glaucoma. In a study that evaluated the retinal pigment epithelium and the optic nerve in patients with vitiligo, Perossini et al¹⁰ found that the fundus examination of the patients was perfectly normal.

In our study, we detected NTG in 18.4% of patients with vitiligo. We did not find a significant statistical difference between patients with and without glaucoma (Table 2). Rogosić et al⁵ found a significant relationship between age and glaucoma incidence, but we did not find such a relationship, which we believe is because the mean age of our patients was lower than the prior study.

In vitiligo, melanocytes are destroyed through an unknown mechanism. Although the cellular and molecular mechanisms causing melanocytic destruction have not yet been determined, various hypotheses have been put forward to explain the etiopathogenesis of vitiligo. Among these, the most commonly held hypotheses are the neural, self-destruction, and autoimmune hypotheses.¹⁶

Based on the observation that stress and serious trauma could precipitate or trigger the onset of vitiligo,¹⁶ the neural hypothesis holds that neurochemical mediators released from the edges of the nerve endings exert toxic effects on melanocytes. The fact that both melanocytes and choroidal pigment cells originate from the mesenchyme and dermatomal spreading of segmental vitiligo are arguments propounded in favor of this hypothesis.¹⁷

The self-destruction hypothesis suggests that the intrinsic protective mechanisms that normally enable melanocytes to eliminate toxic intermediate products or metabolites on the melanogenesis path have been impaired in patients with vitiligo.^18,19 There is evidence of increased oxidative stress over the whole epidermis of patients with vitiligo.²⁰ Thus, free radicals affect melanin and cause membrane damage via lipid peroxidation reactions.²¹

The autoimmune hypothesis proposes a clinical relationship between vitiligo and several diseases believed to be autoimmune. Because the macrophage infiltration observed in vitiligo lesions is more pronounced on the perilesional skin, this hypothesis holds that macrophages may play a role in melanocyte removal.²¹ The Koebner phenomenon observed in vitiligo lends support to the critical role of trauma in the etiopathogenesis of the disease.

Although we could not explain the co-presence of vitiligo and glaucoma, we believe that it may result from the fact that both diseases are observed in tissues that have the same embryologic origin and etiology, perhaps vascular or neural disorders, excessive accumulation of free radicals, or the triggering of apoptosis. Dermatologists should be alert to the presence of glaucoma in patients with vitiligo because glaucoma is an eye disease that progresses slowly and may lead to vision loss.

Practice Gap

Conditions with dyschromia including terra firma-forme dermatosis (TFFD), confluent and reticulate papillomatosis (CARP), and acanthosis nigricans are difficult to distinguish from one another.

Diagnostic Tools

Since its development in 1920, dermatologists have utilized isopropyl alcohol in ways that exceed conventional antimicrobial purposes. If TFFP, CARP, and acanthosis nigricans are suspected, the first step in any algorithmic approach should be to rub the skin with an alcohol pad using firm continuous pressure in an attempt to remove pigmentation. Complete resolution of dyspigmentation strongly supports a diagnosis of TFFD¹ and can be curative (Figure). Alcohol can similarly lighten CARP but to a lesser degree than TFFD.² In contrast, acanthosis nigricans will display minimal to no improvement with isopropyl alcohol.

Practice Implications

Isopropyl alcohol has few side effects and each swab costs less than a dime. It is extremely cost effective compared to biopsy and subsequent pathology and laboratory costs. Patients appreciate a noninvasive initial approach, and it is rewarding to treat a cosmetically disturbing condition with ease.

Swabbing the skin with alcohol pads reflects light and improves visualization of veins that should be avoided during surgery. Alcohol-based gel inhibits bacterial colonization, reduces dermatoscope-related nosocomial infection, and enhances dermoscopic resolution.³ Alcohol swabs quickly remove gentian violet, which aids in porokeratosis diagnosis; the pathognomonic cornoid lamella of porokeratosis retains gentian violet.⁴ A solution of 70% isopropyl alcohol preserves myiasis larvae better than formalin, which causes larval tissue hardening. Alcohol also can be squeezed into the central punctum in myiasis as a form of treatment.⁵ In conclusion, alcohol represents a convenient, inexpensive, and helpful tool in the dermatologist’s armamentarium that should not be forgotten.

Practice Gap

Conditions with dyschromia including terra firma-forme dermatosis (TFFD), confluent and reticulate papillomatosis (CARP), and acanthosis nigricans are difficult to distinguish from one another.

Diagnostic Tools

Since its development in 1920, dermatologists have utilized isopropyl alcohol in ways that exceed conventional antimicrobial purposes. If TFFP, CARP, and acanthosis nigricans are suspected, the first step in any algorithmic approach should be to rub the skin with an alcohol pad using firm continuous pressure in an attempt to remove pigmentation. Complete resolution of dyspigmentation strongly supports a diagnosis of TFFD¹ and can be curative (Figure). Alcohol can similarly lighten CARP but to a lesser degree than TFFD.² In contrast, acanthosis nigricans will display minimal to no improvement with isopropyl alcohol.

Practice Implications

Isopropyl alcohol has few side effects and each swab costs less than a dime. It is extremely cost effective compared to biopsy and subsequent pathology and laboratory costs. Patients appreciate a noninvasive initial approach, and it is rewarding to treat a cosmetically disturbing condition with ease.

Swabbing the skin with alcohol pads reflects light and improves visualization of veins that should be avoided during surgery. Alcohol-based gel inhibits bacterial colonization, reduces dermatoscope-related nosocomial infection, and enhances dermoscopic resolution.³ Alcohol swabs quickly remove gentian violet, which aids in porokeratosis diagnosis; the pathognomonic cornoid lamella of porokeratosis retains gentian violet.⁴ A solution of 70% isopropyl alcohol preserves myiasis larvae better than formalin, which causes larval tissue hardening. Alcohol also can be squeezed into the central punctum in myiasis as a form of treatment.⁵ In conclusion, alcohol represents a convenient, inexpensive, and helpful tool in the dermatologist’s armamentarium that should not be forgotten.

Practice Gap

Conditions with dyschromia including terra firma-forme dermatosis (TFFD), confluent and reticulate papillomatosis (CARP), and acanthosis nigricans are difficult to distinguish from one another.

Diagnostic Tools

Since its development in 1920, dermatologists have utilized isopropyl alcohol in ways that exceed conventional antimicrobial purposes. If TFFP, CARP, and acanthosis nigricans are suspected, the first step in any algorithmic approach should be to rub the skin with an alcohol pad using firm continuous pressure in an attempt to remove pigmentation. Complete resolution of dyspigmentation strongly supports a diagnosis of TFFD¹ and can be curative (Figure). Alcohol can similarly lighten CARP but to a lesser degree than TFFD.² In contrast, acanthosis nigricans will display minimal to no improvement with isopropyl alcohol.

Practice Implications

Isopropyl alcohol has few side effects and each swab costs less than a dime. It is extremely cost effective compared to biopsy and subsequent pathology and laboratory costs. Patients appreciate a noninvasive initial approach, and it is rewarding to treat a cosmetically disturbing condition with ease.

Swabbing the skin with alcohol pads reflects light and improves visualization of veins that should be avoided during surgery. Alcohol-based gel inhibits bacterial colonization, reduces dermatoscope-related nosocomial infection, and enhances dermoscopic resolution.³ Alcohol swabs quickly remove gentian violet, which aids in porokeratosis diagnosis; the pathognomonic cornoid lamella of porokeratosis retains gentian violet.⁴ A solution of 70% isopropyl alcohol preserves myiasis larvae better than formalin, which causes larval tissue hardening. Alcohol also can be squeezed into the central punctum in myiasis as a form of treatment.⁵ In conclusion, alcohol represents a convenient, inexpensive, and helpful tool in the dermatologist’s armamentarium that should not be forgotten.