Quiz

The Diagnosis: Amelanotic Melanoma In Situ

Histopathology revealed a broad asymmetric melanocytic proliferation at the dermoepidermal junction, consisting both of singly dispersed cells as well as randomly positioned nests (Figure 1). The single cells demonstrated junctional confluence and extension along adnexal structures highlighted by melan-A stain 
(Figure 2). The melanocytes were markedly atypical with enlarged and hyperchromatic nuclei containing multiple nucleoli. No dermal involvement was seen. There was papillary dermal fibrosis and an active host lymphocytic response. Based on these findings, a diagnosis of amelanotic melanoma in situ was made.

Figure 1. Histopathology revealed confluence of atypical melanocytes at the dermoepidermal junction and pagetoid scatter of melanocytes to the spinous layer (A)(H&E, original magnification ×4). Higher-power magnification highlighted the atypia of the individual melanocytes (B)(H&E, original magnification ×10).

Subsequent scouting punch biopsies at the superior, anterior, and posterior aspects of the lesion were performed (Figure 3). All 3 revealed a similar nested and single cell proliferation at the dermoepidermal junction, confirming residual amelanotic melanoma in situ. The patient was referred to the otolaryngology department and underwent wide local excision with 5-mm margins and reconstructive repair.

Amelanotic melanoma comprises 2% to 8% of cutaneous melanomas. It is more common in fair-skinned elderly women with an average age of diagnosis of 61.8 years. Because features typically associated with melanoma such as asymmetry, border irregularity, and color variegation often are absent, amelanotic melanoma represents a notable diagnostic challenge for clinicians. Lesions can present nonspecifically as erythematous macules, papules, patches, or plaques and can have associated pruritus and scale.^1,2

Clinical misdiagnoses for amelanotic melanoma include Bowen disease, basal cell carcinoma, actinic keratosis, lichenoid keratosis, intradermal nevus, dermatofibroma, inflamed seborrheic keratosis, nummular dermatitis, pyogenic granuloma, and granuloma annulare.^1-6 There have been few case reports of amelanotic melanoma in situ, with most being the lentigo maligna variant that were initially clinically diagnosed as superficial basal cell carcinoma, 
Bowen disease, or dermatitis.^7,8 In one case report, an amelanotic lentigo maligna was incidentally discovered after performing a mapping shave biopsy on what was normal-appearing skin.⁹

Dermoscopic evidence of vascular structures in lesions, including the presence of dotted vessels, milky red areas, and/or serpentine (linear irregular) vessels, may be the only clues to suggest amelanotic melanoma before biopsy. However, these findings are nonspecific and can be seen in other benign and malignant skin conditions.²

Complete surgical excision is the standard treatment of amelanotic melanoma in situ given its potential for invasion. However, the lack of pigment can make margins difficult to define. Because of its ability to detect disease beyond visual margins, Mohs micrographic surgery may have better cure rates than conventional excision.⁴ Prognosis for amelanotic melanoma is the same as other melanomas of equal thickness and location, though delay in diagnosis can adversely affect outcomes. Furthermore, amelanotic melanoma in situ can rapidly progress to invasive melanoma.^3,5 Thus it is important to maintain clinical suspicion for amelanotic melanoma in fair-skinned elderly women presenting with a persistent or recurring erythematous scaly lesion on sun-exposed skin.

The Diagnosis: Amelanotic Melanoma In Situ

Histopathology revealed a broad asymmetric melanocytic proliferation at the dermoepidermal junction, consisting both of singly dispersed cells as well as randomly positioned nests (Figure 1). The single cells demonstrated junctional confluence and extension along adnexal structures highlighted by melan-A stain 
(Figure 2). The melanocytes were markedly atypical with enlarged and hyperchromatic nuclei containing multiple nucleoli. No dermal involvement was seen. There was papillary dermal fibrosis and an active host lymphocytic response. Based on these findings, a diagnosis of amelanotic melanoma in situ was made.

Figure 1. Histopathology revealed confluence of atypical melanocytes at the dermoepidermal junction and pagetoid scatter of melanocytes to the spinous layer (A)(H&E, original magnification ×4). Higher-power magnification highlighted the atypia of the individual melanocytes (B)(H&E, original magnification ×10).

Subsequent scouting punch biopsies at the superior, anterior, and posterior aspects of the lesion were performed (Figure 3). All 3 revealed a similar nested and single cell proliferation at the dermoepidermal junction, confirming residual amelanotic melanoma in situ. The patient was referred to the otolaryngology department and underwent wide local excision with 5-mm margins and reconstructive repair.

Amelanotic melanoma comprises 2% to 8% of cutaneous melanomas. It is more common in fair-skinned elderly women with an average age of diagnosis of 61.8 years. Because features typically associated with melanoma such as asymmetry, border irregularity, and color variegation often are absent, amelanotic melanoma represents a notable diagnostic challenge for clinicians. Lesions can present nonspecifically as erythematous macules, papules, patches, or plaques and can have associated pruritus and scale.^1,2

Clinical misdiagnoses for amelanotic melanoma include Bowen disease, basal cell carcinoma, actinic keratosis, lichenoid keratosis, intradermal nevus, dermatofibroma, inflamed seborrheic keratosis, nummular dermatitis, pyogenic granuloma, and granuloma annulare.^1-6 There have been few case reports of amelanotic melanoma in situ, with most being the lentigo maligna variant that were initially clinically diagnosed as superficial basal cell carcinoma, 
Bowen disease, or dermatitis.^7,8 In one case report, an amelanotic lentigo maligna was incidentally discovered after performing a mapping shave biopsy on what was normal-appearing skin.⁹

Dermoscopic evidence of vascular structures in lesions, including the presence of dotted vessels, milky red areas, and/or serpentine (linear irregular) vessels, may be the only clues to suggest amelanotic melanoma before biopsy. However, these findings are nonspecific and can be seen in other benign and malignant skin conditions.²

Complete surgical excision is the standard treatment of amelanotic melanoma in situ given its potential for invasion. However, the lack of pigment can make margins difficult to define. Because of its ability to detect disease beyond visual margins, Mohs micrographic surgery may have better cure rates than conventional excision.⁴ Prognosis for amelanotic melanoma is the same as other melanomas of equal thickness and location, though delay in diagnosis can adversely affect outcomes. Furthermore, amelanotic melanoma in situ can rapidly progress to invasive melanoma.^3,5 Thus it is important to maintain clinical suspicion for amelanotic melanoma in fair-skinned elderly women presenting with a persistent or recurring erythematous scaly lesion on sun-exposed skin.

The Diagnosis: Amelanotic Melanoma In Situ

Histopathology revealed a broad asymmetric melanocytic proliferation at the dermoepidermal junction, consisting both of singly dispersed cells as well as randomly positioned nests (Figure 1). The single cells demonstrated junctional confluence and extension along adnexal structures highlighted by melan-A stain 
(Figure 2). The melanocytes were markedly atypical with enlarged and hyperchromatic nuclei containing multiple nucleoli. No dermal involvement was seen. There was papillary dermal fibrosis and an active host lymphocytic response. Based on these findings, a diagnosis of amelanotic melanoma in situ was made.

Figure 1. Histopathology revealed confluence of atypical melanocytes at the dermoepidermal junction and pagetoid scatter of melanocytes to the spinous layer (A)(H&E, original magnification ×4). Higher-power magnification highlighted the atypia of the individual melanocytes (B)(H&E, original magnification ×10).

Subsequent scouting punch biopsies at the superior, anterior, and posterior aspects of the lesion were performed (Figure 3). All 3 revealed a similar nested and single cell proliferation at the dermoepidermal junction, confirming residual amelanotic melanoma in situ. The patient was referred to the otolaryngology department and underwent wide local excision with 5-mm margins and reconstructive repair.

Amelanotic melanoma comprises 2% to 8% of cutaneous melanomas. It is more common in fair-skinned elderly women with an average age of diagnosis of 61.8 years. Because features typically associated with melanoma such as asymmetry, border irregularity, and color variegation often are absent, amelanotic melanoma represents a notable diagnostic challenge for clinicians. Lesions can present nonspecifically as erythematous macules, papules, patches, or plaques and can have associated pruritus and scale.^1,2

Clinical misdiagnoses for amelanotic melanoma include Bowen disease, basal cell carcinoma, actinic keratosis, lichenoid keratosis, intradermal nevus, dermatofibroma, inflamed seborrheic keratosis, nummular dermatitis, pyogenic granuloma, and granuloma annulare.^1-6 There have been few case reports of amelanotic melanoma in situ, with most being the lentigo maligna variant that were initially clinically diagnosed as superficial basal cell carcinoma, 
Bowen disease, or dermatitis.^7,8 In one case report, an amelanotic lentigo maligna was incidentally discovered after performing a mapping shave biopsy on what was normal-appearing skin.⁹

Dermoscopic evidence of vascular structures in lesions, including the presence of dotted vessels, milky red areas, and/or serpentine (linear irregular) vessels, may be the only clues to suggest amelanotic melanoma before biopsy. However, these findings are nonspecific and can be seen in other benign and malignant skin conditions.²

Complete surgical excision is the standard treatment of amelanotic melanoma in situ given its potential for invasion. However, the lack of pigment can make margins difficult to define. Because of its ability to detect disease beyond visual margins, Mohs micrographic surgery may have better cure rates than conventional excision.⁴ Prognosis for amelanotic melanoma is the same as other melanomas of equal thickness and location, though delay in diagnosis can adversely affect outcomes. Furthermore, amelanotic melanoma in situ can rapidly progress to invasive melanoma.^3,5 Thus it is important to maintain clinical suspicion for amelanotic melanoma in fair-skinned elderly women presenting with a persistent or recurring erythematous scaly lesion on sun-exposed skin.

ANSWER 
The correct answer is oral terbinafine or griseofulvin, plus a two-week taper of prednisone (choice “d”); further discussion follows. Most authorities recommend the use of oral steroids with terbinafine (choice “a”) or griseofulvin (choice “b”), to dampen the acute inflammatory reaction to the fungal antigen. Some sources advise the use of itraconazole (choice “c”) but not as a single agent.

DISCUSSION
This case is a classic representation of kerion, a type of tinea capitis. This distinctive presentation results from not only active localized fungal infection with one of the dermatophytes, but also an allergic response to the fungal antigen. (This antigen can also trigger a widespread eczematous rash called an id reaction.) The resulting boggy, tender mass often oozes pus and usually provokes significant localized adenopathy.

A more common type of tinea capitis is uncomplicated dermatophytic infection of the scalp, presenting as mild localized scaling and modest hair loss, with no edema or redness to speak of. Kerion, by contrast, is far more acute and involves an impressive amount of localized redness and edema, along with modest hair loss, purulence, bloody drainage, and marked tenderness. Untreated, kerion can result in permanent scarring alopecia.

Several different dermatophytes have been isolated from kerions, including Trichophyton tonsurans, T violaceum, and various members of the Microsporum family. These zoophilic or geophilic organisms affect children far more than adults. Distinguishing the causative type is significant, because different drugs are required to effectively treat each. This is why a fungal culture is done at the outset.

When the diagnosis is in doubt, a punch biopsy may be necessary, with the sample divided for processing of default H&E stains and for fungal culture. Other information can be obtained by plucking a few hairs from the mass and examining them under 10x power to see if fungal hyphae are confined to the insides of the hair shafts (endothrix) or the outside of the shafts (ectothrix).

This is one situation in which KOH is not helpful for diagnosis: The organisms are too deep to obtain with a superficial scrape.

A number of scalp conditions can mimic a kerion, including lichen planopilaris and folliculitis decalvans. Several years ago, I had a patient who presented with a similar lesion that turned out to be squamous cell carcinoma—which eventually metastasized and led to his death.

TREATMENT
Treatment of more severe types of tinea capitis can be trying, even when the diagnosis is nailed down. The challenge becomes treating the problem long and strong enough to produce a cure.

In this case, I started the patient (who, at age 8, weighed 110 pounds) on a month-long course of terbinafine (250 mg/d) with a two-week taper of prednisone (40 mg). The expectation was that this would rapidly diminish the edema and pain while we waited for the culture results.

If the results showed the expected T tonsurans, treatment would continue as planned. If the cause turned out to be one of the Microsporum species, a switch to griseofulvin, at relatively high doses, would be considered. 

ANSWER 
The correct answer is oral terbinafine or griseofulvin, plus a two-week taper of prednisone (choice “d”); further discussion follows. Most authorities recommend the use of oral steroids with terbinafine (choice “a”) or griseofulvin (choice “b”), to dampen the acute inflammatory reaction to the fungal antigen. Some sources advise the use of itraconazole (choice “c”) but not as a single agent.

DISCUSSION
This case is a classic representation of kerion, a type of tinea capitis. This distinctive presentation results from not only active localized fungal infection with one of the dermatophytes, but also an allergic response to the fungal antigen. (This antigen can also trigger a widespread eczematous rash called an id reaction.) The resulting boggy, tender mass often oozes pus and usually provokes significant localized adenopathy.

A more common type of tinea capitis is uncomplicated dermatophytic infection of the scalp, presenting as mild localized scaling and modest hair loss, with no edema or redness to speak of. Kerion, by contrast, is far more acute and involves an impressive amount of localized redness and edema, along with modest hair loss, purulence, bloody drainage, and marked tenderness. Untreated, kerion can result in permanent scarring alopecia.

Several different dermatophytes have been isolated from kerions, including Trichophyton tonsurans, T violaceum, and various members of the Microsporum family. These zoophilic or geophilic organisms affect children far more than adults. Distinguishing the causative type is significant, because different drugs are required to effectively treat each. This is why a fungal culture is done at the outset.

When the diagnosis is in doubt, a punch biopsy may be necessary, with the sample divided for processing of default H&E stains and for fungal culture. Other information can be obtained by plucking a few hairs from the mass and examining them under 10x power to see if fungal hyphae are confined to the insides of the hair shafts (endothrix) or the outside of the shafts (ectothrix).

This is one situation in which KOH is not helpful for diagnosis: The organisms are too deep to obtain with a superficial scrape.

A number of scalp conditions can mimic a kerion, including lichen planopilaris and folliculitis decalvans. Several years ago, I had a patient who presented with a similar lesion that turned out to be squamous cell carcinoma—which eventually metastasized and led to his death.

TREATMENT
Treatment of more severe types of tinea capitis can be trying, even when the diagnosis is nailed down. The challenge becomes treating the problem long and strong enough to produce a cure.

In this case, I started the patient (who, at age 8, weighed 110 pounds) on a month-long course of terbinafine (250 mg/d) with a two-week taper of prednisone (40 mg). The expectation was that this would rapidly diminish the edema and pain while we waited for the culture results.

If the results showed the expected T tonsurans, treatment would continue as planned. If the cause turned out to be one of the Microsporum species, a switch to griseofulvin, at relatively high doses, would be considered. 

ANSWER 
The correct answer is oral terbinafine or griseofulvin, plus a two-week taper of prednisone (choice “d”); further discussion follows. Most authorities recommend the use of oral steroids with terbinafine (choice “a”) or griseofulvin (choice “b”), to dampen the acute inflammatory reaction to the fungal antigen. Some sources advise the use of itraconazole (choice “c”) but not as a single agent.

DISCUSSION
This case is a classic representation of kerion, a type of tinea capitis. This distinctive presentation results from not only active localized fungal infection with one of the dermatophytes, but also an allergic response to the fungal antigen. (This antigen can also trigger a widespread eczematous rash called an id reaction.) The resulting boggy, tender mass often oozes pus and usually provokes significant localized adenopathy.

A more common type of tinea capitis is uncomplicated dermatophytic infection of the scalp, presenting as mild localized scaling and modest hair loss, with no edema or redness to speak of. Kerion, by contrast, is far more acute and involves an impressive amount of localized redness and edema, along with modest hair loss, purulence, bloody drainage, and marked tenderness. Untreated, kerion can result in permanent scarring alopecia.

Several different dermatophytes have been isolated from kerions, including Trichophyton tonsurans, T violaceum, and various members of the Microsporum family. These zoophilic or geophilic organisms affect children far more than adults. Distinguishing the causative type is significant, because different drugs are required to effectively treat each. This is why a fungal culture is done at the outset.

When the diagnosis is in doubt, a punch biopsy may be necessary, with the sample divided for processing of default H&E stains and for fungal culture. Other information can be obtained by plucking a few hairs from the mass and examining them under 10x power to see if fungal hyphae are confined to the insides of the hair shafts (endothrix) or the outside of the shafts (ectothrix).

This is one situation in which KOH is not helpful for diagnosis: The organisms are too deep to obtain with a superficial scrape.

A number of scalp conditions can mimic a kerion, including lichen planopilaris and folliculitis decalvans. Several years ago, I had a patient who presented with a similar lesion that turned out to be squamous cell carcinoma—which eventually metastasized and led to his death.

TREATMENT
Treatment of more severe types of tinea capitis can be trying, even when the diagnosis is nailed down. The challenge becomes treating the problem long and strong enough to produce a cure.

In this case, I started the patient (who, at age 8, weighed 110 pounds) on a month-long course of terbinafine (250 mg/d) with a two-week taper of prednisone (40 mg). The expectation was that this would rapidly diminish the edema and pain while we waited for the culture results.

If the results showed the expected T tonsurans, treatment would continue as planned. If the cause turned out to be one of the Microsporum species, a switch to griseofulvin, at relatively high doses, would be considered. 

ANSWER
The radiograph shows an enteric tube passing through the gastrointestinal tract. However, it extends low into the left lower quadrant, loops around the right lower quadrant, and then heads up toward the left upper quadrant. Such a course is atypical and concerning for displaced position.

The radiologists concurred, and it was decided to instill some water-soluble contrast and repeat the KUB for further evaluation. That image is shown here. Note that the contrast does not appear to be in the stomach, as no gastric folds are visible. It accumulates in the left upper quadrant, under the diaphragm. Such a finding is concerning for possible gastric perforation.

The tube was promptly withdrawn, and urgent surgical consultation was obtained.

ANSWER
The radiograph shows an enteric tube passing through the gastrointestinal tract. However, it extends low into the left lower quadrant, loops around the right lower quadrant, and then heads up toward the left upper quadrant. Such a course is atypical and concerning for displaced position.

The radiologists concurred, and it was decided to instill some water-soluble contrast and repeat the KUB for further evaluation. That image is shown here. Note that the contrast does not appear to be in the stomach, as no gastric folds are visible. It accumulates in the left upper quadrant, under the diaphragm. Such a finding is concerning for possible gastric perforation.

The tube was promptly withdrawn, and urgent surgical consultation was obtained.

ANSWER
The radiograph shows an enteric tube passing through the gastrointestinal tract. However, it extends low into the left lower quadrant, loops around the right lower quadrant, and then heads up toward the left upper quadrant. Such a course is atypical and concerning for displaced position.

The radiologists concurred, and it was decided to instill some water-soluble contrast and repeat the KUB for further evaluation. That image is shown here. Note that the contrast does not appear to be in the stomach, as no gastric folds are visible. It accumulates in the left upper quadrant, under the diaphragm. Such a finding is concerning for possible gastric perforation.

The tube was promptly withdrawn, and urgent surgical consultation was obtained.

ANSWER
The correct interpretation is normal sinus rhythm with an acute anterior MI (STEMI) and inferolateral injury. In the absence of left ventricular hypertrophy and left bundle-branch block, an acute anterior MI manifests with new ST elevations ≥ 0.1 mV, measured at the J point in leads V₂-V₃. Inferolateral injury is indicated by ST elevations in leads II, III, and aVF, as well as ST elevations in leads V₄-V₆.

Laboratory findings confirmed the diagnosis of a new infarction, and cardiac catheterization revealed significant blockage in the proximal left anterior descending and circumflex coronary arteries. These were treated percutaneously, and the patient recovered without sequelae.

ANSWER
The correct interpretation is normal sinus rhythm with an acute anterior MI (STEMI) and inferolateral injury. In the absence of left ventricular hypertrophy and left bundle-branch block, an acute anterior MI manifests with new ST elevations ≥ 0.1 mV, measured at the J point in leads V₂-V₃. Inferolateral injury is indicated by ST elevations in leads II, III, and aVF, as well as ST elevations in leads V₄-V₆.

Laboratory findings confirmed the diagnosis of a new infarction, and cardiac catheterization revealed significant blockage in the proximal left anterior descending and circumflex coronary arteries. These were treated percutaneously, and the patient recovered without sequelae.

ANSWER
The correct interpretation is normal sinus rhythm with an acute anterior MI (STEMI) and inferolateral injury. In the absence of left ventricular hypertrophy and left bundle-branch block, an acute anterior MI manifests with new ST elevations ≥ 0.1 mV, measured at the J point in leads V₂-V₃. Inferolateral injury is indicated by ST elevations in leads II, III, and aVF, as well as ST elevations in leads V₄-V₆.

Laboratory findings confirmed the diagnosis of a new infarction, and cardiac catheterization revealed significant blockage in the proximal left anterior descending and circumflex coronary arteries. These were treated percutaneously, and the patient recovered without sequelae.

The Diagnosis: Herpes Simplex Vegetans

Histopathologic examination using hematoxylin and eosin stain demonstrated marked pseudoepitheliomatous hyperplasia with granulation tissue, ulceration, and abundant exudate joined by a dense mixed inflammatory cell infiltrate that included a myriad of eosinophils (Figure, A). At higher power (Figure, B), many single and multinucleate acantholytic keratinocytes showed ground-glass nuclei and peripheral margination of chromatin within zones of ulceration and crust. Viral culture and direct fluorescent antibody assay identified herpes simplex virus (HSV) type 2. Based on the clinical and histopathologic findings, the patient was diagnosed with herpes simplex vegetans. He was initially treated with oral acyclovir and then oral famciclovir but showed minimal improvement. Eventually, he was referred to surgery and the mass was totally excised with clear margins and no evidence of underlying malignancy.

Histopathology revealed marked pseudoepitheliomatous hyperplasia, ulceration, and a dense mixed inflammatory cell infiltrate (A)(H&E, original magnification ×20). Many multinucleate acantholytic keratinocytes with ground-glass nuclei and peripheral margination of chromatin were shown (B)(H&E, original magnification ×400).

Herpes simplex virus is one of the most common sexually transmitted infections, with a notably increased incidence and prevalence among individuals with human immunodeficiency virus (HIV) infection.¹ Although typical HSV manifestation in immunocompetent patients includes clustered vesicles and/or ulcerations, immunocompromised patients may have unusual presentations, such as persistent and extensive ulcerations or nodular hyperkeratotic lesions.^2,3 Herpes vegetans, a term used to describe these atypical exophytic lesions, rarely has been reported in literature, but its presence should raise suspicion for possible underlying immunocompromise. The pathogenesis behind the hypertrophic nature of these lesions is not well understood, but it is postulated that the immune dysregulation from concomitant HIV and HSV infection plays a role.² Overproduction of tumor necrosis factor and IL-6 by HIV-infected dermal dendritic cells causes an increase in antiapoptotic factors within the epidermis, resulting in enhanced keratinocyte proliferation and clinical hyperkeratosis.^2,4

The differential diagnosis for herpes vegetans is somewhat broad, owing to the verrucous and often eroded appearance of the lesions. Biopsy and cultures can be obtained to differentiate from condyloma acuminatum, condyloma latum (secondary syphilis), pyoderma vegetans, pemphigus vegetans, granuloma inguinale, extraintestinal Crohn disease, deep fungal infections, cutaneous tuberculosis, and malignancy.^2-4 Histopathology shows epithelial hyperplasia and ulceration with scattered multinucleate keratinocytes, usually at the periphery of the ulcer, and intranuclear inclusions typical of HSV. In addition, a dense dermal infiltrate of lymphocytes, histiocytes, plasma cells, and eosinophils is usually present beneath the base of the ulcer.^2,4

Treatment options for herpes vegetans are limited due to the high prevalence of acyclovir-resistant (ACV-R) HSV-2 strains in HIV patients. Valacyclovir and penciclovir have been largely ineffective against ACV-R HSV due to their dependence on the same enzyme—thymidine kinase—involved in the mechanism of acyclovir resistance. Intravenous foscarnet and cidofovir have shown efficacy against ACV-R virus, but concerns of nephrotoxicity have limited their use over prolonged intervals.⁵ Castelo-Soccio et al⁶ reported promising results with intralesional cidofovir. This route of administration provides the advantage of increased bioavailability with reduced risk for nephrotoxicity.⁶ Finally, surgical resection may be considered for refractory lesions to circumvent the toxicity from systemically administered drugs.³

The Diagnosis: Herpes Simplex Vegetans

Histopathologic examination using hematoxylin and eosin stain demonstrated marked pseudoepitheliomatous hyperplasia with granulation tissue, ulceration, and abundant exudate joined by a dense mixed inflammatory cell infiltrate that included a myriad of eosinophils (Figure, A). At higher power (Figure, B), many single and multinucleate acantholytic keratinocytes showed ground-glass nuclei and peripheral margination of chromatin within zones of ulceration and crust. Viral culture and direct fluorescent antibody assay identified herpes simplex virus (HSV) type 2. Based on the clinical and histopathologic findings, the patient was diagnosed with herpes simplex vegetans. He was initially treated with oral acyclovir and then oral famciclovir but showed minimal improvement. Eventually, he was referred to surgery and the mass was totally excised with clear margins and no evidence of underlying malignancy.

Histopathology revealed marked pseudoepitheliomatous hyperplasia, ulceration, and a dense mixed inflammatory cell infiltrate (A)(H&E, original magnification ×20). Many multinucleate acantholytic keratinocytes with ground-glass nuclei and peripheral margination of chromatin were shown (B)(H&E, original magnification ×400).

Herpes simplex virus is one of the most common sexually transmitted infections, with a notably increased incidence and prevalence among individuals with human immunodeficiency virus (HIV) infection.¹ Although typical HSV manifestation in immunocompetent patients includes clustered vesicles and/or ulcerations, immunocompromised patients may have unusual presentations, such as persistent and extensive ulcerations or nodular hyperkeratotic lesions.^2,3 Herpes vegetans, a term used to describe these atypical exophytic lesions, rarely has been reported in literature, but its presence should raise suspicion for possible underlying immunocompromise. The pathogenesis behind the hypertrophic nature of these lesions is not well understood, but it is postulated that the immune dysregulation from concomitant HIV and HSV infection plays a role.² Overproduction of tumor necrosis factor and IL-6 by HIV-infected dermal dendritic cells causes an increase in antiapoptotic factors within the epidermis, resulting in enhanced keratinocyte proliferation and clinical hyperkeratosis.^2,4

The differential diagnosis for herpes vegetans is somewhat broad, owing to the verrucous and often eroded appearance of the lesions. Biopsy and cultures can be obtained to differentiate from condyloma acuminatum, condyloma latum (secondary syphilis), pyoderma vegetans, pemphigus vegetans, granuloma inguinale, extraintestinal Crohn disease, deep fungal infections, cutaneous tuberculosis, and malignancy.^2-4 Histopathology shows epithelial hyperplasia and ulceration with scattered multinucleate keratinocytes, usually at the periphery of the ulcer, and intranuclear inclusions typical of HSV. In addition, a dense dermal infiltrate of lymphocytes, histiocytes, plasma cells, and eosinophils is usually present beneath the base of the ulcer.^2,4

Treatment options for herpes vegetans are limited due to the high prevalence of acyclovir-resistant (ACV-R) HSV-2 strains in HIV patients. Valacyclovir and penciclovir have been largely ineffective against ACV-R HSV due to their dependence on the same enzyme—thymidine kinase—involved in the mechanism of acyclovir resistance. Intravenous foscarnet and cidofovir have shown efficacy against ACV-R virus, but concerns of nephrotoxicity have limited their use over prolonged intervals.⁵ Castelo-Soccio et al⁶ reported promising results with intralesional cidofovir. This route of administration provides the advantage of increased bioavailability with reduced risk for nephrotoxicity.⁶ Finally, surgical resection may be considered for refractory lesions to circumvent the toxicity from systemically administered drugs.³

The Diagnosis: Herpes Simplex Vegetans

Histopathologic examination using hematoxylin and eosin stain demonstrated marked pseudoepitheliomatous hyperplasia with granulation tissue, ulceration, and abundant exudate joined by a dense mixed inflammatory cell infiltrate that included a myriad of eosinophils (Figure, A). At higher power (Figure, B), many single and multinucleate acantholytic keratinocytes showed ground-glass nuclei and peripheral margination of chromatin within zones of ulceration and crust. Viral culture and direct fluorescent antibody assay identified herpes simplex virus (HSV) type 2. Based on the clinical and histopathologic findings, the patient was diagnosed with herpes simplex vegetans. He was initially treated with oral acyclovir and then oral famciclovir but showed minimal improvement. Eventually, he was referred to surgery and the mass was totally excised with clear margins and no evidence of underlying malignancy.

Histopathology revealed marked pseudoepitheliomatous hyperplasia, ulceration, and a dense mixed inflammatory cell infiltrate (A)(H&E, original magnification ×20). Many multinucleate acantholytic keratinocytes with ground-glass nuclei and peripheral margination of chromatin were shown (B)(H&E, original magnification ×400).

Herpes simplex virus is one of the most common sexually transmitted infections, with a notably increased incidence and prevalence among individuals with human immunodeficiency virus (HIV) infection.¹ Although typical HSV manifestation in immunocompetent patients includes clustered vesicles and/or ulcerations, immunocompromised patients may have unusual presentations, such as persistent and extensive ulcerations or nodular hyperkeratotic lesions.^2,3 Herpes vegetans, a term used to describe these atypical exophytic lesions, rarely has been reported in literature, but its presence should raise suspicion for possible underlying immunocompromise. The pathogenesis behind the hypertrophic nature of these lesions is not well understood, but it is postulated that the immune dysregulation from concomitant HIV and HSV infection plays a role.² Overproduction of tumor necrosis factor and IL-6 by HIV-infected dermal dendritic cells causes an increase in antiapoptotic factors within the epidermis, resulting in enhanced keratinocyte proliferation and clinical hyperkeratosis.^2,4

The differential diagnosis for herpes vegetans is somewhat broad, owing to the verrucous and often eroded appearance of the lesions. Biopsy and cultures can be obtained to differentiate from condyloma acuminatum, condyloma latum (secondary syphilis), pyoderma vegetans, pemphigus vegetans, granuloma inguinale, extraintestinal Crohn disease, deep fungal infections, cutaneous tuberculosis, and malignancy.^2-4 Histopathology shows epithelial hyperplasia and ulceration with scattered multinucleate keratinocytes, usually at the periphery of the ulcer, and intranuclear inclusions typical of HSV. In addition, a dense dermal infiltrate of lymphocytes, histiocytes, plasma cells, and eosinophils is usually present beneath the base of the ulcer.^2,4

Treatment options for herpes vegetans are limited due to the high prevalence of acyclovir-resistant (ACV-R) HSV-2 strains in HIV patients. Valacyclovir and penciclovir have been largely ineffective against ACV-R HSV due to their dependence on the same enzyme—thymidine kinase—involved in the mechanism of acyclovir resistance. Intravenous foscarnet and cidofovir have shown efficacy against ACV-R virus, but concerns of nephrotoxicity have limited their use over prolonged intervals.⁵ Castelo-Soccio et al⁶ reported promising results with intralesional cidofovir. This route of administration provides the advantage of increased bioavailability with reduced risk for nephrotoxicity.⁶ Finally, surgical resection may be considered for refractory lesions to circumvent the toxicity from systemically administered drugs.³

ANSWER
The correct interpretation includes normal sinus rhythm, right atrial enlargement, left ventricular hypertrophy, and a prolonged QT interval. Normal sinus rhythm is indicated by a P for every QRS and a QRS for every P, with a constant PR interval (see rhythm strip of lead I).

Right atrial enlargement is evidenced by the tall P waves in leads II, III, aVF, and V₁. Note that there is no biphasic P wave in lead V₁, so there is no evidence of accompanying left atrial enlargement.

High-voltage limb leads (sum of R in lead I and S in lead III ≥ 25 mm) or precordial leads (sum of S in V1 and R in V₅ or V₆ ≥ 35 mm) are indicative of left ventricular hypertrophy.

The QTc interval of 653 ms with a normal sinus rate is worrisome for prolonged QT syndrome. A review of the history shows the patient to be taking two drugs (lithium, azithromycin) known to prolong the QT interval. Although it is not known whether this patient has inherent QT prolongation, use of these types of agents should be avoided.  

ANSWER
The correct interpretation includes normal sinus rhythm, right atrial enlargement, left ventricular hypertrophy, and a prolonged QT interval. Normal sinus rhythm is indicated by a P for every QRS and a QRS for every P, with a constant PR interval (see rhythm strip of lead I).

Right atrial enlargement is evidenced by the tall P waves in leads II, III, aVF, and V₁. Note that there is no biphasic P wave in lead V₁, so there is no evidence of accompanying left atrial enlargement.

High-voltage limb leads (sum of R in lead I and S in lead III ≥ 25 mm) or precordial leads (sum of S in V1 and R in V₅ or V₆ ≥ 35 mm) are indicative of left ventricular hypertrophy.

The QTc interval of 653 ms with a normal sinus rate is worrisome for prolonged QT syndrome. A review of the history shows the patient to be taking two drugs (lithium, azithromycin) known to prolong the QT interval. Although it is not known whether this patient has inherent QT prolongation, use of these types of agents should be avoided.  

ANSWER
The correct interpretation includes normal sinus rhythm, right atrial enlargement, left ventricular hypertrophy, and a prolonged QT interval. Normal sinus rhythm is indicated by a P for every QRS and a QRS for every P, with a constant PR interval (see rhythm strip of lead I).

Right atrial enlargement is evidenced by the tall P waves in leads II, III, aVF, and V₁. Note that there is no biphasic P wave in lead V₁, so there is no evidence of accompanying left atrial enlargement.

High-voltage limb leads (sum of R in lead I and S in lead III ≥ 25 mm) or precordial leads (sum of S in V1 and R in V₅ or V₆ ≥ 35 mm) are indicative of left ventricular hypertrophy.

The QTc interval of 653 ms with a normal sinus rate is worrisome for prolonged QT syndrome. A review of the history shows the patient to be taking two drugs (lithium, azithromycin) known to prolong the QT interval. Although it is not known whether this patient has inherent QT prolongation, use of these types of agents should be avoided.  

ANSWER
The radiograph shows a nondisplaced fracture of the proximal fibular head. No other fractures are evident. There is some evidence of soft-tissue injury and edema over the tibia.

An orthopedics consultation was obtained, with the presumption that the fracture would be nonsurgically managed.         

ANSWER
The radiograph shows a nondisplaced fracture of the proximal fibular head. No other fractures are evident. There is some evidence of soft-tissue injury and edema over the tibia.

An orthopedics consultation was obtained, with the presumption that the fracture would be nonsurgically managed.         

ANSWER
The radiograph shows a nondisplaced fracture of the proximal fibular head. No other fractures are evident. There is some evidence of soft-tissue injury and edema over the tibia.

An orthopedics consultation was obtained, with the presumption that the fracture would be nonsurgically managed.         

ANSWER
The correct answer is “all of the above” (choice “d”), for reasons discussed in the next section.

DISCUSSION 
Cutaneous horn is the term given to this type of keratotic lesion, for obvious reasons. They range in size from a pinpoint to the larger lesion seen on this patient (and sometimes, even larger). The pathology report in this case confirmed the clinical impression of well-differentiated squamous cell carcinoma (SCC; choice “c”); sun exposure is the most likely causative factor, given the location and the patient’s history of sun damage.

The lesion might have been a wart (choice “a”) caused by a human papillomavirus, some of which can trigger the formation of a type of SCC. Evidence of HPV involvement is often noted in the pathology report.

When skin lesions transition from normal to sun-damaged to cancerous, they often go through an actinic keratosis (choice “b”) stage, usually as a tiny hyperkeratotic papule on the forehead, ears, nose, or other directly sun-exposed area. Some consider actinic keratoses to be a form of early SCC; more prevalent is the view that they are merely “precancerous” with the potential to develop into either a frank SCC or, less often, a basal cell carcinoma. Some actinic keratoses, left completely unmolested, can develop into tag-like lesions and then horny outward projections.

Even when cutaneous horns are found to represent SCC, they are termed well-differentiated, a descriptor meant to denote a relatively benign and nonaggressive prognosis. This is the opposite of a poorly differentiated SCC, which would be expected to behave in a more aggressive, less predictable manner.

For well-differentiated lesions, a deep shave biopsy is probably an adequate method of removal. As such, the case patient did not require re-excision. He was, however, scheduled for a return visit to check the site for the (albeit unlikely) possibility of ­recurrence.   

ANSWER
The correct answer is “all of the above” (choice “d”), for reasons discussed in the next section.

DISCUSSION 
Cutaneous horn is the term given to this type of keratotic lesion, for obvious reasons. They range in size from a pinpoint to the larger lesion seen on this patient (and sometimes, even larger). The pathology report in this case confirmed the clinical impression of well-differentiated squamous cell carcinoma (SCC; choice “c”); sun exposure is the most likely causative factor, given the location and the patient’s history of sun damage.

The lesion might have been a wart (choice “a”) caused by a human papillomavirus, some of which can trigger the formation of a type of SCC. Evidence of HPV involvement is often noted in the pathology report.

When skin lesions transition from normal to sun-damaged to cancerous, they often go through an actinic keratosis (choice “b”) stage, usually as a tiny hyperkeratotic papule on the forehead, ears, nose, or other directly sun-exposed area. Some consider actinic keratoses to be a form of early SCC; more prevalent is the view that they are merely “precancerous” with the potential to develop into either a frank SCC or, less often, a basal cell carcinoma. Some actinic keratoses, left completely unmolested, can develop into tag-like lesions and then horny outward projections.

Even when cutaneous horns are found to represent SCC, they are termed well-differentiated, a descriptor meant to denote a relatively benign and nonaggressive prognosis. This is the opposite of a poorly differentiated SCC, which would be expected to behave in a more aggressive, less predictable manner.

For well-differentiated lesions, a deep shave biopsy is probably an adequate method of removal. As such, the case patient did not require re-excision. He was, however, scheduled for a return visit to check the site for the (albeit unlikely) possibility of ­recurrence.   

ANSWER
The correct answer is “all of the above” (choice “d”), for reasons discussed in the next section.

DISCUSSION 
Cutaneous horn is the term given to this type of keratotic lesion, for obvious reasons. They range in size from a pinpoint to the larger lesion seen on this patient (and sometimes, even larger). The pathology report in this case confirmed the clinical impression of well-differentiated squamous cell carcinoma (SCC; choice “c”); sun exposure is the most likely causative factor, given the location and the patient’s history of sun damage.

The lesion might have been a wart (choice “a”) caused by a human papillomavirus, some of which can trigger the formation of a type of SCC. Evidence of HPV involvement is often noted in the pathology report.

When skin lesions transition from normal to sun-damaged to cancerous, they often go through an actinic keratosis (choice “b”) stage, usually as a tiny hyperkeratotic papule on the forehead, ears, nose, or other directly sun-exposed area. Some consider actinic keratoses to be a form of early SCC; more prevalent is the view that they are merely “precancerous” with the potential to develop into either a frank SCC or, less often, a basal cell carcinoma. Some actinic keratoses, left completely unmolested, can develop into tag-like lesions and then horny outward projections.

Even when cutaneous horns are found to represent SCC, they are termed well-differentiated, a descriptor meant to denote a relatively benign and nonaggressive prognosis. This is the opposite of a poorly differentiated SCC, which would be expected to behave in a more aggressive, less predictable manner.

For well-differentiated lesions, a deep shave biopsy is probably an adequate method of removal. As such, the case patient did not require re-excision. He was, however, scheduled for a return visit to check the site for the (albeit unlikely) possibility of ­recurrence.   

The Diagnosis: Allergic Contact Dermatitis to 
Para-phenylenediamine

To darken the color of henna and increase penetrance and staining, para-phenylenediamine (PPD) is added.¹ Allergic contact dermatitis is the most common type of hypersensitivity to PPD.² A retrospective study that examined severe adverse events from applying henna dyes in children found that angioedema of mucosal tissues was the most common severe adverse event; others included renal failure and shock.³

Black henna is associated with multiple cultural practices. For example, Indian weddings contain a henna decoration ceremony for the bride based on the belief that the longer the henna lasts, the longer the marriage lasts. Black henna is favored for this practice, as it lasts longer than red henna.

Henna (Lawsonia inermis) is a plant that contains the molecule lawsone (naphthoquinone). Lawsone has an intense affinity for keratin; as a result, lawsone is frequently added to temporary body tattoos and hair dyes to create a relatively permanent change in skin or hair color.⁴ Henna is mixed with hennotannic acid to release the lawsone from the plant. Lawsone and hennotannic acid rarely cause allergic reactions.^1,5-7 Once applied to skin, henna takes a few hours to dry, and the resulting color is orange to red.⁸ Often, PPD is added to henna paste to create a black color, to speed up the drying process, and to increase its longevity.

Para-phenylenediamine has been repeatedly reported to cause allergic contact dermatitis. We describe a case of allergic contact dermatitis secondary to PPD in black henna. Our patient is a clear example that PPD is the allergen in black henna given that there was no reaction to the natural red henna tattoo that was applied at the same time to the palmar surfaces of the hands (Figure). Aside from the bullous reaction to black henna dye described here, other reported presentations include erythema multiforme–like and exudative erythema reactions.^9,10

Contact dermatitis lesions from black henna dye can be treated with topical corticosteroids. Patients may develop residual postinflammatory hyperpigmentation or hypopigmentation, leukoderma, keloids, or scars.^1,11,12

The Diagnosis: Allergic Contact Dermatitis to 
Para-phenylenediamine

To darken the color of henna and increase penetrance and staining, para-phenylenediamine (PPD) is added.¹ Allergic contact dermatitis is the most common type of hypersensitivity to PPD.² A retrospective study that examined severe adverse events from applying henna dyes in children found that angioedema of mucosal tissues was the most common severe adverse event; others included renal failure and shock.³

Black henna is associated with multiple cultural practices. For example, Indian weddings contain a henna decoration ceremony for the bride based on the belief that the longer the henna lasts, the longer the marriage lasts. Black henna is favored for this practice, as it lasts longer than red henna.

Henna (Lawsonia inermis) is a plant that contains the molecule lawsone (naphthoquinone). Lawsone has an intense affinity for keratin; as a result, lawsone is frequently added to temporary body tattoos and hair dyes to create a relatively permanent change in skin or hair color.⁴ Henna is mixed with hennotannic acid to release the lawsone from the plant. Lawsone and hennotannic acid rarely cause allergic reactions.^1,5-7 Once applied to skin, henna takes a few hours to dry, and the resulting color is orange to red.⁸ Often, PPD is added to henna paste to create a black color, to speed up the drying process, and to increase its longevity.

Para-phenylenediamine has been repeatedly reported to cause allergic contact dermatitis. We describe a case of allergic contact dermatitis secondary to PPD in black henna. Our patient is a clear example that PPD is the allergen in black henna given that there was no reaction to the natural red henna tattoo that was applied at the same time to the palmar surfaces of the hands (Figure). Aside from the bullous reaction to black henna dye described here, other reported presentations include erythema multiforme–like and exudative erythema reactions.^9,10

Contact dermatitis lesions from black henna dye can be treated with topical corticosteroids. Patients may develop residual postinflammatory hyperpigmentation or hypopigmentation, leukoderma, keloids, or scars.^1,11,12

The Diagnosis: Allergic Contact Dermatitis to 
Para-phenylenediamine

To darken the color of henna and increase penetrance and staining, para-phenylenediamine (PPD) is added.¹ Allergic contact dermatitis is the most common type of hypersensitivity to PPD.² A retrospective study that examined severe adverse events from applying henna dyes in children found that angioedema of mucosal tissues was the most common severe adverse event; others included renal failure and shock.³

Black henna is associated with multiple cultural practices. For example, Indian weddings contain a henna decoration ceremony for the bride based on the belief that the longer the henna lasts, the longer the marriage lasts. Black henna is favored for this practice, as it lasts longer than red henna.

Henna (Lawsonia inermis) is a plant that contains the molecule lawsone (naphthoquinone). Lawsone has an intense affinity for keratin; as a result, lawsone is frequently added to temporary body tattoos and hair dyes to create a relatively permanent change in skin or hair color.⁴ Henna is mixed with hennotannic acid to release the lawsone from the plant. Lawsone and hennotannic acid rarely cause allergic reactions.^1,5-7 Once applied to skin, henna takes a few hours to dry, and the resulting color is orange to red.⁸ Often, PPD is added to henna paste to create a black color, to speed up the drying process, and to increase its longevity.

Para-phenylenediamine has been repeatedly reported to cause allergic contact dermatitis. We describe a case of allergic contact dermatitis secondary to PPD in black henna. Our patient is a clear example that PPD is the allergen in black henna given that there was no reaction to the natural red henna tattoo that was applied at the same time to the palmar surfaces of the hands (Figure). Aside from the bullous reaction to black henna dye described here, other reported presentations include erythema multiforme–like and exudative erythema reactions.^9,10

Contact dermatitis lesions from black henna dye can be treated with topical corticosteroids. Patients may develop residual postinflammatory hyperpigmentation or hypopigmentation, leukoderma, keloids, or scars.^1,11,12

The Diagnosis: Phrynoderma

Phrynoderma, meaning “toad skin,” was first described by Nicholls¹ in 1933 as a condition due to vitamin A deficiency and characterized by follicular hyperkeratosis. Since then, there has been debate in the literature over the etiology of phrynoderma, as studies have demonstrated different causes for this condition,^2-5 which suggests that it is prudent to check several markers of nutritional status including vitamin A, vitamin B, vitamin E, and essential fatty acid studies.

Phrynoderma is most commonly seen in South and East Asia with relatively rare occurrences in the United States. Although it characteristically occurs in children and adolescents aged 5 to 15 years, almost all of the cases reported in the United States have occurred in adults.^6,7 A clear gender predilection has not been established.⁷

Phrynoderma tends to favor the extensor surfaces. In particular, the elbows, thighs, and buttocks are the most commonly affected locations. The face is typically the last site to become involved. On physical examination of a patient with phrynoderma, there are various-sized, discrete, red-brown to flesh-colored papules with a conical keratotic follicular plug (Figure).³ The eruption is often asymptomatic, but mild pruritus may be reported.⁷ Additional signs of vitamin A deficiency may be present, including night blindness, hyperpigmentation, or xerosis. Patients with phrynoderma also may have evidence of other nutritional deficiencies, such as angular stomatitis, cheilitis, or glossitis. The differential diagnosis for a patient with this type of papular eruption may include pityriasis rubra pilaris, keratosis pilaris, lichen spinulosus, crusted scabies, and follicular lichen planus.⁷ History and clinical presentation can generally help to distinguish these diagnoses.

Generalized follicular, erythematous, and scaly papular eruption on the chest (A) and abdomen (B).

Histopathology typically shows moderate hyperkeratosis with distension of the upper portion of the follicle by large keratotic plugs. Sebaceous glands are greatly reduced in size and may exhibit epithelial atrophy.^8,9

A reduced serum vitamin A level can confirm the diagnosis of phrynoderma. Our patient’s laboratory results revealed a vitamin A value of 26 mg/100 dL (reference range, 38–106 mg/100 dL), consistent with his clinical presentation of phrynoderma. Other markers of nutritional status, including vitamins D, E, and K₁, were all within reference range. Treatment consists of replacing the nutritional deficit. High doses of vitamin A, such as 200,000 to 500,000 IU daily for 3 to 5 days or daily doses of 2000 to 50,000 IU, can lead to resolution of the rash in 1 to 4 months.^8,9 Our patient was started on 10,000 IU of oral vitamin A daily at discharge but unfortunately died a few months later.

Vitamin A has been shown to promote maturation and differentiation of the basal keratinocytes as they move up through the epidermis, which may in part explain why this treatment is effective.¹⁰ It is important to be aware of this condition when seeing a patient with follicular hyperkeratosis because even patients in developed countries with malnutrition due to diet or gastrointestinal disease may develop phrynoderma.

The Diagnosis: Phrynoderma

Phrynoderma, meaning “toad skin,” was first described by Nicholls¹ in 1933 as a condition due to vitamin A deficiency and characterized by follicular hyperkeratosis. Since then, there has been debate in the literature over the etiology of phrynoderma, as studies have demonstrated different causes for this condition,^2-5 which suggests that it is prudent to check several markers of nutritional status including vitamin A, vitamin B, vitamin E, and essential fatty acid studies.

Phrynoderma is most commonly seen in South and East Asia with relatively rare occurrences in the United States. Although it characteristically occurs in children and adolescents aged 5 to 15 years, almost all of the cases reported in the United States have occurred in adults.^6,7 A clear gender predilection has not been established.⁷

Phrynoderma tends to favor the extensor surfaces. In particular, the elbows, thighs, and buttocks are the most commonly affected locations. The face is typically the last site to become involved. On physical examination of a patient with phrynoderma, there are various-sized, discrete, red-brown to flesh-colored papules with a conical keratotic follicular plug (Figure).³ The eruption is often asymptomatic, but mild pruritus may be reported.⁷ Additional signs of vitamin A deficiency may be present, including night blindness, hyperpigmentation, or xerosis. Patients with phrynoderma also may have evidence of other nutritional deficiencies, such as angular stomatitis, cheilitis, or glossitis. The differential diagnosis for a patient with this type of papular eruption may include pityriasis rubra pilaris, keratosis pilaris, lichen spinulosus, crusted scabies, and follicular lichen planus.⁷ History and clinical presentation can generally help to distinguish these diagnoses.

Generalized follicular, erythematous, and scaly papular eruption on the chest (A) and abdomen (B).

Histopathology typically shows moderate hyperkeratosis with distension of the upper portion of the follicle by large keratotic plugs. Sebaceous glands are greatly reduced in size and may exhibit epithelial atrophy.^8,9

A reduced serum vitamin A level can confirm the diagnosis of phrynoderma. Our patient’s laboratory results revealed a vitamin A value of 26 mg/100 dL (reference range, 38–106 mg/100 dL), consistent with his clinical presentation of phrynoderma. Other markers of nutritional status, including vitamins D, E, and K₁, were all within reference range. Treatment consists of replacing the nutritional deficit. High doses of vitamin A, such as 200,000 to 500,000 IU daily for 3 to 5 days or daily doses of 2000 to 50,000 IU, can lead to resolution of the rash in 1 to 4 months.^8,9 Our patient was started on 10,000 IU of oral vitamin A daily at discharge but unfortunately died a few months later.

Vitamin A has been shown to promote maturation and differentiation of the basal keratinocytes as they move up through the epidermis, which may in part explain why this treatment is effective.¹⁰ It is important to be aware of this condition when seeing a patient with follicular hyperkeratosis because even patients in developed countries with malnutrition due to diet or gastrointestinal disease may develop phrynoderma.

The Diagnosis: Phrynoderma

Phrynoderma, meaning “toad skin,” was first described by Nicholls¹ in 1933 as a condition due to vitamin A deficiency and characterized by follicular hyperkeratosis. Since then, there has been debate in the literature over the etiology of phrynoderma, as studies have demonstrated different causes for this condition,^2-5 which suggests that it is prudent to check several markers of nutritional status including vitamin A, vitamin B, vitamin E, and essential fatty acid studies.

Phrynoderma is most commonly seen in South and East Asia with relatively rare occurrences in the United States. Although it characteristically occurs in children and adolescents aged 5 to 15 years, almost all of the cases reported in the United States have occurred in adults.^6,7 A clear gender predilection has not been established.⁷

Phrynoderma tends to favor the extensor surfaces. In particular, the elbows, thighs, and buttocks are the most commonly affected locations. The face is typically the last site to become involved. On physical examination of a patient with phrynoderma, there are various-sized, discrete, red-brown to flesh-colored papules with a conical keratotic follicular plug (Figure).³ The eruption is often asymptomatic, but mild pruritus may be reported.⁷ Additional signs of vitamin A deficiency may be present, including night blindness, hyperpigmentation, or xerosis. Patients with phrynoderma also may have evidence of other nutritional deficiencies, such as angular stomatitis, cheilitis, or glossitis. The differential diagnosis for a patient with this type of papular eruption may include pityriasis rubra pilaris, keratosis pilaris, lichen spinulosus, crusted scabies, and follicular lichen planus.⁷ History and clinical presentation can generally help to distinguish these diagnoses.

Generalized follicular, erythematous, and scaly papular eruption on the chest (A) and abdomen (B).

Histopathology typically shows moderate hyperkeratosis with distension of the upper portion of the follicle by large keratotic plugs. Sebaceous glands are greatly reduced in size and may exhibit epithelial atrophy.^8,9

A reduced serum vitamin A level can confirm the diagnosis of phrynoderma. Our patient’s laboratory results revealed a vitamin A value of 26 mg/100 dL (reference range, 38–106 mg/100 dL), consistent with his clinical presentation of phrynoderma. Other markers of nutritional status, including vitamins D, E, and K₁, were all within reference range. Treatment consists of replacing the nutritional deficit. High doses of vitamin A, such as 200,000 to 500,000 IU daily for 3 to 5 days or daily doses of 2000 to 50,000 IU, can lead to resolution of the rash in 1 to 4 months.^8,9 Our patient was started on 10,000 IU of oral vitamin A daily at discharge but unfortunately died a few months later.

Vitamin A has been shown to promote maturation and differentiation of the basal keratinocytes as they move up through the epidermis, which may in part explain why this treatment is effective.¹⁰ It is important to be aware of this condition when seeing a patient with follicular hyperkeratosis because even patients in developed countries with malnutrition due to diet or gastrointestinal disease may develop phrynoderma.