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The Diagnosis: Herpes Zoster Opthalmicus 

Due to the potential concern of vision loss, the patient was directed to a local emergency department for immediate ophthalmologic evaluation. He was diagnosed with herpes zoster ophthalmicus (HZO) and treated with oral acyclovir and prednisone. The rash and periorbital swelling resolved within 2 weeks of treatment, and he remained asymptomatic at follow-up 3 months later.  

Herpes zoster ophthalmicus presents with an erythematous and vesicular rash in the distribution of cranial nerve V1. The herpetiform grouping of lesions on the forehead is diagnostic of HZO. Varicella-zoster virus (VZV) infection presents in 2 distinct forms. Primary infection (commonly known as chickenpox) presents clinically as a vesicular rash usually located on the face, arms, and trunk. Although the initial presentation usually occurs in childhood and is self-limited, the virus becomes latent in the dorsal root ganglia of sensory neurons. Varicella-zoster virus may become reactivated later in life and is termed herpes zoster (commonly known as shingles). It most often presents as a painful vesicular rash that may later form pustules.  

Zoster outbreaks typically do not cross the midline but may in disseminated disease. Patients may experience a prodrome in the form of pain or less commonly pruritus or paresthesia along the dermatome between 1 and 10 days before the rash appears. Triggers for herpes zoster include illness, medications, malnutrition, surgery, or the natural decline in immune function due to aging. Trauma is another important precipitating event for VZV reactivation; one case-control study showed that zoster patients were 3.4 times more likely than controls to have had trauma the week prior.¹ Patients with cranial zoster are more than 25 times more likely to have experienced trauma in the preceding week. Local trauma may predispose these patients to VZV reactivation by stimulating local sensory nerves or by disrupting local cutaneous immunity.² 

Herpes zoster ophthalmicus occurs when zoster presents in the ophthalmic division of the fifth cranial nerve. It is a serious, vision-threatening condition with a presentation that can include conjunctivitis, scleritis, keratitis, optic neuritis, exophthalmos, lid retraction, ptosis, and extraocular muscle palsies. Treatment includes antiviral medication (eg, acyclovir, valacyclovir, famciclovir) and prompt ophthalmologic consultation due to potential vision-threatening complications, such as acute retinal necrosis. Acute pain control may be necessary with nonsteroidal anti-inflammatory drugs, opioids, steroids, tricyclic antidepressants, or anticonvulsants.³ Wet-to-dry dressings with sterile saline or Burow solution and/or calamine lotion can provide symptomatic relief of itching.  

Periorbital and preseptal cellulitis typically present with more erythema of the skin surrounding the eye and without the accompanying rash. Periorbital cellulitis is the more serious infection and may be clinically distinguished by the presence of pain with extraocular muscle movement. Contact dermatitis and pemphigus vulgaris are possibilities, but both were less likely than HZO in this case presentation given the distribution of the rash and the patient history. Contact dermatitis typically presents with no prodrome with a main concern of pruritus. Pemphigus vulgaris nearly always includes involvement of the oral mucous membranes. 

The Diagnosis: Herpes Zoster Opthalmicus 

Due to the potential concern of vision loss, the patient was directed to a local emergency department for immediate ophthalmologic evaluation. He was diagnosed with herpes zoster ophthalmicus (HZO) and treated with oral acyclovir and prednisone. The rash and periorbital swelling resolved within 2 weeks of treatment, and he remained asymptomatic at follow-up 3 months later.  

Herpes zoster ophthalmicus presents with an erythematous and vesicular rash in the distribution of cranial nerve V1. The herpetiform grouping of lesions on the forehead is diagnostic of HZO. Varicella-zoster virus (VZV) infection presents in 2 distinct forms. Primary infection (commonly known as chickenpox) presents clinically as a vesicular rash usually located on the face, arms, and trunk. Although the initial presentation usually occurs in childhood and is self-limited, the virus becomes latent in the dorsal root ganglia of sensory neurons. Varicella-zoster virus may become reactivated later in life and is termed herpes zoster (commonly known as shingles). It most often presents as a painful vesicular rash that may later form pustules.  

Zoster outbreaks typically do not cross the midline but may in disseminated disease. Patients may experience a prodrome in the form of pain or less commonly pruritus or paresthesia along the dermatome between 1 and 10 days before the rash appears. Triggers for herpes zoster include illness, medications, malnutrition, surgery, or the natural decline in immune function due to aging. Trauma is another important precipitating event for VZV reactivation; one case-control study showed that zoster patients were 3.4 times more likely than controls to have had trauma the week prior.¹ Patients with cranial zoster are more than 25 times more likely to have experienced trauma in the preceding week. Local trauma may predispose these patients to VZV reactivation by stimulating local sensory nerves or by disrupting local cutaneous immunity.² 

Herpes zoster ophthalmicus occurs when zoster presents in the ophthalmic division of the fifth cranial nerve. It is a serious, vision-threatening condition with a presentation that can include conjunctivitis, scleritis, keratitis, optic neuritis, exophthalmos, lid retraction, ptosis, and extraocular muscle palsies. Treatment includes antiviral medication (eg, acyclovir, valacyclovir, famciclovir) and prompt ophthalmologic consultation due to potential vision-threatening complications, such as acute retinal necrosis. Acute pain control may be necessary with nonsteroidal anti-inflammatory drugs, opioids, steroids, tricyclic antidepressants, or anticonvulsants.³ Wet-to-dry dressings with sterile saline or Burow solution and/or calamine lotion can provide symptomatic relief of itching.  

Periorbital and preseptal cellulitis typically present with more erythema of the skin surrounding the eye and without the accompanying rash. Periorbital cellulitis is the more serious infection and may be clinically distinguished by the presence of pain with extraocular muscle movement. Contact dermatitis and pemphigus vulgaris are possibilities, but both were less likely than HZO in this case presentation given the distribution of the rash and the patient history. Contact dermatitis typically presents with no prodrome with a main concern of pruritus. Pemphigus vulgaris nearly always includes involvement of the oral mucous membranes. 

The Diagnosis: Herpes Zoster Opthalmicus 

Due to the potential concern of vision loss, the patient was directed to a local emergency department for immediate ophthalmologic evaluation. He was diagnosed with herpes zoster ophthalmicus (HZO) and treated with oral acyclovir and prednisone. The rash and periorbital swelling resolved within 2 weeks of treatment, and he remained asymptomatic at follow-up 3 months later.  

Herpes zoster ophthalmicus presents with an erythematous and vesicular rash in the distribution of cranial nerve V1. The herpetiform grouping of lesions on the forehead is diagnostic of HZO. Varicella-zoster virus (VZV) infection presents in 2 distinct forms. Primary infection (commonly known as chickenpox) presents clinically as a vesicular rash usually located on the face, arms, and trunk. Although the initial presentation usually occurs in childhood and is self-limited, the virus becomes latent in the dorsal root ganglia of sensory neurons. Varicella-zoster virus may become reactivated later in life and is termed herpes zoster (commonly known as shingles). It most often presents as a painful vesicular rash that may later form pustules.  

Zoster outbreaks typically do not cross the midline but may in disseminated disease. Patients may experience a prodrome in the form of pain or less commonly pruritus or paresthesia along the dermatome between 1 and 10 days before the rash appears. Triggers for herpes zoster include illness, medications, malnutrition, surgery, or the natural decline in immune function due to aging. Trauma is another important precipitating event for VZV reactivation; one case-control study showed that zoster patients were 3.4 times more likely than controls to have had trauma the week prior.¹ Patients with cranial zoster are more than 25 times more likely to have experienced trauma in the preceding week. Local trauma may predispose these patients to VZV reactivation by stimulating local sensory nerves or by disrupting local cutaneous immunity.² 

Herpes zoster ophthalmicus occurs when zoster presents in the ophthalmic division of the fifth cranial nerve. It is a serious, vision-threatening condition with a presentation that can include conjunctivitis, scleritis, keratitis, optic neuritis, exophthalmos, lid retraction, ptosis, and extraocular muscle palsies. Treatment includes antiviral medication (eg, acyclovir, valacyclovir, famciclovir) and prompt ophthalmologic consultation due to potential vision-threatening complications, such as acute retinal necrosis. Acute pain control may be necessary with nonsteroidal anti-inflammatory drugs, opioids, steroids, tricyclic antidepressants, or anticonvulsants.³ Wet-to-dry dressings with sterile saline or Burow solution and/or calamine lotion can provide symptomatic relief of itching.  

Periorbital and preseptal cellulitis typically present with more erythema of the skin surrounding the eye and without the accompanying rash. Periorbital cellulitis is the more serious infection and may be clinically distinguished by the presence of pain with extraocular muscle movement. Contact dermatitis and pemphigus vulgaris are possibilities, but both were less likely than HZO in this case presentation given the distribution of the rash and the patient history. Contact dermatitis typically presents with no prodrome with a main concern of pruritus. Pemphigus vulgaris nearly always includes involvement of the oral mucous membranes. 

The Diagnosis: Adnexal Neoplasm Arising in a Nevus Sebaceus 

Biopsy of the lesion showed a proliferation of basaloid-appearing cells with focal ductal differentiation and ulceration consistent with poroma (Figure 1). Due to the superficial nature of the biopsy, the pathologist recommended excision to ensure complete removal and to rule out a well-differentiated porocarcinoma. Excision of the lesion showed large basaloid aggregates with a hypercellular stroma and a surrounding papillomatous epidermis with well-developed sebaceous lobules consistent with a trichoblastoma and a nevus sebaceus, respectively (Figure 2). There also was evidence of poroma; however, there were no findings concerning for porocarcinoma, which could lead to metastasis (Figure 3). 

Nevus sebaceus is a benign, hamartomatous, congenital growth that occurs in approximately 1% of patients presenting to dermatology offices. It usually presents as a single asymptomatic plaque on the scalp (62.5%) or face (24.5%) that changes in morphology over its lifetime.^1,2 In children, a nevus manifests as a yellowish, smooth, waxy skin lesion. As the sebaceous glands become more developed during adolescence, the lesion takes on more of a verrucous appearance and also can darken.  

Although nevus sebaceus is benign, it may give rise to both benign and malignant neoplasms. In a 2014 study of 707 cases of nevus sebaceus, 21.4% developed secondary neoplasms, 88% of which were benign.² The origins of these neoplasms can be epithelial, sebaceous, apocrine, and/or follicular. The 3 most common secondary neoplasms found in nevus sebaceus are trichoblastoma (34.7%), syringocystadenoma papilliferum (24.7%), and apocrine/eccrine adenoma (10%), all of which are benign.² Trichoblastomas represent a type of hair follicle tumor. Malignant lesions manifest in approximately 2.5% of cases, with basal cell carcinoma (BCC) being the most common (5.3% of all neoplasms), followed by squamous cell carcinoma (2.7% of all neoplasms).² Differentiating BCC from trichoblastoma can be difficult, but histologically BCCs usually have tumor stromal clefting while trichoblastomas do not.³ The incidence of secondary tumors in nevus sebaceus displays a strong correlation with age; thus, the highest proportion of neoplasms occur in adults.  

Treatment of nevus sebaceus depends on the patient's age. In children, because of the low probability of secondary neoplasms, observation in lieu of surgical excision is a common approach. In adults, the approach typically is surgical excision or close follow-up, as there is a concern for secondary neoplasm and the potential for malignant degeneration.  

A nevus sebaceus leading to 2 or more tumors within the same lesion is rare (seen in only 4.2% of lesions). The most common combination is trichoblastoma with syringocystadenoma papilliferum (0.6% of all cases).² Poromas represent sweat gland tumors that usually appear on the soles (65%) or palms (10%).⁴ It is uncommon for these neoplasms to manifest on the scalp or within a nevus sebaceus. Three independent studies (N=596; N=707; N=450) did not report any occurrences of eccrine poroma.^1,2,5 Eccrine poroma in conjunction with nodular trichoblastoma arising in a nevus sebaceus is unusual, and definitive excision should be strongly considered because of the possibility to develop a porocarcinoma.⁶ 

Atypical fibroxanthoma presents on sun-exposed areas as an exophytic nodule or plaque that frequently ulcerates. Pathology of this tumor shows a spindled cell proliferation that can stain positively for CD10 and procollagen 1. Basal cell carcinoma presents as a pearly papule or nodule displaying basaloid-appearing aggregates with tumor stromal clefting and can stain with Ber-EP4. Cylindromas typically present on the scalp as large rubbery-appearing plaques and nodules. Cylindromas usually present as a solitary tumor, but in the familial form there can be clusters of multiple nodules. Metastatic renal cell carcinoma frequently appears as a bleeding nodule on the scalp in patients with known renal cell cancer or as the initial presentation. 

The Diagnosis: Adnexal Neoplasm Arising in a Nevus Sebaceus 

Biopsy of the lesion showed a proliferation of basaloid-appearing cells with focal ductal differentiation and ulceration consistent with poroma (Figure 1). Due to the superficial nature of the biopsy, the pathologist recommended excision to ensure complete removal and to rule out a well-differentiated porocarcinoma. Excision of the lesion showed large basaloid aggregates with a hypercellular stroma and a surrounding papillomatous epidermis with well-developed sebaceous lobules consistent with a trichoblastoma and a nevus sebaceus, respectively (Figure 2). There also was evidence of poroma; however, there were no findings concerning for porocarcinoma, which could lead to metastasis (Figure 3). 

Nevus sebaceus is a benign, hamartomatous, congenital growth that occurs in approximately 1% of patients presenting to dermatology offices. It usually presents as a single asymptomatic plaque on the scalp (62.5%) or face (24.5%) that changes in morphology over its lifetime.^1,2 In children, a nevus manifests as a yellowish, smooth, waxy skin lesion. As the sebaceous glands become more developed during adolescence, the lesion takes on more of a verrucous appearance and also can darken.  

Although nevus sebaceus is benign, it may give rise to both benign and malignant neoplasms. In a 2014 study of 707 cases of nevus sebaceus, 21.4% developed secondary neoplasms, 88% of which were benign.² The origins of these neoplasms can be epithelial, sebaceous, apocrine, and/or follicular. The 3 most common secondary neoplasms found in nevus sebaceus are trichoblastoma (34.7%), syringocystadenoma papilliferum (24.7%), and apocrine/eccrine adenoma (10%), all of which are benign.² Trichoblastomas represent a type of hair follicle tumor. Malignant lesions manifest in approximately 2.5% of cases, with basal cell carcinoma (BCC) being the most common (5.3% of all neoplasms), followed by squamous cell carcinoma (2.7% of all neoplasms).² Differentiating BCC from trichoblastoma can be difficult, but histologically BCCs usually have tumor stromal clefting while trichoblastomas do not.³ The incidence of secondary tumors in nevus sebaceus displays a strong correlation with age; thus, the highest proportion of neoplasms occur in adults.  

Treatment of nevus sebaceus depends on the patient's age. In children, because of the low probability of secondary neoplasms, observation in lieu of surgical excision is a common approach. In adults, the approach typically is surgical excision or close follow-up, as there is a concern for secondary neoplasm and the potential for malignant degeneration.  

A nevus sebaceus leading to 2 or more tumors within the same lesion is rare (seen in only 4.2% of lesions). The most common combination is trichoblastoma with syringocystadenoma papilliferum (0.6% of all cases).² Poromas represent sweat gland tumors that usually appear on the soles (65%) or palms (10%).⁴ It is uncommon for these neoplasms to manifest on the scalp or within a nevus sebaceus. Three independent studies (N=596; N=707; N=450) did not report any occurrences of eccrine poroma.^1,2,5 Eccrine poroma in conjunction with nodular trichoblastoma arising in a nevus sebaceus is unusual, and definitive excision should be strongly considered because of the possibility to develop a porocarcinoma.⁶ 

Atypical fibroxanthoma presents on sun-exposed areas as an exophytic nodule or plaque that frequently ulcerates. Pathology of this tumor shows a spindled cell proliferation that can stain positively for CD10 and procollagen 1. Basal cell carcinoma presents as a pearly papule or nodule displaying basaloid-appearing aggregates with tumor stromal clefting and can stain with Ber-EP4. Cylindromas typically present on the scalp as large rubbery-appearing plaques and nodules. Cylindromas usually present as a solitary tumor, but in the familial form there can be clusters of multiple nodules. Metastatic renal cell carcinoma frequently appears as a bleeding nodule on the scalp in patients with known renal cell cancer or as the initial presentation. 

The Diagnosis: Adnexal Neoplasm Arising in a Nevus Sebaceus 

Biopsy of the lesion showed a proliferation of basaloid-appearing cells with focal ductal differentiation and ulceration consistent with poroma (Figure 1). Due to the superficial nature of the biopsy, the pathologist recommended excision to ensure complete removal and to rule out a well-differentiated porocarcinoma. Excision of the lesion showed large basaloid aggregates with a hypercellular stroma and a surrounding papillomatous epidermis with well-developed sebaceous lobules consistent with a trichoblastoma and a nevus sebaceus, respectively (Figure 2). There also was evidence of poroma; however, there were no findings concerning for porocarcinoma, which could lead to metastasis (Figure 3). 

Nevus sebaceus is a benign, hamartomatous, congenital growth that occurs in approximately 1% of patients presenting to dermatology offices. It usually presents as a single asymptomatic plaque on the scalp (62.5%) or face (24.5%) that changes in morphology over its lifetime.^1,2 In children, a nevus manifests as a yellowish, smooth, waxy skin lesion. As the sebaceous glands become more developed during adolescence, the lesion takes on more of a verrucous appearance and also can darken.  

Although nevus sebaceus is benign, it may give rise to both benign and malignant neoplasms. In a 2014 study of 707 cases of nevus sebaceus, 21.4% developed secondary neoplasms, 88% of which were benign.² The origins of these neoplasms can be epithelial, sebaceous, apocrine, and/or follicular. The 3 most common secondary neoplasms found in nevus sebaceus are trichoblastoma (34.7%), syringocystadenoma papilliferum (24.7%), and apocrine/eccrine adenoma (10%), all of which are benign.² Trichoblastomas represent a type of hair follicle tumor. Malignant lesions manifest in approximately 2.5% of cases, with basal cell carcinoma (BCC) being the most common (5.3% of all neoplasms), followed by squamous cell carcinoma (2.7% of all neoplasms).² Differentiating BCC from trichoblastoma can be difficult, but histologically BCCs usually have tumor stromal clefting while trichoblastomas do not.³ The incidence of secondary tumors in nevus sebaceus displays a strong correlation with age; thus, the highest proportion of neoplasms occur in adults.  

Treatment of nevus sebaceus depends on the patient's age. In children, because of the low probability of secondary neoplasms, observation in lieu of surgical excision is a common approach. In adults, the approach typically is surgical excision or close follow-up, as there is a concern for secondary neoplasm and the potential for malignant degeneration.  

A nevus sebaceus leading to 2 or more tumors within the same lesion is rare (seen in only 4.2% of lesions). The most common combination is trichoblastoma with syringocystadenoma papilliferum (0.6% of all cases).² Poromas represent sweat gland tumors that usually appear on the soles (65%) or palms (10%).⁴ It is uncommon for these neoplasms to manifest on the scalp or within a nevus sebaceus. Three independent studies (N=596; N=707; N=450) did not report any occurrences of eccrine poroma.^1,2,5 Eccrine poroma in conjunction with nodular trichoblastoma arising in a nevus sebaceus is unusual, and definitive excision should be strongly considered because of the possibility to develop a porocarcinoma.⁶ 

Atypical fibroxanthoma presents on sun-exposed areas as an exophytic nodule or plaque that frequently ulcerates. Pathology of this tumor shows a spindled cell proliferation that can stain positively for CD10 and procollagen 1. Basal cell carcinoma presents as a pearly papule or nodule displaying basaloid-appearing aggregates with tumor stromal clefting and can stain with Ber-EP4. Cylindromas typically present on the scalp as large rubbery-appearing plaques and nodules. Cylindromas usually present as a solitary tumor, but in the familial form there can be clusters of multiple nodules. Metastatic renal cell carcinoma frequently appears as a bleeding nodule on the scalp in patients with known renal cell cancer or as the initial presentation. 

The Diagnosis: Talon Noir

Paring of the stratum corneum overlying the lesion revealed coagulated blood, leading to a diagnosis of talon noir. Talon noir, also known as calcaneal petechiae, is a benign lesion that is typically found on the heel of the foot or palm of the hand.¹ To the naked eye, talon noir appears as a brown-black asymmetric macule often with an overlying callus. Dermatoscopic visualization reveals grouped, reddish-colored globules composed of intracorneal hemorrhages, often in a linear pattern without any disruption of the normal skin surface architecture^.1,2

Talon noir is the product of shear stress and often is seen in individuals who participate in sports such as baseball, hockey, soccer, and football.^1,3 Lateral shearing forces cause tearing of blood vessels within the papillary dermis, which leads to punctate papillary dermal hemorrhages and extravasation of blood into the epidermis, resulting in intracorneal hemorrhage.^1,4 Talon noir lesions are completely asymptomatic and typically resolve without intervention within 2 to 3 weeks of discontinuation of the precipitating sport or trauma.⁴

Recognizing talon noir is important, as it can occasionally be mistaken for acral lentiginous melanoma junctional nevus, tinea nigra, or verruca vulgaris. Paring of a lesion that is suspicious for talon noir is a simple and important step for ruling out a more ominous diagnosis (ie, acral lentiginous melanoma). If paring reveals coagulated blood, then junctional nevus, acral lentiginous melanoma, and tinea nigra can be excluded from the differential diagnosis. To rule out verruca vulgaris, one must prove that there is no disruption of the normal skin architecture, which can be confirmed with dermatoscopic visualization. Verrucae characteristically cause disruption of normal skin architecture, and junctional nevi would reveal a pigment pattern on dermatoscopy. This case illustrates how simple bedside procedures—dermoscopy and paring—can reassure patients and caregivers of the benign nature of talon noir. 

The Diagnosis: Talon Noir

Paring of the stratum corneum overlying the lesion revealed coagulated blood, leading to a diagnosis of talon noir. Talon noir, also known as calcaneal petechiae, is a benign lesion that is typically found on the heel of the foot or palm of the hand.¹ To the naked eye, talon noir appears as a brown-black asymmetric macule often with an overlying callus. Dermatoscopic visualization reveals grouped, reddish-colored globules composed of intracorneal hemorrhages, often in a linear pattern without any disruption of the normal skin surface architecture^.1,2

Talon noir is the product of shear stress and often is seen in individuals who participate in sports such as baseball, hockey, soccer, and football.^1,3 Lateral shearing forces cause tearing of blood vessels within the papillary dermis, which leads to punctate papillary dermal hemorrhages and extravasation of blood into the epidermis, resulting in intracorneal hemorrhage.^1,4 Talon noir lesions are completely asymptomatic and typically resolve without intervention within 2 to 3 weeks of discontinuation of the precipitating sport or trauma.⁴

Recognizing talon noir is important, as it can occasionally be mistaken for acral lentiginous melanoma junctional nevus, tinea nigra, or verruca vulgaris. Paring of a lesion that is suspicious for talon noir is a simple and important step for ruling out a more ominous diagnosis (ie, acral lentiginous melanoma). If paring reveals coagulated blood, then junctional nevus, acral lentiginous melanoma, and tinea nigra can be excluded from the differential diagnosis. To rule out verruca vulgaris, one must prove that there is no disruption of the normal skin architecture, which can be confirmed with dermatoscopic visualization. Verrucae characteristically cause disruption of normal skin architecture, and junctional nevi would reveal a pigment pattern on dermatoscopy. This case illustrates how simple bedside procedures—dermoscopy and paring—can reassure patients and caregivers of the benign nature of talon noir. 

The Diagnosis: Talon Noir

Paring of the stratum corneum overlying the lesion revealed coagulated blood, leading to a diagnosis of talon noir. Talon noir, also known as calcaneal petechiae, is a benign lesion that is typically found on the heel of the foot or palm of the hand.¹ To the naked eye, talon noir appears as a brown-black asymmetric macule often with an overlying callus. Dermatoscopic visualization reveals grouped, reddish-colored globules composed of intracorneal hemorrhages, often in a linear pattern without any disruption of the normal skin surface architecture^.1,2

Talon noir is the product of shear stress and often is seen in individuals who participate in sports such as baseball, hockey, soccer, and football.^1,3 Lateral shearing forces cause tearing of blood vessels within the papillary dermis, which leads to punctate papillary dermal hemorrhages and extravasation of blood into the epidermis, resulting in intracorneal hemorrhage.^1,4 Talon noir lesions are completely asymptomatic and typically resolve without intervention within 2 to 3 weeks of discontinuation of the precipitating sport or trauma.⁴

Recognizing talon noir is important, as it can occasionally be mistaken for acral lentiginous melanoma junctional nevus, tinea nigra, or verruca vulgaris. Paring of a lesion that is suspicious for talon noir is a simple and important step for ruling out a more ominous diagnosis (ie, acral lentiginous melanoma). If paring reveals coagulated blood, then junctional nevus, acral lentiginous melanoma, and tinea nigra can be excluded from the differential diagnosis. To rule out verruca vulgaris, one must prove that there is no disruption of the normal skin architecture, which can be confirmed with dermatoscopic visualization. Verrucae characteristically cause disruption of normal skin architecture, and junctional nevi would reveal a pigment pattern on dermatoscopy. This case illustrates how simple bedside procedures—dermoscopy and paring—can reassure patients and caregivers of the benign nature of talon noir. 

The Diagnosis: Infantile Digital Fibromatosis

Infantile digital fibromatosis (IDF), or recurring digital fibrous tumor of childhood, is a benign juvenile myofibromatosis that presents as a firm, flesh-colored or slightly erythematous, dome-shaped papule or nodule on the dorsolateral aspects of the digits, usually sparing the thumbs and great toes.¹ The tumor appears most commonly at birth and in infants younger than 1 year. It grows slowly over the first month, then rapidly over the next 10 to 14 months.^1,2  

Although lesions usually regress spontaneously within a few years, excision may be necessary when functional impairment and joint deformity occur. Tumors, however, may recur locally.^1,2  

Histologically, IDFs are composed of spindled myofibroblasts with characteristic round eosinophilic intracytoplasmic inclusion bodies, which represent actin and vimentin filaments.¹ In our case, histopathologic evaluation showed a proliferation of fibrous spindle cells with pathognomonic eosinophilic intracytoplasmic inclusions consistent with IDF (Figure).  

Fibrosarcomas are high-grade and low-grade soft-tissue neoplasms comprised of atypical spindle cells in a herringbone pattern with mitotic figures on pathology.³ They typically present as a slowly growing subcutaneous tumor on the lower extremities of young to middle-aged adults that may progress to become a palpable tender nodule. Infantile hemangiomas, the most common benign soft-tissue tumors of childhood, are vascular proliferations more commonly seen in low-birth-weight female white infants of multiple gestation pregnancies. Superficial hemangiomas present as bright red and lobular nodules or plaques. Deep hemangiomas present as ill-defined, blue-violaceous nodules with no overlying skin changes. Mixed hemangiomas present with features of both superficial and deep hemangiomas. Infantile hemangiomas experience a proliferative phase until 9 to 12 months of age, followed by a gradual involutional phase ending with possible residual telangiectases or fibrofatty change. Unlike IDFs, infantile hemangiomas favor the head and neck over other areas of the body. Keloids are firm, smooth, variably colored papules or plaques of haphazardly arranged thick dermal collagen bundles. They usually develop within a year of skin injury and extend beyond the original injury margin into normal tissue. Supernumerary digits present as small fleshy papules or larger nodules with a vestigial nail, most commonly on the ulnar side of the fifth finger or the radial side of the thumb. Histologically, they are composed of fascicles of nerve fibers.³ 

Treatment in our patient included partial amputation of the left second toe and excision with local tissue rearrangement by a plastic surgeon. His postoperative course was complicated by a minor wound infection, which resolved with a 7-day course of cephalexin. Since then, the patient has healed well, with gradual toe tissue and nail growth. No recurrence was reported 11 months after surgery.  

The Diagnosis: Infantile Digital Fibromatosis

Infantile digital fibromatosis (IDF), or recurring digital fibrous tumor of childhood, is a benign juvenile myofibromatosis that presents as a firm, flesh-colored or slightly erythematous, dome-shaped papule or nodule on the dorsolateral aspects of the digits, usually sparing the thumbs and great toes.¹ The tumor appears most commonly at birth and in infants younger than 1 year. It grows slowly over the first month, then rapidly over the next 10 to 14 months.^1,2  

Although lesions usually regress spontaneously within a few years, excision may be necessary when functional impairment and joint deformity occur. Tumors, however, may recur locally.^1,2  

Histologically, IDFs are composed of spindled myofibroblasts with characteristic round eosinophilic intracytoplasmic inclusion bodies, which represent actin and vimentin filaments.¹ In our case, histopathologic evaluation showed a proliferation of fibrous spindle cells with pathognomonic eosinophilic intracytoplasmic inclusions consistent with IDF (Figure).  

Fibrosarcomas are high-grade and low-grade soft-tissue neoplasms comprised of atypical spindle cells in a herringbone pattern with mitotic figures on pathology.³ They typically present as a slowly growing subcutaneous tumor on the lower extremities of young to middle-aged adults that may progress to become a palpable tender nodule. Infantile hemangiomas, the most common benign soft-tissue tumors of childhood, are vascular proliferations more commonly seen in low-birth-weight female white infants of multiple gestation pregnancies. Superficial hemangiomas present as bright red and lobular nodules or plaques. Deep hemangiomas present as ill-defined, blue-violaceous nodules with no overlying skin changes. Mixed hemangiomas present with features of both superficial and deep hemangiomas. Infantile hemangiomas experience a proliferative phase until 9 to 12 months of age, followed by a gradual involutional phase ending with possible residual telangiectases or fibrofatty change. Unlike IDFs, infantile hemangiomas favor the head and neck over other areas of the body. Keloids are firm, smooth, variably colored papules or plaques of haphazardly arranged thick dermal collagen bundles. They usually develop within a year of skin injury and extend beyond the original injury margin into normal tissue. Supernumerary digits present as small fleshy papules or larger nodules with a vestigial nail, most commonly on the ulnar side of the fifth finger or the radial side of the thumb. Histologically, they are composed of fascicles of nerve fibers.³ 

Treatment in our patient included partial amputation of the left second toe and excision with local tissue rearrangement by a plastic surgeon. His postoperative course was complicated by a minor wound infection, which resolved with a 7-day course of cephalexin. Since then, the patient has healed well, with gradual toe tissue and nail growth. No recurrence was reported 11 months after surgery.  

The Diagnosis: Infantile Digital Fibromatosis

Infantile digital fibromatosis (IDF), or recurring digital fibrous tumor of childhood, is a benign juvenile myofibromatosis that presents as a firm, flesh-colored or slightly erythematous, dome-shaped papule or nodule on the dorsolateral aspects of the digits, usually sparing the thumbs and great toes.¹ The tumor appears most commonly at birth and in infants younger than 1 year. It grows slowly over the first month, then rapidly over the next 10 to 14 months.^1,2  

Although lesions usually regress spontaneously within a few years, excision may be necessary when functional impairment and joint deformity occur. Tumors, however, may recur locally.^1,2  

Histologically, IDFs are composed of spindled myofibroblasts with characteristic round eosinophilic intracytoplasmic inclusion bodies, which represent actin and vimentin filaments.¹ In our case, histopathologic evaluation showed a proliferation of fibrous spindle cells with pathognomonic eosinophilic intracytoplasmic inclusions consistent with IDF (Figure).  

Fibrosarcomas are high-grade and low-grade soft-tissue neoplasms comprised of atypical spindle cells in a herringbone pattern with mitotic figures on pathology.³ They typically present as a slowly growing subcutaneous tumor on the lower extremities of young to middle-aged adults that may progress to become a palpable tender nodule. Infantile hemangiomas, the most common benign soft-tissue tumors of childhood, are vascular proliferations more commonly seen in low-birth-weight female white infants of multiple gestation pregnancies. Superficial hemangiomas present as bright red and lobular nodules or plaques. Deep hemangiomas present as ill-defined, blue-violaceous nodules with no overlying skin changes. Mixed hemangiomas present with features of both superficial and deep hemangiomas. Infantile hemangiomas experience a proliferative phase until 9 to 12 months of age, followed by a gradual involutional phase ending with possible residual telangiectases or fibrofatty change. Unlike IDFs, infantile hemangiomas favor the head and neck over other areas of the body. Keloids are firm, smooth, variably colored papules or plaques of haphazardly arranged thick dermal collagen bundles. They usually develop within a year of skin injury and extend beyond the original injury margin into normal tissue. Supernumerary digits present as small fleshy papules or larger nodules with a vestigial nail, most commonly on the ulnar side of the fifth finger or the radial side of the thumb. Histologically, they are composed of fascicles of nerve fibers.³ 

Treatment in our patient included partial amputation of the left second toe and excision with local tissue rearrangement by a plastic surgeon. His postoperative course was complicated by a minor wound infection, which resolved with a 7-day course of cephalexin. Since then, the patient has healed well, with gradual toe tissue and nail growth. No recurrence was reported 11 months after surgery.  

The Diagnosis: Steatocystoma Multiplex 

The punch biopsy of an abdominal lesion demonstrated a folded cyst wall with a wavy eosinophilic cuticle (Figure), characteristics consistent with steatocystoma multiplex (SM).  

Also known as eruptive steatocystoma, SM consists of numerous flesh-colored, dome-shaped papules and nodules that most commonly arise during adolescence, with a median age of onset of 26 years.¹ These hamartomatous nevoid malformations arise in areas with well-developed pilosebaceous units, such as the upper extremities, neck, axillae, and trunk.^1,2 They occur less commonly on the scalp, face, and acral surfaces.^2-5 The lesions range in size from 2 to 30 mm⁶ and usually are asymptomatic.¹ Occasionally, steatocystomas become tender or can rupture.⁷ 

Steatocystoma multiplex may arise sporadically or may be inherited in an autosomal-dominant fashion. Mutations in exon 1 of the keratin 17 gene, KRT17, have been identified in autosomal-dominant SM.^6,8KRT17 mutations also are responsible for pachyonychia congenita type 2, which is associated with SM.⁹ Some patients with pachyonychia congenita type 2 who have prominent SM and mild nail findings may be misdiagnosed as having pure SM.² 

The histopathologic features of SM were described in a study by Cho and colleagues¹ of 64 patients. Steatocystomas have cyst walls that may be either intricately folded or round/oval, comprised of an average of 4.9 epithelial cell layers. In most cases, the cyst wall contains sebaceous lobules. In all cases, an acellular eosinophilic cuticle was present, and no granular layer was seen. Few vellus hairs may be observed in the cystic cavity.¹ 

The differential diagnosis of SM includes eruptive vellus hair cysts, lipomas, Muir-Torre syndrome, and Gardner syndrome. Some have suggested that eruptive vellus hair cysts and SM exist on a disease spectrum because of their similar clinical presentation.¹⁰ In contrast to SM, however, eruptive vellus hair cysts originate in the infundibulum of the hair shaft rather than the sebaceous duct, and more numerous vellus hair shafts are seen on histopathology.¹ 

Various treatment modalities have been described, including isotretinoin for inflamed lesions,¹¹ cryotherapy for noninflamed lesions,¹¹ aspiration of lesions smallerthan 1 cm,¹² and electrocautery combined with topical retinoids.¹³ Laser treatment has been described, with a 1450-nm diode laser used to target the abnormal sebaceous glands and a 1550-nm fractionated erbium-doped fiber laser used to target the dermal cysts.¹⁴ Carbon dioxide lasers also may be used to open the cyst for drainage.¹⁵ Surgical excision or mini-incision also may be performed.^16,17  
 
Acknowledgment
The authors thank Garth Fraga, MD (Kansas City, Kansas), for his assistance with interpretation of the dermatopathology in this case.  

The Diagnosis: Steatocystoma Multiplex 

The punch biopsy of an abdominal lesion demonstrated a folded cyst wall with a wavy eosinophilic cuticle (Figure), characteristics consistent with steatocystoma multiplex (SM).  

Also known as eruptive steatocystoma, SM consists of numerous flesh-colored, dome-shaped papules and nodules that most commonly arise during adolescence, with a median age of onset of 26 years.¹ These hamartomatous nevoid malformations arise in areas with well-developed pilosebaceous units, such as the upper extremities, neck, axillae, and trunk.^1,2 They occur less commonly on the scalp, face, and acral surfaces.^2-5 The lesions range in size from 2 to 30 mm⁶ and usually are asymptomatic.¹ Occasionally, steatocystomas become tender or can rupture.⁷ 

Steatocystoma multiplex may arise sporadically or may be inherited in an autosomal-dominant fashion. Mutations in exon 1 of the keratin 17 gene, KRT17, have been identified in autosomal-dominant SM.^6,8KRT17 mutations also are responsible for pachyonychia congenita type 2, which is associated with SM.⁹ Some patients with pachyonychia congenita type 2 who have prominent SM and mild nail findings may be misdiagnosed as having pure SM.² 

The histopathologic features of SM were described in a study by Cho and colleagues¹ of 64 patients. Steatocystomas have cyst walls that may be either intricately folded or round/oval, comprised of an average of 4.9 epithelial cell layers. In most cases, the cyst wall contains sebaceous lobules. In all cases, an acellular eosinophilic cuticle was present, and no granular layer was seen. Few vellus hairs may be observed in the cystic cavity.¹ 

The differential diagnosis of SM includes eruptive vellus hair cysts, lipomas, Muir-Torre syndrome, and Gardner syndrome. Some have suggested that eruptive vellus hair cysts and SM exist on a disease spectrum because of their similar clinical presentation.¹⁰ In contrast to SM, however, eruptive vellus hair cysts originate in the infundibulum of the hair shaft rather than the sebaceous duct, and more numerous vellus hair shafts are seen on histopathology.¹ 

Various treatment modalities have been described, including isotretinoin for inflamed lesions,¹¹ cryotherapy for noninflamed lesions,¹¹ aspiration of lesions smallerthan 1 cm,¹² and electrocautery combined with topical retinoids.¹³ Laser treatment has been described, with a 1450-nm diode laser used to target the abnormal sebaceous glands and a 1550-nm fractionated erbium-doped fiber laser used to target the dermal cysts.¹⁴ Carbon dioxide lasers also may be used to open the cyst for drainage.¹⁵ Surgical excision or mini-incision also may be performed.^16,17  
 
Acknowledgment
The authors thank Garth Fraga, MD (Kansas City, Kansas), for his assistance with interpretation of the dermatopathology in this case.  

The Diagnosis: Steatocystoma Multiplex 

The punch biopsy of an abdominal lesion demonstrated a folded cyst wall with a wavy eosinophilic cuticle (Figure), characteristics consistent with steatocystoma multiplex (SM).  

Also known as eruptive steatocystoma, SM consists of numerous flesh-colored, dome-shaped papules and nodules that most commonly arise during adolescence, with a median age of onset of 26 years.¹ These hamartomatous nevoid malformations arise in areas with well-developed pilosebaceous units, such as the upper extremities, neck, axillae, and trunk.^1,2 They occur less commonly on the scalp, face, and acral surfaces.^2-5 The lesions range in size from 2 to 30 mm⁶ and usually are asymptomatic.¹ Occasionally, steatocystomas become tender or can rupture.⁷ 

Steatocystoma multiplex may arise sporadically or may be inherited in an autosomal-dominant fashion. Mutations in exon 1 of the keratin 17 gene, KRT17, have been identified in autosomal-dominant SM.^6,8KRT17 mutations also are responsible for pachyonychia congenita type 2, which is associated with SM.⁹ Some patients with pachyonychia congenita type 2 who have prominent SM and mild nail findings may be misdiagnosed as having pure SM.² 

The histopathologic features of SM were described in a study by Cho and colleagues¹ of 64 patients. Steatocystomas have cyst walls that may be either intricately folded or round/oval, comprised of an average of 4.9 epithelial cell layers. In most cases, the cyst wall contains sebaceous lobules. In all cases, an acellular eosinophilic cuticle was present, and no granular layer was seen. Few vellus hairs may be observed in the cystic cavity.¹ 

The differential diagnosis of SM includes eruptive vellus hair cysts, lipomas, Muir-Torre syndrome, and Gardner syndrome. Some have suggested that eruptive vellus hair cysts and SM exist on a disease spectrum because of their similar clinical presentation.¹⁰ In contrast to SM, however, eruptive vellus hair cysts originate in the infundibulum of the hair shaft rather than the sebaceous duct, and more numerous vellus hair shafts are seen on histopathology.¹ 

Various treatment modalities have been described, including isotretinoin for inflamed lesions,¹¹ cryotherapy for noninflamed lesions,¹¹ aspiration of lesions smallerthan 1 cm,¹² and electrocautery combined with topical retinoids.¹³ Laser treatment has been described, with a 1450-nm diode laser used to target the abnormal sebaceous glands and a 1550-nm fractionated erbium-doped fiber laser used to target the dermal cysts.¹⁴ Carbon dioxide lasers also may be used to open the cyst for drainage.¹⁵ Surgical excision or mini-incision also may be performed.^16,17  
 
Acknowledgment
The authors thank Garth Fraga, MD (Kansas City, Kansas), for his assistance with interpretation of the dermatopathology in this case.  

The Diagnosis: Scleromyxedema 

Scleromyxedema is a rare skin disorder characterized by a diffuse eruption of small waxy papules that are linearly arranged and closely spaced together. As the papular lesions coalesce, the skin thickens. Firm induration of the skin is widespread and--unlike the distribution in scleroderma and scleredema--amplified over the facial convexities, especially the glabella and ears. Histopathology reveals the classic triad of mucin accumulation, proliferation of fibroblasts, and collagen deposition with associated fibrotic changes.¹ 

In this case, the patient exhibited the characteristic doughnut sign over the second interphalangeal joint of the right hand due to thickening and dimpling of the skin (quiz image). Histopathology from the right second finger showed the dermis with a spindled histiocytic infiltrate, fibroblasts, fibrosis, and increased interstitial mucin deposition highlighted with colloidal iron stain (Figures 1 and 2). Multinucleated giant cells also were seen in the dermis (Figure 3), and a Shikata orcein stain illustrated decreased elastic fibers (stained black) in the superficial dermis within areas of increased collagen deposition (Figure 4).  

Scleromyxedema is strongly associated with a monoclonal gammopathy, which is generally mild and, in almost 80% of cases, related to λ IgG. However, the clinical implications are unclear.^2,3 Scleromyxedema also is accompanied by systemic features, most commonly dysphagia, myalgias, and arthralgias, which distinguishes it from other cutaneous mucinoses. Notable morbidity and mortality are associated with involvement of the central nervous system, which can manifest as encephalopathy, seizures, or coma. Mucin deposition may be found in the myocardium and the coronary and pulmonary vasculature, resulting in rare cases of cardiac and pulmonary disease.^4,5  

Clinically, scleroderma also demonstrates progressive generalized skin tightening. Histopathology reveals hyalinization and thickening of the connective tissue of the deep dermis, subcutaneous fat, and muscular fascia. These changes are accompanied by a perivascular and focal interstitial lymphocytic and plasma cell infiltrate with prominent myofibroblast proliferation. In this case, the normal nail fold capillaries and absence of Raynaud phenomenon help to distinguish the diagnosis from scleroderma. In limited scleroderma, common findings include calcinosis, esophageal dysmotility, telangiectasia, and pulmonary hypertension, while systemic sclerosis can involve the internal organs, with the greatest morbidity stemming from interstitial lung disease.^3,6,7  

Nephrogenic systemic fibrosis is another disorder of skin thickening that involves the extremities and trunk. It is a rare complication of exposure to gadolinium contrast media in patients with advanced renal disease and those undergoing dialysis; use of gadolinium is now strictly avoided in patients with at least moderately impaired glomerular filtration rate.⁸ Although nephrogenic systemic fibrosis histologically looks similar to scleromyxedema, it involves deeper tissues. There is fibrosis with haphazard collagen bundle deposition in the deep dermis and subcutaneous septa. Fibroblasts and histiocytes are increased between the collagen bundles, with surrounding edema and mucin buildup. Multinucleated giant cells may or may not be present.⁹ 

Patients with scleredema present with nonpitting edema and dermal hardening over the neck, face, upper trunk, and arms. Lesional skin appears shiny and indurated. The skin is characteristically difficult to wrinkle, and the face may appear expressionless. Skin biopsy will show a thickened reticular dermis with mucin deposition and eccrine glands appearing in the upper third or mid dermis. Fibroblasts are normal in number. Scleredema generally is associated with poorly controlled diabetes, a monoclonal gammopathy, or as the aftermath of an acute infection, especially streptococcal pharyngitis. The condition may develop at any age, though nearly 50% of cases occur in children and adolescents.^3,10  

Interstitial granuloma annulare (GA) is a common, benign, and self-limiting dermatosis. Distinct from other skin-thickening disorders, GA is composed of smooth annular papules and plaques that do not result in skin hardening. Although GA may manifest in a generalized distribution, it is more frequently localized to the distal extremities.¹¹ The presence of an inflammatory infiltrate surrounded by abundant mucin and collagen resembles scleromyxedema. However, GA is distinguished by palisading granulomas of histiocytes, fibroblasts, and lymphocytes lining a necrobiotic center of collagen, mucin, and fibrin.¹² 

This patient's skin showed an immediate and marked response to intravenous immunoglobulin with dramatic softening. Such a response is well reported in the literature, and intravenous immunoglobulin is considered first-line therapy for scleromyxedema, typically in conjunction with steroids.⁵ Other immunosuppressive agents have been employed with reported efficacy, as have several treatments used for multiple myeloma, including thalidomide and lenalidomide.  

Although spontaneous improvement infrequently occurs, a chronic progressive course is far more common with scleromyxedema. Studies are ongoing to elucidate the etiopathogenesis of scleromyxedema, scleroderma, and similar disorders to uncover the triggers that provoke the underlying dysregulation of dermal fibroblast activation and proliferation, which could offer a more precise target for effective treatments.^5,13-15

The Diagnosis: Scleromyxedema 

Scleromyxedema is a rare skin disorder characterized by a diffuse eruption of small waxy papules that are linearly arranged and closely spaced together. As the papular lesions coalesce, the skin thickens. Firm induration of the skin is widespread and--unlike the distribution in scleroderma and scleredema--amplified over the facial convexities, especially the glabella and ears. Histopathology reveals the classic triad of mucin accumulation, proliferation of fibroblasts, and collagen deposition with associated fibrotic changes.¹ 

In this case, the patient exhibited the characteristic doughnut sign over the second interphalangeal joint of the right hand due to thickening and dimpling of the skin (quiz image). Histopathology from the right second finger showed the dermis with a spindled histiocytic infiltrate, fibroblasts, fibrosis, and increased interstitial mucin deposition highlighted with colloidal iron stain (Figures 1 and 2). Multinucleated giant cells also were seen in the dermis (Figure 3), and a Shikata orcein stain illustrated decreased elastic fibers (stained black) in the superficial dermis within areas of increased collagen deposition (Figure 4).  

Scleromyxedema is strongly associated with a monoclonal gammopathy, which is generally mild and, in almost 80% of cases, related to λ IgG. However, the clinical implications are unclear.^2,3 Scleromyxedema also is accompanied by systemic features, most commonly dysphagia, myalgias, and arthralgias, which distinguishes it from other cutaneous mucinoses. Notable morbidity and mortality are associated with involvement of the central nervous system, which can manifest as encephalopathy, seizures, or coma. Mucin deposition may be found in the myocardium and the coronary and pulmonary vasculature, resulting in rare cases of cardiac and pulmonary disease.^4,5  

Clinically, scleroderma also demonstrates progressive generalized skin tightening. Histopathology reveals hyalinization and thickening of the connective tissue of the deep dermis, subcutaneous fat, and muscular fascia. These changes are accompanied by a perivascular and focal interstitial lymphocytic and plasma cell infiltrate with prominent myofibroblast proliferation. In this case, the normal nail fold capillaries and absence of Raynaud phenomenon help to distinguish the diagnosis from scleroderma. In limited scleroderma, common findings include calcinosis, esophageal dysmotility, telangiectasia, and pulmonary hypertension, while systemic sclerosis can involve the internal organs, with the greatest morbidity stemming from interstitial lung disease.^3,6,7  

Nephrogenic systemic fibrosis is another disorder of skin thickening that involves the extremities and trunk. It is a rare complication of exposure to gadolinium contrast media in patients with advanced renal disease and those undergoing dialysis; use of gadolinium is now strictly avoided in patients with at least moderately impaired glomerular filtration rate.⁸ Although nephrogenic systemic fibrosis histologically looks similar to scleromyxedema, it involves deeper tissues. There is fibrosis with haphazard collagen bundle deposition in the deep dermis and subcutaneous septa. Fibroblasts and histiocytes are increased between the collagen bundles, with surrounding edema and mucin buildup. Multinucleated giant cells may or may not be present.⁹ 

Patients with scleredema present with nonpitting edema and dermal hardening over the neck, face, upper trunk, and arms. Lesional skin appears shiny and indurated. The skin is characteristically difficult to wrinkle, and the face may appear expressionless. Skin biopsy will show a thickened reticular dermis with mucin deposition and eccrine glands appearing in the upper third or mid dermis. Fibroblasts are normal in number. Scleredema generally is associated with poorly controlled diabetes, a monoclonal gammopathy, or as the aftermath of an acute infection, especially streptococcal pharyngitis. The condition may develop at any age, though nearly 50% of cases occur in children and adolescents.^3,10  

Interstitial granuloma annulare (GA) is a common, benign, and self-limiting dermatosis. Distinct from other skin-thickening disorders, GA is composed of smooth annular papules and plaques that do not result in skin hardening. Although GA may manifest in a generalized distribution, it is more frequently localized to the distal extremities.¹¹ The presence of an inflammatory infiltrate surrounded by abundant mucin and collagen resembles scleromyxedema. However, GA is distinguished by palisading granulomas of histiocytes, fibroblasts, and lymphocytes lining a necrobiotic center of collagen, mucin, and fibrin.¹² 

This patient's skin showed an immediate and marked response to intravenous immunoglobulin with dramatic softening. Such a response is well reported in the literature, and intravenous immunoglobulin is considered first-line therapy for scleromyxedema, typically in conjunction with steroids.⁵ Other immunosuppressive agents have been employed with reported efficacy, as have several treatments used for multiple myeloma, including thalidomide and lenalidomide.  

Although spontaneous improvement infrequently occurs, a chronic progressive course is far more common with scleromyxedema. Studies are ongoing to elucidate the etiopathogenesis of scleromyxedema, scleroderma, and similar disorders to uncover the triggers that provoke the underlying dysregulation of dermal fibroblast activation and proliferation, which could offer a more precise target for effective treatments.^5,13-15

The Diagnosis: Scleromyxedema 

Scleromyxedema is a rare skin disorder characterized by a diffuse eruption of small waxy papules that are linearly arranged and closely spaced together. As the papular lesions coalesce, the skin thickens. Firm induration of the skin is widespread and--unlike the distribution in scleroderma and scleredema--amplified over the facial convexities, especially the glabella and ears. Histopathology reveals the classic triad of mucin accumulation, proliferation of fibroblasts, and collagen deposition with associated fibrotic changes.¹ 

In this case, the patient exhibited the characteristic doughnut sign over the second interphalangeal joint of the right hand due to thickening and dimpling of the skin (quiz image). Histopathology from the right second finger showed the dermis with a spindled histiocytic infiltrate, fibroblasts, fibrosis, and increased interstitial mucin deposition highlighted with colloidal iron stain (Figures 1 and 2). Multinucleated giant cells also were seen in the dermis (Figure 3), and a Shikata orcein stain illustrated decreased elastic fibers (stained black) in the superficial dermis within areas of increased collagen deposition (Figure 4).  

Scleromyxedema is strongly associated with a monoclonal gammopathy, which is generally mild and, in almost 80% of cases, related to λ IgG. However, the clinical implications are unclear.^2,3 Scleromyxedema also is accompanied by systemic features, most commonly dysphagia, myalgias, and arthralgias, which distinguishes it from other cutaneous mucinoses. Notable morbidity and mortality are associated with involvement of the central nervous system, which can manifest as encephalopathy, seizures, or coma. Mucin deposition may be found in the myocardium and the coronary and pulmonary vasculature, resulting in rare cases of cardiac and pulmonary disease.^4,5  

Clinically, scleroderma also demonstrates progressive generalized skin tightening. Histopathology reveals hyalinization and thickening of the connective tissue of the deep dermis, subcutaneous fat, and muscular fascia. These changes are accompanied by a perivascular and focal interstitial lymphocytic and plasma cell infiltrate with prominent myofibroblast proliferation. In this case, the normal nail fold capillaries and absence of Raynaud phenomenon help to distinguish the diagnosis from scleroderma. In limited scleroderma, common findings include calcinosis, esophageal dysmotility, telangiectasia, and pulmonary hypertension, while systemic sclerosis can involve the internal organs, with the greatest morbidity stemming from interstitial lung disease.^3,6,7  

Nephrogenic systemic fibrosis is another disorder of skin thickening that involves the extremities and trunk. It is a rare complication of exposure to gadolinium contrast media in patients with advanced renal disease and those undergoing dialysis; use of gadolinium is now strictly avoided in patients with at least moderately impaired glomerular filtration rate.⁸ Although nephrogenic systemic fibrosis histologically looks similar to scleromyxedema, it involves deeper tissues. There is fibrosis with haphazard collagen bundle deposition in the deep dermis and subcutaneous septa. Fibroblasts and histiocytes are increased between the collagen bundles, with surrounding edema and mucin buildup. Multinucleated giant cells may or may not be present.⁹ 

Patients with scleredema present with nonpitting edema and dermal hardening over the neck, face, upper trunk, and arms. Lesional skin appears shiny and indurated. The skin is characteristically difficult to wrinkle, and the face may appear expressionless. Skin biopsy will show a thickened reticular dermis with mucin deposition and eccrine glands appearing in the upper third or mid dermis. Fibroblasts are normal in number. Scleredema generally is associated with poorly controlled diabetes, a monoclonal gammopathy, or as the aftermath of an acute infection, especially streptococcal pharyngitis. The condition may develop at any age, though nearly 50% of cases occur in children and adolescents.^3,10  

Interstitial granuloma annulare (GA) is a common, benign, and self-limiting dermatosis. Distinct from other skin-thickening disorders, GA is composed of smooth annular papules and plaques that do not result in skin hardening. Although GA may manifest in a generalized distribution, it is more frequently localized to the distal extremities.¹¹ The presence of an inflammatory infiltrate surrounded by abundant mucin and collagen resembles scleromyxedema. However, GA is distinguished by palisading granulomas of histiocytes, fibroblasts, and lymphocytes lining a necrobiotic center of collagen, mucin, and fibrin.¹² 

This patient's skin showed an immediate and marked response to intravenous immunoglobulin with dramatic softening. Such a response is well reported in the literature, and intravenous immunoglobulin is considered first-line therapy for scleromyxedema, typically in conjunction with steroids.⁵ Other immunosuppressive agents have been employed with reported efficacy, as have several treatments used for multiple myeloma, including thalidomide and lenalidomide.  

Although spontaneous improvement infrequently occurs, a chronic progressive course is far more common with scleromyxedema. Studies are ongoing to elucidate the etiopathogenesis of scleromyxedema, scleroderma, and similar disorders to uncover the triggers that provoke the underlying dysregulation of dermal fibroblast activation and proliferation, which could offer a more precise target for effective treatments.^5,13-15

The Diagnosis: Lichenoid Reaction With Pseudoepitheliomatous Hyperplasia 

A shave biopsy of the left ankle and a punch biopsy of the left medial calf were performed and sent for histologic examination and acid-fast stain. Bacterial, fungal, and mycobacterial tissue cultures also were sent for testing. The findings from direct examination were negative, and tissue cultures exhibited no growth. The shave and punch biopsies and histology revealed pseudoepitheliomatous hyperplasia (PEH) with keratinocyte necrosis, satellitosis, and areas of acute folliculitis (Figure 1). A lichenoid hypersensitivity mixed infiltrate that included histiocytes admixed with anthracotic and red-orange pigment, lymphocytes, plasma cells, neutrophils, and rare eosinophils was noted in the dermis. Given these clinical and histopathologic findings, the patient was diagnosed with red-pigment tattoo lichenoid reaction with PEH.  

Tattoo-related inflammatory reactions can manifest clinically as allergic contact dermatitis, photodermatitis, infection, malignancy, foreign body granulomas, and delayed hypersensitivity reactions with myriad associated histopathologic patterns including spongiotic, psoriasiform, granulomatous, and lichenoid (as seen in our patient). Lichenoid tattoo reactions are the most common histopathologic variants of delayed hypersensitivity seen, mostly with cinnabar or red dye.¹ However, there is a paucity of cases in the literature of PEH following tattooing with red dye. Interestingly, lichenoid tissue reaction accompanies PEH in all reported cases.²  

Pseudoepitheliomatous hyperplasia can mimic squamous cell carcinoma and keratoacanthoma (KA) both clinically and histologically. All 3 conditions may exhibit epithelial hyperplasia with prominent dilated hyperplastic infundibula. In a case series of 11 presumed KAs within tattoos, Fraga and Prossick² reported 82% (9/11) of the lesions were located strictly in areas with red pigment, and many were associated with a lichenoid tissue reaction. Kazlouskaya and Junkins-Hopkins³ previously described cases of KAs in tattoos that may represent PEH.  

When treating lesions with this histologic appearance, consider the clinical and histologic overlap between KAs and PEH. Our patient was managed with clobetasol ointment 0.05% under occlusion followed by intralesional triamcinolone acetonide with notable improvement of the verrucous plaques on the left lateral malleolus (Figure 2). He also noted near resolution of the papules on the pretibial shin and complete resolution of all associated pruritus and burning. Calcineurin inhibitors, photochemotherapy, CO₂ laser, excimer laser, and surgical removal with interval grafting also were considered.  

It is important to recognize PEH in the differential of eruptions occurring within tattoos to avoid unnecessary invasive surgical procedures such as complete surgical excision of a KA to avoid malignant transformation. 

The Diagnosis: Lichenoid Reaction With Pseudoepitheliomatous Hyperplasia 

A shave biopsy of the left ankle and a punch biopsy of the left medial calf were performed and sent for histologic examination and acid-fast stain. Bacterial, fungal, and mycobacterial tissue cultures also were sent for testing. The findings from direct examination were negative, and tissue cultures exhibited no growth. The shave and punch biopsies and histology revealed pseudoepitheliomatous hyperplasia (PEH) with keratinocyte necrosis, satellitosis, and areas of acute folliculitis (Figure 1). A lichenoid hypersensitivity mixed infiltrate that included histiocytes admixed with anthracotic and red-orange pigment, lymphocytes, plasma cells, neutrophils, and rare eosinophils was noted in the dermis. Given these clinical and histopathologic findings, the patient was diagnosed with red-pigment tattoo lichenoid reaction with PEH.  

Tattoo-related inflammatory reactions can manifest clinically as allergic contact dermatitis, photodermatitis, infection, malignancy, foreign body granulomas, and delayed hypersensitivity reactions with myriad associated histopathologic patterns including spongiotic, psoriasiform, granulomatous, and lichenoid (as seen in our patient). Lichenoid tattoo reactions are the most common histopathologic variants of delayed hypersensitivity seen, mostly with cinnabar or red dye.¹ However, there is a paucity of cases in the literature of PEH following tattooing with red dye. Interestingly, lichenoid tissue reaction accompanies PEH in all reported cases.²  

Pseudoepitheliomatous hyperplasia can mimic squamous cell carcinoma and keratoacanthoma (KA) both clinically and histologically. All 3 conditions may exhibit epithelial hyperplasia with prominent dilated hyperplastic infundibula. In a case series of 11 presumed KAs within tattoos, Fraga and Prossick² reported 82% (9/11) of the lesions were located strictly in areas with red pigment, and many were associated with a lichenoid tissue reaction. Kazlouskaya and Junkins-Hopkins³ previously described cases of KAs in tattoos that may represent PEH.  

When treating lesions with this histologic appearance, consider the clinical and histologic overlap between KAs and PEH. Our patient was managed with clobetasol ointment 0.05% under occlusion followed by intralesional triamcinolone acetonide with notable improvement of the verrucous plaques on the left lateral malleolus (Figure 2). He also noted near resolution of the papules on the pretibial shin and complete resolution of all associated pruritus and burning. Calcineurin inhibitors, photochemotherapy, CO₂ laser, excimer laser, and surgical removal with interval grafting also were considered.  

It is important to recognize PEH in the differential of eruptions occurring within tattoos to avoid unnecessary invasive surgical procedures such as complete surgical excision of a KA to avoid malignant transformation. 

The Diagnosis: Lichenoid Reaction With Pseudoepitheliomatous Hyperplasia 

A shave biopsy of the left ankle and a punch biopsy of the left medial calf were performed and sent for histologic examination and acid-fast stain. Bacterial, fungal, and mycobacterial tissue cultures also were sent for testing. The findings from direct examination were negative, and tissue cultures exhibited no growth. The shave and punch biopsies and histology revealed pseudoepitheliomatous hyperplasia (PEH) with keratinocyte necrosis, satellitosis, and areas of acute folliculitis (Figure 1). A lichenoid hypersensitivity mixed infiltrate that included histiocytes admixed with anthracotic and red-orange pigment, lymphocytes, plasma cells, neutrophils, and rare eosinophils was noted in the dermis. Given these clinical and histopathologic findings, the patient was diagnosed with red-pigment tattoo lichenoid reaction with PEH.  

Tattoo-related inflammatory reactions can manifest clinically as allergic contact dermatitis, photodermatitis, infection, malignancy, foreign body granulomas, and delayed hypersensitivity reactions with myriad associated histopathologic patterns including spongiotic, psoriasiform, granulomatous, and lichenoid (as seen in our patient). Lichenoid tattoo reactions are the most common histopathologic variants of delayed hypersensitivity seen, mostly with cinnabar or red dye.¹ However, there is a paucity of cases in the literature of PEH following tattooing with red dye. Interestingly, lichenoid tissue reaction accompanies PEH in all reported cases.²  

Pseudoepitheliomatous hyperplasia can mimic squamous cell carcinoma and keratoacanthoma (KA) both clinically and histologically. All 3 conditions may exhibit epithelial hyperplasia with prominent dilated hyperplastic infundibula. In a case series of 11 presumed KAs within tattoos, Fraga and Prossick² reported 82% (9/11) of the lesions were located strictly in areas with red pigment, and many were associated with a lichenoid tissue reaction. Kazlouskaya and Junkins-Hopkins³ previously described cases of KAs in tattoos that may represent PEH.  

When treating lesions with this histologic appearance, consider the clinical and histologic overlap between KAs and PEH. Our patient was managed with clobetasol ointment 0.05% under occlusion followed by intralesional triamcinolone acetonide with notable improvement of the verrucous plaques on the left lateral malleolus (Figure 2). He also noted near resolution of the papules on the pretibial shin and complete resolution of all associated pruritus and burning. Calcineurin inhibitors, photochemotherapy, CO₂ laser, excimer laser, and surgical removal with interval grafting also were considered.  

It is important to recognize PEH in the differential of eruptions occurring within tattoos to avoid unnecessary invasive surgical procedures such as complete surgical excision of a KA to avoid malignant transformation. 

The Diagnosis: Dermatitis Herpetiformis 

Dermatitis herpetiformis (DH), also known as Duhring disease, is a rare autoimmune disease. It is the cutaneous manifestation of gluten sensitivity with antibodies targeting epidermal transglutaminase.¹ Symptoms of DH generally arise in the fourth decade of life, and children are less commonly affected,² though the diagnosis should be considered at any age, as our patient was aged 19 years at the time of presentation. Dermatitis herpetiformis predominantly affects white individuals of Northern European heritage, and males more often are affected than females.² There is a strong association with HLA-B8, HLA-DR3, and HLA-DQw2.³ It also is associated with other autoimmune disorders, including autoimmune thyroid disease, type 1 diabetes mellitus, and pernicious anemia.² 

Clinically, DH is characterized by groups of intensely pruritic papulovesicles that are symmetrically located on the extensor surfaces of the upper and lower extremities, scalp, nuchal area, back, and buttocks (quiz image). Less often, the groin also may be involved, as it was in our patient (Figure 1).⁴ Lesions can be papulovesicular or bullous, though they often are excoriated, and primary lesions may be difficult to identify.² The disease may have spontaneous remissions with frequent relapses. Most patients with DH have an asymptomatic gluten-sensitive enteropathy.³ 

A punch biopsy of a representative nonexcoriated lesion from our patient showed the characteristic collections of neutrophils and fibrin at the tips of dermal papillae on hematoxylin and eosin staining (Figure 2). These findings are suggestive of DH.¹ However, other bullous diseases, such as linear IgA dermatosis and epidermolysis bullosa acquisita, may have similar appearance on histology.¹ Direct immunofluorescence (DIF) of perilesional skin is the gold standard for diagnosing DH, with a sensitivity and specificity close to 100%.¹ Deposits of IgA generally are concentrated in previously involved skin or noninflamed perilesional skin; DIF of erythematous or lesional skin may be false negative.⁵ In our patient, DIF of perilesional uninvolved skin showed granular deposits of IgA at the dermoepidermal junction with accentuation in the dermal papillae (Figure 3), further suggestive of the diagnosis of DH.⁶ 

Patients with DH frequently will have specific IgA antibodies including anti-tissue transglutaminase (tTG), anti-epidermal transglutaminase, antiendomysial antibodies, and anti-synthetic deamidated gliadin peptides.¹ Only some of these tests are widely available, and the anti-tTG enzyme-linked immunosorbent assay is the least expensive and easiest to perform. A positive anti-tTG antibody test has a sensitivity ranging from 47% to 95% and a specificity greater than 90%.¹ Our patient tested positive for anti-tTG and anti-deamidated synthetic gliadin-derived peptides. A diagnostic algorithm based on current evidence suggests that in patients with clinical evidence of DH, typical DIF findings combined with positive anti-tTG antibodies confirms the diagnosis of DH, as was seen in our patient.^1,7 In situations where histopathology and/or antibody testing are inconclusive, additional testing to include HLA antigen typing, duodenal biopsy, and supplemental skin biopsies may be performed to help confirm or exclude a diagnosis of DH. It is unnecessary to perform a duodenal biopsy in patients with a confirmed diagnosis of DH, as DH is considered the specific cutaneous manifestation of celiac disease, and the diagnosis of DH is a diagnosis of celiac disease.¹  

Although pruritic papules may be found in several conditions, clinical, histopathologic, and DIF findings can help to confirm the diagnosis. Allergic contact dermatitis is a type IV hypersensitivity reaction causing eruptions of varying morphology, generally manifesting as pruritic scaly plaques that can occur anywhere on the body exposed to the offending allergen. Key histopathologic features of allergic contact dermatitis are eosinophilic spongiosis and exocytosis of eosinophils and lymphocytes.⁸ Papular urticaria is a hypersensitivity disorder to insect bites that consists of pruritic papules on exposed areas of skin, typically in children younger than 10 years. Genital and axillary areas usually are spared. The diagnosis is clinical.⁹ Recurrent herpes simplex virus infection is a short-lived outbreak that generally improves within 10 days. Herpes simplex virus infections usually are comprised of small vesicular or ulcerative lesions. Tzanck smear, skin biopsy, direct fluorescent antibody, viral culture, and polymerase chain reaction are diagnostic methods for herpes simplex virus.¹⁰ Scabies lesions typically are pruritic, erythematous, often excoriated papules and burrows located most commonly in the webs of fingers, wrists, axillae, areolae, waist, and genitalia. Diagnosis can be confirmed with scabies preparation (skin scraping showing mites, eggs, or feces), dermoscopy showing mites and burrows in vivo, or biopsy.¹¹  

First-line treatment in patients with DH and celiac disease is a strict gluten-free diet (GFD).¹ A GFD will resolve the cutaneous and gastrointestinal manifestations and is the only thing that will reduce the risk for lymphoma and other diseases associated with gluten-induced enteropathy.^1,2 A GFD alone will provide symptomatic relief over several months; dapsone and sulfapyridine can provide rapid relief of the pruritus and skin manifestations and usually can be weaned or discontinued after several months of following a strict GFD.¹² Patients on sulfone therapy require regular follow-up and monitoring due to the risk for hemolytic anemia and other adverse effects as well as to determine the appropriate time to discontinue the medication.¹² Although some patients are able to tolerate reintroduction of gluten into their diets after a period of remission, most will experience recurrent dermatologic manifestations if they continue to consume gluten.³ 

Because of our patient's impending move out of the area, no oral medications were started, and he was instructed to follow a GFD and seek medical care at his new location. The patient was contacted 6 months later and reported resolution of all skin lesions with just a GFD. The patient continued to follow-up with a dermatologist and gastroenterologist at his new location.

The Diagnosis: Dermatitis Herpetiformis 

Dermatitis herpetiformis (DH), also known as Duhring disease, is a rare autoimmune disease. It is the cutaneous manifestation of gluten sensitivity with antibodies targeting epidermal transglutaminase.¹ Symptoms of DH generally arise in the fourth decade of life, and children are less commonly affected,² though the diagnosis should be considered at any age, as our patient was aged 19 years at the time of presentation. Dermatitis herpetiformis predominantly affects white individuals of Northern European heritage, and males more often are affected than females.² There is a strong association with HLA-B8, HLA-DR3, and HLA-DQw2.³ It also is associated with other autoimmune disorders, including autoimmune thyroid disease, type 1 diabetes mellitus, and pernicious anemia.² 

Clinically, DH is characterized by groups of intensely pruritic papulovesicles that are symmetrically located on the extensor surfaces of the upper and lower extremities, scalp, nuchal area, back, and buttocks (quiz image). Less often, the groin also may be involved, as it was in our patient (Figure 1).⁴ Lesions can be papulovesicular or bullous, though they often are excoriated, and primary lesions may be difficult to identify.² The disease may have spontaneous remissions with frequent relapses. Most patients with DH have an asymptomatic gluten-sensitive enteropathy.³ 

A punch biopsy of a representative nonexcoriated lesion from our patient showed the characteristic collections of neutrophils and fibrin at the tips of dermal papillae on hematoxylin and eosin staining (Figure 2). These findings are suggestive of DH.¹ However, other bullous diseases, such as linear IgA dermatosis and epidermolysis bullosa acquisita, may have similar appearance on histology.¹ Direct immunofluorescence (DIF) of perilesional skin is the gold standard for diagnosing DH, with a sensitivity and specificity close to 100%.¹ Deposits of IgA generally are concentrated in previously involved skin or noninflamed perilesional skin; DIF of erythematous or lesional skin may be false negative.⁵ In our patient, DIF of perilesional uninvolved skin showed granular deposits of IgA at the dermoepidermal junction with accentuation in the dermal papillae (Figure 3), further suggestive of the diagnosis of DH.⁶ 

Patients with DH frequently will have specific IgA antibodies including anti-tissue transglutaminase (tTG), anti-epidermal transglutaminase, antiendomysial antibodies, and anti-synthetic deamidated gliadin peptides.¹ Only some of these tests are widely available, and the anti-tTG enzyme-linked immunosorbent assay is the least expensive and easiest to perform. A positive anti-tTG antibody test has a sensitivity ranging from 47% to 95% and a specificity greater than 90%.¹ Our patient tested positive for anti-tTG and anti-deamidated synthetic gliadin-derived peptides. A diagnostic algorithm based on current evidence suggests that in patients with clinical evidence of DH, typical DIF findings combined with positive anti-tTG antibodies confirms the diagnosis of DH, as was seen in our patient.^1,7 In situations where histopathology and/or antibody testing are inconclusive, additional testing to include HLA antigen typing, duodenal biopsy, and supplemental skin biopsies may be performed to help confirm or exclude a diagnosis of DH. It is unnecessary to perform a duodenal biopsy in patients with a confirmed diagnosis of DH, as DH is considered the specific cutaneous manifestation of celiac disease, and the diagnosis of DH is a diagnosis of celiac disease.¹  

Although pruritic papules may be found in several conditions, clinical, histopathologic, and DIF findings can help to confirm the diagnosis. Allergic contact dermatitis is a type IV hypersensitivity reaction causing eruptions of varying morphology, generally manifesting as pruritic scaly plaques that can occur anywhere on the body exposed to the offending allergen. Key histopathologic features of allergic contact dermatitis are eosinophilic spongiosis and exocytosis of eosinophils and lymphocytes.⁸ Papular urticaria is a hypersensitivity disorder to insect bites that consists of pruritic papules on exposed areas of skin, typically in children younger than 10 years. Genital and axillary areas usually are spared. The diagnosis is clinical.⁹ Recurrent herpes simplex virus infection is a short-lived outbreak that generally improves within 10 days. Herpes simplex virus infections usually are comprised of small vesicular or ulcerative lesions. Tzanck smear, skin biopsy, direct fluorescent antibody, viral culture, and polymerase chain reaction are diagnostic methods for herpes simplex virus.¹⁰ Scabies lesions typically are pruritic, erythematous, often excoriated papules and burrows located most commonly in the webs of fingers, wrists, axillae, areolae, waist, and genitalia. Diagnosis can be confirmed with scabies preparation (skin scraping showing mites, eggs, or feces), dermoscopy showing mites and burrows in vivo, or biopsy.¹¹  

First-line treatment in patients with DH and celiac disease is a strict gluten-free diet (GFD).¹ A GFD will resolve the cutaneous and gastrointestinal manifestations and is the only thing that will reduce the risk for lymphoma and other diseases associated with gluten-induced enteropathy.^1,2 A GFD alone will provide symptomatic relief over several months; dapsone and sulfapyridine can provide rapid relief of the pruritus and skin manifestations and usually can be weaned or discontinued after several months of following a strict GFD.¹² Patients on sulfone therapy require regular follow-up and monitoring due to the risk for hemolytic anemia and other adverse effects as well as to determine the appropriate time to discontinue the medication.¹² Although some patients are able to tolerate reintroduction of gluten into their diets after a period of remission, most will experience recurrent dermatologic manifestations if they continue to consume gluten.³ 

Because of our patient's impending move out of the area, no oral medications were started, and he was instructed to follow a GFD and seek medical care at his new location. The patient was contacted 6 months later and reported resolution of all skin lesions with just a GFD. The patient continued to follow-up with a dermatologist and gastroenterologist at his new location.

The Diagnosis: Dermatitis Herpetiformis 

Dermatitis herpetiformis (DH), also known as Duhring disease, is a rare autoimmune disease. It is the cutaneous manifestation of gluten sensitivity with antibodies targeting epidermal transglutaminase.¹ Symptoms of DH generally arise in the fourth decade of life, and children are less commonly affected,² though the diagnosis should be considered at any age, as our patient was aged 19 years at the time of presentation. Dermatitis herpetiformis predominantly affects white individuals of Northern European heritage, and males more often are affected than females.² There is a strong association with HLA-B8, HLA-DR3, and HLA-DQw2.³ It also is associated with other autoimmune disorders, including autoimmune thyroid disease, type 1 diabetes mellitus, and pernicious anemia.² 

Clinically, DH is characterized by groups of intensely pruritic papulovesicles that are symmetrically located on the extensor surfaces of the upper and lower extremities, scalp, nuchal area, back, and buttocks (quiz image). Less often, the groin also may be involved, as it was in our patient (Figure 1).⁴ Lesions can be papulovesicular or bullous, though they often are excoriated, and primary lesions may be difficult to identify.² The disease may have spontaneous remissions with frequent relapses. Most patients with DH have an asymptomatic gluten-sensitive enteropathy.³ 

A punch biopsy of a representative nonexcoriated lesion from our patient showed the characteristic collections of neutrophils and fibrin at the tips of dermal papillae on hematoxylin and eosin staining (Figure 2). These findings are suggestive of DH.¹ However, other bullous diseases, such as linear IgA dermatosis and epidermolysis bullosa acquisita, may have similar appearance on histology.¹ Direct immunofluorescence (DIF) of perilesional skin is the gold standard for diagnosing DH, with a sensitivity and specificity close to 100%.¹ Deposits of IgA generally are concentrated in previously involved skin or noninflamed perilesional skin; DIF of erythematous or lesional skin may be false negative.⁵ In our patient, DIF of perilesional uninvolved skin showed granular deposits of IgA at the dermoepidermal junction with accentuation in the dermal papillae (Figure 3), further suggestive of the diagnosis of DH.⁶ 

Patients with DH frequently will have specific IgA antibodies including anti-tissue transglutaminase (tTG), anti-epidermal transglutaminase, antiendomysial antibodies, and anti-synthetic deamidated gliadin peptides.¹ Only some of these tests are widely available, and the anti-tTG enzyme-linked immunosorbent assay is the least expensive and easiest to perform. A positive anti-tTG antibody test has a sensitivity ranging from 47% to 95% and a specificity greater than 90%.¹ Our patient tested positive for anti-tTG and anti-deamidated synthetic gliadin-derived peptides. A diagnostic algorithm based on current evidence suggests that in patients with clinical evidence of DH, typical DIF findings combined with positive anti-tTG antibodies confirms the diagnosis of DH, as was seen in our patient.^1,7 In situations where histopathology and/or antibody testing are inconclusive, additional testing to include HLA antigen typing, duodenal biopsy, and supplemental skin biopsies may be performed to help confirm or exclude a diagnosis of DH. It is unnecessary to perform a duodenal biopsy in patients with a confirmed diagnosis of DH, as DH is considered the specific cutaneous manifestation of celiac disease, and the diagnosis of DH is a diagnosis of celiac disease.¹  

Although pruritic papules may be found in several conditions, clinical, histopathologic, and DIF findings can help to confirm the diagnosis. Allergic contact dermatitis is a type IV hypersensitivity reaction causing eruptions of varying morphology, generally manifesting as pruritic scaly plaques that can occur anywhere on the body exposed to the offending allergen. Key histopathologic features of allergic contact dermatitis are eosinophilic spongiosis and exocytosis of eosinophils and lymphocytes.⁸ Papular urticaria is a hypersensitivity disorder to insect bites that consists of pruritic papules on exposed areas of skin, typically in children younger than 10 years. Genital and axillary areas usually are spared. The diagnosis is clinical.⁹ Recurrent herpes simplex virus infection is a short-lived outbreak that generally improves within 10 days. Herpes simplex virus infections usually are comprised of small vesicular or ulcerative lesions. Tzanck smear, skin biopsy, direct fluorescent antibody, viral culture, and polymerase chain reaction are diagnostic methods for herpes simplex virus.¹⁰ Scabies lesions typically are pruritic, erythematous, often excoriated papules and burrows located most commonly in the webs of fingers, wrists, axillae, areolae, waist, and genitalia. Diagnosis can be confirmed with scabies preparation (skin scraping showing mites, eggs, or feces), dermoscopy showing mites and burrows in vivo, or biopsy.¹¹  

First-line treatment in patients with DH and celiac disease is a strict gluten-free diet (GFD).¹ A GFD will resolve the cutaneous and gastrointestinal manifestations and is the only thing that will reduce the risk for lymphoma and other diseases associated with gluten-induced enteropathy.^1,2 A GFD alone will provide symptomatic relief over several months; dapsone and sulfapyridine can provide rapid relief of the pruritus and skin manifestations and usually can be weaned or discontinued after several months of following a strict GFD.¹² Patients on sulfone therapy require regular follow-up and monitoring due to the risk for hemolytic anemia and other adverse effects as well as to determine the appropriate time to discontinue the medication.¹² Although some patients are able to tolerate reintroduction of gluten into their diets after a period of remission, most will experience recurrent dermatologic manifestations if they continue to consume gluten.³ 

Because of our patient's impending move out of the area, no oral medications were started, and he was instructed to follow a GFD and seek medical care at his new location. The patient was contacted 6 months later and reported resolution of all skin lesions with just a GFD. The patient continued to follow-up with a dermatologist and gastroenterologist at his new location.

Shiitake Mushroom Dermatitis 

Given the scattered and erythematous 1- to 2-mm macules and patches in a flagellate pattern on the shoulders, back, and neck, the differential diagnosis included shiitake mushroom dermatitis, bleomycin-induced flagellate dermatitis, dermatomyositis flagellate erythema, excoriation disorder, dermatographism, and keratosis lichenoides chronica. On further questioning, the patient indicated that he had consumed raw shiitake mushrooms 3 days before the onset of the rash. Although the clinical variability for all the conditions on the differential is notable, our patient had a history of consuming raw shiitake mushrooms, denied taking any medications, reported no repeated trauma, and had no muscular involvement or systemic symptoms, making shiitake mushroom dermatitis the most likely diagnosis.¹ Skin biopsy and blood tests were deemed unnecessary. Instead, the patient was prescribed triamcinolone cream 0.1%, counseled to avoid raw or undercooked shiitake mushrooms in the future, and told to follow-up if symptoms did not resolve. The patient's symptoms resolved, as expected. 

Nakamura² first described shiitake mushroom dermatitis in 1977. The condition also is known as flagellate mushroom dermatitis or shiitake toxicoderma. It classically manifests in susceptible patients as a pruritic, linear, flagellated dermatitis within 24 to 48 hours after the consumption of raw or undercooked shiitake mushrooms (Lentinula edodes).³ Although the complete pathogenesis remains unclear, research suggests that either a toxic reaction or a type IV hypersensitivity reaction to lentinan causes the eruption. Lentinan is a thermolabile polysaccharide within the mushroom that is believed to increase the production of IL-1 and cause vasodilatation.⁴  

Shiitake mushroom dermatitis is a clinical diagnosis based on the most common findings of a flagellate-pattern dermatitis consisting of pruritic and erythematous papular or urticarial lesions, usually found on the trunk. Laboratory tests, skin biopsies, and allergy tests have been shown to be nonspecific and inconsistent.⁵ 

Shiitake mushroom dermatitis is a self-limiting condition, with the majority of symptoms resolving after one to several weeks.⁵ The mainstay of treatment is aimed at symptomatic management and usually consists of topical corticosteroids and antihistamines.³ More rapid resolution of symptoms has been reported with the use of short-term balneo-psoralen plus UVA therapy.⁶ 

Although a 2017 review of the literature described only 9 published cases of shiitake mushroom dermatitis within the United States as of July 2015, this number may be misleading given the possibility of more variable and subtle presentations misdiagnosed as a nonspecific dermatitis.⁵ Given this information and the fact that shiitake mushrooms continue to be a popular choice in American cuisine, this case reminds health care providers of the clinical manifestations, differential diagnosis, and management of flagellate dermatitis caused by consuming shiitake mushrooms.

Shiitake Mushroom Dermatitis 

Given the scattered and erythematous 1- to 2-mm macules and patches in a flagellate pattern on the shoulders, back, and neck, the differential diagnosis included shiitake mushroom dermatitis, bleomycin-induced flagellate dermatitis, dermatomyositis flagellate erythema, excoriation disorder, dermatographism, and keratosis lichenoides chronica. On further questioning, the patient indicated that he had consumed raw shiitake mushrooms 3 days before the onset of the rash. Although the clinical variability for all the conditions on the differential is notable, our patient had a history of consuming raw shiitake mushrooms, denied taking any medications, reported no repeated trauma, and had no muscular involvement or systemic symptoms, making shiitake mushroom dermatitis the most likely diagnosis.¹ Skin biopsy and blood tests were deemed unnecessary. Instead, the patient was prescribed triamcinolone cream 0.1%, counseled to avoid raw or undercooked shiitake mushrooms in the future, and told to follow-up if symptoms did not resolve. The patient's symptoms resolved, as expected. 

Nakamura² first described shiitake mushroom dermatitis in 1977. The condition also is known as flagellate mushroom dermatitis or shiitake toxicoderma. It classically manifests in susceptible patients as a pruritic, linear, flagellated dermatitis within 24 to 48 hours after the consumption of raw or undercooked shiitake mushrooms (Lentinula edodes).³ Although the complete pathogenesis remains unclear, research suggests that either a toxic reaction or a type IV hypersensitivity reaction to lentinan causes the eruption. Lentinan is a thermolabile polysaccharide within the mushroom that is believed to increase the production of IL-1 and cause vasodilatation.⁴  

Shiitake mushroom dermatitis is a clinical diagnosis based on the most common findings of a flagellate-pattern dermatitis consisting of pruritic and erythematous papular or urticarial lesions, usually found on the trunk. Laboratory tests, skin biopsies, and allergy tests have been shown to be nonspecific and inconsistent.⁵ 

Shiitake mushroom dermatitis is a self-limiting condition, with the majority of symptoms resolving after one to several weeks.⁵ The mainstay of treatment is aimed at symptomatic management and usually consists of topical corticosteroids and antihistamines.³ More rapid resolution of symptoms has been reported with the use of short-term balneo-psoralen plus UVA therapy.⁶ 

Although a 2017 review of the literature described only 9 published cases of shiitake mushroom dermatitis within the United States as of July 2015, this number may be misleading given the possibility of more variable and subtle presentations misdiagnosed as a nonspecific dermatitis.⁵ Given this information and the fact that shiitake mushrooms continue to be a popular choice in American cuisine, this case reminds health care providers of the clinical manifestations, differential diagnosis, and management of flagellate dermatitis caused by consuming shiitake mushrooms.

Shiitake Mushroom Dermatitis 

Given the scattered and erythematous 1- to 2-mm macules and patches in a flagellate pattern on the shoulders, back, and neck, the differential diagnosis included shiitake mushroom dermatitis, bleomycin-induced flagellate dermatitis, dermatomyositis flagellate erythema, excoriation disorder, dermatographism, and keratosis lichenoides chronica. On further questioning, the patient indicated that he had consumed raw shiitake mushrooms 3 days before the onset of the rash. Although the clinical variability for all the conditions on the differential is notable, our patient had a history of consuming raw shiitake mushrooms, denied taking any medications, reported no repeated trauma, and had no muscular involvement or systemic symptoms, making shiitake mushroom dermatitis the most likely diagnosis.¹ Skin biopsy and blood tests were deemed unnecessary. Instead, the patient was prescribed triamcinolone cream 0.1%, counseled to avoid raw or undercooked shiitake mushrooms in the future, and told to follow-up if symptoms did not resolve. The patient's symptoms resolved, as expected. 

Nakamura² first described shiitake mushroom dermatitis in 1977. The condition also is known as flagellate mushroom dermatitis or shiitake toxicoderma. It classically manifests in susceptible patients as a pruritic, linear, flagellated dermatitis within 24 to 48 hours after the consumption of raw or undercooked shiitake mushrooms (Lentinula edodes).³ Although the complete pathogenesis remains unclear, research suggests that either a toxic reaction or a type IV hypersensitivity reaction to lentinan causes the eruption. Lentinan is a thermolabile polysaccharide within the mushroom that is believed to increase the production of IL-1 and cause vasodilatation.⁴  

Shiitake mushroom dermatitis is a clinical diagnosis based on the most common findings of a flagellate-pattern dermatitis consisting of pruritic and erythematous papular or urticarial lesions, usually found on the trunk. Laboratory tests, skin biopsies, and allergy tests have been shown to be nonspecific and inconsistent.⁵ 

Shiitake mushroom dermatitis is a self-limiting condition, with the majority of symptoms resolving after one to several weeks.⁵ The mainstay of treatment is aimed at symptomatic management and usually consists of topical corticosteroids and antihistamines.³ More rapid resolution of symptoms has been reported with the use of short-term balneo-psoralen plus UVA therapy.⁶ 

Although a 2017 review of the literature described only 9 published cases of shiitake mushroom dermatitis within the United States as of July 2015, this number may be misleading given the possibility of more variable and subtle presentations misdiagnosed as a nonspecific dermatitis.⁵ Given this information and the fact that shiitake mushrooms continue to be a popular choice in American cuisine, this case reminds health care providers of the clinical manifestations, differential diagnosis, and management of flagellate dermatitis caused by consuming shiitake mushrooms.

The Diagnosis: Birt-Hogg-Dubé Syndrome 

Histopathologic examination revealed a collection of bland spindle cells with perifollicular fibrosis consistent with a fibrofolliculoma, confirming the diagnosis of Birt-Hogg-Dubé syndrome (Figure). Cosmetic treatment with ablative therapy was offered, but the patient declined.  

Birt-Hogg-Dubé syndrome is an autosomal-dominant genodermatosis caused by a loss-of-function mutation in the folliculin gene, FLCN, on chromosome arm 17p11.2.¹ Cutaneous findings include benign follicular hamartomas, such as fibrofolliculomas and trichodiscomas. Angiofibromas, perifollicular fibromas, oral papillomas, and acrochordons also can be present.¹ Cutaneous lesions usually appear on the head and neck in the third decade of life.  

Patients with Birt-Hogg-Dubé syndrome are at an increased risk for pneumothorax and renal cancer, specifically hybrid oncocytic-chromophobe renal cell carcinomas.² In a study of 89 patients with a FLCN mutation, 90% (80/89) of patients had cutaneous lesions, 84% (34/89) had pulmonary cysts, and 34% (30/89) had kidney tumors. Affected individuals were at a higher risk for pneumothorax and kidney tumors if there was a family history of these tumors.²  

Proposed diagnostic criteria include any 1 of the following: 2 or more skin lesions clinically consistent with fibrofolliculomas and 1 histologically confirmed fibrofolliculoma; multiple bilateral pulmonary cysts in the basilar lung with or without pneumothorax before 40 years of age; bilateral multifocal chromophobe renal carcinomas or hybrid oncocytic tumors; combination of cutaneous, pulmonary, or renal manifestation in the patient and family; or a FLCN mutation.³  

Current recommendations for the workup of a patient with Birt-Hogg-Dubé syndrome include referral to genetic counseling for the patient and family, a baseline computed tomography of the chest to evaluate for pulmonary cysts, and gadolinium-enhanced abdominal magnetic resonance imaging starting at 20 years of age and repeated every 3 to 4 years to screen for renal tumors.¹ Pulmonary function tests can be considered if the patient is symptomatic or has a high cyst burden. Patients should be advised against smoking and scuba diving. 

The differential diagnosis of multiple facial papules includes Cowden syndrome, tuberous sclerosis, Brooke-Spiegler syndrome, and Muir-Torre syndrome. Cowden syndrome is caused by a mutation in the protein tyrosine phosphatase gene, PTEN.⁴ The characteristic cutaneous findings on the face are trichilemmomas, which appear as flesh-colored papules that may have a verrucous surface.  

Tuberous sclerosis is caused by mutations in hamartin (TSC1) or tuberin (TSC2). Angiofibromas are most commonly found on the face and appear as flesh-colored to red-brown papules. Fibrous plaques, periungual fibromas, gingival fibromas, hypopigmented macules, and connective tissue nevi also are found in tuberous sclerosis.⁵  

Brooke-Spiegler syndrome is caused by a mutation in the CYLD lysine 63 deubiquitinase gene, CYLD. Trichoepitheliomas, cylindromas, and spiradenomas are caused by the CYLD mutation and appear on the head and neck. Trichoepitheliomas are flesh-colored to pink papules found on the face, often concentrated in the nasolabial folds.⁶ Cylindromas and spiradenomas are flesh-colored to pink papules or nodules most commonly found on the scalp.⁶  

Muir-Torre syndrome is caused by a mutation in DNA mismatch repair genes MSH2 and/or MLH1.⁷ Sebaceous neoplasms, including sebaceous adenomas, sebaceomas, and less frequently sebaceous carcinomas, are characteristic cutaneous findings and appear as pink to yellow papules commonly found on the head and neck.  

Careful history taking, physical examination, and histopathologic analysis are important in recognizing the features of Birt-Hogg-Dubé syndrome. Accurate and timely diagnosis is essential for the appropriate care of patients and their families, given the syndrome's systemic implications.  

The Diagnosis: Birt-Hogg-Dubé Syndrome 

Histopathologic examination revealed a collection of bland spindle cells with perifollicular fibrosis consistent with a fibrofolliculoma, confirming the diagnosis of Birt-Hogg-Dubé syndrome (Figure). Cosmetic treatment with ablative therapy was offered, but the patient declined.  

Birt-Hogg-Dubé syndrome is an autosomal-dominant genodermatosis caused by a loss-of-function mutation in the folliculin gene, FLCN, on chromosome arm 17p11.2.¹ Cutaneous findings include benign follicular hamartomas, such as fibrofolliculomas and trichodiscomas. Angiofibromas, perifollicular fibromas, oral papillomas, and acrochordons also can be present.¹ Cutaneous lesions usually appear on the head and neck in the third decade of life.  

Patients with Birt-Hogg-Dubé syndrome are at an increased risk for pneumothorax and renal cancer, specifically hybrid oncocytic-chromophobe renal cell carcinomas.² In a study of 89 patients with a FLCN mutation, 90% (80/89) of patients had cutaneous lesions, 84% (34/89) had pulmonary cysts, and 34% (30/89) had kidney tumors. Affected individuals were at a higher risk for pneumothorax and kidney tumors if there was a family history of these tumors.²  

Proposed diagnostic criteria include any 1 of the following: 2 or more skin lesions clinically consistent with fibrofolliculomas and 1 histologically confirmed fibrofolliculoma; multiple bilateral pulmonary cysts in the basilar lung with or without pneumothorax before 40 years of age; bilateral multifocal chromophobe renal carcinomas or hybrid oncocytic tumors; combination of cutaneous, pulmonary, or renal manifestation in the patient and family; or a FLCN mutation.³  

Current recommendations for the workup of a patient with Birt-Hogg-Dubé syndrome include referral to genetic counseling for the patient and family, a baseline computed tomography of the chest to evaluate for pulmonary cysts, and gadolinium-enhanced abdominal magnetic resonance imaging starting at 20 years of age and repeated every 3 to 4 years to screen for renal tumors.¹ Pulmonary function tests can be considered if the patient is symptomatic or has a high cyst burden. Patients should be advised against smoking and scuba diving. 

The differential diagnosis of multiple facial papules includes Cowden syndrome, tuberous sclerosis, Brooke-Spiegler syndrome, and Muir-Torre syndrome. Cowden syndrome is caused by a mutation in the protein tyrosine phosphatase gene, PTEN.⁴ The characteristic cutaneous findings on the face are trichilemmomas, which appear as flesh-colored papules that may have a verrucous surface.  

Tuberous sclerosis is caused by mutations in hamartin (TSC1) or tuberin (TSC2). Angiofibromas are most commonly found on the face and appear as flesh-colored to red-brown papules. Fibrous plaques, periungual fibromas, gingival fibromas, hypopigmented macules, and connective tissue nevi also are found in tuberous sclerosis.⁵  

Brooke-Spiegler syndrome is caused by a mutation in the CYLD lysine 63 deubiquitinase gene, CYLD. Trichoepitheliomas, cylindromas, and spiradenomas are caused by the CYLD mutation and appear on the head and neck. Trichoepitheliomas are flesh-colored to pink papules found on the face, often concentrated in the nasolabial folds.⁶ Cylindromas and spiradenomas are flesh-colored to pink papules or nodules most commonly found on the scalp.⁶  

Muir-Torre syndrome is caused by a mutation in DNA mismatch repair genes MSH2 and/or MLH1.⁷ Sebaceous neoplasms, including sebaceous adenomas, sebaceomas, and less frequently sebaceous carcinomas, are characteristic cutaneous findings and appear as pink to yellow papules commonly found on the head and neck.  

Careful history taking, physical examination, and histopathologic analysis are important in recognizing the features of Birt-Hogg-Dubé syndrome. Accurate and timely diagnosis is essential for the appropriate care of patients and their families, given the syndrome's systemic implications.  

The Diagnosis: Birt-Hogg-Dubé Syndrome 

Histopathologic examination revealed a collection of bland spindle cells with perifollicular fibrosis consistent with a fibrofolliculoma, confirming the diagnosis of Birt-Hogg-Dubé syndrome (Figure). Cosmetic treatment with ablative therapy was offered, but the patient declined.  

Birt-Hogg-Dubé syndrome is an autosomal-dominant genodermatosis caused by a loss-of-function mutation in the folliculin gene, FLCN, on chromosome arm 17p11.2.¹ Cutaneous findings include benign follicular hamartomas, such as fibrofolliculomas and trichodiscomas. Angiofibromas, perifollicular fibromas, oral papillomas, and acrochordons also can be present.¹ Cutaneous lesions usually appear on the head and neck in the third decade of life.  

Patients with Birt-Hogg-Dubé syndrome are at an increased risk for pneumothorax and renal cancer, specifically hybrid oncocytic-chromophobe renal cell carcinomas.² In a study of 89 patients with a FLCN mutation, 90% (80/89) of patients had cutaneous lesions, 84% (34/89) had pulmonary cysts, and 34% (30/89) had kidney tumors. Affected individuals were at a higher risk for pneumothorax and kidney tumors if there was a family history of these tumors.²  

Proposed diagnostic criteria include any 1 of the following: 2 or more skin lesions clinically consistent with fibrofolliculomas and 1 histologically confirmed fibrofolliculoma; multiple bilateral pulmonary cysts in the basilar lung with or without pneumothorax before 40 years of age; bilateral multifocal chromophobe renal carcinomas or hybrid oncocytic tumors; combination of cutaneous, pulmonary, or renal manifestation in the patient and family; or a FLCN mutation.³  

Current recommendations for the workup of a patient with Birt-Hogg-Dubé syndrome include referral to genetic counseling for the patient and family, a baseline computed tomography of the chest to evaluate for pulmonary cysts, and gadolinium-enhanced abdominal magnetic resonance imaging starting at 20 years of age and repeated every 3 to 4 years to screen for renal tumors.¹ Pulmonary function tests can be considered if the patient is symptomatic or has a high cyst burden. Patients should be advised against smoking and scuba diving. 

The differential diagnosis of multiple facial papules includes Cowden syndrome, tuberous sclerosis, Brooke-Spiegler syndrome, and Muir-Torre syndrome. Cowden syndrome is caused by a mutation in the protein tyrosine phosphatase gene, PTEN.⁴ The characteristic cutaneous findings on the face are trichilemmomas, which appear as flesh-colored papules that may have a verrucous surface.  

Tuberous sclerosis is caused by mutations in hamartin (TSC1) or tuberin (TSC2). Angiofibromas are most commonly found on the face and appear as flesh-colored to red-brown papules. Fibrous plaques, periungual fibromas, gingival fibromas, hypopigmented macules, and connective tissue nevi also are found in tuberous sclerosis.⁵  

Brooke-Spiegler syndrome is caused by a mutation in the CYLD lysine 63 deubiquitinase gene, CYLD. Trichoepitheliomas, cylindromas, and spiradenomas are caused by the CYLD mutation and appear on the head and neck. Trichoepitheliomas are flesh-colored to pink papules found on the face, often concentrated in the nasolabial folds.⁶ Cylindromas and spiradenomas are flesh-colored to pink papules or nodules most commonly found on the scalp.⁶  

Muir-Torre syndrome is caused by a mutation in DNA mismatch repair genes MSH2 and/or MLH1.⁷ Sebaceous neoplasms, including sebaceous adenomas, sebaceomas, and less frequently sebaceous carcinomas, are characteristic cutaneous findings and appear as pink to yellow papules commonly found on the head and neck.  

Careful history taking, physical examination, and histopathologic analysis are important in recognizing the features of Birt-Hogg-Dubé syndrome. Accurate and timely diagnosis is essential for the appropriate care of patients and their families, given the syndrome's systemic implications.