Primary Cutaneous Dermal Mucinosis on Herpes Zoster Scars

Mucin is an amorphous gelatinous substance that is found in a large variety of tissues. There are 2 types of cutaneous mucin: dermal and epithelial. Both types appear as basophilic shreds and granules with hematoxylin and eosin stain.1 Epithelial mucin (sialomucin) is found mainly in the gastrointestinal tract and lungs. In the skin, it is present in the cytoplasm of the dark cells of the eccrine glands and in the apocrine secretory cells. Epithelial mucin contains both neutral and acid glycosaminoglycans, stains positive with Alcian blue (pH 2.5) and periodic acid–Schiff, is resistant to hyaluronidase, and does not stain metachromatically with toluidine blue. Dermal mucin is composed of acid glycosaminoglycans (eg, dermatan sulfate, chondroitin 6-sulfate, chondroitin 4-sulfate, hyaluronic acid) and normally is produced by dermal fibroblasts. Dermal mucin stains positive with Alcian blue (pH 2.5); is periodic acid–Schiff negative and sensitive to hyaluronidase; and shows metachromasia with toluidine blue, methylene blue, and thionine.

Cutaneous mucinosis comprises a heterogeneous group of skin disorders characterized by the deposition of mucin in the interstices of the dermis. These diseases may be classified as primary mucinosis with the mucin deposition as the main histologic feature resulting in clinically distinctive lesions and secondary mucinosis with the mucin deposition as an additional histologic finding within the context of an independent skin disease or lesion (eg, basal cell carcinoma) with deposits of mucin in the stroma. Primary cutaneous mucinosis may be subclassified into 2 groups: degenerative-inflammatory mucinoses and neoplastic-hamartomatous mucinoses. According to the histologic features, the degenerative-inflammatory mucinoses are better divided into dermal and follicular mucinoses.² We describe a case of primary cutaneous dermal mucinosis on herpes zoster (HZ) scars as an isotopic response.

Case Report

A 33-year-old man presented to the dermatology department with slightly pruritic lesions on the left side of the chest and back that had appeared progressively at the site of HZ scars that had healed without treatment 9 months prior. Dermatologic examination revealed sharply defined whitish papules (Figure 1) measuring 2 to 4 mm in diameter with a smooth surface and linear distribution over the area of the left T8 and T9 dermatomes. The patient reported no postherpetic neuralgia and was otherwise healthy. Laboratory tests including a complete blood cell count, biochemistry, urinalysis, and determination of free thyroid hormones were within reference range. Serologic tests for human immunodeficiency virus, hepatitis B and C viruses, and syphilis were negative. Antinuclear antibodies also were negative.

Figure 1. Linear distribution of small whitish papules with a smooth surface on the left side of the chest.

Histopathology demonstrated abundant bluish granular material between collagen bundles of the papillary dermis (Figure 2). No cytopathologic signs of active herpetic infection were seen. The Alcian blue stain at pH 2.5 was strongly positive for mucin, which confirmed the diagnosis of primary cutaneous dermal mucinosis.

Topical corticosteroids were applied for 2 months with no notable improvement. The lesions gradually improved without any other therapy during the subsequent 6 months.

Figure 2. Histopathology showed bluish granular material between collagen bundles of the papillary dermis (A) (H&E, original magnification ×10). Higher magnification showed abundant mucin in the papillary dermis (B), as well as mucin, fibroblasts, and some melanophages filling the dermal papilla (C)(H&E, original magnifications ×100 and ×400). Mucin was strongly positive on Alcian blue (pH 2.5) stain (D)(original magnification ×100).

Comment

The occurrence of a new skin disease at the exact site of a prior unrelated cutaneous disorder that had already resolved was first reported by Wyburn-Mason³ in 1955. Forty years later, the term isotopic response was coined by Wolf et al⁴ to describe this phenomenon. Diverse types of skin diseases such as herpes simplex virus,⁵ varicella-zoster infections,⁴ and thrombophlebitis⁴ have been implicated in cases of isotopic response, but the most frequently associated primary disorder by far is cutaneous HZ.

Several benign and malignant disorders may occur at sites of resolved HZ lesions, including granulomatous dermatitis,⁶ granuloma annulare,⁷ fungal granuloma,⁸ fungal folliculitis,⁹ psoriasis,¹⁰ morphea,¹¹ lichen sclerosus,¹² Kaposi sarcoma,¹³ the lichenoid variant of chronic graft-versus-host disease,¹⁴ cutaneous sarcoidosis,¹⁵ granulomatous folliculitis,¹⁶ comedones,¹⁷ furuncles,¹⁸ erythema annulare centrifugum,¹⁹ eosinophilic dermatosis,²⁰ cutaneous pseudolymphoma,²¹ granulomatous vasculitis,²² Rosai-Dorfman disease,¹² xanthomatous changes,²³ tuberculoid granulomas,²⁴ acneform eruption,²⁵ lichen planus,²⁶ acquired reactive perforating collagenosis,²⁷ lymphoma,²⁸ leukemia,²⁹ angiosarcoma,³⁰ basal cell carcinoma,³¹ squamous cell carcinoma, and cutaneous metastasis from internal carcinoma.³² The interval between the acute HZ episode and presentation of the second disease is quite variable, ranging from days to several months. Postzoster isotopic response has been described in individuals with varying degrees of immune response, affecting both immunocompetent¹² and immunocompromised patients.¹⁴ There is no predilection for age, sex, or race. It also seems that antiviral treatment during the active episode does not prevent the development of secondary reactions.Kim et al³³ reported a 59-year-old woman who developed flesh-colored or erythematous papules on HZ scars over the area of the left T1 and T2 dermatomes 1 week after the active viral process. Histopathologic study demonstrated deposition of mucin between collagen bundles in the dermis. The authors established the diagnosis of secondary cutaneous mucinosis as an isotopic response.³³ Nevertheless, we believe that based on the aforementioned classification of cutaneous mucinosis,² both this case and our case are better considered as primary cutaneous dermal mucinosis, as the mucin deposition in the dermis was the main histologic finding resulting in a distinctive cutaneous disorder. In the case reported by Kim et al,³³ a possible relationship between cutaneous mucinosis and postherpetic neuralgia was suggested based on the slow regression of skin lesions in accordance with the improvement of the neuralgic pain; however, our patient did not have postherpetic neuralgia and the lesions persisted unchanged several months after the acute HZ episode. In the literature, there are reports of primary cutaneous dermal mucinosis associated with altered thyroid function³⁴; autoimmune connective tissue diseases, mostly lupus erythematosus³⁵; monoclonal gammopathy³⁶; and human immunodeficiency virus infection,³⁷ but these possibilities were ruled out in our patient by pertinent laboratory studies.