Postherpetic nevus comedonicus with annular pattern: A rare isotopic response

This is the authors' abstract. We don't add key points for this paper.

Dear Editor, The isotopic response, as described by Wolf, denotes the emergence of a new cutaneous disease at the site of a previously healed and unrelated dermatosis.[1] Here, we present a case of postherpetic nevus comedonicus, which is a rare isotopic response. A 69-year-old male with a history of systemic lupus erythematosus and end-stage renal disease presented with blackish papules over the chest and back for five months. Physical examination showed multiple, grouping, blackish, comedo-like lesions distributing along the left T3 dermatome [Figure 1a-c]. The lesions display an annular distribution along the dermatome. The histopathological examination showed dilated follicular infundibula and small cysts lined by stratified squamous epithelium with keratinization in the upper dermis [Figure 1d]. A review of the patient's medical history revealed an episode of herpes zoster infection at the same site six months ago, which had resolved after oral valacyclovir treatment. A diagnosis of postherpetic nevus comedonicus, a rare Wolf's isotopic response, was made.Figure 1: (a-c) Multiple, blackish, comedone-like lesions distributing along the left T3 dermatome with central-sparing pattern. (d) Histopathological examination showed dilated follicles filled with keratin in the upper dermis. (H and E, ×40).Wolf's isotopic response, first described by Wolf et al., in 1985, refers to the occurrence of a new skin disorder at the site of another unrelated and healed skin lesion.[1] However, the definition was considered ambiguous by some authors. In specific, a skin area of previous herpes zoster was generally considered a "vulnerable area" and its distinction from the Koebner phenomenon had raised debates.[2] In 2017, Wolf et al. further published a commentary in an attempt to clarify the distinction between the Wolf's isotopic response and Koebner isomorphic reaction.[3] According to the commentary, the isotopic response refers to the appearance of a "new" disease at the same site as that of a healed one, whereas the term isomorphic should be reserved for the appearance of an "existing" disease at a new damaged location.[3] Our case aligns with the definition of isotopic response, as the patient exhibited no preexisting similar lesions before the episode of herpes zoster. The pathogenesis of postherpetic isotopic response remains elusive, with proposed hypotheses encompassing etiologies of viral, immunological, neural, vascular, and interactions between these factors. Nerve damage can lead to the release of neuropeptides and immune modulators, rendering the involved site more susceptible to subsequent skin diseases.[4] We present the case of a 69-year-old man presenting of nevus comedonicus with multiple comedones densely distributed in the annular pattern along the T3 dermatome after a herpes zoster infection. To our knowledge, fewer than 30 cases of comedone-like lesions on healed herpetic lesions have been reported [Supplementary Table 1]. Given its rarity, the emergence of comedones following herpes zoster infection is obscure in pathogenesis and the proposed mechanisms are largely theoretical. It may be due to true comedogenesis or secondary to invaginated epithelium as seen in typical nevus comedonicus. Comedogenesis may be attributed to abnormal keratinization of the infundibulum resulting from localized inflammation. Another hypothesis suggests that substance P release from damaged nerve endings may stimulate lipogenesis of the sebaceous gland and induce the formation of comedones.[5] In addition, the release of certain chemotactic molecules during viral infection and the activation of fibroblast growth factor pathways during nerve regeneration might induce epithelial invagination, resembling the formation of rudimentary follicles in typical nevus comedonicus.[6] Further investigation is warranted to elaborate more on the pathogenesis of postherpetic nevus comedonicus. Our case displays a striking central-sparing pattern that had never been mentioned in the literature. A possible explanation is that the central part of the dermatome scarred and lost all the hair follicles. However, this hypothesis seems unlikely because no clinically detectable scarring, fibrosis, or atrophy was noted within most of the central part. Previous investigations have revealed complex abnormalities in cutaneous nerve density, morphology, and immunochemistry in postherpes zoster skin.[7] We believe that the annular pattern in our case represents different degrees of damage and responses within the herpes zoster lesion. In the center of the involved dermatome, the nerves were "burned out" due to constant damage, resulting in more severe denervation or a loss of adaptability of the nerve endings, whereas the perilesional nerves remained responsive and release cytokines and neuromodulators in response to inflammation. This finding may further support the mechanism of altered neuroimmunity in postherpetic skin diseases. In most of the reported cases, conservative management was sufficient, and resolution occurred within six months, with or without medical treatment. Treatment options include topical retinoic acid or mechanical extraction of comedones.[8] Spontaneous resolution has been documented within two to four months after the initial presentation. In our case, topical salicylic acid was given and showed gradual improvement. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent form. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed. Data availability statement Data sharing not applicable to this article as no datasets were generated or analyzed during the current study. Financial support and sponsorship Nil. Conflicts of interest Prof. Chen-Yi Wu, an editorial board member at Dermatologica Sinica, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.