Pityriasis Versicolor Involving the Healed Herpes Zoster Scar – A Case of Wolf’s Isotopic Response

Dear Editor, “Wolf’s isotopic response” describes the occurrence of a new, unrelated disease at the same site as a previously healed, another unrelated disease. A 65-year-old diabetic woman presented to our outpatient department with multiple grouped fluid-filled lesions on the left half of her back involving thoracic (T2 to T4) dermatomes associated with shooting pain along the distribution of the lesions. A clinical diagnosis of herpes zoster was made, and the patient was started on anti-viral medication. The lesions healed with atrophy within 2 weeks. The same patient visited us about 2 months later with the appearance of hypopigmented patches, involving only the site of healed herpes zoster, sparing the rest of the back [Figure 1]. A biopsy was taken from one of these lesions and sent for histopathology and PAS (Periodic Acid Schiff) stain, revealing fungal elements in the stratum corneum [Figure 2]. A diagnosis of pityriasis versicolor was made, and the patient was started on tablet fluconazole (400 mg), two doses 2 weeks apart, and topical 2% ketoconazole cream with complete recovery of lesions within 3 weeks [Figure 3].Figure 1: Multiple hypopigmented patches with minimal scaling involving the previously healed herpes zoster scar, while sparing the other areasFigure 2: Histopathology (400 ×) with per iodic acid stain showing abundant short, septate hyphae and spores in between layers of keratinFigure 3: Healed versicolor lesions after anti-fungal therapyThe precise mechanism of the Wolf’s isotopic phenomenon eludes our understanding. The two dermatoses involved in Wolf’s isotopic response are unrelated in their morphology; however, the seeds of the second disease may be sown during the healing process of the first disease, explained by the fact that the healed skin may show microscopic changes for a long time after the initial insult. This may be responsible for the occurrence of the second dermatosis. In 1985, Wolf and Wolf gave a term, “isoloci response,” to describe this phenomenon. It was renamed to “isotopic response” by Wolf, and finally reframed as Wolf’s isotopic response. The interval between initial infection and the development of secondary disease varies widely, from days to years. Jaka-Moreno et al.[1] found intervals from 15 days to 7 months. The most reported secondary diseases are granuloma annulare, malignancies (breast cancer, squamous cell, and basal cell carcinoma), leukemic/lymphomatous infiltration, inflammatory reactions (lichen planus), contact dermatitis, psoriasis, and infections (mycosis, molluscum contagiosum, verruca vulgaris, furunculosis). There are also reported cases of perforating collagenosis, comedones and acneiform eruptions, morphea, graft versus host disease, eosinophilic dermatoses, Kaposi’s sarcoma, angiosarcoma, erythema annulare centrifugum, sub-corneal pustular dermatoses, and chronic hives.[2] Various theories, such as the viral hypothesis, vascular hypothesis, immunologic hypothesis, and neural hypothesis, have been proposed. None of these hypotheses solely explains the pathogenesis of isotopic response. These factors, either alone or in combination, are involved in the causation of a new disease along “locus Minoris Resistentiae,” that is, the area of lessened resistance. Ruocco’s immunocompromised cutaneous district[3] defines a local regional immune dysfunction causing an altered immune response in a particular region. This is like what is described in Koebner’s/isomorphic phenomenon, reverse isomorphic phenomenon, Wolf’s isotopic response, or isotopic nonresponse. Local immunosuppression, altered microcirculation, collagen rearrangement, loss of appendages, mast cell activation, incomplete skin barrier within the scar, and so on elevate the risk of invasion by pathogens or inflammatory or neoplastic conditions. However, Verma et al.[4] proposed immune dysregulation instead of immune compromise as the cause of the same, and called it “immune dysregulated district” rather than “immunocompromised cutaneous district” as proposed by Ruocco et al. Although varicella zoster virus DNA has not been found in these cases yet, the association between herpes zoster and isotopic response cannot be coincidental. Various dermatoses, such as erythema multiforme after herpes simplex, can be the first dermatoses in the Wolf’s isotopic response. Hence, the herpes virus, because of its ability to invade neural tissue, is important in isotopic response. Herpetic infection is proposed to prepare the ground for a new dermatosis due to neurovascular alterations in the affected area.[1] Herpes zoster infection leads to damage of A delta and C nerve fibers in the dermis, which leads to damaged nerve endings post the first dermatoses. This damage leads to the release of neuropeptides and nerve signals, acting as the initial event in the isotopic response. These neuropeptides include substance P, bradykinin, serotonin, vasoactive intestinal peptide (VIP), calcitonin gene-related peptide, and α-melanocyte-stimulating hormone. Symptoms like itching and pain may be directly induced by these peptides, and the abnormal activation of the immune system is their main function.[2] Natural killer cell activity and substance P lead to T cell proliferation, while neuropeptides like VIP increase the monocyte chemotaxis. Additionally, a positive feedback cycle can be initiated by the stimulation of peripheral nerves via cytokines. Tumor necrosis factor-α may be involved. The alterations in local vasculature as a result of prior skin disease cause a favorable environment for the localization of immune cells to the same site by increasing the appearance of adhesion molecules, explaining the localized nature of this phenomenon.[5] Wolf’s isotopic response at the site of healed herpes zoster, showing the appearance of pityriasis versicolor, has not been previously reported. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understand that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Use of artificial intelligence (AI) The preparation of this manuscript was carried out entirely by the authors without the use of artificial intelligence technologies.