Reverse Isotopic Response: A Novel Phenomenon in Xeroderma Pigmentosum

Dear Editor, Sparing phenomena in dermatology have been described in cases of infections and drug reactions. The reverse isotopic phenomenon, also known as isotopic nonresponse, refers to the sparing of healed lesions of a dermatosis by a new, unrelated dermatosis. This phenomenon has been reported in infections, dermatitis, and drug-induced rashes. This is a case of premalignant lesions sparing healed varicella simplex scars in a patient with xeroderma pigmentosum (XP). A 22-year-old woman with XP type V presented with photosensitivity and multiple hyperkeratotic papules and plaques on sun-exposed areas. Notably, the lesions spared areas of atrophic hypopigmented scars, remnants of varicella simplex infection acquired during childhood [Figure 1]. Figure 2 shows a closer view that highlights the sparing of atrophic scars caused by varicella infection. These scars were unaffected by the adjacent solar damage commonly seen in patients with xeroderma pigmentosum.Figure 1: Xeroderma pigmentosum showing sparing of atrophic scars from healed varicella simplex infectionFigure 2: Close-up view illustrating the sparing of healed varicella scars by lesions of xeroderma pigmentosumWolf’s isotopic response describes the involvement of a healed lesion by a new, unrelated dermatosis.[1] In contrast, the reverse Wolf’s isotopic response or isotopic nonresponse is characterized by the sparing of healed lesions by a new dermatosis.[2] This phenomenon has been documented in conditions, such as drug rashes, infections, contact dermatitis, and erythema multiforme.[3] For instance, Wolf’s isotopic response has been reported in cases of leukemia cutis at the sites of healed herpes zoster and varicella simplex lesions.[3] Moreno et al.[3] proposed that the mechanism for malignancy at sites of healed viral infections is likely due to immune dysregulation, resulting in reduced local immunity. XP is an autosomal recessive disorder caused by defects in nucleotide excision repair mechanisms, resulting in an inability to repair UV-induced DNA damage. These defects lead to premature aging, pigmentary changes, and the early development of cutaneous malignancies, including actinic keratoses, basal cell carcinomas, and melanomas.[4] The sparing of varicella scars in this case is unusual, as sites of healed viral infections are often prone to immune dysregulation and secondary malignancies. Potential mechanisms for sparing in the areas of varicella scars in this patient with XP might involve several factors, such as localized immune memory, where the healed areas may retain a distinct immune profile, characterized by persistent immune surveillance or molecular markers that inhibit subsequent pathological changes.[2,3] The tissue remodeling that results in the fibrotic varicella scars might provide a less favorable microenvironment for UV-induced premalignant changes.[3] Genetic or epigenetic alterations within the healed lesion possibly inhibit DNA damage or hyperproliferation, mechanisms typically associated with XP.[4] Ruocco et al.[5] in 2009 collectively encapsulated these diverse concepts in a newly coined term known as immunocompromised districts (ICDs). It encompasses all the possible causes involved in a local immune destabilization, such as locus minoris resistentiae and locus majoris resistentiae. An ICD is an area on the skin that has a local dysregulation of the immune control, which facilitates or hampers the local onset of other skin diseases. Such ICDs are fertile grounds for opportunistic infections and tumors. However, systemic immune disorders or malignancies usually spare such districts. The pathomechanisms involved in this sectorial immune destabilization may reside in damaged local lymph drainage that hinders the normal trafficking of immunocompetent cells or sensory nerve fiber damage that releases immune-related peptides.[5] This case presents a rare counterpoint to the usual malignancy-prone nature of healed viral lesion sites. It highlights the complexity of immune and genetic interactions in conditions like XP and raises important questions about the role of localized immunity and tissue microenvironments in influencing isotopic phenomena. 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 understands 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) This article was written without the assistance of artificial intelligence tools.