Abstract
Wolf isotopic response is the occurrence of new dermatoses on areas of the skin with previous but still active dermatoses. Vitiligo is an acquired disorder characterized by the loss of functional melanocytes which manifests as circumscribed depigmented macules and patches. Dermatophytoses are superficial fungal infections caused by three genera of fungi (Microsporum, Trichophyton, and Epidermophyton) that have the unique ability to invade and multiply within keratinized tissue (skin, hair, and nail). The appearance of dermatophyte infection on previously present vitiligo lesion is an uncommon example of Wolf response. We describe a case series of five vitiligo patients that presented to our OPD over 1 year period.
Keywords: Dermatophytoses, tinea, vitiligo, wolf isotopic response
Introduction
Vitiligo is an acquired hypopigmentation disorder characterized by loss of functional melanocytes. Broadly, vitiligo can be divided into two categories: segmental and generalized. Dermatophytoses (tinea corporis) is a superficial fungal infection of the skin of the trunk and extremities, characterized by annular scaly lesions associated with pruritus and burning. The most common cause of tinea corporis is T. rubrum followed by T. mentagrophytes.
Wolf isotopic response is the occurrence of new dermatoses on areas of skin with previous but still active dermatoses. The occurrence of tinea corporis on previously present vitiligo patches is an example of a Wolf response. We describe a case series of five vitiligo patients that presented to our OPD over 1 year period. The cases were diagnosed on the grounds of history and physical examination supplemented with a skin scraping and 10% KOH examination.
Case Reports
Case 1
A 52-year-old male presented with acro-facial vitiligo for the last 25 years involving upper extremities, lower extremities, and lips. There was no Koebner phenomenon. The patient had associated hypothyroidism and type 2 diabetes. The patient was treated with PUVAsol and topical superpotent steroids in the past and was receiving no treatment in the present. The patient presented with scaly, pruritic, oval lesions with papules at the active border on the left ankle over a patch of vitiligo for the last 3 months [Figure 1]. On skin scraping and KOH mount, plenty of fungal elements were seen. Culture on fungal media showed growth of T. mentagrophytes. He was treated with ketoconazole cream and oral griseofulvin for 6 weeks with complete resolution of tinea.
Figure 1.
Tinea over vitiligo patches on the left ankle for the last 3 months
Case 2
A 52-year-old female attended Dermatology OPD with vitiligo vulgaris for the last 20 years involving the scalp, trunk, upper, and lower extremities. There was no Koebner phenomenon. The patient was known diabetic and hypertensive. The patient was treated with oral corticosteroids and topical superpotent steroids in the past and was receiving no treatment in the present. Scaly, pruritic, erythematous oval lesions with papules at the active border on the anterior abdomen over vitiligo patches were observed for the last 1 month [Figure 2a]. On skin scraping and KOH mount, plenty of fungal elements were seen. Culture on fungal media showed growth of T. mentagrophytes. She was treated with ketoconazole cream and oral itraconazole for 6 weeks with complete resolution of tinea.
Figure 2.
(a): Tinea over vitiliginous skin on the anterior abdomen for the last 1 month; (b): Tinea over vitiliginous skin on the anterior abdomen for the last 3 months
Case 3
A 50-year-old non-diabetic, nonhypertensive female presented with generalized vitiligo for the last 12 years involving almost the whole body. There was no Koebner phenomenon. The patient received no treatment for vitiligo. Scaly, pruritic, erythematous oval lesions with papules at the active border on the right flank and right lateral trunk were present for the last 1.5 months [Figure 3]. On skin scraping and KOH mount, plenty of fungal elements were seen. Culture on fungal media showed growth of T. rubrum. She was treated with sertaconazole cream and oral terbinafine for 8 weeks with complete resolution of tinea.
Figure 3.
Tinea over vitiliginous skin on the right lateral trunk and right flank for the last 1 month
Case 4
A female patient aged 50 years attended Skin OPD with vitiligo vulgaris for the last 20 years involving the anterior abdomen. There was no Koebner phenomenon. The patient was known diabetic but nonhypertensive. The patient was treated with topical superpotent steroids and calcineurin inhibitors in the past and was receiving no treatment in the present. The patient complained of scaly, pruritic, erythematous polycyclic lesions on the anterior abdomen over vitiligo patches for the last 3 months [Figure 2b]. On skin scraping and KOH mount, plenty of fungal elements were seen. Culture on fungal media showed growth of T. mentagrophytes. She was treated with luliconazole cream and oral terbinafine for 10 weeks with complete resolution of tinea.
Case 5
A young nondiabetic, nonhypertensive female of 30 years age presented with vitiligo vulgaris for the last 8 months involving the scalp, face, trunk, upper, and lower extremities. There was no Koebner phenomenon. The patient was being treated with topical calcineurin inhibitors. The patient complained of multiple, pruritic, erythematous annular lesions on the left lower neck over the vitiligo patch for the last 20 days [Figure 4]. On skin scraping and KOH mount, plenty of fungal elements were seen. Culture on fungal media showed growth of T. rubrum. She was treated with sertaconazole cream and oral terbinafine for 6 weeks with complete resolution of tinea.
Figure 4.
Tinea over vitiliginous skin on the left lower neck for the last 20 days
Discussion
“Wolf isotopic response” was coined in 1995 to refer to the occurrence of a new dermatosis on areas of skin with previous lesions that had healed and that bore no relationship with the new lesions.[1] A recent classification defined the isotopic response as the occurrence of a dermatosis that develops in the same area of skin as another previously present but still active dermatosis.[2]
In 1955, Wyburn-Mason[3] first described the occurrence of new skin disease at the site of another skin disease that had already healed. Numerous such cases were reported in the literature till Wolf and Wolf[1] in 1985 gave it the term “isoloci response” (same locus). It was changed to “isotopic response” (same place) by Wolf et al.,[4] and finally renamed as Wolf's isotopic response by Ruocco et al.[5] Dermatoses that appear after exposure to external agents such as chemicals and radiation should not be included in the isotopic response.
Although the two dermatoses are unrelated in morphology, the second disease might be due to changes during the healing phase of the first disease. The healed skin shows microscopic and physiologic changes for a long duration after the initial insult, and some of these changes might be responsible for the occurrence of new dermatosis.[6] The dermatoses which present as a consequence of isotopic response have been categorized into infections, granulomatous reactions, leukemic infiltrates, malignant tumors, dermatoses secondary to immunologic dysfunction, comedonic reactions, and miscellaneous.
The classic examples of Wolf response are lesions of urticaria, comedones, lichen planus, fungal infections, vitiligo, etc. occurring over healed herpes zoster lesions.
Dermatophytosis is a common superficial fungal infection that is precipitated by factors such as advanced age, Cushing's disease, iatrogenic corticosteroid therapy, hematologic malignancy, chronic mucocutaneous candidiasis, diabetes mellitus, atopy, etc. The local defense against dermatophytoses involves epidermal Langerhans cells, antifungal properties of sebum, T-lymphocytes, and metalloproteases synthesis. Chronic dermatophytoses were found to be associated with poor T-cell–mediated response to fungal antigens. Langerhans cells also act as antigen-presenting cell for dermatophyte antigens.
Vitiligo is associated with many autoimmune diseases. There is well-documented evidence that epidermal dendritic cells (Langerhans cells and intermediate cells) are absent in vitiligo patches. The epidermal cells derived from vitiligo patches show a lower stimulatory effect in the allogeneic mixed skin cell lymphocyte culture reaction than those from normal skin, suggesting a possibility of functional impairment of Langerhans cells in vitiliginous skin.[7] The occurrence of dermatophytoses in vitiligo patches might be due to the local immune defects either directly to reduced or absent melanocytes or indirectly to the reduced number of Langerhans cells in a vitiligo patch. There might be some role of altered T-cells in dermatophytoses within the vitiligo patches. Associated diabetes could also play some role and the use of topical steroids, calcineurin inhibitors, and PUVA used in the treatment of vitiligo should also be taken into account, as they have an immunomodulatory effect that lower the local defenses against fungal infections.
Two cases have been reported in the literature. Parimalam et al. reported a case of tinea limited to vitiligo patch in a 70-year-old diabetic female.[8] AG Rao reported a case of tinea bordering vitiligo patch in a 30-year-old nondiabetic female on treatment with tacrolimus and PUVA.[9]
All of the five patients had developed lesions of tinea that were localized to vitiliginous skin but in two patients, the lesions extended beyond vitiligo borders. Four out of our five patients received immunomodulatory treatment at some point in the past (steroids, PUVA, tacrolimus) for vitiligo, and three patients were diabetic. Four patients were elderly, and only one patient was 30 years old. Four patients had long-standing vitiligo, whereas only one patient had vitiligo for the last 8 months. All patients had no Koebner phenomenon. Fungal elements were demonstrated in KOH mount from all cases [Figure 5]. T. mentagrophytes was isolated from three patients, and T. rubrum was isolated from two patients. All the patients responded to a combination of oral and topical antifungals, and the lesions of dermatophytoses resolved completely after treatment.
Figure 5.
Fungal elements in KOH mount of skin scrapings (40 ×)
Conclusion
The present data shows that in all the cases, there are some factors that contribute to the occurrence of tinea over vitiligo patches such as advanced age, diabetes mellitus, immunomodulatory treatment, apart from local immunosuppression in vitiligo patches inherent to the disease process. The dermatophytoses were also well responsive to antifungal treatment.
There should be judicious use of immunomodulators in vitiligo patients, and one needs to be more vigilant about dermatophytoses in vitiligo patients.
Our case series is unique as there are very few reports of tinea corporis occurring on vitiligous skin, and the condition is more under-recognized than rare.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
- 1.Wolf R, Wolf D, Ruocco E, Brunetti G, Ruocco V. Wolf's isotopic response. Clin Dermatol. 2011;29:237–40. doi: 10.1016/j.clindermatol.2010.09.015. [DOI] [PubMed] [Google Scholar]
- 2.Kannangara AP, Yosipovitch G, Fleischer AB., Jr Proposed classification for Koebner, Wolf isotopic, Renbok, Koebner nonreaction, isotopic nonreaction and other related phenomen? Dermatol Online J. 2014;20:13030/qt96s656b4. doi: 10.5070/D32011024682. [PubMed] [Google Scholar]
- 3.Wyburn-Mason R. Malignant change arising in tissues affected by herpes. Br Med J. 1955;2:1106–9. doi: 10.1136/bmj.2.4948.1106. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Wolf R, Brenner S, Ruocco V, Filioli FG. Isotopic response. Int J Dermatol. 1995;34:341–8. doi: 10.1111/j.1365-4362.1995.tb03616.x. [DOI] [PubMed] [Google Scholar]
- 5.Ruocco V, Ruocco E, Ghersetich I, Bianchi B, Lotti T. Isotopic response after herpesvirus infection: An update. J Am Acad Dermatol. 2002;46:90–4. doi: 10.1067/mjd.2002.118362. [DOI] [PubMed] [Google Scholar]
- 6.Gibney MD, Nahass GT, Leonardi CL. Cutaneous reactions following herpes zoster infections: Report of three cases and a review of the literature. Br J Dermatol. 1996;134:504–9. [PubMed] [Google Scholar]
- 7.Hatchome N, Aiba S, Kato T, Torinuki W, Tagami H. Possible functional impairment of Langerhans' cells in vitiliginous skin.Reduced ability to elicit dinitrochlorobenzene contact sensitivity reaction and decreased stimulatory effect in the allogeneic mixed skin cell lymphocyte culture reaction. Arch Dermatol. 1987;123:51–4. doi: 10.1001/archderm.123.1.51. [DOI] [PubMed] [Google Scholar]
- 8.Parimalam K, Dinesh D K, Thomas J. Vitiligo delimiting dermatophyte infection. Indian J Dermatol. 2015;60:91–3. doi: 10.4103/0019-5154.147816. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Rao AG. Dermatophyte infection encircling vitiligo. Indian Dermatol Online J. 2015;6(Suppl S1):60–3. doi: 10.4103/2229-5178.171056. [DOI] [PMC free article] [PubMed] [Google Scholar]