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Wolf’s Isotopic Response in a Post Herpes Zoster Patient Forming Superficial Basal Cell Carcinoma

Sachin Dhawan*,  Komal Sharma
Published in International Journal of Clinical Dermatology (Volume 8, Issue 2)
Received: 21 July 2025     Accepted: 5 August 2025     Published: 26 August 2025
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Abstract

Basal cell carcinoma (BCC) is a common cutaneous malignancy in Caucasians but has a low incidence in Indian skin. Most commonly, BCC is found in sun-exposed areas, with intermittent ultraviolet exposure as a major risk factor. Although rarely fatal, BCC can cause tissue damage if left untreated. Varicella zoster virus affects both nerve endings and skin, thereby presenting as a rash that may resolve with persisting pain as a symptom. Wolf’s isotopic response (WIR) phenomenon is the formation of a new unrelated disease in the area of a previously healed disease. A 72-year-old housewife with a clinical history of resolved herpes zoster on the scalp presented with an erythematous, atrophic lesion with crusting and fissuring. The post-herpetic neuralgia gradually resolved, but the lesion was not responding to any form of treatment. The histopathological examination demonstrated a picture consistent with superficial basal cell carcinoma. The neurotransmitters released by the nerve endings during an episode of varicella alter the immune control process. This can be a probable cause of a second, unrelated disease, i.e., viral activation in a specific ganglion may alter local immunity, therefore triggering a neoplastic transformation.

Published in International Journal of Clinical Dermatology (Volume 8, Issue 2)
DOI 10.11648/j.ijcd.20250802.12
Page(s) 51-56
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This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

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Copyright © The Author(s), 2025. Published by Science Publishing Group
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Keywords

Wolf’s Isotopic Response Phenomenon, Basal Cell Carcinoma, Varicella Zoster

1. Introduction
Basal cell carcinoma is a common cutaneous malignancy affecting one in five Americans, though the incidence of BCC in Indian skin is low.
[1, 2]
Gross differences are noted in the percentage of skin cancer in the Asians (2-4%) and Blacks (1-2%) as compared to the Caucasians (35-40%).
[3]
Major contributory risk factors include intermittent rather than constant ultraviolet (UV) exposure, and a possible role of arsenic and pesticides.
[2]
Most commonly, BCC is found on the sun-exposed areas, typically presenting as a gradually increasing, shiny, pink- or flesh-coloured papule or a nodule with surface telangiectasias.
[1]
Although rarely fatal, it can cause tissue destruction if not treated or if the treatment is delayed. Varicella simplex viruses are epidermoneurotropic viruses that affect both skin and nerve endings. These viruses and the neurotransmitters released by the nerve endings cause changes in the immune control process.
[4]
This can cause formation of a dermatosis in an area previously affected by varicella virus that has now completely healed. This is called Wolf’s isotopic response.
[5]
Although such presentations are rare and underreported, this case report highlights the importance of regular follow-up in these patients.
2. Case Presentation
A 72-year-old housewife presented to our clinic with a history of herpes zoster (HPZ) involving the mandibular division of the trigeminal nerve (V3), with severe neuralgic pain on the left side of the scalp in October 2021. The herpetic lesions had resolved within three weeks with anti-viral treatment prescribed by a dermatologist. Two to three weeks later, she had complaints of the formation of a single, progressive lesion at the same site. She had consulted a dermatologist before presenting to us, where she was diagnosed as a case of post-herpetic neuralgia (PHN) with sebopsoriasis. The patient had been put on 100mg gabapentin for PHN and 0.05% clobetasol with sertaconazole nitrate cream on alternate nights. After four months, the patient presented to us with a single lesion associated with brown crusting and pain on the left side of the scalp (Figure 1). The PHN had slowly reduced, but the lesion had a nil to negligible response to the previous medication. The lesion was well defined, 4x4 cm in size, erythematous, associated with adherent brownish crusting, fissuring, and atrophy. She was put on seratconazole nitrate cream daily, ciclopirox and zinc pyrithione shampoo twice weekly, oral itraconazole 100mg twice daily for 3 weeks, and oral vitamin B12 supplements. It was also observed that the patient had female pattern hair loss and had complaints of photo-sensitivity; hence, an oral biotin supplement was also added. The patient showed no improvement after three weeks. Hence, topical salicylic acid ointment was added along with the previous treatment to remove the crust for dermoscopy. Leaf-like, bulbous extensions forming the border of the lesion, along with well-defined grey-brown dots scattered within the lesion, were observed. (Figure 2) The patient was counselled for a skin biopsy from the border of the lesion with differential diagnosis of basal cell carcinoma, cutaneous sarcoidosis, lichen simplex atrophicus, and actinic porokeratosis. Histopathology revealed increased pigment deposits, mitosis, and an increased basaloid cell proliferation with retraction artefact at the dermo-epidermal junction (DEJ). These features are diagnostic for BCC. (Figure 3) The patient was referred to an oncology surgeon for wide excision of the lesion with full-thickness skin grafting from the lateral aspect of the left thigh under general anaesthesia. The patient visited us about a month later with contact pustulosis due to neomycin ointment on the recipient site, which resolved after treatment with 10 days of oral doxycycline. (Figure 4).
Figure 1. A single lesion on the left side of the scalp with brown crust and associated pain.
Figure 2. Dermoscopic findings: well-defined grey-brown dots scattered within the lesion (arrow A and arrow B). Leaf-like (Maple leaf-like), bulbous extensions forming the border of the lesion (arrow C). Maple leaf-like areas and brown to blue-grey dots and globules are among the classic BCC-associated dermoscopic features.
Figure 3. Skin biopsy from the border of the lesion. (A) Haematoxylin and Eosin stain, 40X scanner view. (B) Haematoxylin and Eosin stain, 100X: increased pigment deposits, mitosis, and an increased basaloid cell proliferation with retraction artefact at dermo-epidermal junction (DEJ).
Figure 4. (A) Contact pustulosis due to neomycin ointment on the recipient site. (B) Resolution of contact pustulosis after treatment with 10 days of oral doxycycline.
3. Discussion
Table 1. Reported cases of diseases demonstrating Wolf’s isotopic response.

Primary disease

Secondary lesions

Herpes simplex virus infection

[6]

Urticaria

Herpes zoster virus infection

[7,
9, 11, 12]

Chronic GVHD, Acquired perforating folliculitis, Granuloma annulare, acne and comedones, lichen planus, Morphea, linear IgA disease, fungal granuloma, psoriasis, squamous cell carcinoma, basal cell carcinoma, herpetiform pemphigus

Dermatophytosis

[6]

Lichen planus

Scrofuloderma

[6]

Herpes Simplex Virus infection

Contact dermatitis

[9,
13]

Bullous lichen sclerosis et atrophicus, Lichen planus
Wolf’s isotopic response (WIR) describes the occurrence of a new, unrelated disease at the same location as a previously healed disease.
[5]
Various diseases have been reported to demonstrate WIR (Table 1). HPZ is the most common primary disease to induce WIR.
[7]
Although the pathogenesis remains unclear, several theories have been proposed. Wolf et al suggested that two diseases affecting the same area can be a reason for the decrease in the local resistance of that area, and such an event can be caused by two different unrelated stimuli (e.g., HPZ on exposed area due to viral activation in a particular ganglion, followed by carcinoma due to previous sun exposure).
[5]
Viral, vascular, immunologic, as well as neural hypotheses have been suggested for WIR. Some authors believe that an exaggerated immune response to viral antigens, immune complex deposits, or altered local antigens might play a role in the mechanism of WIR. This might be due to the long-term immunologic changes caused by the primary disease that make the skin vulnerable to the second disease.
[5]
In HPZ, the nerves might not be directly involved in the pathogenesis of the second disease, but the influence of the nervous system through interaction with the immune system can be a cause. Secretion of neuropeptides from sensory fibres in the skin affects the mast cells, T lymphocytes, monocytes, and endothelial cells.
[8]
Wang et al evaluated 24 patients with WIR post HPZ and proposed that the mechanism of neuro-immune destabilization at the site of HPZ is caused by the continuous immunological effect of the persisting viral DNA.
[9]
The new dermatosis can be anything ranging from a granulomatous reaction to a malignancy and vascular tumors.
[10]
There have been a few case reports of formation of BCC after HPZ. Formation of nodular BCC six months after HPZ has been reported.
[11]
(Figure 5).
Figure 5. Suggested hypothesis of pathogenesis of Wolf’s Isotopic Response.
Superficial BCCs commonly occur on the trunk with a predilection for shoulders, chest, or back. Sometimes multiple lesions can be present. They are particularly slow growing, often flat, well-demarcated, pink to red in colour, scaly macules or plaques which may have telangiectasias. Clinically, the lesions can appear similar to inflammatory dermatoses such as eczema or psoriasis. Therefore, one should consider the diagnosis of superficial BCC in case of a persistent, erythematous, and scaly plaque. There are also pigmented variants of superficial BCC. Portions of superficial basal cell carcinomas can evolve into nodular BCC over time.
[1, 4]
There have been various cases reporting the formation of BCC and other malignancies secondary to a previous lesion or trauma (Table 2).
Table 2. Reported cases with neoplasms presenting as secondary lesions.

Primary disease

Secondary lesions

Herpes Zoster

[10,
11, 13-17]

BCC and Bowenoid papulosis

Acute myeloid leukemia

Vitiligo

[18]

BCC

Nevus sebaceous

[19]

BCC

Hirudiniasis

[20]

BCC

History of trauma (burn, sharp or blunt trauma, varicella scars, vaccination sites)

[21-23]

SCC and SCC

Chronic radiodermatitis

[24]

BCC
The presence of a treatment-resistant dermatosis on the same site as HPZ, and dermoscopic findings indicative of superficial BCC, prompted a skin biopsy in our patient. WIR is a known entity in dermatology, but the patho-mechanism of this phenomenon remains elusive. There are a few case reports demonstrating WIR post HPZ forming BCC, hence making this a rare case report worth noting. Such case reports become pertinent is elucidating further studies on the pathology of WIR.
Abbreviations

BCC

Basal Cell Carcinoma

UV

Ultraviolet

HPZ

Herpes Zoster

PHN

Post-Herpetic Neuralgia

DEJ

Dermo-Epidermal Junction

WIR

Wolf’s Isotopic Response
Declaration
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.
Conflicts of Interest
The authors declare no conflicts of interest.
References
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https://www.ncbi.nlm.nih.gov/books/NBK482439/

[2] Kumar S, Mahajan BB, Kaur S, Yadav A, et al. A study of Basal cell carcinoma in South Asians for risk factor and clinicopathological characterization: A hospital based study. J Skin Cancer. 2014; 2014: 173582.
[3] Bradford PT. Skin cancer in skin of color. Dermatol Nurs. 2009; 21(4): 170-8.
[4] Ruocco V, Ruocco E, Brunetti G, Russo T, Gambardella A, Wolf R. Wolf's post-herpetic isotopic response: Infections, tumors, and immune disorders arising on the site of healed herpetic infection. Clin Dermatol. 2014 Sep-Oct; 32(5): 561-8.
[5] Wolf R, Brenner S, Ruocco V, Filioli FG. Isotopic response. Int J Dermatol. 1995; 34(5): 341-8.
[6] Mahajan R, De D, Saikia U. Wolf's isotopic response: Report of a case and review of literature. Indian J Dermatol. 2014; 59(3): 275-82.
[7] Gupta M. Acneiform eruption at the site of healed herpes zoster: A case of wolf’s isotopic response. Australas J Dermatol. 2016; 57(3): 241.
[8] Earber EM. Psycboneuroimmunology and dermatology. Int J Dermatol. 1993; 32(2): 93-4.
[9] Wang T, Zhang M, Zhang Y, Zhang Y, Zhang S, et al. Wolf’s Isotropic Response after Herpes Zoster Infection: A Study of 24 New Cases and Literature Review. Acta Derm Venereol. 2019; 99(11): 953-9.
[10] Jaka-Moreno A, López-Pestaña A, López-Núñez M, Ormaechea-Pérez N, et al. Wolf's Isotopic Response: A Series of 9 Cases. Actas Dermosifiliogr. 2012; 103(9): 795-805.
[11] Lunge S B, Raichur S R, Wolf's isotopic response of basal cell carcinoma following facial herpes zoster infection: a rare presentation. IP Indian J Clin Exp Dermatol. 2016; 2(2): 64-6.
[12] Tang L, Zhu Y, Wu W. A case report of Wolf’s post-herpetic isotopic response: herpetiform pemphigus. J Inflamm Res. 2025; 18: 4211-6.
[13] Bruin P, McCoy IV WH, Leonardi CL, Martin AG. Wolf’s isotopic response of lichen planus following contact dermatitis. J Am Acad Dermatol. 2022; 27: 128-130.
[14] Kwak JH, Na CH, Kim MS, Choi H. Superficial basal cell carcinoma at the site of herpes zoster: Wolf’s isotopic response or idiopathic? Indian J Dermatol Venereol Leprol. 2024; 91(1): 84-8.
[15] Mishra D, Raji MA. Squamous cell carcinoma occurring at the site of prior herpes zoster of the scalp: Case report of Marjolin ulcer. J Am Geriatr Soc. 2004; 52(7): 1221-2.
[16] Zhu Y, Wu W. Cutaneous myelodysplastic syndrome progressing to acute myeloid leukemia: an unusual presentation of Wolf's isotopic response. An Bras Dermatol. 2024; 99(3): 261-4.
[17] Ruocco E, Cutrì FT, Baroni A. Bowenoid papulosis at the site of herpes progenitalis. Skinmed. 2004; 3(6): 347-9.
[18] Rustemeyer, J.; Günther, L.; Deichert, L. A rare association: Basal cell carcinoma in a vitiliginous macula. Oral Maxillofac. Surg. 2011; 15(3): 175-7.
[19] Dilek N, Bedir R, Yüksel D, Ataseven A. A case of basal cell carcinoma secondary to nevus sebaceous. Int J Case Rep Images. 2014; 5(4): 277-80.
[20] S. Shamsaddini, S. Dabiri. Basal cell carcinoma on nickel dematitis after leech applying. East Mediterr Health J. 2000; 6(1): 197-200.
[21] Noodleman FR, Pollack SV. Trauma as a possible etiologic factor in Basal Cell Carcinoma. J Dermatol Surg Oncol. 1986; 12(8): 841-6.
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[24] Meibodi NT, Maleki M, Javidi Z, Nahidi Y. Clinicopathological evaluation of radiation induced basal cell carcinoma. Indian J Dermatol. 2008; 53(3): 137-9.
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    Dhawan, S., Sharma, K. (2025). Wolf’s Isotopic Response in a Post Herpes Zoster Patient Forming Superficial Basal Cell Carcinoma. International Journal of Clinical Dermatology, 8(2), 51-56. https://doi.org/10.11648/j.ijcd.20250802.12

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    ACS Style

    Dhawan, S.; Sharma, K. Wolf’s Isotopic Response in a Post Herpes Zoster Patient Forming Superficial Basal Cell Carcinoma. Int. J. Clin. Dermatol. 2025, 8(2), 51-56. doi: 10.11648/j.ijcd.20250802.12

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    AMA Style

    Dhawan S, Sharma K. Wolf’s Isotopic Response in a Post Herpes Zoster Patient Forming Superficial Basal Cell Carcinoma. Int J Clin Dermatol. 2025;8(2):51-56. doi: 10.11648/j.ijcd.20250802.12

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  • @article{10.11648/j.ijcd.20250802.12,
  author = {Sachin Dhawan and Komal Sharma},
  title = {Wolf’s Isotopic Response in a Post Herpes Zoster Patient Forming Superficial Basal Cell Carcinoma
},
  journal = {International Journal of Clinical Dermatology},
  volume = {8},
  number = {2},
  pages = {51-56},
  doi = {10.11648/j.ijcd.20250802.12},
  url = {https://doi.org/10.11648/j.ijcd.20250802.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijcd.20250802.12},
  abstract = {Basal cell carcinoma (BCC) is a common cutaneous malignancy in Caucasians but has a low incidence in Indian skin. Most commonly, BCC is found in sun-exposed areas, with intermittent ultraviolet exposure as a major risk factor. Although rarely fatal, BCC can cause tissue damage if left untreated. Varicella zoster virus affects both nerve endings and skin, thereby presenting as a rash that may resolve with persisting pain as a symptom. Wolf’s isotopic response (WIR) phenomenon is the formation of a new unrelated disease in the area of a previously healed disease. A 72-year-old housewife with a clinical history of resolved herpes zoster on the scalp presented with an erythematous, atrophic lesion with crusting and fissuring. The post-herpetic neuralgia gradually resolved, but the lesion was not responding to any form of treatment. The histopathological examination demonstrated a picture consistent with superficial basal cell carcinoma. The neurotransmitters released by the nerve endings during an episode of varicella alter the immune control process. This can be a probable cause of a second, unrelated disease, i.e., viral activation in a specific ganglion may alter local immunity, therefore triggering a neoplastic transformation.},
 year = {2025}
}

    Copy | Download 

  • TY  - JOUR
T1  - Wolf’s Isotopic Response in a Post Herpes Zoster Patient Forming Superficial Basal Cell Carcinoma

AU  - Sachin Dhawan
AU  - Komal Sharma
Y1  - 2025/08/26
PY  - 2025
N1  - https://doi.org/10.11648/j.ijcd.20250802.12
DO  - 10.11648/j.ijcd.20250802.12
T2  - International Journal of Clinical Dermatology
JF  - International Journal of Clinical Dermatology
JO  - International Journal of Clinical Dermatology
SP  - 51
EP  - 56
PB  - Science Publishing Group
SN  - 2995-1305
UR  - https://doi.org/10.11648/j.ijcd.20250802.12
AB  - Basal cell carcinoma (BCC) is a common cutaneous malignancy in Caucasians but has a low incidence in Indian skin. Most commonly, BCC is found in sun-exposed areas, with intermittent ultraviolet exposure as a major risk factor. Although rarely fatal, BCC can cause tissue damage if left untreated. Varicella zoster virus affects both nerve endings and skin, thereby presenting as a rash that may resolve with persisting pain as a symptom. Wolf’s isotopic response (WIR) phenomenon is the formation of a new unrelated disease in the area of a previously healed disease. A 72-year-old housewife with a clinical history of resolved herpes zoster on the scalp presented with an erythematous, atrophic lesion with crusting and fissuring. The post-herpetic neuralgia gradually resolved, but the lesion was not responding to any form of treatment. The histopathological examination demonstrated a picture consistent with superficial basal cell carcinoma. The neurotransmitters released by the nerve endings during an episode of varicella alter the immune control process. This can be a probable cause of a second, unrelated disease, i.e., viral activation in a specific ganglion may alter local immunity, therefore triggering a neoplastic transformation.
VL  - 8
IS  - 2
ER  -

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Author Information

  • Sachin Dhawan

    Derpartment of Dermatology, Aesthetics and Dental Clinic, Gurgaon, India

    Contact Email

  • Komal Sharma

    Department of Dermatology, Healing Hospital, Chandigarh, India

    Contact Email

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