Epidermodysplasia verruciformis successfully treated with cimetidine

Introduction

Epidermodysplasia verruciformis (EDV) is a rare, inherited, or acquired genodermatosis characterized by lifelong susceptibility to specific human papillomavirus (HPV) genotypes, resulting in widespread cutaneous lesions and an increased risk of nonmelanoma skin cancer.

Clinically, lesions may present as hypo- and hyperpigmented macules, flat-topped papules, thin scaly plaques, or occasionally verrucous nodules that may mimic pityriasis versicolor or verruca plana. Lesions most often involve the trunk, neck, and upper extremities.¹ Both inherited and acquired forms of EV, particularly in immunocompromised patients, carry an elevated risk (30% to 50%) of nonmelanoma skin cancer.^2,3 No standardized therapy exists. We present an HIV-associated EV case demonstrating marked clinical improvement with oral cimetidine, an H₂-receptor antagonist with immunomodulatory potential.

Case report

A 37-year-old man with congenital human immunodeficiency virus (HIV) infection well controlled on bictegravir/emtricitabine/tenofovir alafenamide antiretroviral therapy presented with a chronic asymptomatic rash that initially presented at around age 5. Physical examination revealed multiple erythematous papules and thin plaques, a few hypopigmented macules, and some flat-topped and mildly scaly lesions, distributed symmetrically on the chest, neck, shoulders, and extensor forearms (Fig 1). Patient reported no family history of similar lesions.

Fig 1.

Clinical photographs demonstrating numerous erythematous plaques and papules across chest and trunk, with a few hypopigmented macules on chest.

Histopathologic examination of a biopsy taken revealed epidermal hyperplasia with papillomatosis and groups of enlarged keratinocytes scattered throughout the epidermis showed abundant bluish cytoplasmic changes (Fig 2, A). High-power examination revealed pleomorphic lesional cells with marked nuclear enlargement relative to adjacent normal keratinocytes and prominent nucleoli. Nuclear hyperchromasia was absent. The characteristic blue-gray cytoplasmic alteration of EDV was distinctly evident (Fig 2, B). HPV genotyping of skin lesions was discussed but not pursued due to resource limitations.

Fig 2.

A, H&E histological image. B, High power, H&E histological image demonstrating pleomorphic lesional keratinocytes with significant nuclear enlargement.

Prior treatments, including topical 5-fluorouracil, imiquimod, salicylic acid, and cryotherapy, were ineffective. The patient declined systemic retinoids due to needle phobia and desire to avoid laboratory monitoring. Given these considerations, oral cimetidine was selected for its reported immunomodulatory properties and favorable safety profile. Therapy was initiated at 800 mg orally 3 times daily for 8 weeks.

At 1-month follow-up, the patient demonstrated notable improvement with decreased erythema and scaling. Erythema and inflammation had largely resolved, with mild post-inflammatory hyperpigmentation remaining (Fig 3). At 3-month follow-up, the patient sustained the improvement without recurrence or adverse effects (Fig 4).

Fig 3.

Clinical photographs obtained at 1-month follow-up.

Fig 4.

Clinical photographs obtained at 3-month follow-up.

Discussion

EDV is exceedingly rare, with approximately 500 cases reported globally.⁴ Most available data arise from case reports and small series, and optimal management remains unclear. Reported therapies include systemic retinoids, interferons, topical immunomodulators, and excision, with mixed and often limited responses.⁵ Cimetidine, a histamine-2 receptor antagonist, has been explored due to its proposed immunomodulatory activity, though published outcomes vary.

The most recognized complication of EDV is the development of nonmelanoma skin cancers, particularly squamous cell carcinoma, which arises in approximately 30% to 50% of patients, typically on sun-exposed areas during the third or fourth decade of life.^2,3 This distribution underscores the role of ultraviolet radiation as a co-carcinogen alongside HPV infection. Consequently, counseling on photoprotection and adherence to preventive strategies remains an essential component of long-term management.

Cimetidine has demonstrated multiple immunologic effects. These include reversal of histamine-mediated suppression of T-cell immunity, upregulation of Th1-associated cytokines (IL-2, IL-12, IFN-γ), promotion of wart regression and decreased IL-18 expression in HPV-associated warts.^6,7 Collectively, these mechanisms suggest a plausible therapeutic benefit in disorders of persistent HPV infection such as EDV, which are characterized by impaired cell-mediated immunity to HPV-infected keratinocytes.

High doses of cimetidine (>1000 mg/d) have been associated with anti-androgenic effects such as gynecomastia or decreased libido, particularly with prolonged use.⁸ These adverse events are dose- and duration-dependent and did not occur during this short treatment course.

Reports on cimetidine in EDV show inconsistent results. Micali et al described marked improvement in a 16-year-old treated with cimetidine for 3 months, whereas Oliveira et al found minimal benefit in 8 female adult patients.^9,10 Variability in age, sex, immune status, and disease duration may contribute to these discrepancies.

Conclusion

In this report, we describe a case of HIV-associated epidermodysplasia verruciformis that demonstrated notable clinical improvement with cimetidine monotherapy. Although evidence for cimetidine in EV remains limited and inconsistent, our patient's response highlights the potential utility of this therapy in select scenarios where treatment options are constrained. Given the absence of standardized management strategies for EV, particularly in immunocompromised individuals, additional studies are needed to clarify which patients may benefit from cimetidine and to further assess its long-term safety and durability of response.

Conflicts of interest

None disclosed.