Case Reports

Epidermodysplasia Verruciformis: Successful Treatment With Squaric Acid Dibutylester

Author and Disclosure Information

Epidermodysplasia verruciformis (EV) is a rare disorder characterized by disseminated cutaneous warts in predisposed patients who are highly susceptible to genus ß-papillomavirus infections. We present the case of a 40-year-old lymphocytopenic woman with a balanced chromosomal translocation and a 25-year history of refractory EV that was successfully treated with squaric acid dibutylester (SADBE) contact immunotherapy.

Practice Points

  • Epidermodysplasia verruciformis (EV) is a rare immune deficiency. Associated warts are difficult to treat.
  • Topical immunotherapy with squaric acid dibutylester (SADBE) has successfully treated long-standing warts in an EV patient.
  • Consider immunotherapy with a contact sensitizer such as SADBE to treat resistant warts, even in immune deficiency patients.


 

References

Epidermodysplasia verruciformis (EV) is an uncommon autosomal-recessive inherited disorder characterized by disseminated cutaneous warts in predisposed patients who are highly susceptible to genus â-papillomavirus infections. Squaric acid dibutylester (SADBE) is a contact sensitizer agent that has gained general acceptance over the years for the treatment of a variety of dermatologic diseases, including alopecia areata and cutaneous warts. We report the case of a 40-year-old woman with a balanced chromosomal translocation and lymphocytopenia who presented with the sole clinical finding of refractory multiple flat warts that had been present for 25 years. After failed attempts at therapy with oral isotretinoin, cryotherapy with topical trichloroacetic acid, and topical tretinoin, the lesions were successfully eradicated with topical SADBE with prior sensitization.

Case Report

A 40-year-old woman presented with multiple flat warts on the bilateral arms and legs of 25 years’ duration (Figure 1) that had been unsuccessfully treated by an outside physician with imiquimod cream 5% and tazarotene gel 0.1%. Her medical history was remarkable for recurrent upper respiratory tract infections, urinary tract infections, yeast infections, and otitis media. She also reported a history of 6 spontaneous miscarriages that had been attributed to a balanced chromosomal translocation between chromosomes 12 and 14.

Figure 1. Numerous warts on the right shin prior to squaric acid dibutylester sensitization.

Figure 2. Histologic analysis of a lesion on the right leg revealed epidermal hyperplasia and koilocytosis (H&E, original magnification ×400).

Laboratory evaluation revealed leukopenia, lymphopenia, and hypogammaglobulinemia, with a white blood cell count of 3600/μL (reference range, 4500–11,000/mL), a lymphocyte count of 12.1% (20%–45%), absolute CD4 count of 77 cells/μL (490–1740 cells/μL), absolute CD8 count of 56 cells/mL (180–1170 cells/μL), and serum IgM level of 17 mg/dL (48–271 mg/dL). Human immunodeficiency virus (HIV) titers were negative.

On physical examination numerous pink, flat-topped papules were noted on the forehead and bilateral arms and legs. Histologic analysis of a tangential plane biopsy of a lesion on the right leg revealed hyperkeratosis of the stratum corneum and epidermal hyperplasia (Figure 2). The epidermis also showed focal papillomatosis with areas of hypergranulosis and viropathic changes; these findings were consistent with a diagnosis of verruca plana. Human papillomavirus (HPV) DNA typing by polymerase chain reaction from the verrucous lesions showed HPV type 20, which has been associated with EV. Based on the patient’s clinical findings and HPV subtype, she was diagnosed with atypical EV.

Subsequent treatment with liquid nitrogen, tretinoin cream 0.1%, and topical trichloroacetic acid 50% failed. She received oral isotretinoin at a dosage of 80 mg daily for 9 months, but the lesions persisted and she developed alopecia and ankle stiffness; therefore, the isotretinoin was discontinued. Candida antigen testing revealed that the patient was anergic, and SADBE sensitization was subsequently initiated. Squaric acid dibutylester was utilized as a sensitizing agent, and it was formulated as 2% and 0.2% solutions in acetone, supplied in 20-mL tinted glass bottles.

Squaric acid dibutylester solution 2% under occlusion was applied to a test area on the right forearm. Three days later, results indicated prominent erythema and inflammation at the application site. Two weeks later, a chronic dermatitic response was noted at the test site (Figure 3). Squaric acid dibutylester 0.2% was then applied to an affected area on the right shin and was kept under occlusion for 48 hours. One month later, no notable changes in the lesions were observed, and no further treatments were performed. Three months later, the patient returned for evaluation and it was noted that the flat warts on the right shin that had been treated with SADBE 0.2% 4 months prior had resolved (Figure 4). Subsequently, it was noted that all of the lesions had regressed, even those that had not been treated with SADBE.

Comment

Epidermodysplasia verruciformis is a rare genodermatosis caused by a group of phylogenetically related viruses1 belonging to the β-papillomavirus genus.2,3 It is characterized by a combination of pityriasis versicolor–like lesions, reddish verrucalike plaques, and seborrheic keratosis–like plaques,1,4 preferentially on sun-exposed areas.5 The lesions undergo malignant transformation in 30% to 60% of patients,3,6 especially into squamous cell carcinomas.7 The most frequent HPV types found in EV skin lesions are 5, 8, 9, 12, 14, 15, 17, and 19 to 25; types 5 and 8 are found in 90% of cutaneous squamous cell carcinomas in EV patients.2 Human papillomavirus type 20, the type identified in our patient, has been isolated from warts in EV patients,1,2 though it is not the most common type. It has been shown that more than one HPV type could be present concurrently in the same EV patient,1 which necessitates close follow-up for skin cancer evaluation in all EV patients, as oncogenic strains may be present in some lesions.

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