Interferon gamma immunotherapy for generalized verrucosis in thesetting of chronic immunodeficiency
Authors: Anthony A. Gaspari, Alicia Zalka
Journal: Journal of the American Academy of Dermatology (1998)

We read with great interest the case report by Asadullah et al. regarding generalized verrucosis in the setting of a chronic immune deficiency (J Am Acad Dermatol 1997;36:850-2). In this report, they describe the clinical course of a 24-year-old man with treatment-resistant extensive warts of the hands and feet that first appeared when the patient was 10 years old. This patient was atopic, anergic to recall skin testing, and had a history of oral candidiasis and sinusitis. Immunologic evaluation revealed a markedly decreased CD4 cell count, decreased gamma globulins, and low antibody titers to vaccines. In vitro studies of his lymphocytes revealed a defect in interferon gamma production. The patient underwent two rounds of intravenous interferon beta therapy (3 million IU in 10 days followed by 30 million IU in 10 days) with some clearing of the warts, although they continued to evolve. This report is similar to a case report recently published by our group.1Gaspari AA Zalka AD Payne D Bunce LA Abboud CN Tyring SK Successful treatment of a generalized human papillomavirus infection with GM-CSF and interferon-gamma in a patient with a primary immunodeficiency and cyclic neutropenia.Arch Dermatol. 1997; 133: 491-496Crossref PubMed Google Scholar We described an 18-year-old woman with generalized verrucosis (human papillomavirus type 2), onset at age 9 years. This patient had more than 300 warts, distributed on her hands, feet, face, elbows, and knees. This patient also had a history of cyclic neutropenia, with respiratory tract infections and stomatitis related to the fluctuations in her neutrophil count. Our immunologic evaluation revealed a chronic leukopenia with neutropenia and a profoundly decreased T-lymphocyte count (< 25% of the normal range, with a normal CD4/CD8 ratio); in vitro stimulation of our patient's CD4+T lymphocytes revealed a defect in proliferation and a severe defect in interferon gamma production. Our patient's gamma globulins were decreased, although there was evidence of antibody responses to infections or immunizations. Finally, our patient was not anergic to intradermal recall skin testing and was not atopic. We initially treated our patient's cyclic neutropenia with granulocyte-macrophage colony-stimulating factor (GM-CSF), 300 mg, administered by daily subcutaneous injections. Although this treatment was of great benefit in treating the cyclic neutropenia, it had no discernible effects on her extensive warts. Interferon gamma, 100 mg, was then administered three times per week by subcutaneous injection as specific immunotherapy for her warts. Interferon gamma therapy was gradually increased to 100 mg administered five times per week, and the GM-CSF dosage (500 mg/daily) was increased to compensate for the interferon-induced leukopenia. The interferon and GM-CSF therapies were continued for approximately 9 months and were well tolerated, even in a patient with underlying cyclic neutropenia. Except for a few warts on the soles, there was a dramatic complete regression of all of her warts (> 300 warts disappeared). In the 3 years after the discontinuation of her combined immunotherapy (interferon gamma and GM-CSF), none of her warts have recurred. Because of our success in treating a disseminated human papillomavirus infection with a protracted course of escalating interferon gamma therapy, we recommend this regimen for patients with similar immuno-deficiencies and widespread warts. The patient described by Asadullah et al. was afflicted with immunologic abnormalities similar to those in our patient and did not completely respond to two courses of intravenous interferon beta infusions. The patient may be a candidate for our interferon gamma regimen.1Gaspari AA Zalka AD Payne D Bunce LA Abboud CN Tyring SK Successful treatment of a generalized human papillomavirus infection with GM-CSF and interferon-gamma in a patient with a primary immunodeficiency and cyclic neutropenia.Arch Dermatol. 1997; 133: 491-496Crossref PubMed Google Scholar Interferon gamma therapy may also benefit this patient's atopic dermatitis, as has been previously demonstrated by Hanifin et al.2Hanifin JM Schneider LC Leung DYM Ellis CN Jaffe HS Izu AE et al.Recombinant interferon gamma therapy for atopic dermatitis.J Am Acad Dermatol. 1993; 28: 189-197Abstract Full Text PDF PubMed Scopus (283) Google Scholar Finally, it is noteworthy that recombinant interferon immunotherapy is contraindicated in patients with allergy to interferons, underlying autoimmune diseases, pregnancy, and organ transplant recipients receiving long-term immunosuppressive therapy. Congenital immunodeficiency is not a contraindication for interferon gamma therapy because it is used routinely in patients with chronic granulomatous disease.3Asnis LA Gaspari AA Cutaneous reactions to recombinant cytokine therapy.J Am Acad Dermatol. 1995; 33: 393-410Abstract Full Text PDF PubMed Scopus (103) Google Scholar