Consideration of underlying immunodeficiency in refractory or recalcitrant warts: A review of the literature

Abstract

Although the exact mechanisms have yet to be elucidated, it is clear that cellular immunity plays a role in clearance of human papillomavirus (HPV) infections as it relates to the development of warts. Patients with extensive, recalcitrant, or treatment‐refractory warts may have an underlying immune system impairment at the root of HPV susceptibility. Early recognition of genetic disorders associated with immunologic defects that allow for recalcitrant HPV infection may expedite appropriate treatment for patients. Early recognition is often pivotal in preventing subsequent morbidity and/or mortality that may arise from inborn errors of immunity, such as WHIM (Warts, Hypogammaglobulinemia, Infections, Myelokathexis) syndrome. Among these, cervical cancer is one of the most common malignancies associated with HPV, can be fatal if not treated early, and is seen more frequently in patients with underlying immune deficiencies. A review of diseases with susceptibility to HPV provides clues to understanding the pathophysiology of warts. We also present diagnostic guidance to facilitate the recognition of inborn errors of immunity in patients with extensive and/or recalcitrant HPV infections.

Cutaneous Squamous Cell Carcinoma Masquerading as a Verruca: Case Report and Literature Review of Coexisting Wart and Invasive Squamous Cell Carcinoma on the Hand

“…Alpha human papillomavirus predominantly infects mucosal epithelia; however, it has been associated with benign skin lesions and cutaneous warts. In contrast, beta human papillomavirus preferentially infects cutaneous sites [ 1 , 7 ].…”

“…There are several inherited immunodeficiencies in which patients affected by the conditions have demonstrated an increased development of warts: ataxia telangiectasia, DOCK8 (dedicator of cytokinesis 8) deficiency causing a hyperimmunoglobulin E syndrome, epidermodysplasia verruciformis, GATA2 (GATA binding factor 2) deficiency, IL2RG (interleukin 2 receptor subunit gamma) deficiency, JAK3 (Janus kinase 3) deficiency, LAD1 (leucocyte adhesion deficiency 1), Netherton syndrome, severe combined immunodeficiency, NEMO (nuclear factor kappa-B essential modulator) deficiency syndrome, T-cell CD28 (cluster of differentiation 28) deficiency, WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome, and Whiskott-Aldrich syndrome. Similarly, increased human papillomavirus susceptibility has been associated with conditions and medications associated with acquired immunodeficiency including biologic therapy (such as tumor necrosis factor-alpha inhibitors), chemotherapy, connective tissue diseases (such as rheumatoid arthritis and systemic lupus erythematosus), human immunodeficiency virus infection, immunosuppressive agents (in solid organ transplant recipients), malignancy, and voriconazole [ 1 , 7 , 8 ].…”

“…Common management approaches for treating a verruca can either be destructive (cantharidin, citric acid, cryotherapy, electrosurgery, formic acid, glycolic acid, laser surgery, monochloroacetic acid, phenol, pyruvic acid, salicylic acid, silver nitrate, surgical excision, trichloroacetic acid, and zinc oxide), immune modulating (interferon, intralesional candida antigen, Th-1 (T helper type 1) stimulating vaccination, and topical imiquimod), antiproliferative (bleomycin, 5-fluorouracil, podophyllin, podophyllotoxin, and vitamin D analogues), or antiviral (cidofovir and retinoids). Researchers have also suggested to consider evaluating a patient for immunodeficiency if they have recalcitrant warts, despite treatment with two or more modalities, that persist for more than 18 months [ 1 , 2 ]. In addition, it might be reasonable to consider a biopsy of the clinically suspected verruca in a patient whose lesion is chronic and/or fails to respond to therapy.…”

“…Therefore, there are several clinical variants of this contagious viral infection and each is associated with one or more human papillomavirus strains. The types of verrucae include butcher’s warts, common warts (such as filiform warts and verruca vulgaris), cystic warts, flat (plane) warts, genital warts, oral warts, and palmar and plantar warts [ 1 , 2 ].…”

Efficacy of intralesional bleomycin in treatment resistant viral warts

“…Dermatology Review/Przegląd Dermatologiczny 2022/4 thors propose a definition of warts that persist for > 18 months [3].…”