Interleukin-18 serum level before and after intralesional immunotherapy with tuberculin purified protein derivative in patients with cutaneous and genital warts.

BACKGROUND: Several studies demonstrated the efficacy of intralesional purified protein derivative (PPD) immunotherapy in warts eradication. Nevertheless, the precise induced immune mechanisms are undetermined. Injected PPD is hypothesized to induce a delayed hypersensitivity reaction associated with cytokines release. Interleukin (IL)-18 has a major role in defense against viral infection via inducing interferon-γ release from T-helper 1 and natural killer (NK) cells. Moreover, IL-18 triggers Fas ligand expression on cytotoxic T cells and NK cells enhancing their cytotoxicity against virally infected cells. AIM: The aim of this study was to assess the role of IL-18 in the response to intralesional PPD injection in patients with warts. METHODS: The study included 25 patients with warts and 25 HCs. Patients underwent PPD skin test, and only patients with positive tests were included and received intralesional PPD injections starting 72 h after the test then every 2 weeks until wart clearance or a maximum of 3 sessions. Serum IL-18 level was measured via enzyme-linked immune-sorbent assay in patients (pre-treatment and 2 weeks after the last injection) and HCs. RESULTS: After 3 sessions of injection, six (24%) patients were designated responders, nine (36%) patients showed partial response, and 10 (40%) patients were designated non-responders. Serum IL-18 level, post-treatment, was significantly higher than pre-treatment level (p = 0.025) and level in HCs (p = 0.036). Furthermore, the post-treatment level was significantly higher in responders than non-responders (p = 0.025). CONCLUSION: IL-18 is probably implicated in the immune mechanisms induced by PPD injection that cause eradication of warts.

Intralesional Measles-Mumps-Rubella Vaccine for Genital Warts: Report of two cases with a review of literature.

Genital warts are caused by several strains of Human Papilloma Viruses. Although asymptomatic in most cases, they can be psychologically and physically distressing for patients. Recently, intralesional immunotherapy using different antigens-such as Bacille Calmette-Guerin vaccine, candida antigen and measles, mumps, and rubella (MMR) vaccine-have shown promising efficacy in the treatment of genital warts. We report two cases in Omani males who presented to the Dermatology Department at Barka Polyclinic with recalcitrant genital warts that resolved completely with intralesional injection of the MMR vaccine.

Human papillomavirus-negative epithelial proliferations resembling condylomata acuminata in a patient receiving vemurafenib for Stage IV melanoma.

With the discovery of v-Raf murine sarcoma viral oncogene homolog B (BRAF) inhibitors, new treatment possibilities arose against metastatic melanoma. A frequent adverse effect of BRAF inhibitor therapy is the induction of epithelial proliferations such as cutaneous squamous cell carcinoma and verrucous papilloma. Here, we describe a case in which a patient developed extensive anal epithelial proliferations resembling condylomata acuminata, after starting vemurafenib treatment. This adverse effect has rarely been reported in the literature. Interestingly, the lesions in our patient were negative for human papillomavirus, and mutations in BRAF, Neuroblastoma rat sarcoma viral oncogene homolog (NRAS), Kirsten rat sarcoma viral oncogene homolog (KRAS), and Harvey rat sarcoma viral oncogene homolog (HRAS) were not detected. Different pathways can contribute to these epithelial proliferations resembling condylomata acuminata. We show the relevance of a detailed history at the beginning and during treatment, instructions, education, and dermatological follow-up (including the genital area) for patients treated with BRAF inhibitors. Condylomata acuminata can influence the quality of life and are treated, in an early stage, with cryotherapy, coagulation, imiquimod, and/or CO2 laser therapy.

Genital condylomata in a patient receiving infliximab for Crohn's disease.

Infliximab is a monoclonal antibody against tumour necrosis factor-alpha. Recent studies have shown that it is effective in treating patients with refractory Crohn's disease and in those with Crohn's fistulae. Though this drug is found to be safe in clinical trials, sporadic reports of serious complications have been recorded in the literature. The case of a patient who developed profuse genital warts after infliximab treatment is reported. The literature is reviewed and information is presented on side effects and complications as a result of infliximab therapy.

Development of human papillomavirus-associated Buschke-Löwenstein penile carcinoma during cyclosporine therapy for generalized pustular psoriasis.

Buschke-Löwenstein-type giant penile condyloma developed in a human immunodeficiency virus-negative, 25-year-old man after 4 years of intermittent cyclosporine therapy (5 mg/kg/day) for pustular psoriasis. Microscopic examination showed multifocal areas of invasive squamous cell carcinoma. Dot blot analysis of amplified polymerase chain reaction products with primers directed at the L1 region demonstrated signals for several human papillomavirus genotypes, including human papillomavirus type 16, that correlated with different histologic patterns consisting of verrucous and bowenoid changes and invasive carcinoma. This case conforms to the enhanced risk of cutaneous carcinogenesis from either papillomavirus infection or chronic actinic damage that has become evident in patients with organ allografts and cyclosporine therapy.

Oral contraceptives and human papillomavirus infection in cervical intraepithelial neoplasia.

We report about 142 patients from whom colposcopically directed cervical punch biopsies were taken which showed condylomatous lesions with or without cervical intraepithelial neoplasia (CIN). Fifty-six (39.4%) of these women used oral contraceptives (OC) for at least two years before examination. We used DNA in situ hybridization on all biopsies for detection of human papillomavirus (HPV)-DNA. Among OC users a significant trend towards higher HPV infection rates in high grade CIN (odds ratio 2.9, P less than 0.05) was found, whereas non-users of oral contraceptives had the highest HPV infection rate in condylomatous lesions without CIN (odds ratio 0.5, P less than 0.05). Thus in OC users HPV infection was about 24 times more likely in CIN III as in condyloma, while among non-users the trend was the other way round (7-fold likelihood of HPV positivity in condyloma compared to CIN III). Other known risk factors for cervical carcinoma did not influence HPV infection rates in either group.

The physical state of human papillomavirus type 16 DNA in benign and malignant genital tumours.

Cloned DNA from human papillomavirus (HPV) type 16 was subjected to restriction enzyme analysis. A genome size of 7.8 +/- 0.1 kb was determined and restriction maps were prepared. Fragments of HPV 16 DNA were nick-translated and hybridized with fragments of HPV 6b DNA. The two genomes appeared to be colinear. The physical state of HPV 16 DNA in genital tumours was analysed. In each of six benign tumours the viral DNA was detected exclusively as 8 kb circles. In four malignant tumours the viral DNA appeared to be integrated within the host genome but one cervical carcinoma and one case of Bowen's disease also contained oligomeric episomal molecules of viral DNA. One cervical carcinoma (WV 2965), containing only integrated viral DNA, was examined in detail. HPV 16 DNA was integrated as head-to-tail tandem repeats at more than one site. Three virus/cell junction fragments from this tumour were cloned. Two contained lengths of repetitive cellular DNA and one a length of apparently single copy cellular DNA.