Prevalence of cervical human papillomavirus in kidney transplant recipients: A systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aims to investigate the prevalence of cervical high-risk human papillomavirus (hrHPV) among kidney transplant recipients (KTRs) and, furthermore to compare it to that in immunocompetent controls. METHODS: A systematic literature search was conducted in PubMed, EMBASE, and Cochrane Library databases from January 2000 to February 2023, to identify studies investigating the prevalence of cervical hrHPV in KTRs. Pooled cervical hrHPV prevalences, odds ratios (ORs) comparing KTRs to controls and corresponding confidence intervals (CIs) were estimated using random effects logistic regression models. Heterogeneity between studies was assessed through the I2 statistic, and the significance was evaluated by the Cochrane's Q test. RESULTS: Altogether, 16 studies covering >1200 KTRs were included. The prevalence of cervical hrHPV in KTRs was 27.7% (95% CI 21.3-35.1) with substantial interstudy heterogeneity. Stratification indicated a higher prevalence in recent years (2019-2023) and in Asia (39% (95% CI 11.2-61.4)). The prevalence of HPV16 and HPV18 in KTRs was 8.0% (95% CI 3.9-15.9) and 1.7% (95% CI 0.8-3.7), respectively. Comparing hrHPV prevalence in KTRs and controls based on six studies including >500 KTRs and 1000 controls, the OR for hrHPV was 2.0 (95% CI 1.1-3.6). CONCLUSIONS: This meta-analysis establishes an increased cervical hrHPV prevalence in KTRs compared to controls. The increased risk may be associated with immunosuppressive therapy post-transplantation. Further research is needed to explore the potential benefits of HPV vaccination, including potential revaccination strategies in KTRs.

PD-L1 expression in vulvar cancer: a systematic review and meta-analysis.

Programmed cell death ligand-1 (PD-L1) expression in cancer may predict clinical response to immunotherapeutic treatment with PD-1/PD-L1 inhibitors. Within the vulvar cancer field, PD-L1 expression has only been assessed by a few studies. We conducted a meta-analysis to examine the prevalence of PD-L1 positivity in vulvar cancer. PubMed, Embase, and Cochrane were searched for articles reporting on PD-L1 expression in vulvar cancer. Study selection and data extraction were performed independently by two authors. We extracted data on PD-L1 prevalence in vulvar cancer according to combined positive score (CPS) and tumour proportion score (TPS). Cutoff values for positivity were ≥1 or ≥10 for CPS and ≥1% and ≥5% for TPS. Random-effects models were used to estimate pooled PD-L1 prevalence, with 95% confidence intervals (CIs). Tests of between-study heterogeneity were evaluated by the I2 statistics. Sources of heterogeneity were explored by subgroup analyses and meta-regression. In total, 19 studies were included. Pooled PD-L1 prevalence in vulvar cancer was 83.4% (95% CI: 70.8-91.3; I2 = 80.0) and 53.9% (95% CI: 37.4-69.6; I2 = 93.0) according to CPS and TPS, respectively. Based on TPS, human papillomavirus (HPV)-associated vulvar squamous cell carcinomas (SCC) showed a lower PD-L1 prevalence (39.9%; 95% CI: 13.3-74.2) compared with HPV-independent SCC (62.6%; 95% CI: 33.7-84.6), but meta-regression showed no significant variation in PD-L1 prevalence by HPV status. PD-L1 prevalence was similar in advanced (44.9%; 95% CI: 29.8-61.1) and localized vulvar cancer (56.7%; 95% CI: 18.9-76.7). In conclusion, PD-L1 expression in vulvar cancer is frequent but between-study heterogeneity was high. Based on a subgroup of heterogenous studies, we found no strong variation in PD-L1 prevalence according to HPV status and stage.

The influence of overweight and obesity on participation in cervical cancer screening: A systematic review and meta-analysis.

The prevalence of obesity is increasing worldwide. The incidence of cervical cancer has decreased after implementation of cervical cancer screening, however, obese women have higher risk of cervical cancer than women of normal weight. This might be caused by a lower participation rate in cervical cancer screening. The aim of this systematic review and meta-analysis was to examine the influence of overweight and obesity on adherence to cervical cancer screening recommendations. We conducted a thorough systematic literature search of electronic databases to identify studies examining screening participation among overweight and obese women compared to women of normal weight. Based on a random effect model, we calculated pooled odds ratios (OR) of screening participation with corresponding 95% confidence intervals (CI). I2 statistic was used to describe heterogeneity. A total of 32 papers were included. The pooled OR of screening participation was 0.94 (95%CI: 0.89-0.99) for overweight women and 0.79 (95%CI: 0.68-0.92) for obese women compared to women of normal weight. The heterogeneity was substantial (overweight: I2 = 89%; obese: I2 = 93%). The OR for screening adherence was 0.91 (95%CI: 0.80-1.05), 0.85 (95%CI: 0.70-1.03) and 0.67 (95%CI: 0.54-0.84) for women in obesity class I, II and III, respectively. The OR varied by geographical region and race. In conclusion, obese women are less likely to participate in cervical cancers screening compared to women of normal weight. In addition, the likelihood of adherence to screening recommendations decreases with increasing obesity class. This stresses the need for targeted intervention to increase screening adherence for overweight and obese women.

Cervical human papillomavirus prevalence according to socioeconomic and demographic characteristics in a large Danish screening population.

AIM: The aim of this study was to investigate high-risk human papillomavirus (hrHPV) prevalence according to socioeconomic and demographic characteristics in a Danish screening population. METHODS: We used data from HPV SCREEN DENMARK, which was an implementation study embedded into the routine cervical cancer screening programme. During 2017-2020, women aged 30-59 years screened in the Region of Southern Denmark were offered HPV testing or cytology. In the HPV group, liquid-based cytology samples were tested for 14 hrHPV types. We obtained registry information on socioeconomic and demographic characteristics and used log-binomial regression to estimate the prevalence ratio (PR) of hrHPV in three age groups (30-39, 40-49, 50-59 years), adjusting for age and marital status. RESULTS: We included 31,124 HPV unvaccinated women. In all age groups, the age-adjusted hrHPV prevalence was higher in women with basic versus higher education (e.g. age 30-39: 11.9% vs. 9.5%; PRage-adjusted=1.24; 95% confidence interval (CI): 1.02-1.50); women who were unemployed vs. employed (e.g. age 30-39: 11.6% vs. 10.4%; PRage-adjusted=1.11; 95% CI: 0.95-1.28); and in women with highest vs. lowest income (e.g. age 30-39: 11.6% vs. 9.5%, PRage-adjusted=1.18, 95% CI: 0.98-1.44). In models adjusted for marital status, these associations largely disappeared. CONCLUSIONS: We found slightly higher hrHPV prevalences in women with basic education, low income and unemployment. The differences largely disappeared when taking into account marital status as a potential proxy for sexual behaviour. Our findings support a need for targeted information on safe sexual practices and promoting socioeconomic equality in HPV vaccination and cervical cancer screening participation.

Risk of CIN3 or worse with persistence of 13 individual oncogenic HPV types.

Human papillomavirus (HPV) is essential in cervical carcinogenesis, however, less is known about the carcinogenic potential of individual HPV types. Our aim was to examine the risk of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) after persistence of 13 individual oncogenic HPV types. Liquid-based cervical samples (n = 40,399) collected in 2002-2005 were tested for HPV by hybrid capture 2 and genotyped with INNO-LiPAv2. Persistence was defined as having the same genotype twice 1-4.5 years apart. The absolute risk of CIN3+ was estimated by the Aalen-Johansen estimator and Cox proportional hazard regression was used to compare the rates of CIN3+ according to HPV type adjusting for age and time between HPV tests. Of 2,875 oncogenic HPV-positive women, 874 had persistence of one or more types and 761 persisted for one oncogenic HPV type only. Persistent HPV16 infection was associated with the highest risk of CIN3+, with an 8-year absolute risk of 55% (95% CI: 45%-66%), followed by HPV33 (33% (95% CI: 20%-50%)), HPV18 (32% (95% CI: 20%-48%)) and HPV31 (31% (95% CI: 21%-46%)). Other HPV types, including HPV52 and HPV45, were also associated with high risks. Persistent HPV56 had the lowest 8-year absolute risk of CIN3+ (3% (95% CI: 0.4%-20%)). In Cox analyses, a similar pattern remained after adjustment for age and time between tests. Our results add knowledge about the varying carcinogenic potential of individual persistent oncogenic HPV types, which may have implications for the clinical use of HPV testing.

The prognostic value of p16 and p53 expression for survival after vulvar cancer: A systematic review and meta-analysis.

The tumor suppressor proteins p16 and p53 have been suggested to have prognostic value in some human papillomavirus (HPV)-associated cancers, however, this has been less well established for vulvar cancer. The aim of this review and meta-analysis was to examine the prognostic value of p16 and p53 expression status on survival after vulvar squamous cell carcinoma (VSCC). We conducted a thorough systematic literature search of multiple databases to identify studies examining survival after histolocally verified VSCC that were tested for p16 and/or p53. A total of 18 eligible studies were included. Using a fixed-effects model we calculated study-specific and pooled hazard ratios (HRs) of 5-year overall survival (OS). In the analyses of OS, we included 475 VSCC cases tested for p16 expression of which 38% were p16 positive. The pooled HRp16 was 0.40 (95% CI: 0.29-0.55). In addition, the majority of results from studies with adjusted analyses on the prognostic value of p16 indicated that p16 expression status could be an independent prognostic marker for OS in women diagnosed with VSCC, and the same pattern was seen for disease specific survival (DSS). We also included 310 VSCC cases tested for p53 expression of which 54% were p53 positive. The pooled HRp53 was 1.81 (95% CI: 1.22-2.68) indicating that p53 positive VSCC have a significantly lower 5-year OS compared to p53 negative. The results in relation to p53 reported from adjusted analyses OS and on DSS and disease free survival were more equivocal. This meta-analysis and review suggests that p53 and especially p16 expression status are of prognostic importance in women diagnosed with VSCC. This may be clinically important in the future design of targeted therapy and when planning the optimal follow-up strategy. Future studies should include the combined use of biomarkers such as p16, p53 and HPV status.

Human papillomavirus and p16 in squamous cell carcinoma and intraepithelial neoplasia of the vagina.

We estimated the overall and type-specific prevalence of human papillomavirus (HPV) and p16 overexpression in vaginal cancer and vaginal intraepithelial neoplasia (VaIN). We conducted a systematic search of PubMed, Embase and Cochrane Library to identify studies published between 1986 and 2017 using PCR-based or Hybrid Capture 2 tests to evaluate the presence of HPV DNA and/or using any method to detect p16 overexpression in VaIN, vaginal squamous cell carcinoma (VaSCC), or other types of vaginal cancer. Applying a random effects model, we estimated the pooled prevalence of HPV and p16 overexpression along with 95% confidence intervals (CIs). The I2 statistic was used to assess heterogeneity. We included 26 studies, reporting HPV prevalence and six studies evaluating p16 overexpression. The pooled HPV prevalences in VaSCC (n = 593) and VaIN (n = 1,374) were 66.7% (95% CI = 54.7-77.8) and 85.2% (95% CI = 78.2-91.0), respectively. Substantial inter-study heterogeneity was observed, and analyses stratified on geographic region, type of tissue, HPV detection method or PCR primer type did not fully explain the observed heterogeneity. The most predominant HPV type among the HPV positive VaSCC and VaIN cases was HPV16, followed by HPV33, and HPV45 (in VaIN) and HPV18, and HPV33 (in VaSCC). In pooled analyses, 89.9% (95% CI = 81.7-94.6) of HPV positive and 38.9% (95% CI = 0.9-90.0) of HPV negative vaginal cancers were positive for p16 overexpression. Our findings suggest that vaccination against HPV might prevent a substantial proportion of vaginal neoplasia and highlight the need for further studies of the possible clinical value of p16 testing in these patients.

Prevalence of human papillomavirus DNA and p16INK4a in penile cancer and penile intraepithelial neoplasia: a systematic review and meta-analysis.

BACKGROUND: Although previous meta-analyses have examined human papillomavirus (HPV) DNA prevalence in penile cancer, none, to our knowledge, have assessed pooled HPV DNA prevalence in penile intraepithelial neoplasia or p16INK4a percent positivity in penile cancer and penile intraepithelial neoplasia. Therefore, we aimed to examine the prevalence of HPV DNA and p16INK4a positivity in penile cancer and penile intraepithelial neoplasia worldwide. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, and the Cochrane Library until July 24, 2017, for English-language articles published from Jan 1, 1986, onwards reporting the prevalence of HPV DNA and p16INK4a positivity, either alone or in combination, in at least five cases of penile cancer or penile intraepithelial neoplasia. Only studies that used PCR or hybrid capture for the detection of HPV DNA and immunohistochemical staining or methylation for the detection of p16INK4a were included. Data were extracted and subsequently crosschecked, and inconsistencies were discussed to reach consensus. Using random-effects models, we estimated the pooled prevalence and 95% CI of HPV DNA and p16INK4a positivity in penile cancer and penile intraepithelial neoplasia, stratifying by histological subtype and HPV DNA or p16INK4a detection method. Type-specific prevalence of HPV6, HPV11, HPV16, HPV18, HPV31, HPV33, and HPV45 in penile cancer was estimated. FINDINGS: Our searches identified 1836 non-duplicate records, of which 73 relevant papers (71 studies) were found to be eligible. The pooled HPV DNA prevalence in penile cancer (52 studies; n=4199) was 50·8% (95% CI 44·8-56·7; I2=92·6%, pheterogeneity<0·0001). A high pooled HPV DNA prevalence was seen in basaloid squamous cell carcinomas (84·0%, 95% CI 71·0-93·6; I2=48·0%, pheterogeneity=0·0197) and in warty-basaloid carcinoma (75·7%, 70·1-81·0; I2=0%, pheterogeneity=0·52). The predominant oncogenic HPV type in penile cancer was HPV16 (68·3%, 95% CI 58·9-77·1), followed by HPV6 (8·1%, 4·0-13·7) and HPV18 (6·9%, 2·9-12·4). The pooled HPV DNA prevalence in penile intraepithelial neoplasia (19 studies; n=445) was 79·8% (95% CI 69·3-88·6; I2=83·2%, pheterogeneity<0·0001). The pooled p16INK4a percent positivity in penile cancer (24 studies; n=2295) was 41·6% (95% CI 36·2-47·0; I2=80·6%, pheterogeneity<0·0001), with a high pooled p16INK4a percent positivity in HPV-related squamous cell carcinoma (85·8%, 95% CI 72·1-95·4; I2=56·4%, pheterogeneity=0·0011) as compared with non-HPV-related squamous cell carcinoma (17·1%, 7·9-29·1; I2=78·3%, pheterogeneity<0·0001). Moreover, among HPV-positive cases of penile cancer, the p16INK4a percent positivity was 79·6% (95% CI 65·7-90·7; I2=89·9%, pheterogeneity<0·0001), compared with 18·5% (9·6-29·6; I2=89·3%, pheterogeneity<0·0001) in HPV-negative penile cancers. The pooled p16INK4a percent positivity in penile intraepithelial neoplasia (six studies; n=167) was 49·5% (95% CI 18·6-80·7). INTERPRETATION: A large proportion of penile cancers and penile intraepithelial neoplasias are associated with infection with HPV DNA (predominantly HPV16), emphasising the possible benefits of HPV vaccination in men and boys. FUNDING: None.

Prognostic Significance of HPV and p16 Status in Men Diagnosed with Penile Cancer: A Systematic Review and Meta-analysis.

It has been shown that human papillomavirus (HPV) and p16 status has prognostic value in some HPV-associated cancers. However, studies examining survival in men with penile cancer according to HPV or p16 status are often inconclusive, mainly because of small study populations. The aim of this systematic review and meta-analysis was to examine the association between HPV DNA and p16 status and survival in men diagnosed with penile cancer. Multiple electronic databases were searched. Twenty studies were ultimately included and study-specific and pooled HRs of overall survival and disease-specific survival (DSS) were calculated using a fixed effects model. In the analysis of DSS, we included 649 men with penile cancer tested for HPV (27% were HPV-positive) and 404 men tested for p16 expression (47% were p16-positive). The pooled HRHPV of DSS was 0.61 [95% confidence interval (CI), 0.38-0.98], and the pooled HRp16 of DSS was 0.45 (95% CI, 0.30-0.69). In conclusion, men with HPV or p16-positive penile cancer have a significantly more favorable DSS compared with men with HPV or p16-negative penile cancer. These findings point to the possible clinical value of HPV and p16 testing when planning the most optimal management and follow-up strategy. Cancer Epidemiol Biomarkers Prev; 27(10); 1123-32. ©2018 AACR.

The Use and Safety of TNF Inhibitors during Pregnancy in Women with Psoriasis: A Review.

Psoriasis is a chronic immune-mediated inflammatory disease affecting women of childbearing potential. Biologic agents, notably Tumor Necrosis Factor inhibitors (TNFi), are the only current non-contraindicated systemic treatment option during pregnancy. TNFi comprised of complete immunoglobulin G (IgG) antibodies antibodies (adalimumab, golimumab, and infliximab) actively cross the placenta from the second trimester and are detectable in the child up to one year postpartum. Data on safety of TNFi are conflicting; however a trend towards drug-specific harm has been reported, with increased risk of congenital malformations and preterm birth. TNFi exposure may alter the immune system of the infant towards hypersensitivity and reduced response to intracellular infections. Confounding by indication should be considered, as chronic inflammatory disease itself may pose a risk of adverse pregnancy outcomes. The quality of the current evidence is very low and no studies specifically address TNFi safety in women with psoriasis. Nonetheless, risks associated with TNFi treatment must be balanced against the as-yet uncertain risk of adverse outcomes in infants born to women with severe psoriasis. We searched PubMed using Medical Subject Headings (MeSH) terms and identified relevant studies and guidelines. Herein, we present the current knowledge of the use and safety of TNFi during pregnancy in women with psoriasis.

Skin diseases of the vulva: inflammatory, erosive-ulcerating and apocrine gland diseases, zinc and vitamin deficiency, vulvodynia and vestibulodynia.

Chronic, inflammatory and ulcerating mucocutaneous diseases that can affect the vulvar area are reviewed: lichen sclerosus, lichen planus, plasma cell vulvitis, complex aphthosis, Behcet's disease, pyoderma gangrenosum, metastatic Crohn's disease, dyskeratotic skin diseases (Hailey-Hailey disease and Darier's disease), autoimmune bullous diseases (mucous membrane pemphigoid and pemphigus vulgaris) and hidradenitis suppurativa. Also, vulvodynia and vestibulodynia, zinc and vitamin B deficiency are described.

Long-term risk of cervical cancer following conization of cervical intraepithelial neoplasia grade 3-A Danish nationwide cohort study.

Using nationwide Danish registries we examined the long-term risk of cervical cancer in women diagnosed with cervical intraepithelial neoplasia grade 3 (CIN3) (including adenocarcinoma in situ (AIS)) on the cone compared to women with a normal cytology test. Initially, we identified women born 1918-1990, who were recorded as living in Denmark between January 1, 1978 and December 31, 2012. From the Pathology Data Bank information on CIN3 on the cone, margins status, histological type of CIN3 and cervical cytology results was extracted. Cox proportional hazard model was used to estimate the relative risk of subsequent cervical cancer. We included 59,464 women with CIN3 on the cone and 1,918,508 women with a normal cytology test. Overall, women diagnosed with CIN3 had a higher risk of subsequent cervical cancer compared to women with normal cytology (HR = 2.06; 95%CI: 1.81-2.35). Analyses according to time since conization showed elevated risks in all time periods, and 25 years or more after conization the relative risk was significantly increased (HR = 2.56; 95%CI: 1.37-4.77). Twenty years or more after conization, also women with negative margins had an increased relative risk (HR = 2.49; 95%CI: 1.12-5.57). In addition, the long-term relative risk of cervical cancer varied with the different histological types of CIN3 and was highest for AIS (HR = 7.50; 95%CI: 1.87-30.01, 10-14 years after conization). In conclusion, women diagnosed with CIN3 on the cone have a long-lasting increased risk of cervical cancer even when the margins on the cone are negative.

Does HPV status influence survival after vulvar cancer?

High-risk human papillomavirus (HPV) infection is essential in the carcinogenesis of a substantial part of anogenital and oropharyngeal cancers and has additionally been shown to be a possible predictive marker for survival, especially in oropharyngeal cancer. Studies examining the influence of HPV status on survival after vulvar cancer have been conflicting and limited by small study populations. Therefore, the aim of this review and meta-analysis was to examine whether HPV status influences survival after vulvar cancer, which, to our knowledge, has not been done before. We conducted a systematic search of PubMed, Cochrane Library and Embase to identify studies examining survival after histologically verified and HPV tested vulvar cancer. A total of 18 studies were eligible for inclusion. Study-specific and pooled HRs of the 5-year OS and DFS were calculated using a fixed effects model. The I2 statistic was used to describe heterogeneity. The studies included a total of 1,638 women with HPV tested vulvar cancers of which 541 and 1,097 were HPV-positive and HPV-negative, respectively. Fifteen studies included only squamous cell carcinomas. We found a pooled HR of 0.61 (95% CI: 0.48-0.77) and 0.75 (95% CI: 0.57-1.00) for 5-year OS and DFS, respectively. Across study heterogeneity was moderate to high (OS: I2 = 51%; DFS: I2 = 73%). In conclusion, women with HPV-positive vulvar cancers have a superior survival compared to women with HPV-negative, which could be of great clinical interest and provides insight into the differences in the natural history of HPV-positive and negative vulvar cancers.

Clinician's Update on the Benign, Premalignant, and Malignant Skin Tumours of the Vulva: The Dermatologist's View.

Correct and rapid diagnosis of skin tumours often requires biopsy and histopathological examination to differentiate benign lesions such as seborrhoeic keratoses or melanocytic naevi from premalignant and malignant lesions such as malignant melanoma. Particularly, to the untrained eye, any benign skin tumour-pigmented or nonpigmented-is easily mistaken for a malignant lesion. Qualified clinical evaluation is paramount in order to reduce the frequency of unwarranted skin biopsies. Herein, the most common benign, premalignant, and malignant vulvar skin tumours are reviewed.

Skin diseases of the vulva: Infectious diseases.

A multitude of infectious diseases of viral (genital herpes, herpes zoster, genital warts and molluscum contagiosum), bacterial (syphilis, chancroid, lymphogranuloma venereum, donovanosis, erysipelas, cellulitis and necrotising fasciitis, folliculitis, impetigo, bartholin gland abscess, trichomycosis and erythrasma), fungal (candidiasis and dermatophytosis) and parasitic (pediculosis pubis) origin may affect the vulvar area. Herein, we review the infections and their skin manifestations in the vulvar area.

Long-Term Risk for Noncervical Anogenital Cancer in Women with Previously Diagnosed High-Grade Cervical Intraepithelial Neoplasia: A Danish Nationwide Cohort Study.

BACKGROUND: High-risk human papillomavirus (HPV) is essential for developing high-grade cervical intraepithelial neoplasia (CIN2 and CIN3) and has also been associated with noncervical anogenital cancers. However, limited knowledge exists about the long-term risk for anal, vulvar, and vaginal cancer following CIN2 or CIN3 diagnosis. METHODS: In a nationwide cohort study, we followed nearly 2.8 million women born in 1918-1990 who were recorded as living in Denmark between January 1, 1978 and December 31, 2012. The cohort was linked to multiple nationwide registers to obtain information on cancer diagnoses and confounders. Follow-up started when the women reached 18 years, date of immigration, or January 1978, and continued until emigration, death, December 31, 2012, or the date of first diagnosis of anogenital or rectal cancer. RESULTS: Women with a history of CIN2 or CIN3 had higher risks for subsequent anal, vulvar, and vaginal cancer than women with no such history. The relative risks were higher for CIN3 than CIN2. No excess risk was found for rectal cancer. Analyses in which time since first CIN3 was taken into account showed increased relative risks for anal [HR = 4.8; 95% confidence interval (CI), 3.3-7.0], vulvar (HR = 3.2; 95% CI, 2.0-5.3), and vaginal (HR = 5.5; 95% CI, 2.4-12.3) cancers ≥25 years after CIN3 diagnosis. CONCLUSION: Women with a history of CIN2 or CIN3 have a long-term increased relative risk for developing anal, vulvar, and vaginal cancer due to an impaired ability to control a persistent HPV infection. IMPACT: This finding adds to our understanding of the relation between HPV infection and noncervical anogenital cancer. Cancer Epidemiol Biomarkers Prev; 25(7); 1090-7. ©2016 AACR.

Off-label use of TNF-alpha inhibitors in a dermatological university department: retrospective evaluation of 118 patients.

Tumor necrosis factor-alpha (TNF)-alpha inhibitors are licensed for patients with severe refractory psoriasis and psoriatic arthritis. However, TNF-alpha inhibitors have also been used off-label for various recalcitrant mucocutaneous diseases. This study aimed to evaluate the efficacy and safety of TNF-alpha inhibitors used for off-label dermatological indications. We retrospectively evaluated patient records of 118 patients treated off-label with TNF-alpha inhibitors in a dermatological university department. Patients presented with severe aphthous stomatitis/genital aphthous lesions (26), chronic urticaria (25), hidradenitis suppurativa (29), acne conglobata (11), dissecting cellulitis of the scalp (two), orofacial granulomatosis (four), sarcoidosis (four), granuloma annulare (two), granulomatous rosacea (one), granuloma faciale (one), subcorneal pustulosis (one), pyoderma gangrenosum (four), Sweet's syndrome (four), Well's syndrome (one), benign familial pemphigus (one), lichen planus (one), and folliculitis decalvans (one). A significant number of these patients went into remission during therapy with TNF-alpha inhibitors. A total of 11 patients (9%) experienced severe adverse effects during therapy. Off-label therapy with TNF-alpha inhibitors may be considered for selected patients with severe recalcitrant mucocutaneous diseases. The risk of severe adverse effects signals that a thorough benefit-risk assessment should be performed before initiating off-label treatment with TNF-alpha inhibitors for these conditions.