Energy-Based Devices for the Treatment of Cutaneous Verrucae: A Systematic Review.

BACKGROUND: Warts are one of the most common benign neoplasms caused by human papillomavirus infection and often pose a therapeutic challenge. OBJECTIVE: To summarize the current evidence on the safety and efficacy of laser and energy-based devices for the treatment of cutaneous verrucae. METHODS: A comprehensive systematic review of the literature on laser and energy-based devices for the treatment of cutaneous verrucae was performed. RESULTS: A total of 904 unique studies were identified, of which 109 were included in this review. The most commonly used lasers as a single treatment modality for verrucae included the long-pulsed Nd:Yag (n = 20) and pulsed dye (n = 18) lasers. Other modalities included the CO2 ablative laser (n = 10), photodynamic therapy (n = 11), local hyperthermia (n = 11), microwave therapy (n = 2), and nanopulse stimulation (n = 1). Other studies combined energy-based modalities with additional treatments, such as retinoids, imiquimod, and intralesional bleomycin. Overall, such devices were generally well-tolerated, with only a mild side effect profile. CONCLUSION: Overall, the use of laser and energy-based devices is a safe and well-tolerated option for cutaneous verrucae that is relatively less invasive than surgical interventions. Future studies using more consistent outcome assessment tools will be valuable to help clinicians develop device-specific protocols and treatment regimens to ensure replicable and effective outcomes.

CXCR4 WHIM syndrome is a cancer predisposition condition for virus-induced malignancies.

Warts, hypogammaglobulinaemia, infections and myelokathexis syndrome (WHIMS) is a rare combined primary immunodeficiency caused by the gain of function of the CXCR4 chemokine receptor. We present the prevalence of cancer in WHIMS patients based on data from the French Severe Chronic Neutropenia Registry and an exhaustive literature review. The median follow-up of the 14 WHIMS 'patients was 28.5 years. A central review and viral evaluation of pathological samples were organized, and we conducted a thorough literature review to identify all reports of WHIMS cases. Six French patients were diagnosed with cancer at a median age of 37.6 years. The 40-year risk of malignancy was 39% (95% confidence interval [CI]: 6%-74%). We observed two human papillomavirus (HPV)-induced vulvar carcinomas, three lymphomas (two Epstein-Barr virus [EBV]-related) and one basal cell carcinoma. Among the 155 WHIMS cases from the literature, 22 cancers were reported in 16 patients, with an overall cancer 40-year risk of 23% (95% CI: 13%-39%). Malignancies included EBV-associated lymphoproliferative disorders and HPV-positive genital and anal cancers as in the French cohort. Worldwide, nine cases of malignancy were associated with HPV and four with EBV. Immunocompromised WHIMS patients appear to be particularly susceptible to developing early malignancy, mainly HPV-induced carcinomas, followed by EBV-related lymphomas.

CXCR4: from B-cell development to B cell-mediated diseases.

Chemokine receptors are members of the G protein-coupled receptor superfamily. The C-X-C chemokine receptor type 4 (CXCR4), one of the most studied chemokine receptors, is widely expressed in hematopoietic and immune cell populations. It is involved in leukocyte trafficking in lymphoid organs and inflammatory sites through its interaction with its natural ligand CXCL12. CXCR4 assumes a pivotal role in B-cell development, ranging from early progenitors to the differentiation of antibody-secreting cells. This review emphasizes the significance of CXCR4 across the various stages of B-cell development, including central tolerance, and delves into the association between CXCR4 and B cell-mediated disorders, from immunodeficiencies such as WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome to autoimmune diseases such as systemic lupus erythematosus. The potential of CXCR4 as a therapeutic target is discussed, especially through the identification of novel molecules capable of modulating specific pockets of the CXCR4 molecule. These insights provide a basis for innovative therapeutic approaches in the field.

Comparative study on the age-related incidence of seborrheic keratosis and verruca plana in patients with verruca plana-like lesions.

Seborrheic keratosis (SK) is a common skin disease in the elderly. However, in cases where SK presenting as multiple skin-colored or clustered lesions can be easily misdiagnosed as verruca plana (VP), especially in the young population. This retrospective study investigated the prevalence of SK and VP in the lesions that appear clinically similar to VP according to age. We examined the pathology slides of the skin tissue and photographs of patients who were clinically suspected to have VP. A total of 503 patients were included in the study, out of which 174 patients were finally diagnosed with SK (34.6%) and 132 with VP (26.2%). The mean ages of the SK- and VP-diagnosed group were 39.3 and 35.4 years, respectively. SK had a higher prevalence among individuals older than 30 years, and relative frequency of SK should not be ignored in patients with a grouped distribution in their 20 s and 30 s. Therefore, our study suggests that multiple verrucous skin-colored to brownish plaques are also commonly diagnosed as SK in young people as well as VP, and the prevalence of SK and VP may not always depend solely on chronological aging, and the prevalence of SK among young people may be higher than commonly believed stereotypes suggest.

Does HPV biotype influence the characteristics and evolution of plantar warts?

BACKGROUND: Few studies have addressed the relationship of human papillomavirus (HPV) biotypes to patient characteristics and the clinical signs, course, and response to the treatment of plantar warts. OBJECTIVE: Analyze the HPV types associated with plantar warts and their relationship with warts characteristics, patient characteristics and response to treatment. METHODS: A total of 372 patients sampled for hyperkeratosis of a plantar wart were included. Multiplex polymerase chain reaction (PCR) was performed to detect the HPV biotype. RESULTS: The prevalence of HPV was 81.2%, and HPV1 was the most prevalent biotype (36.1%). HPV1 was the most prevalent biotype in patients < 70 years old (90.9% in < 10 years), and biotypes 2, 19 and 27 were the most prevalent in patients > 70 years old (p = 0.012). HPV1 was the most frequent in patients with one (39,9%) or two (47.1%) warts and HPV5 (33.3%) in patients with three warts (p < 0.001). Cure, spontaneous resolution, and recurrence were higher in HPV1 (p < 0.001). HPV14 warts healed the fastest (2 months quartile 1-3 (2.0-2.0)), and HPV5 (10.977 (6.0-20.0)) and HPV27 (7.5 (3.0-10.0)) warts (p = 0.033) took the longest to heal. CONCLUSIONS: HPV biotype is associated with age and the number of warts and appears to influence the natural history of warts and their response to treatment.

A target enrichment approach for enhanced recovery of Synchytrium endobioticum nuclear genome sequences.

Potato wart disease is caused by the obligate fungal pathogen Synchytrium endobioticum. DNA extraction from compost, purified spores and crude wart tissue derived from tuber galls of infected potatoes often results in low S. endobioticum DNA concentration or highly contaminated with DNA coming from other microorganisms and the potato host. Therefore, Illumina sequencing of these samples generally results in suboptimal recovery of the nuclear genome sequences of S. endobioticum. A hybridization-based target enrichment protocol was developed to strongly enhance the recovery of S. endobioticum DNA while off-target organisms DNA remains uncaptured. The design strategy involved creating a set of 180,000 molecular baits targeting both gene and non-gene regions of S. endobioticum. The baits were applied to whole genome amplified DNA samples of various S. endobioticum pathotypes (races) in compost, from purified spores and crude wart tissue samples. This was followed by Illumina sequencing and bioinformatic analyses. Compared to non-enriched samples, target enriched samples: 1) showed a significant increase in the proportion of sequenced bases mapped to the S. endobioticum nuclear genome, especially for crude wart tissue samples; 2) yielded sequencing data with higher and better nuclear genome coverage; 3) biased genome assembly towards S. endobioticum sequences, yielding smaller assembly sizes but higher representation of putative S. endobioticum contigs; 4) showed an increase in the number of S. endobioticum genes detected in the genome assemblies. Our hybridization-based target enrichment protocol offers a valuable tool for enhancing genome sequencing and NGS-based molecular detection of S. endobioticum, especially in difficult samples.

Periodontal disease in patients with WHIM syndrome.

AIM: WHIM (warts, hypogammaglobulinaemia, infections and myelokathexis) syndrome is a rare combined primary immunodeficiency disease caused by gain-of-function (GOF) mutations in the chemokine receptor CXCR4 and includes severe neutropenia as a common feature. Neutropenia is a known risk factor for periodontitis; however, a detailed periodontal evaluation of a WHIM syndrome cohort is lacking. This study aimed to establish the evidence base for the periodontal status of patients with WHIM syndrome. MATERIALS AND METHODS: Twenty-two adult WHIM syndrome patients and 22 age- and gender-matched healthy volunteers (HVs) were evaluated through a comprehensive medical and periodontal examination. A mouse model of WHIM syndrome was assessed for susceptibility to naturally progressing or inducible periodontitis. RESULTS: Fourteen patients with WHIM syndrome (63.6%) and one HV (4.5%) were diagnosed with Stage III/IV periodontitis. No WHIM patient presented with the early onset, dramatic clinical phenotypes typically associated with genetic forms of neutropenia. Age, but not the specific CXCR4 mutation or absolute neutrophil count, was associated with periodontitis severity in the WHIM cohort. Mice with a Cxcr4 GOF mutation did not exhibit increased alveolar bone loss in spontaneous or ligature-induced periodontitis. CONCLUSIONS: Overall, WHIM syndrome patients presented with an increased severity of periodontitis despite past and ongoing neutrophil mobilization treatments. GOF mutations in CXCR4 may be a risk factor for periodontitis in humans.

Superficial radiotherapy (SRT-100) for refractory plantar warts: An alternative noninvasive treatment strategy.

BACKGROUND: Verrucas that occur on the soles of the feet are called plantar warts, most of which can recur repeatedly and are difficult to eradicate. Hypertrophic and refractory plantar warts are often accompanied by pain and discomfort, which cause many inconveniences in patients' daily lives. AIM: This study aimed to analyze the therapeutic effect of superficial radiotherapy (SRT-100) on refractory plantar warts and further create favorable conditions for the subsequent treatment of this disease with a high recurrence rate. METHODS: A retrospective analysis was conducted for refractory plantar warts treated with superficial radiotherapy in our outpatient department from January to June 2023. RESULTS: A total of 30 patients were included in our study (median age, 33 years). The female-to-male ratio was 1:3.29. Two to six months after radiotherapy, all of the warts subsided in 23 (76.67%) patients, most of the warts subsided in 4 (13.33%) patients, 3 (10%) patients did not respond to treatment, and 7 (23.33%) patients had recurrent or new warts after their warts subsided. CONCLUSIONS: Most patients with refractory plantar warts improved after superficial radiotherapy. Our study presented that men are more susceptible to plantar warts than women, and young and middle-aged people are the main population affected by the disease. Superficial radiotherapy is an effective treatment for refractory plantar warts, which can quickly remove the warts in a short period. It is safe and noninvasive, with minimal adverse reactions. Some patients relapse after the lesion is clear, and superficial radiotherapy can create favorable conditions for the subsequent treatment of viral warts in clinical practice.

Topical antimitotic treatments for plantar warts are more beneficial: A Bayesian network meta-analysis of randomized controlled trials.

BACKGROUND: Plantar warts are common infectious cutaneous growths causing severe physiological and psychological discomforts in patients and heaving global financial burdens. However, paucity of clear-cut guidelines for plantar warts, selecting appropriate treatments for plantar warts remains challenging. The objective of the study is to evaluate the efficacy and safety of common treatments for plantar warts. METHODS: PubMed, EMbase, and The Cochrane Library were searched from inception to March 1, 2023 for randomized controlled trials (RCTs) of plantar warts. The primary outcome (complete response) and secondary outcome (recurrence and pain) were extracted and combined using Bayesian network meta-analysis (NMA) with random-effect and fixed-effect models. RESULTS: Totally, 33 RCTs were included in the systematic review and quantitative NMA. In NMA of complete response, topical application of 1% cantharidin, 20% podophylotoxin, 30% salicylic acid (CPS), microneedles plus bleomycin (MNB), and intralesional bleomycin injection (INB) were the only three treatments significantly superior to no treatment (NT) and CPS was of the highest possibility to be the top-ranked treatment (SUCRA = 0.9363). However, traditional warts treatments, salicylic acid (SA) and cryotherapy were not superior to NT. CONCLUSIONS: The NMA has produced evidence for using CPS, MNB, and INB, which are all topical antimitotic treatments, to improve the management of plantar warts. The classic treatment modalities for plantar warts, including SA and cryotherapy, may play a less important role in the clinical practice of plantar warts.

Autoinoculation Therapy for the Treatment of Widespread Cutaneous Warts.

BACKGROUND: Cutaneous warts are common lesions that are often unresponsive to various therapeutic modalities. OBJECTIVE: To assess the role of autoinoculation therapy in the treatment of widespread cutaneous warts. MATERIALS AND METHODS: This interventional study included patients with widespread skin warts who did not respond to conventional treatments. Two methods were used to perform the autoinoculation therapy. The first procedure was performed by obtaining a small piece of the wart and inoculating it into a subcutaneous pocket. The second method was developed by the investigator and was performed by inserting a needle into the center of the wart toward the nearby subcutaneous tissue, with multiple forward and backward movements in several directions around the lesion. RESULTS: The prospective study included 23 patients. The illness duration ranged from 3 months to 5 years. Autoinoculation interventions revealed full recovery of all warts in 20 cases (87%) within 20 to 90 days (mean: 40.7 days). CONCLUSION: Autoinoculation procedures demonstrated effectiveness, less cost, lesser pain, less invasiveness, without leaving skin scars in comparison with other conventional therapies.

Cold urticaria as a complication of cryotherapy in the treatment of viral warts.

Cryotherapy with liquid nitrogen has been established as the first-line treatment for pediatric patients with viral warts. Cold-induced urticaria (CU) is a rare skin reaction triggered by cold stimuli. We present the case of a pediatric patient with viral warts who developed CU after receiving cryotherapy.

Korean sexually transmitted infection guidelines 2023 revision, guideline update of viral infections: Genital herpes and anogenital warts.

The Korean Association of Urogenital Tract Infection and Inflammation and the Korea Disease Control and Prevention Agency regularly update, revise, and develop new content for the Korean sexually transmitted infection (STI) guidelines. These professional bodies respond to changing epidemiological trends and evolving scientific evidence, and consider advances in laboratory diagnostics and research. The principal recommendations of the 2023 Korean STI guidelines in terms of viral infection follow: 1) If genital herpes recurs more than 4-6 times annually, suppressive therapy with acyclovir 400 mg orally 2 times/day or famciclovir 250 mg orally 2 times/day or valacyclovir 500 mg orally once a day (for patients with <10 episodes/year) or valacyclovir 1 g orally once daily (for patients with ≥10 episodes/year) is recommended to prevent recurrence; 2) molecular human papillomavirus (HPV) testing is not recommended as a routine test for STI status, nor for determination of HPV vaccination status; and 3) patients should inform their current sexual partners about anogenital warts because the types of HPV that cause such warts can be passed to partners. These guidelines will be updated every 5 years and will be revised when new knowledge on STIs becomes available and there is a reasonable need to improve the guidelines. Physicians and other healthcare providers can use the guidelines to assist in the prevention and treatment of STIs.

Building gender-specific sexually transmitted infection risk prediction models using CatBoost algorithm and NHANES data.

BACKGROUND AND AIMS: Sexually transmitted infections (STIs) are a significant global public health challenge due to their high incidence rate and potential for severe consequences when early intervention is neglected. Research shows an upward trend in absolute cases and DALY numbers of STIs, with syphilis, chlamydia, trichomoniasis, and genital herpes exhibiting an increasing trend in age-standardized rate (ASR) from 2010 to 2019. Machine learning (ML) presents significant advantages in disease prediction, with several studies exploring its potential for STI prediction. The objective of this study is to build males-based and females-based STI risk prediction models based on the CatBoost algorithm using data from the National Health and Nutrition Examination Survey (NHANES) for training and validation, with sub-group analysis performed on each STI. The female sub-group also includes human papilloma virus (HPV) infection. METHODS: The study utilized data from the National Health and Nutrition Examination Survey (NHANES) program to build males-based and females-based STI risk prediction models using the CatBoost algorithm. Data was collected from 12,053 participants aged 18 to 59 years old, with general demographic characteristics and sexual behavior questionnaire responses included as features. The Adaptive Synthetic Sampling Approach (ADASYN) algorithm was used to address data imbalance, and 15 machine learning algorithms were evaluated before ultimately selecting the CatBoost algorithm. The SHAP method was employed to enhance interpretability by identifying feature importance in the model's STIs risk prediction. RESULTS: The CatBoost classifier achieved AUC values of 0.9995, 0.9948, 0.9923, and 0.9996 and 0.9769 for predicting chlamydia, genital herpes, genital warts, gonorrhea, and overall STIs infections among males. The CatBoost classifier achieved AUC values of 0.9971, 0.972, 0.9765, 1, 0.9485 and 0.8819 for predicting chlamydia, genital herpes, genital warts, gonorrhea, HPV and overall STIs infections among females. The characteristics of having sex with new partner/year, times having sex without condom/year, and the number of female vaginal sex partners/lifetime have been identified as the top three significant predictors for the overall risk of male STIs. Similarly, ever having anal sex with a man, age and the number of male vaginal sex partners/lifetime have been identified as the top three significant predictors for the overall risk of female STIs. CONCLUSIONS: This study demonstrated the effectiveness of the CatBoost classifier in predicting STI risks among both male and female populations. The SHAP algorithm revealed key predictors for each infection, highlighting consistent demographic characteristics and sexual behaviors across different STIs. These insights can guide targeted prevention strategies and interventions to alleviate the impact of STIs on public health.

Strengthening the relationship between intractable plantar keratosis and human papillomavirus.

The aim of the study was to determine the presence of human papillomavirus (HPV) in patients with intractable plantar keratosis (IPK) by comparing the histopathological findings of biopsies. A prospective, observational, and concordance study was carried out. Three different specimens were taken from each IPK. A first punch was sent for histopathological examination, and a second punch and a superficial skin scraping were both sent for HPV  polymerase chain reaction (PCR) and type determination. A total of 51 patients were included. From the histopathological examination, it was determined that 35 (68.6%) samples were diagnosed as warts and 16 (31.3%) as keratosis. However, the presence of HPV was confirmed by PCR in 49 (96.1%) and in 42 (82.4%) samples obtained by punch and superficial scraping, respectively. In the 49 PCR-positive samples, the most common HPV types were HPV1, HPV2, HPV27, HPV57, and HPV65, accounting for 81.6% of the samples. In conclusion, this study demonstrates that HPV infection and IPK lesions are very closely related. Although we cannot confirm that HPV is the cause of the development of IPK, the high prevalence of HPV observed in these lesions calls for a change to the procedures for managing IPK.

The expression and significance of PD-L1 in condyloma acuminatum.

BACKGROUND: It has been reported that programmed death-ligand 1 (PD-L1) is highly expressed in cells during viral infection, which helps the virus escape host immunity. However, the relationship between human papillomavirus (HPV) and PD-L1 in condyloma acuminatum and whether they participate in immunosuppression have not been reported. In this paper, we aimed to explore the expression and significance of PD-L1 in condyloma acuminatum. METHODS: The expression of PD-L1 in the wart of condyloma acuminatum patients and the foreskin of healthy individuals was evaluated. Lentivirus transfection was used to introduce the HPV11-E7 gene into HaCaT cells to investigate whether HPV infection could affect the expression of PD-L1. The successfully constructed HPV11-E7 HaCaT cells were cocultured with Jurkat cells, and Jurkat cell apoptosis and proliferation as well as the Jurkat cell cycle were evaluated by flow cytometry and cell counting kit-8 (CCK-8) assays. RESULTS: PD-L1 was highly expressed in keratinocytes of genital warts. Through the construction of a cell model, we found that HPV11-E7 could upregulate the expression of PD-L1 in HaCaT cells. Furthermore, HPV11-E7 HaCaT cells can promote the apoptosis of Jurkat cells, inhibit the proliferation of Jurkat cells and mediate the cell cycle arrest of Jurkat cells through the PD-1/PD-L1 signalling pathway. CONCLUSIONS: HPV infection may upregulate PD-L1 expression in the keratinocytes of genital warts and participate in the inhibition of local T-cell function.

Application of cantharidin, retinoic acid cream and salicylic acidy in multiple palmoplantar warts.

OBJECTIVE: Multiple palmoplantar warts, caused by human papillomavirus (HPV) infection, were investigated for clinical efficacy using cantharidin, retinoic acid cream, and salicylic acid cream. METHODS: A total of 110 patients with multiple palmoplantar warts were enrolled. The experimental group (54 cases) received a 1:1:1 combination (CRS) of 0.25% cantharidin, 0.1% retinoic acid cream, and 5% salicylic acid, applied with pressurized encapsulation for 8 h every night, three times per week. The control group (56 cases) underwent conventional liquid nitrogen freezing. Monthly follow-ups assessed cure rate, effective rate, dermatological life quality index (DLQI), visual analog scale (VAS), and cost, with evaluations conducted after 3 months. RESULTS: The treatment group exhibited a cure rate of 85.19% and a total effective rate of 96.30%, surpassing the control group with rates of 39.29% and 51.79%, respectively (p < 0.05). The treatment group's DLQI score (1.84 ± 1.06) was significantly lower than the control group's score (6.04 ± 1.78) (p = 0.0005). Additionally, the treatment group's VAS score (1.84 ± 1.06) was notably lower than the control group's score (8.56 ± 1.07) (p < 0.0001). The treatment group's total cost (43.20 ± 2.85) was markedly lower than the control group's cost (206.38 ± 90.81), with a statistically significant difference (p < 0.0001). CONCLUSION: The combination of cantharidin, retinoic acid cream, and salicylic acid with local encapsulation is a safe, effective, economical, and convenient treatment method for multiple palmoplantar warts, exhibiting few side effects and showing promise.