Association of vitamin D with risk of warts: A retrospective and Mendelian randomization study.

BACKGROUND: The clinical strategy of oral supplementation of Vitamin D (VD) as a preventive and therapeutic measure for warts needs further exploration. METHODS: The clinical data of patients with skin diseases who visited the Children's Hospital affiliated with Chongqing Medical University from February 2018 to June 2024 were collected. The serum VD levels in patients with warts (common warts, flat warts, and plantar warts) and patients with other common skin diseases (atopic dermatitis, psoriasis, alopecia areata, vitiligo, and chronic urticaria) were compared. Two-sample bidirectional Mendelian randomization (MR) analysis was performed to investigate potential causal associations between VD and warts. RESULTS: The average serum VD level of children with warts was 23.27 ± 7.07 ng/mL, which showed no statistically significant difference compared to children with other common skin diseases. The inverse variance weighted (IVW) method analysis indicated a positive causal relationship between VD and warts (Odds Ratio [OR] = 1.86, [95% CI: 1.19-2.92], p = 0.007). Sensitivity analysis did not show any indication of horizontal pleiotropy or heterogeneity. The MR-PRESSO method did not identify any outliers. CONCLUSION: The levels of serum VD in children with warts do not significantly decrease compared to children with other common skin conditions. The evidence from the MR analysis indicates a positive causal relationship between VD and warts, suggesting caution in supplementing VD for children with warts who have normal or elevated serum VD levels. Further clinical studies are needed for validation in the future.

The complex nature of CXCR4 mutations in WHIM syndrome.

Heterozygous autosomal dominant mutations in the CXCR4 gene cause WHIM syndrome, a severe combined immunodeficiency disorder. The mutations primarily affect the C-terminal region of the CXCR4 chemokine receptor, specifically several potential phosphorylation sites critical for agonist (CXCL12)-mediated receptor internalization and desensitization. Mutant receptors have a prolonged residence time on the cell surface, leading to hyperactive signaling that is responsible for some of the symptoms of WHIM syndrome. Recent studies have shown that the situation is more complex than originally thought, as mutant WHIM receptors and CXCR4 exhibit different dynamics at the cell membrane, which also influences their respective cellular functions. This review examines the functional mechanisms of CXCR4 and the impact of WHIM mutations in both physiological and pathological conditions.

Expanding CXCR4 variant landscape in WHIM syndrome: integrating clinical and functional data for variant interpretation.

Warts, Hypogammaglobulinemia, Infections, Myelokathexis (WHIM) syndrome is a rare, combined immunodeficiency disease predominantly caused by gain-of-function variants in the CXCR4 gene that typically results in truncation of the carboxyl terminus of C-X-C chemokine receptor type 4 (CXCR4) leading to impaired leukocyte egress from bone marrow to peripheral blood. Diagnosis of WHIM syndrome continues to be challenging and is often made through clinical observations and/or genetic testing. Detection of a pathogenic CXCR4 variant in an affected individual supports the diagnosis of WHIM syndrome but relies on an appropriate annotation of disease-causing variants. Understanding the genotypic-phenotypic associations in WHIM syndrome has the potential to improve time to diagnosis and guide appropriate clinical management, resulting in a true example of precision medicine. This article provides an overview of the spectrum of CXCR4 variants in WHIM syndrome and summarizes the various lines of clinical and functional evidence that can support interpretation of newly identified variants.

Successfully treated with siltuximab and prednisone in a 7-year-old girl with DOCK8-deficiency presenting as recurrent wart-like lesions: a case report.

Dedicator of cytokinesis 8 (DOCK8) deficiency represents a primary immunodeficiency with a wide range of clinical symptoms, including recurrent infections, atopy, and increased malignancy risk. This study presents a case of a 6-year-old girl with DOCK8 deficiency, characterized by severe, treatment-resistant herpetic infections who was successfully treated with siltuximab and glucocorticoids. The successful use of siltuximab in achieving remission highlights the pivotal role of interleukin-6 (IL-6) in DOCK8 deficiency pathogenesis and suggests that IL-6 modulation can be critical in managing DOCK8 deficiency-related viral infections, which may inform future therapeutic strategies for DOCK8 deficiency and similar immunodeficiencies.

Deep learning-assisted multispectral imaging for early screening of skin diseases.

INTRODUCTION: Melanocytic nevi (MN), warts, seborrheic keratoses (SK), and psoriasis are four common types of skin surface lesions that typically require dermatoscopic examination for definitive diagnosis in clinical dermatology settings. This process is labor-intensive and resource-consuming. Traditional methods for diagnosing skin lesions rely heavily on the subjective judgment of dermatologists, leading to issues in diagnostic accuracy and prolonged detection times. OBJECTIVES: This study aims to introduce a multispectral imaging (MSI)-based method for the early screening and detection of skin surface lesions. By capturing image data at multiple wavelengths, MSI can detect subtle spectral variations in tissues, significantly enhancing the differentiation of various skin conditions. METHODS: The proposed method utilizes a pixel-level mosaic imaging spectrometer to capture multispectral images of lesions, followed by reflectance calibration and standardization. Regions of interest were manually extracted, and the spectral data were subsequently exported for analysis. An improved one-dimensional convolutional neural network is then employed to train and classify the data. RESULTS: The new method achieves an accuracy of 96.82 % on the test set, demonstrating its efficacy. CONCLUSION: This multispectral imaging approach provides a non-contact and non-invasive method for early screening, effectively addressing the subjective identification of lesions by dermatologists and the prolonged detection times associated with conventional methods. It offers enhanced diagnostic accuracy for a variety of skin lesions, suggesting new avenues for dermatological diagnostics.

Intralesional acyclovir versus intralesional Hepatitis-B vaccine in treatment of resistant plantar warts: a randomized controlled trial.

Treating plantar warts is still a challenging problem with a long list of diverse treatment options that none of them seems to be definitive. To evaluate the effectiveness of intralesional acyclovir versus intralesional Hepatitis-B vaccine (HBV) in treatment of multiple resistant plantar warts. Forty-eight patients with resistant plantar warts completed the study with no dropouts. They were randomized into 3 groups; group(A) receiving intralesional HBV, group (B) receiving intralesional acyclovir and group (C) receiving intralesional saline as a control group over 5 biweekly sessions or until wart clearance. Clinical outcome was assessed through sequential digital lesion photographing upon each visit. Treatment related adverse reactions were recorded. 43.8%, 37.5% & 18.7% of Groups A, B &C respectively showed a complete response. pain was obvious in 100% and 56.3% of cases receiving intralesional acyclovir and HBV respectively. Up to the 6 month follow up period, none of the complete responders in all groups returned with a recurrence. Both acyclovir and HBV showed comparable efficacy and seem to be promising options for treating plantar warts being safe, affordable, and theoretically safe in immunocompromised cases.

Intralesional combined digoxin and furosemide versus intralesional 5-flurouracil for the treatment of recalcitrant plantar warts: a prospective, randomized study.

There are many therapeutic modalities for plantar warts, however treating it remains challenging. Intralesional injection of 5-fluorouarcil and combined digoxin and furosemide were observed to be effective and safe, however no comparison study between them was done. Our study was conducted to evaluate the efficacy of both therapies in the treatment of plantar warts. 90 adult patients with multiple recalcitrant plantar warts were included in our study. They were randomly allocated to one of three groups; combined digoxin and furosemide, 5-fluorouarcil, or normal saline group. Fortnightly injections were done into all studied warts till complete clearance or up to 5 sessions. Warts were evaluated clinically and dermoscopically. Clinical response was reported in 24 patients (80%) of the combined digoxin and furosemide group with 40% complete response and in 24 patients (80%) of the 5-fluorouarcil group with 33.3% complete response. No statistically significant difference was observed between the two groups concerning efficacy and safety. Intralesional injection of 5-fluorouarcil and combined digoxin and furosemide are nearly equivalent in efficacy and safety for plantar wart treatment. Dermoscopy helps to take the truthful judgment about complete clearance of warts.

[Multiple verruca plantaris treated with modified fire-needle technique and herbal bathing-repairing therapy of TCM: a randomized controlled trial].

OBJECTIVE: To observe the clinical effect of modified fire-needle technique and herbal bathing-repairing therapy of TCM on multiple verruca plantaris. METHODS: Seventy patients with multiple verruca plantaris were randomly divided into an observation group (35 cases, 1 case was eliminated) and a control group (35 cases, 2 cases dropped out). In the control group, the herbal bathing-repairing therapy of TCM was adopted. In the observation group, besides the treatment as the control group, fire needling and cauterization were delivered on the base of skin lesion or the sites with rich blood vessels under the dermoscope. The intervention was provided once a week, one course of treatment was composed of 3 weeks, and two courses were required in each group. The score of the self-designed symptom scale, the score of dermatology life quality index (DLQI) and the area of typical skin lesion were observed before and after treatment. The clinical effect was evaluated after treatment and the recurrence was assessed 2 months after treatment completion in the two groups. RESULTS: After treatment, the scores of the self-designed symptom scale and DLQI were lower and the area of typical skin lesion was smaller compared with those before treatment in the two groups (P<0.05). The scores of the self-designed symptom score and DLQI in the observation group were reduced (P<0.05), and the area of typical lesion was smaller (P<0.05) in comparison with those in the control group. The total effective rate was 91.2% (31/34) in the observation group, higher than that in the control group (60.6%, 20/33, P<0.05). The recurrence rate was 6.5% (2/31) in the observation group, lower than that in the control group (35.0%, 7/20, P<0.05). CONCLUSION: Modified fire-needle technique combined with herbal bathing-repairing therapy ameliorates clinical symptoms and the quality of life in the patients with multiple verruca plantaris and reduces the recurrence of the disease.

Strong association of TLR2 and TLR3 polymorphisms with keratoacanthoma and common warts: a case-control study.

AIM: To determine variations in allele and genotype frequencies between keratoacanthoma (KA) and common warts (CW), compared with the control group, in three single nucleotide polymorphisms (SNPs) within the TLR2, TLR3, and TLR9 genes. METHODS: This case-control study involved samples from 161 patients with KA, 152 patients with CW, and 469 controls. DNA was isolated from formalin-fixed paraffin-embedded tissue sections. Three SNPs - rs4696480 in TLR2, rs7657186 in TLR9, and rs35213 in TLR3 - were genotyped with TaqMan Genotyping Assays on the 7500 Real-Time PCR System. RESULTS: TLR2 rs4696480 and TLR3 rs7657186 were significantly overrepresented in KA and CW compared with controls (P<0.001). The association was stronger for CW than for KA, as evidenced by higher frequencies of the A allele and AA genotype for rs4696480. Both KA and CW patients had higher frequencies of the G allele and GG genotype for rs7657186 than controls. rs7657186 was moderately associated with KA and CW, with the G allele and GG genotype being more prevalent in CW cases, where no AA homozygotes were found. CONCLUSION: Genetic variants in TLR2 (rs4696480) and TLR3 (rs7657186) genes may affect KA and CW development, influencing immune responses and susceptibility to these skin lesions. Further research is required to elucidate TLR expression patterns and their role in KA development.

Common Skin Conditions in Children and Adolescents: Nonbacterial Infections.

Tinea infections are caused by dermatophytes, except for tinea versicolor, which is caused by yeasts in the Malassezia genus. If available, potassium hydroxide preparation should be performed to confirm diagnosis of tinea capitis or onychomycosis. In some cases, fungal culture, UV light examination, or periodic acid-Schiff stain can be helpful. Topical drugs are effective for tinea corporis, tinea cruris, and tinea pedis. Tinea incognito is an atypical presentation that usually requires systemic treatment. Management of tinea capitis always requires oral drugs. Oral drugs are preferred for onychomycosis treatment but should not be prescribed without confirmation of fungal infection. Localized cases of tinea versicolor can be managed with topical drugs, but oral drugs might be needed for severe, widespread, or recurrent cases. Warts are superficial human papillomavirus infections. Common treatments include irritant, destructive (eg, cryotherapy), immune stimulant (eg, intralesional Candida antigen), and debridement and excision methods. Scabies infestation results in intensely itchy papules, nodules, or vesicles. Mites and burrows on the skin are pathognomonic but difficult to identify. Dermoscopy, particularly with UV light, can make identification easier. Topical permethrin and oral ivermectin are two of the most commonly used treatments. All household and close contacts should be treated regardless of the presence or absence of symptoms.

Safety and efficacy of intralesional polidocanol sclerotherapy in the treatment of plantar warts: a pilot study.

Plantar warts are common skin lesions that continue to represent a therapeutic challenge. They are still resistant to therapy and are highly recurrent, despite the diverse number of treatments available. Therapies targeting vasculature, such as pulsed dye laser, have been used successfully in the treatment of plantar warts. Polidocanol, a detergent sclerosant approved for the sclerotherapy of incompetent and dilated saphenous veins, has also been used as an off-label therapy for a wide range of skin conditions with vascular components such as hemangiomas and pyogenic granuloma. The current, open-label, prospective, pilot study aimed to evaluate the safety and efficacy of the intralesional polidocanol 3% in the treatment of plantar warts. Twenty patients (11 females and 9 males), with plantar warts, aged 12-50 years received biweekly sessions of intralesional polidocanol 3% until complete clearance or for a maximum of 6 sessions. Response to treatment was graded as complete (100% clearance), partial (50-99%), and no response (< 50%). At the end of the study, 12 (60%) patients achieved complete clearance of their warts after 1-5 sessions, 5 (25%) patients had only partial response, and 3 (15%) patients did not achieve any clearance of their warts. The procedure was largely tolerable by patients. Pain at the injection site and bruises were reported by 9 (45%) and 2 (10%) patients, respectively. Both side effects resolved spontaneously and completely within a few days. The findings of the current study suggest that intralesional injection of 3% polidocanol in biweekly sessions may be a safe, effective, and tolerable method for the treatment of plantar warts.

Verrucous carcinoma presenting as recalcitrant verruca plantaris.

Verrucous carcinoma (VC) is a rare, low-grade variant of well-differentiated squamous cell carcinoma. Plantar verrucous carcinoma presents as a slow-growing, exophytic, verrucous plaque on weight bearing areas of the foot. Verrucous carcinomas have low metastatic potential, but are high risk for local invasion. We describe a patient with a 20-year history of a slowly growing, ulcerated, verrucous plaque on the sole of the left foot that was erroneously treated for years as verruca plantaris and was eventually diagnosed as invasive verrucous carcinoma. Verrucous carcinomas are a diagnostic challenge due to clinical and histopathologic mimicry of benign lesions. Mohs micrographic surgery should be employed to allow the ability to intraoperatively assess tumor margins while excising the minimal amount of necessary tissue. It is important for clinicians to recognize the characteristics and accurately diagnose verrucous carcinomas. Delays in treatment may require more extensive dissection or amputation.

A phase 3 randomized trial of mavorixafor, a CXCR4 antagonist, for WHIM syndrome.

ABSTRACT: We investigated efficacy and safety of mavorixafor, an oral CXCR4 antagonist, in participants with warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome, a rare immunodeficiency caused by CXCR4 gain-of-function variants. This randomized (1:1), double-blind, placebo-controlled, phase 3 trial enrolled participants aged ≥12 years with WHIM syndrome and absolute neutrophil count (ANC) ≤0.4 × 103/µL. Participants received once-daily mavorixafor or placebo for 52 weeks. The primary end point was time (hours) above ANC threshold ≥0.5 × 103/µL (TATANC; over 24 hours). Secondary end points included TAT absolute lymphocyte count ≥1.0 × 103/µL (TATALC; over 24 hours); absolute changes in white blood cell (WBC), ANC, and absolute lymphocyte count (ALC) from baseline; annualized infection rate; infection duration; and total infection score (combined infection number/severity). In 31 participants (mavorixafor, n = 14; placebo, n = 17), mavorixafor least squares (LS) mean TATANC was 15.0 hours and 2.8 hours for placebo (P < .001). Mavorixafor LS mean TATALC was 15.8 hours and 4.6 hours for placebo (P < .001). Annualized infection rates were 60% lower with mavorixafor vs placebo (LS mean 1.7 vs 4.2; nominal P = .007), and total infection scores were 40% lower (7.4 [95% confidence interval [CI], 1.6-13.2] vs 12.3 [95% CI, 7.2-17.3]). Treatment with mavorixafor reduced infection frequency, severity, duration, and antibiotic use. No discontinuations occurred due to treatment-emergent adverse events (TEAEs); no related serious TEAEs were observed. Overall, mavorixafor treatment demonstrated significant increases in LS mean TATANC and TATALC, reduced infection frequency, severity/duration, and was well tolerated. The trial was registered at www.clinicaltrials.gov as #NCT03995108.