Cantharidin (1%), podophyllin (5%), and salicylic acid (30%) formulation in recalcitrant plantar warts: Analysis of 48 patients.

A plantar wart is a benign hyperplasia that appears on the feet due to the human papillomavirus (HPV). One method used for the treatment of recalcitrant plantar warts, those lasting over 2 years or persisting after at least two treatment attempts, is the cantharidin (1%), podophyllin (5%), and salicylic acid (30%) formulation, also known as the CPS formulation. Although this method is in use, there are few studies on it. This study's objective was to ascertain its cure rate. For this retrospective observational study, we reviewed the medical records of patients treated with the CPS formulation at a podiatric clinic specializing in plantar wart treatment. Our sample size was 48 subjects. The CPS formulation had a cure rate of 62.5%. Out of the cured patients, 86.67% (26/30) required one or two applications. There was no observable correlation (p > 0.05) between wart resolution and virus biotype, evolution time, patient's morphological and clinical attributes, location, number of warts, or preceding treatments. The CPS formulation presents a relatively high efficacy rate for treating recalcitrant HPV plantar warts. Still, additional studies are necessary to evaluate its safety and efficiency.

Increased Susceptibility of WHIM Mice to Papillomavirus-induced Disease is Dependent upon Immune Cell Dysfunction.

Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) syndrome is a rare primary immunodeficiency disease in humans caused by a gain of function in CXCR4, mostly due to inherited heterozygous mutations in CXCR4. One major clinical symptom of WHIM patients is their high susceptibility to human papillomavirus (HPV) induced disease, such as warts. Persistent high risk HPV infections cause 5% of all human cancers, including cervical, anogenital, head and neck and some skin cancers. WHIM mice bearing the same mutation identified in WHIM patients were created to study the underlying causes for the symptoms manifest in patients suffering from the WHIM syndrome. Using murine papillomavirus (MmuPV1) as an infection model in mice for HPV-induced disease, we demonstrate that WHIM mice are more susceptible to MmuPV1-induced warts (papillomas) compared to wild type mice. Namely, the incidence of papillomas is higher in WHIM mice compared to wild type mice when mice are exposed to low doses of MmuPV1. MmuPV1 infection facilitated both myeloid and lymphoid cell mobilization in the blood of wild type mice but not in WHIM mice. Higher incidence and larger size of papillomas in WHIM mice correlated with lower abundance of infiltrating T cells within the papillomas. Finally, we demonstrate that transplantation of bone marrow from wild type mice into WHIM mice normalized the incidence and size of papillomas, consistent with the WHIM mutation in hematopoietic cells contributing to higher susceptibility of WHIM mice to MmuPV1-induced disease. Our results provide evidence that MmuPV1 infection in WHIM mice is a powerful preclinical infectious model to investigate treatment options for alleviating papillomavirus infections in WHIM syndrome.

Biomolecular Dynamics of Nitric Oxide Metabolites and HIF1α in HPV Infection.

INTRODUCTION: Viral infections cause oxygen deprivation, leading to hypoxia or anoxia in certain tissues. The limitation of mitochondrial respiration is one of the major events during hypoxia that induces alternative metabolic activities and increased levels of certain biomolecules such as nitric oxide (NO) metabolites. In this study, we aimed to investigate the role of NO metabolites and hypoxia in HPV infection. MATERIALS AND METHODS: We included 36 patients with palmoplantar warts and 36 healthy subjects and performed serum determinations of NO metabolites (direct nitrite, total nitrite, nitrate, and 3-nitrotyrosine) and HIF1α, a marker of hypoxia. RESULTS: We found elevated serum levels in NO metabolites and HIF1α, and decreased direct nitrite/nitrate ratios in patients with warts versus controls. Additionally, we identified statistically significant positive correlations between NO metabolites and HIF1α levels, except for 3-nitrotyrosine. CONCLUSIONS: Our findings show that HPV infection causes hypoxia and alterations in NO metabolism and suggest a link between wart development and cellular stress. Our research could provide new insights for a comprehensive understanding of the pathogenesis of cutaneous HPV infections.

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.

Treatment of Plantar Warts with a Nitric-Zinc Complex Solution: A Review of 72 Cases.

BACKGROUND: There are multiple conservative treatment options for plantar warts, but none have proven to be universally effective. Nitric acid is often used empirically by podiatrists in the treatment of plantar warts. A novel medical device or topical solution of nitric-zinc complex solution (NZCS) could potentially offer an effective and safe alternative for the targeted treatment of plantar warts. OBJECTIVE: To observe the rate of complete healing of NZCS in a series of plantar wart cases and to establish the minimum number of product applications and time needed for healing. This will help standardize and protocolize its use. METHODS: A descriptive study was conducted involving 72 patients who exhibited symptoms of plantar warts. These patients underwent chemical treatment using a nitric-zinc complex. RESULTS: The cure rate with NZCS was 59.2%. The average number of NZCS applications was 5.9 ± 3.0 and the mean duration of treatment was 9.4 ± 7.1 weeks. A recurrence rate of 6.7% was observed. CONCLUSIONS: The topical solution of the nitric-zinc complex is an effective treatment for plantar warts, which can be considered a first-line treatment option in the general population.

From thinning to disappearance: A case report on the healing pattern of multiple and giant plantar warts.

RATIONALE: Plantar warts, caused by human papillomavirus (HPV) infection, are a common skin condition on the plantar surface. Despite the availability of various treatments, achieving satisfactory outcomes remains elusive. This study explores a novel therapeutic approach combining traditional Chinese medicine (TCM) soaking therapy with cryotherapy to address this challenge. PATIENTS CONCERNS: This study focuses on 3 patients who presented with multiple and giant plantar warts, each with a disease duration exceeding 2 years. These patients had undergone numerous unsuccessful cryotherapy treatments, leaving them with persistent and troublesome warts. DIAGNOSES: All 3 patients were diagnosed with multiple and giant plantar warts caused by HPV infection. INTERVENTIONS: Following unsuccessful cryotherapies, the patients were administered TCM soaking therapy as an adjunct treatment. OUTCOMES: Remarkably, all 3 patients achieved complete remission of their plantar warts within 2 to 4 months after combining cryotherapy with TCM soaking therapy. LESSONS: Our findings suggest that relying solely on cryotherapy is insufficient for effectively treating plantar warts. The key to successful treatment lies in inhibiting wart proliferation and continuously thinning them, which can be achieved through soaking in TCM. This study demonstrates the potential of combining cryotherapy with TCM soaking as a novel and effective therapeutic approach for treating multiple and giant plantar warts.

Unexpected diagnosis of WHIM syndrome in refractory autoimmune cytopenia.

ABSTRACT: WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome is a rare primary immunodeficiency predominantly caused by heterozygous gain-of-function mutations in the C-terminus of the gene CXCR4. These CXCR4 variants display impaired receptor trafficking with persistence of the CXCR4 receptor on the surface, resulting in hyperactive downstream signaling after CXCL12 stimulation. In turn, this results in defective lymphoid differentiation, and reduced blood neutrophil and lymphocyte numbers. Here, we report a CXCR4 mutation that in 2 members of a kindred, led to life-long autoimmunity and lymphoid hypertrophy as the primary clinical manifestations of WHIM syndrome. We examine the functional effects of this mutation, and how these have affected phosphorylation, activation, and receptor internalization.

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.

Mavorixafor: First Approval.

Mavorixafor (XOLREMDI™) is an oral, selective C-X-C chemokine receptor 4 (CXCR4) antagonist developed by X4 Pharmaceuticals that blocks the binding of C-X-C chemokine ligand 12 (also known as stromal derived factor-1) to CXCR4. In April 2024, it became the first therapy to be approved for WHIM syndrome (named by an acronym for its observed characteristics of Warts, Hypogammaglobulinaemia, Infections and Myelokathexis) in the USA, where it is indicated for use in patients aged ≥ 12 years with WHIM syndrome to increase the number of circulating mature neutrophils and lymphocytes. Clinical development of mavorixafor is ongoing for chronic neutropenic disorders. This article summarizes the milestones in the development of mavorixafor leading to this first approval for use in patients aged ≥ 12 years with WHIM syndrome to increase the number of circulating mature neutrophils and lymphocytes.

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.

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.

[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.

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.

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.

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.