Warts

Background: * WHIMS (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis Syndrome) is caused by various genetic changes that increase the activity of the chemokine receptor, CXCR4. Excessive function of this receptor causes mature neutrophils (part of the white blood cells) to be retained within the bone marrow rather than being released to the blood and is one of the causes of severe inherited neutropenia (low white blood counts). In neutropenia, the body is less able to fight off infection. Patients with WHIMS usually are at risk for skin, soft tissue, sinus, and lung infections, which can result in loss of hearing, teeth, and lung function. * Current treatment for WHIMS consists of regular injections of a white blood cell growth stimulating medication called granulocyte colony stimulating factor (G-CSF), and supplemental immunoglobulin (antibody). These therapies are expensive, nonspecific, have significant side effects and toxicities, and do not fully correct all problems, especially warts and cancers related to human papillomavirus (HPV). * A drug called Mozobil has been approved for use in combination with G-CSF to increase the number of stem cells that can be collected prior to bone marrow transplantation. Mozobil may offer a specific and well-tolerated new treatment for WHIMS and other syndromes characterized by neutropenia. Objectives: * To evaluate whether Mozobil is safe and effective to treat neutropenia (low white blood cell count) in patients with WHIMS. * To determine an appropriate treatment dose of Mozobil, within currently approved dosage levels. Eligibility: \- Individuals between 18 and 75 years of age who have been diagnosed with WHIMS and have a history of severe infections. Design: * Potential participants will undergo a screening with a medical history, physical examination, questionnaire, heart and lung function scans, and blood and urine samples. Tests will also be done for hepatitis B and C virus, and human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS), as well as to check neutrophil function. * Patients who are being treated with G-CSF will stop injections for 2 days before being admitted to the National Institutes of Health (NIH) Clinical Center. * Patients may participate in a Dose Escalation study and receive increasing doses of Mozobil over 5 days of treatment until their white blood cell count improves sufficiently or the maximum approved dose is reached. Blood samples will be taken regularly throughout the treatment process. Patients will then receive an additional dose of Mozobil at the maximum approved dose or the dose sufficient to cause improvement, before restarting the G-CSF injections. * Patients may also participate in a long-term Chronic Dosing study and receive Mozobil once or twice a day for up to a maximum of 60 months.

Background: * Idiopathic CD4+ lymphocytopenia (ICL) is a condition in which there is a decreased level of CD4+ lymphocytes (a type of white blood cell), which can lead to opportunistic infections or autoimmune disorders and diseases. Objectives: * To characterize the natural history with regard to CD4+ T cell count and onset of infection, malignancy, and autoimmunity. * To describe the immunological status of patients affected by ICL while providing the best possible standard therapy to eradicate opportunistic infections. * To establish the timeline of CD4 lymphocytopenia, with particular focus on defining subgroups of patients according to the decline, stabilization, or rise of CD4+ T cell counts over time. * To characterize the opportunistic infections that occur in ICL patients at microbiologic and molecular levels. * To characterize the immunophenotype and possible genetic immunodeficiency causes of ICL. * To determine whether measurable immunologic parameters correlate with the development of opportunistic infections or other comorbidities such as lymphoma in patients with ICL. * To determine whether there is any association between ICL and autoimmunity. * To determine CD4+ T cell turnover, survival, functionality, and cytokine responsiveness in ICL patients. Eligibility: * Patients 2 years of age and older with an absolute CD4 count less than 300 in children 6 years or older and adults or less than 20% of T cells in children younger than 6 on two occasions at least 6 weeks apart. * Patients with negative results of HIV testing by ELISA, Western Blot, and viral load. * Patients must not have underlying immunodeficiency conditions, be receiving cytotoxic chemotherapy (anti-cancer drugs that kill cells), or have cancer. Design: * At the initial visit to the National Institutes of Health, the following evaluations will be conducted: * Personal and family medical histories. * Physical examination, including rheumatology evaluation and other consultations as medically indicated (e.g., dermatology, pulmonology, ophthalmology, imaging studies). * Blood samples for analysis of red and white blood cell counts, liver function, immune hormones, and antibody and autoantibody levels, white blood cell growth and function, and DNA. * Urinalysis and urine pregnancy testing for female patients of childbearing age. * Evaluation and treatment of active infections as medically indicated, including biopsies, buccal swabs, pulmonary function tests, and imaging studies. * Follow-up visits will take place approximately every 12 months or more frequently if indicated, and will continue for a minimum of 4 years and a maximum of 10 years. * Evaluations at follow-up will include blood samples (i.e., CBC with differential, biochemical profile, HIV testing, etc.) and urinalysis and rheumatology consults.

This is a Phase 3, double-blind, randomized, vehicle-controlled study (Study number VP-CW-302; referred to as COVE-3 \[Cantharidin and Occlusion in Verruca Epithelium\]) to evaluate the efficacy and safety of YCANTH (VP-102/TO-208) treatment in subjects with common warts.

People who participated in either the COVE-2 or COVE-3 study for common warts, may be eligible to enroll into this Long Term Follow Up (LTFU) study COVE-4. The main question(s) to answer in this LTFU study are: * To assess the safety of YCANTH (also known as VP-102 in the United Sates or TO-208 in Japan) by assessing concomitant medication use, and adverse events (AEs), including expected local skin reactions (LSRs). * To evaluate the efficacy of continued skin application of YCANTH (VP-102/TO-208) when applied to each common wart once every 21 days for a maximum of 4 additional treatments. Participants with eligible common warts present will receive YCANTH (VP-102/TO-208) with an interval of 21 (± 4) days between applications until there is a wart count of zero (ie, completed clearance has been achieved) or a maximum of 4 additional treatments. Participants with complete clearance will attend Observation Visits at intervals of 42 (± 4) days without treatment. Participants who develop a new wart after having a wart count of zero will resume Treatment Visits every 21 (± 4) days for a maximum of 4 additional treatments. All subjects will attend visits until the End-of-Study (EOS) Visit, which is on Day 378 (0/+ 8 days). If participants still have warts present after 4 additional treatments of YCANTH (VP-102/TO-208) the wart(s) will be discontinued from study and participants will be allowed to seek treatment but should be limited to destructive therapy such as cryosurgery and warts cannot be within 10 mm of any warts that receive(d) study drug treatment . The exact interval of Treatment Visits will be determined by evaluation of the treatment site, taking into account any ongoing local skin reactions (LSRs), which are defined as temporary application site: vesiculation, pain, pruritus, scabbing, erythema, discoloration, dryness, edema and erosion that is expected and consistent with historical treatment with YCANTH (VP-102/TO-208). Participants may receive treatment until all treatable common warts are clear, up to a maximum of 4 treatment sessions, or until Day 357, whichever occurs first. Treatment: For participants with warts present at the time of study entry, the first treatment application may occur on the same day as transition from the parent study. All required parent study assessments must be complete, including the final evaluation of response to treatment (ERT; as defined in Assessments and procedures). In addition, eligibility for participation in the LTFU study must have been determined, and informed consent/assent for participation in this LTFU study obtained. YCANTH (VP-102/TO-208) will be applied by the Investigator or qualified member of the research team to treatable common warts, including an approximate 1 to 2 mm margin of healthy, surrounding skin. After YCANTH (VP-102/TO- 208) is applied, warts are to be covered with occlusive tape (occlusive tape with similar properties should be used across all clinical sites) that will remain in place overnight and should be removed 24 hours after application of study drug and just before a 24-hour ERT. Before application of study drug, wart paring, if necessary, will be completed with a sharp surgical instrument (eg, scalpel or flexible medical blade) to remove any adherent thick scale from a treatable common wart. Wart paring is required to be performed at any treatment visit when adherent thick scale is present, and the Investigator feels paring can be safely performed. Paring should be conducted by a trained practitioner and in compliance with any local regulations and should be discontinued if it results in punctate bleeding or significant pain. Not all treatable common warts may require paring. If adherent scale is not present, study drug can be applied without paring. The assessment for complete clearance may be made once all treatable common warts are evaluable and not obscured by an ongoing LSR. If the Investigator is unable to evaluate or treat 1 or more warts due to ongoing LSRs, no warts should be treated, and the visit will be documented as an Unscheduled Visit. The timing of the next treatment visit will be determined by resolution of the LSRs. The research team will be in contact with the Participant until all LSRs are resolved. Once LSRs have resolved, a Treatment Visit will be scheduled within 21 (± 4) days of the previous treatment application, noting it may be longer than 21 (± 4) days depending on the length of time until LSR resolution. All treatable common warts that are not completely clear should undergo treatment with study drug. Study duration from Days 84, 105, or 147 of the parent study (COVE-2 or COVE-3) through the final EOS visit of this LTFU study (Day 378) is approximately 294 days.

Hyperthermia treatment (hyperthermia) refers to treating diseases with temperature (39-45 ° C) beyond normal body temperature,. It has been reported that local warming at 44 ° C is able to effectively mobilize the body's immunity and clear HPV infected lesions, such as condyloma acuminatum and verruca vulgaris, etc. Significant progress has been made in the application of hyperthermia for viral skin diseases. Clinically, the addition of hydrogen peroxide solution can enhance the efficacy of hyperthermia in treating HPV infection. As a common transdermal drug delivery method, microneedles can increase drug penetration and thereby further improve treatment outcomes. Based on these findings, this study aims to explore an adjunctive approach to hyperthermia for treating viral warts to further enhance therapeutic efficacy. This study employs a randomized, parallel-group, assessor-blinded design. Participants will be randomly assigned to three groups: hyperthermia alone, hyperthermia combined with microneedle patch (loaded with 0.9% saline), and hyperthermia combined with hydrogen peroxide microneedle patch (experimental group). An adaptive design will be adopted. The sample size is estimated at 70 participants per group, accounting for a potential 20% dropout rate. Interim analyses will be conducted during follow-up, and enrollment will be stopped when a positive result is reached for the primary efficacy endpoint (cure rate), at which point the sample size will be adjusted accordingly.

To compare between the efficacy and safety of topical ivermectin alone, microneedling with topical ivermectin and topical salicylic acid in treatment of cutaneous warts. topical ivermectin 1% will be applied on warts whole night clinical assessment will be done every 2 weeks Microneedling will be performed on the lesion using a microneedling pen type device with a 1-cm tip diameter at a 2-mm depth setting for 2-3 minutes until pinpoint bleebing occurs 1 mL of topical ivermectin 1% will be applied on to the wart tissue. Sessions: Sessions will be performed every 2 weeks until complete cure or for maximum 6 sessions (total 3 month)

This is a Phase 3, double-blind, randomized, vehicle-controlled study (Study number VP-CW-301; referred to as COVE-2 \[Cantharidin and Occlusion in Verruca Epithelium\]) to evaluate the efficacy and safety of YCANTH (VP-102) treatment in subjects with common warts.

Hyperthermia refers to treating diseases with temperatures beyond normal body temperature (39-45℃), and moxibustion therapy of traditional Chinese medicine belongs to the category of hyperthermia. It has been reported at home and abroad that the local temperature of 44℃ can effectively mobilize the body's immunity and remove HPV infection lesions, such as condyloma acuminatum and verruca vulgaris. Our research group conducted randomized controlled experiments on patients with viral warts in the early clinical practice, and the cure rate of the hyperthermia group reached 45-55%, which was superior to the traditional method in the aspects of no trauma, low recurrence rate, easy to tolerate and so on. Our research group's preliminary research on hyperthermia of viral warts has been included in the British Medical Association's guidelines for viral warts therapy. The equipment our research group developed has been obtained the medical device registration certificate, and is in the process of national promotion. Hyperthermia is to mobilize systemic immunity through local warm heat, the preliminary clinical study of the research group shows that the therapeutic effect of hyperthermia is usually "all or none": "all" that is, after hyperthermia, all viral warts are removed, including non-treatment lesions;"None" means that some patients with viral warts do not respond to hyperthermia. Cellular immunity plays a very important role in the removal of warts. At present, some special clinical patients such as pregnant women, children, patients with autoimmune diseases, diabetes, immunosuppressants after organ transplantation and other patients with skin/mucosal HPV infection, their warts show more extensive proliferation or a longer and repeated course of disease, treatment resistance, etc. It has increased the difficulty of clinical treatment, and the specific mechanism is still unclear. Therefore, for these special populations, how to further enhance the therapeutic effect of hyperthermia is the top priority of current research. In view of the above findings, this research group intends to study the efficacy and safety of hyperthermia in the treatment of viral warts in the special population (pregnant women, children, patients with autoimmune diseases, diabetes, and immunosuppressants after organ transplantation, etc.) in a multicenter real-world study of skin/mucosal HPV infection in the special population.

To follow up the efficacy and safety of Candida antigen, bivalent HPV vaccine in treatment of common warts either mono or combined intralesional therapy

To assess the clinical efficacy and safety of topical imiquimod 5% cream combined with cryotherapy versus either of theme alone for the treatment of common warts by clinical and dermoscopic assessments.

Hyperthermia treatment (hyperthermia) refers to treating diseases with temperature (39-45 ° C) beyond normal body temperature,. It has been reported that local warming at 44 ° C is able to effectively mobilize the body's immunity and clear HPV infected lesions, such as condyloma acuminatum and verruca vulgaris, etc. Hydrogen peroxide (H2O2) is a commonly used disinfectant for skin debridement. It has been reported that high concentration of H2O2 (45% H2O2) is effective in the treatment of warts vulgaris, however, high concentration of H2O2 will cause more local pain, itching and burning sensation. 3% hydrogen peroxide is commonly used as skin debridement disinfectant. The purpose of the study is to evaluate the efficacy and safety of 44℃ hyperthermia combined with 3% hydrogen peroxide in treating verruca virus.

This double-blinded clinical trial randomly assigns participants with refractory cutaneous warts to receive either treatment with the human papillomavirus (HPV) vaccine or a placebo to assess the efficacy of HPV vaccination for the treatment of refractory cutaneous warts.