Efficacy and safety of local candida immunotherapy in recalcitrant warts in pediatric kidney transplantation:A case report

BACKGROUND Warts are common in recipients of kidney transplantation(KT).Resistant warts which are not amenable to conventional therapies may lead to significant morbidity.Limited data exists on safety and efficacy of local immunotherapy among immunocompromised KT recipients.CASE SUMMARY We report a seven-year-old child who presented with recalcitrant plantar periungual warts in the early KT period.Immunosuppression consisted of tacrolimus,mycophenolate and steroid.Due to failure of conventional anti-wart therapies,he was treated with two sessions of intralesional(IL)candida immunotherapy along with liquid nitrogen cryotherapy leading to complete resolution of the warts.Interestingly,de novo BK viremia was seen about three weeks following the last candida immunotherapy.This required reduction of immunosuppression and other anti-BK viral therapies.Allograft function remained stable but there were donor specific antibodies detected.There also was elevated level of plasma donor derived cell-free DNA.A pneumocystis jirovecii pneumonia occurred ten months following completion of immunotherapy that was successfully treated with trimethoprim-sulfamethoxazole.During this ten-month follow-up period,there have been no recurrence of warts,and transplant kidney function has remained stable.CONCLUSION Stimulation of cell-mediated immunity against the human papilloma virus induced by the IL candida immunotherapy is thought to be a cause for wart resolution.With this therapy,whether it is necessary to augment the immunosuppression to prevent rejection is unclear as that may come with a risk of infectious complications.Larger,prospective studies in pediatric KT recipients are needed to explore these important issues.

A 1-bp deletion in the MC04g1399 is highly associated with failure to produce fruit wart in bitter gourd

Fruit wart is an important appearance trait influencing consumer preferences of bitter gourd(Momordica charantia L.).The molecular genetic mechanisms underlying fruit wart formation in bitter gourd are largely unknown.In this study,genetic analysis based on four generations showed that fruit wart formation in bitter gourd was controlled by a single dominant locus named as Fwa.The Fwa locus was initially mapped into a 4.82 Mb region on pseudochromosome 4 by BSA-seq analysis and subsequently narrowed down to a 286.30 kb region by linkage analysis.A large F2population consisting of 2360 individuals was used to screen recombinants,and the Fwa locus was finally fine mapped into a 22.70 kb region harboring four protein-coding genes through recombination analysis.MC04g1399,encoding an epidermal patterning factor 2-like protein,was proposed as the best candidate gene for Fwa via sequence variation and expression analysis.In addition,a 1-bp insertion and deletion(InDel)variation within MC04g1399 was converted to a cleaved amplified polymorphic sequence(CAPS)marker that could precisely distinguish between the warty and non-warty types with an accuracy rate of 100%among a wide panel of 126 bitter gourd germplasm resources.Our results not only provide a scientific basis for deciphering the molecular mechanisms underlying fruit wart formation but also provide a powerful tool for efficient genetic improvement of fruit wart via marker-assisted selection.

Combination of Circumcision and Microwave in Treatment of Genital Warts in Uncircumcised Patients

Objective: To investigate the efficacy of combina-tion of circumcision and microwave on genital wartsin uncircumcised men. Methods: A randomized, prospective study of 109uncircumcised adult men with genital warts was con-ducted in a STD clinic in Zhanjiang, Guangdong. Onegroup (n=54) received microwave therapy only, whilethe other group (n=55) was taken the combination ofcircumcision and microwave therapy. The recurrenceswere observed at the end of months 3, 6 and 12, andoperative complications were also recorded. Results: There were no significant differences inthe mean age and duration of the disease between twogroups (P>0.05). No serious operative complicationswere documented. The recurrence rate in circumci-sion plus microwave group was markedly lower thanthat in microwave group (12.7% vs 29.6%, P<0.05),while the differences in early and late recurrencesbetween two groups showed no statistical significance(P>0.05). Conclusion: Circumcision can be safely performedunder local anesthesia in an outpatient setting. Com-bination of circumcision and microwave can produceexcellent effect as well as less tissue damage,therefore, it may be ideal for uncircumcised patientswith extensive condylomas.

Detection of HPV Types and Neutralizing Antibodies in Women with Genital Warts in Tianjin City,China

The serum samples and corresponding cervical swabs were collected from 50 women with genital warts from Tianjin city, China. The neutralizing antibodies against HPV-16, -18, -58, -45, -6 and -11 in serum samples were tested by using pseudovirus-based neutralization assays and HPV DNAs in cervical swabs were also tested by using a typing kit that can detect 21 types of HPV. The results revealed that 36% （18/50） of sera were positive for type-specific neutralizing antibodies with a titer range of 160-2560, of which 22%（11/50）, 12%（6/50）, 10%（5/50）, 4%（2/50）, 4%（2/50） and 2%（1/50） were against HPVs -6, -16, -18, -58, -45 and -1 l, respectively. Additionally, 60% （30/50） of samples were HPV DNA-positive, in which the most common types detected were HPV-68（18%）, HPV-16（14%）, HPV-58（12%）, HPV-33（8%） and HPV-6, HPV-11, HPV-18 and HPV-52 （6% each）. The concordance between HPV DNA and corresponding neutralizing antibodies was 56% （28/50） with a significant difference （P〈0.05）. The full-length sequences of five HPV types （HPV -42, -52, -53, -58 and -68） were determined and exhibited 98%-100% identities with their reported genomes. The present data may have utility for investigating the natural history of HPV infection and promote the development of HPV vaccines.

Molecular Epidemiological Study on Prevalence of Human Papillomaviruses in Patients with Common Warts in Beijing Area

Objective To study the circulation, distribution, and genomic diversity of HPVs in common warts in Beijing area of China. Methods Forty eight patients with pathologically diagnosed common warts were screened for the presence of HPV with HPV type-specific PCR and direct sequencing analysis. The genomic diversity of HPVs prevalent in Chinese patients was analyzed based on LCR. Results Forty one （85.5%） samples were positive for HPV DNA, 13（31.7%）-HPV-57, 12（29.3%）-HPV-la, 7（17%）-HPV-27 and 5（12.2%）-HPV-2a. Four cases were infected with two different HPV types, two （4.9%） with HPV-la and HPV-27, one （2.4%） with HPV-1 and HPV-57 and one （2.4%） with HPV-27 and HPV-57. In contrast to the prevalence of single strain of novel HPV-57 variant and HPV-1 prototype, two HPV-2 and three HPV-27 novel variants were found to circulate in Beijing. Conclusion HPV-1, -2, -27 and -57 are predominantly prevalent in patients with common warts in Beijing.

Primary intestinal lymphangiectasia with generalized warts

Primary intestinal lymphangiectasia(PIL) is a rare protein-losing enteropathy with lymphatic leakage into the small intestine. Dilated lymphatics in the small intestinal wall and mesentery are observed in this disease. Laboratory tests of PIL patients revealed hypoalbuminemia, lymphocytopenia, hypogammaglobulinemia and increased stool α-1 antitrypsin clearance. Cell-mediated immunodeficiency is also present in PIL patients because of loss of lymphocytes. As a result, the patients are vulnerable to chronic viral infection and lymphoma. However, cases of PIL with chronic viral infection, such as human papilloma virus-induced warts, are rarely reported. We report a rare case of PIL with generalized warts in a 36-year-old male patient. PIL was diagnosed by capsule endoscopy and colonoscopic biopsy with histological tissue confirmation. Generalized warts were observed on the head, chest, abdomen, back, anus, and upper and lower extremities, including the hands and feet of the patient.

Effects of shallomin and podophyllin solution 25% for genital HPV warts in women: a randomized controlled trial

Objective: To compare the effect of shallomin (pure fraction of Allium hirtifolium) with podophyllin 25% solution on external genital human papillomavirus warts in women. Methods: This study was a randomized controlled trial which was performed on two groups of 25 Iranian women with external genital warts at Imam Khomeini Hospital in Ahvaz, Iran. In the first group, shallomin was used once a day for six weeks at home. In the second group, 25% podophyllin solution, was applied on the lesion once weekly for six weeks. Results: Shallomin and podophyllin resulted in wart clearance in 13/23 (56.5%), and 12/24 (50%) of patients, respectively. The clearance rate for shallomin was not significantly different from that of podophyllin (P=0.082). Six weeks after the treatment, the sizes of the lesions in the shallomin group and the podophyllin group decreased by (1.43±0.53) mm and (1.64±0.70) mm, respectively. Conclusion: Shallomin is an effective treatment for genital warts, with similar efficacy to that of podophyllin.

Tuberculin as Intralesional Therapy for Viral Warts—Single-Blind, Split, Placebo, Controlled Study

Background: BCG vaccine as an antigen has proved its effectiveness as an immunotherapy for viral warts. Tuberculin is an antigenic extract of M. tuberculosis capable of eliciting an immunological skin reaction. Objective: To assess the efficacy of tuberculin intralesional injection in the treatment of viral warts. Patients and Methods: This single ,blind, placebo controlled study was conducted at the Department of Dermatology, Baghdad Teaching Hospital, Baghdad, Iraq from March 2010 to July 2011.Forty-one patients with different types of viral warts were enrolled in this study;tuberculin test was done to patients prior to instillation of intralesional treatment. Then the patients treated by intralesional tuberculin in each lesion located on the right side of the body, and intralesional distilled water in each lesion located on the left side of to a maximum of 3 injections, at 2 weeks interval or until full resolution of these lesions. Patients were evaluated every 2 weeks to assess the regression of their lesions and to record any local and systemic adverse effects. The response to treatment was evaluated by decrease in size and reduction in number of warts. Scoring of response to treatment was as follow: 1) Responders: including patients who showed complete cure or those with good response (>50% reduction). 2) Non responders: including patients who showed minimal response (<50% reduction), or those with no improvement (stable disease and disease progression). The follow up period lasted up to 2 months after the last dose. Results: Thirty out of 41 patients had completed the study, of them 14 (46.66%) patients showed response of their lesions on the right side of the body that were treated with tuberculin;15 patients showed no response, 1 patient showed minimal response, 7 patients showed good response and 7 patients showed complete cure (23.33%). Regarding the lesions treated with intralesional distilled water, 25 patients showed no response, 3 patients showed minimal response, 2(6.66) patients showed good response and no patient showed complete cure of their warts. Of the 14 responder patients to intralesional tuberculin, 10 patients were tuberculin tested positive, and 4 patients were tested negative, and of the 16 non responder patients to intralesional tuberculin, 3 patients were tuberculin tested positive, and 13 patients were tuberculin tested negative which was statistically significant difference. No side effects reported from tuberculin therapy apart from mild pain at site of injection. Conclusion: Intralesional injection of tuberculin is an effective therapy for viral warts when compared with control, possibly through its local immunological action and had no systemic immunological response. Patients with previous BCG vaccine showed better response to tuberculin injection.

Genital Warts in Infants and Children <br>—Re-Evaluation of Podophylline 15% as an Effective Topical Therapy

Background: Condylomataacuminata is an infection caused by Human Papilloma Virus, rarely reported in infants and children. Podophylline as a treatment for this condition has been used cautiously in this age group. Objective: To report the cases of anogenital warts including condy lomataacuminata in infants and children and to evaluate the effectiveness and side effects of 15% podophyllin in treatment of genital warts. Patient and Methods: Thirty infants and young children were seen in Department of Dermatology and Venereology—Baghdad Teaching Hospital in this case descriptive and therapeutic trial, in the period from January 2011 to August 2012. Their ages ranged from 8 - 72 (30.43 ± 15.85) months, 20 females and 10 males with a female:male ratio of 2:1. The duration of the disease ranged from 1 - 12 (5.26 ± 4.00) months. All demographics data were recorded in this study. History and examination were carried out to all patients. Family members including mothers were assessed about the presence of any type of viral warts in other location of body. Podophyllin (15%) in tincture benzoin was applied once weekly to all viral warts and the parents advised to wash out after 2 hours of application. The number of applications was repeated until full recovery. Follow-up after recovery was carried out for 6 months to watch for any relapse and to record local or systemic side effects. Results: The clinical pictures were mostly acondylomata acuminata in a form of cauliflower like warts in 20 (73.33%) patients, while in 10 (26.77%) patients there were ordinary verruca vulgaris like warts. The location of warts was perianal in 23 (76.66%) patients, genital only in 2 (6.66%) patients, and mixed in 5 (16.66%) patients. Topical applications of podophyllin 15% gave a full recovery in 27 (90%) patients, while in 3 (10%) patients there was partial response. The number of applications ranged from 1 - 4 (2.7 ± 1.42) applications. Follow up for 6 months after recovery showed relapse in only one patient, and no side effects were reported in any patients. Conclusion: There is upsurge of cases of anogenital warts among infants and children. Podophyllin (15%) in tincture benzoin is an effective therapy and no local or systemic side effects were recorded in any case.

Tuberculosis of the Spine (L5, S1) Secondary to Scrofuloderma with Viral Warts in a 15-Year-Old Male

We report this case of a 15-year-old male who presented to the children outpatient clinic (CHOP) of Abia State University Teaching Hospital (ABSUTH), Aba on the 5th of November 2015. He had tuberculosis (TB) of the skin (scrofuloderma) which was not diagnosed and had received treatment other than anti-TB medication. He now presented 9 years after with multiple body discharging sinuses, cicatricial skin lesions, tuberculosis of the spine (L5, S1) with contracture of the Achilles Tendon and genital warts. Subsequent treatment with full anti-TB drugs led to resolution of his illness. A higher index of suspicion is required for early diagnosis of extrapulmonary TB. Prompt and adequate treatment with anti-TB medication ensures cure in such cases. Appropriate control program is also known to improve the outcome and reduce sequelae.

Managing Recalcitrant Warts: Facts about Bacillus Calmette-Guerin (BCG), Mycobacterium Indicus Pranii (Mw Vaccine), and Purified Protein Derivative (PPD) as Immunotherapy

Recalcitrant warts can accurately be defined as warts that persist after six months of conventional therapy. Up to one-third of non-genital warts, especially periungual and plantar warts, become recalcitrant. Traditional treatment options for warts include topical salicylic acid, cryotherapy, and electrocautery;however, patients with recalcitrant warts remain a major therapeutic challenge. There is evidence that immunotherapy can clear recalcitrant warts if traditional treatment fails. Given this, clinical studies published in PubMed and Google Scholar that used Bacillus Calmette-Guerin (BCG), Mycobacterium Indicus Pranii (Mw vaccine), and purified protein derivative (PPD) as immunotherapy for wart, were reviewed in this study. Neither of these treatments has been subjected to a randomized controlled trial, thus to date, there are no standardized protocols to use them. Our review highlights the scientific facts in the clinical applications of the previous options to treat recalcitrant warts and investigate the differences among them, concerning efficacy, adverse effects, dosage, and route of administration.

Treatment of Recalcitrant Viral Warts with Photodynamic Therapy with Mal and Red Light

Background: Photodynamic therapy (PDT) is a treatment for non-melanoma skin cancer. In recent years, its use has expanded to new indications. Viral warts (VW) are some of the most promising. Methods: A retrospective, descriptive, observational study was carried out. Patients who did not respond to cryotherapy were selected and were occluded with methyl aminolevulinate (MAL) for three hours and they were illuminated with red light. Tolerance to treatment was evaluated using a visual analog scale for pain (from 0 to 10). Results: A total of 15 patients with 134 VW were treated. A complete response was obtained in 13 of 15 patients (87%) and in 127 of 134 lesions (95%). The mean number of sessions was 3.1 (range 1 to 6) and the average pain score was 3.1 (range 0 to 8). Conclusions: PDT is a treatment that offers good results in the treatment of VW that are resistant to routine treatment. The treatment was well tolerated in our patient group.

Huge Recalcitrant Warts Treated with Pulse Dye Laser after Conventional Therapies and Others Destructive Physical Modalities Failed

Cutaneous infections with the human papilloma virus, despite being almost always asymptomatic, can induce slow-growing lesions knowed as warts that can remain subclinical for long periods of time. There are several therapeutical options namely keratolytics, retinoids, imiquimod, cryotherapy, electrosurgery, lasers and classic surgery, but none has antiviral effects. We describe the case of a patient with large warts located on the dorsal surface of the right hand, treated with cryotherapy, CO2 laser and topical imiquimod having either no clinical response or quick relapse. Treatment with PDL was started and after 13 sessions, the patient was without lesions, with a good cosmetic result and so far without relapse. This case report is relevant to us and deserves to be published because of the size of the lesions and the great response to PDL despite all the failures with the other treatments.

Local hyperthermia cleared multiple cutaneous warts on a nephrotic syndrome patient

Cutaneous warts are caused by human papillomavirus infection. Immunosuppressive state is one of the risk factors of human papillomavirus infection. A girl diagnosed of nephrotic syndrome and on immunosuppressive therapy developed multiple common warts. We treated her on a single lesion by local hyperthermia therapy at 44 ℃ for 3 consecutive days, each therapy lasted for 30 min. Ten days later, the patient received another 2 consecutive therapy. All lesions are completely resolved at the 9th week after the treatment. No recurrent sign was observed in a 3-mo follow-up. Side effects included burning sensation, stabbing pain at the target site during treatment.

Perianal verrucous epidermal nevus masquerading as warts

Verrucous epidermal naevus(VEN) is a rare form of epidermal naevus. We present a case of VEN occurring over the perianal region of a 7-year-old boy. The lesion was initially thought to be an area of chronic dermatitis; however it was refractory to treatment. Histopathology confirmed the diagnosis of VEN. VEN in the inguinogenital region may be misdiagnosed as flexural psoriasis, genital warts or sexual abuse. This is what precisely happened to our patient for a duration of more than 1 year.

A Correlative Analysis of Cervical Lesions in Patients with Vulva Condyloma Acuminatum

OBJECTIVE To analyze the relation ship among vulva condyloma acuminatum, high-risk human papillomavirus （HPV） infections and cervical epithelium lesions. METHODS From May 2002 to April 2004 patients with vulva condyloma acuminatum were examined employing vulva biospy, colposcopy, highrisk HPV-DNA test and cervical bioscopy. RESUTS In 418 cases of vulva condyloma acuminatum, verified by pathologic analysis, high-risk HPV （＋） infections were detected in 68.7% （287/418） of the cases. Among those patients, 20,6% （59/287） had concurrent subclinical cervical intraepithelial neoplastic （CIN） lesions. Among the high-risk HPV（-） 31.3 % （131）, patients 7,6% （10/131） had concurrent subclinical CIN lesions, Pathological examination results： cervicitis, 167 （40.0%）; cervical HPV infection, 182 （43.5%）; CIN-Ⅰ, 51（12.2%）; CIN- Ⅱ, 16 （3.83%）; CIN-Ⅲ, 2 （0,5%）; cervical cancer, none. Another patient had vulva condyloma acuminatum with valva intraepithelial neoplasia （VIN） Ⅱ-Ⅲ, CONCLUSION It was concluded that simultaneous cervical HPV infection of many types,was rather common in patients with vulva condyloma acuminatum. Vulva condyloma acuminatum is the chief clinical symptom which hints at a high possibility of infection with high-risk HPV. The patients are at high-risk for CIN and cervical cancer. We must pay more attention to the cervix in cases with vulva condyloma acuminatum.

Therapeutic Observation on Twenty－one Cases of Common Wart Treated by Acupuncture

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Age-specific distribution of Human Papilloma Virus (HPV) mucosal infection among young females

The goal of our study was to describe the age-specific distribution of HPV genotypes and related disease among females under the age of 25 years. A prospective cohort study was carried out. We enrolled 85 young females aged 16 - 25 years (30 aged 16 - 19 and 55 aged 20 - 25 years) referred to our colposcopic unit after a repeated abnormal Pap smear result. Every patient underwent an HPV DNA testing, a colposcopy and eventually a cervical biopsy. Participants were proposed to follow-up or treatment on request. Treatment was performed by destructive or excisional laser CO2 therapy. Data were analyzed by Fisher’s Exact test. The overall prevalence of low-risk HPV amounted to 80% among 16 - 19-year-old girls, while the overall prevalence of high-risk HPV was 85.5% among 20 - 25-year-old patients. The univariate analysis of chosen characteristics of HPV-disease demonstrates the statistically significative difference of this infection between the two groups of age (P < 0.005). We observed a particular age-specific stratification of HPV genotypes and related disease, which appeared to be characterized by a cut-off at the age of 20 years. According to our data, cervical screening program in Italy seems to start later than the beginning of HPV-related pathology.

Effects of a Carbonated Soft Drink on Epitheial Tumor Incidence in Drosophila melanogaster

Diet represents an important risk factor for tumor development and numerous food dyes have been tested for their carcinogenic potential. Caramel IV colorant and its byproduct, the 4-methylimidazole （4-MI）, are part of the composition of cola soft drinks, although in undefined concentration. Considering that this concentration depends on the manufacturing place, we aimed to evaluate the potential carcinogenic activity of cola soft drinks from Brazil, Canada, Egypt and Netherlands, through the test for detection of epithelial tumor clones （warts） in somatic cells of Drosophila melanogaster. We used 72-hour larvae resulting from the crossing of wts/TM3, Sb^1 virgin females and mwh/mwh males. Larvae were exposed to the media containing the cola soft drinks for 48 hours and the analysis was performed in adults after transformation. Cola soft drinks from Brazil significantly induced epithelial tumor in D. melanogaster, while those from Canada, Egypt and Netherlands did not. In fact, the concentration of 4-MI is higher in cola soft drink commercialized in Brazil. Our results highlight the importance of investigating the toxic potential of current drinks, which may correlate with the rising incidence of malignant diseases.

The Feasibility of Treatment for Skin Diseases Using the Ultrasonic Surgical Aspirator

Ultrasound energy liquefies high fluid content tissues, such as epidermis and sweat glands via cavitation, but minimally affects dermis, blood vessels, and nerves at the same energy level. We have used ultrasonic surgical aspirator to treat several skin diseases such as Bowen’s disease, wart, prurigo nodularis, and osmidrosis. The ultrasonic surgical aspirator offers an effective and safe method to treat them with few complications. We expect several other skin diseases could likely be cured using ultrasonic surgical aspirator by accumulating additional cases.