Intralesional immunotherapy for non-genital warts: A systematic review and meta-analysis.

Background Intralesional immunotherapy has been reported to be effective for warts and to show good safety profiles, but this has not yet been systematically studied. Aims To determine the efficacy and safety of intralesional immunotherapy for treating non-genital warts. Methods We comprehensively searched the MEDLINE, Embase, Web of Science and Cochrane Library databases from the times of their inception to January 3, 2020. The primary outcome was the rate of complete response of all lesions. The distant complete response rate of warts located in an anatomically different body part and the recurrence rate were also analyzed. Results A total of 54 prospective studies was ultimately included. The immunotherapeutic agents used were Mycobacterium w vaccine, measles, mumps and rubella vaccine, purified protein derivative, Candida antigen, interferon, bacillus Calmette-Guérin vaccine and others. The pooled rate of complete response among all patients with non-genital warts treated using intralesional immunotherapy was 60.6% (95% confidence interval 54.8-66.5%). The pooled recurrence rate was 2.0% (95% confidence interval, 1.1-2.9%). All reported adverse events were mild and transient. Limitations The heterogeneity among studies Conclusion Intralesional immunotherapy is suggested for use in patients with multiple warts, given its promising results, good safety profile and low recurrence rate.

Prevention of transmission of leprosy: The current scenario.

With the worldwide implementation of WHO multidrug therapy in the 1980s, the global burden of leprosy has decreased. However, the annual new case detection rate around the world has remained nearly static over the past decade with India, Brazil, and Indonesia contributing the majority of these new cases. This has been attributed to the ongoing transmission of Mycobacterium leprae from existing untreated cases and partly to the intensive new case detection programs operative in endemic areas. The WHO has called for a "global interruption of transmission of leprosy by 2020". Targeted chemoprophylaxis of contacts may help bring down the number of new cases. The single-dose rifampicin currently in use for post-exposure prophylaxis (PEP) has limitations and so newer antileprosy drugs and regimens have been trialed for chemoprophylaxis. BCG re-vaccination in combination with chemoprophylaxis for the prevention of leprosy transmission has not been very encouraging. The use of the anti-phenolic glycolipid-1 (PGL-1) antibody test to detect subclinical cases and administer targeted chemoprophylaxis was unsuccessful owing to its low sensitivity and technical difficulties in a field setup. There is a pressing need for newer multidrug chemoprophylactic regimens using second-line antileprosy drugs. The Netherlands Leprosy Relief has proposed an enhanced PEP++ regimen. A simple but highly sensitive and specific serological test to detect subclinical cases at the field level needs to be developed. Although there are a number of challenges in the large-scale implementation of strategies to halt leprosy transmission, it is important to overcome these in order to move towards a "leprosy-free world."

Falknor's needling method as a potential immunotherapy in palmo-plantar warts.

BACKGROUND AND AIM: Treatment of palmoplantar warts is a challenge for dermatologists. We aimed to study the efficacy and safety of Falknor's needling method in palmoplantar warts. METHODS: In an open, nonrandomized study, the index wart of eligible patients was punctured several times with a 26-gauge needle to produce a "beefy" red wound. Patients were followed up to 6 months. RESULTS: Out of 82 patients, complete resolution occurred in 58 (70.7%) and partial response in 5 (6.1%) patients. Nine (10.9%) patients developed secondary infection. LIMITATIONS: Small sample size, No comparison group. CONCLUSION: Falknor's needling method provides a high rate of complete resolution after a single treatment session. It is easy to perform and is cost effective.

Updates on the use of vaccines in dermatological conditions.

Numerous vaccines are being actively developed for use in dermatologic diseases. Advances in the fields of immunotherapy, genetics and molecular medicine have allowed for the design of prophylactic and therapeutic vaccines with immense potential in managing infections and malignancies of the skin. This review addresses the different vaccines available for use in dermatological diseases and those under development for future potential use. The major limitation of our review is its complete reliance on published data. Our review is strictly limited to the availability of published research online through available databases. We do not cite any of the authors' previous publications nor have we conducted previous original research studies regarding vaccines in dermatology. Strength would have been added to our paper had we conducted original studies by our research team regarding the candidate vaccines delineated in the paper.

Fate of T Cells and their Secretory Proteins During the Progression of Leprosy.

Leprosy is an infectious disease caused by non-cultivable bacteria Mycobacterium leprae. Ridley and Jopling classified the disease into five polar forms, Tuberculoid (TT) and Lepromatous (LL), in between two forms of the disease Borderline tuberculoid (BT), Borderline (BB) and Borderline lepromatous (BL) are laid. The tuberculoid type (BT/TT) leprosy patients show good recall of cellmediated immune (CMI) response and Th1 type of immune response, while lepromatous leprosy (LL) patients show defect in cell-mediated immunity to the causative agent and Th2 type of immune response. Due to distinct clinical and immunological spectra of the disease, leprosy attracted immunologists to consider an ideal model for the study of deregulations of various immune reactions. Recent studies show that Tregs, Th3 (TGF-ß, IL-10), IL-35 producing Treg immune response associated with the immune suppressive environment, survival of bugs. IL-17 producing Th17 immune response associated with tuberculoid leprosy and play protective role. γδ T cells also increased from tuberculoid to lepromatous pole of leprosy. In this review, we will discuss the role of various subtypes of T-cell and their cytokines in the pathogenesis of leprosy.

DNAhsp65 Vaccine as Therapy against Paracoccidioidomycosis.

The conventional treatment for fungal diseases usually shows long periods of therapy and the high frequency of relapses and sequels. New strategies of the treatment are necessary. We have shown that the Mycobacterium leprae HSP65 gene can be successfully used as therapy against murine Paracoccidioidomycosis (PCM). Here, we described the methodology of DNAhsp65 immunotherapy in mice infected with the dimorphic fungus Paracoccidioides brasiliensis, one of PCM agent, evaluating cytokines levels, fungal burden, and lung injury. Our results provide a new prospective on the immunotherapy of mycosis.

Successful treatment of Rosai-Dorfman disease using in situ photoimmunotherapy.

Rosai-Dorfman disease is difficult to cure. In situ photoimmunotherapy combines local photothermal therapy with immunoadjuvant. In the present case report, a 39-year-old Chinese man with Rosai-Dorfman disease lesions below the left nostril and left preauricular region was treated with in situ photoimmunotherapy. The patient was treated with daily application of topical imiquimod (5%) and laser irradiations every 2 weeks for 8 weeks. After three cycles of treatment, the lesions improved markedly without adverse effects. Our results showed that in situ photoimmunotherapy can be used as an effective treatment for Rosai-Dorfman disease.

Immunotherapy in viral warts with intradermal Bacillus Calmette-Guerin vaccine versus intradermal tuberculin purified protein derivative: A double-blind, randomized controlled trial comparing effectiveness and safety in a tertiary care center in Eastern India.

BACKGROUND: Current therapeutic modalities for viral warts are mostly ablative and are limited by high recurrence rates besides being unsuitable for numerous lesions. Immunotherapy has the potential to overcome these limitations. AIMS: The aim of this study was to compare the effectiveness and safety of Bacillus Calmette-Guerin vaccine versus tuberculin purified protein derivative in the immunotherapy of warts. METHODS: Patients received three doses of 0.1 ml of Bacillus Calmette-Guerin vaccine or tuberculin purified protein derivative intradermally over the deltoid region at 4-weekly intervals. They were followed-up for another month. Number of warts, complete cure rates and quality of life were assessed. RESULTS: A total of 60 patients were included. Complete clearance was noted in 16 (48.5%) out of 33 patients in the Bacillus Calmette-Guerin group and in 5 (18.5%) out of 27 in the tuberculin purified protein derivative group (P = 0.121). The number of lesions reduced statistically significantly from baseline in both the groups (P < 0.001) from the first follow-up visit onward (P < 0.05). The reduction was statistically significantly more in the Bacillus Calmette-Guerin group than in the tuberculin purified protein derivative group from the second follow-up onward. Dermatologic life quality index improved statistically significantly with both treatments. Adverse events (pain during injection, abscess formation and scarring at injection site) were more frequent with Bacillus Calmette-Guerin. No recurrence was seen after lesions cleared. LIMITATIONS: Patients were not followed up for more than 4 weeks after treatment. We could not estimate the cytokine levels or the peripheral blood mononuclear cell proliferation in response to Bacillus Calmette-Guerin/tuberculin purified protein derivative injections. CONCLUSION: Both intradermal Bacillus Calmette-Guerin and tuberculin purified protein derivative hold promise in the treatment of viral warts. Bacillus Calmette-Guerin may be more effective, though it had more adverse events in our study.

Generalized granulomatous dermatitis following Mycobacterium w (Mw) immunotherapy in lepromatous leprosy.

Mycobacterium w (Mw) vaccine is a heat-killed suspension derived from a nonpathogenic, cultivable, atypical mycobacterium named Mycobacterium indicus pranii. Mw immunotherapy has been reported to be efficacious as an adjunct to multidrug therapy multibacillary regimen in leprosy patients with high bacillary index. Cutaneous reactions are predominant adverse effects associated with the administration of vaccines. Cutaneous adverse effects ascribed to Mw vaccine are generally limited to the site of injection. We herein describe two cases of lepromatous leprosy who developed an unusual generalized cutaneous reaction following Mw immunotherapy. A high index of suspicion is needed to identify such manifestations in leprosy cases to avoid misdiagnosis of a relapse or a reaction and for appropriate treatment.

Minocycline successfully treats exaggerated granulomatous hypersensitivity reaction to Mw immunotherapy.

Mycobacterium W (Mw) vaccine has been found to be effective in the treatment of leprosy and warts. Despite increasing use of Mw immunotherapy, data on its safety is limited. We report a series of eight patients who developed persisting injection site granulomatous reaction following Mw immunotherapy and were successfully treated with minocycline. Eight patients with persistent nodular swelling at the site of Mw injections were identified. Seven of them had received Mw immunotherapy for cutaneous warts and one for verrucous epidermal nevus. The lesions were firm, erythematous, succulent, non-tender nodules confined to the sites of Mw vaccine injections. In 6 of these patients nodules also involved the previously injected areas. Skin biopsy from all patients showed eosinophil rich inflammation admixed with histiocytes and lymphocytes. In addition granulomas were seen in all with septal and nodular panniculitis in four patients. Broken and granular acid-fast bacilli were identified in two cases. All patients were treated with oral minocycline 100 mg/day for a mean of 9 weeks and showed good clinical response. Granulomatous reaction is a rare but significant adverse effect of Mw immunotherapy at cosmetically and functionally imperative sites. Oral minocycline appears to be effective therapy in this situation.

Immune checkpoints in leprosy: immunotherapy as a feasible approach to control disease progression

Leprosy remains a health problem in several countries. Current management of patients with leprosy is complex and requires multidrug therapy. Nonetheless, antibiotic treatment is insufficient to prevent nerve disabilities and control Mycobacterium leprae. Successful infectious disease treatment demands an understanding of the host immune response against a pathogen. Immune-based therapy is an effective treatment option for malignancies and infectious diseases. A promising therapeutic approach to improve the clinical outcome of malignancies is the blockade of immune checkpoints. Immune checkpoints refer to a wide range of inhibitory or regulatory pathways that are critical for maintaining self-tolerance and modulating the immune response. Programmed cell-death protein-1 (PD-1), programmed cell death ligand-1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4, and lymphocyte-activation gene-3 are the most important immune checkpoint molecules. Several pathogens, including M. leprae, are supposed to utilize these mechanisms to evade the host immune response. Regulatory T cells and expression of co-inhibitory molecules on lymphocytes induce specific T-cell anergy/exhaustion, leading to disseminated and progressive disease. From this perspective, we outline how the co-inhibitory molecules PD-1, PD-L1, and Th1/Th17 versus Th2/Treg cells are balanced, how antigen-presenting cell maturation acts at different levels to inhibit T cells and modulate the development of leprosy, and how new interventions interfere with leprosy development.