[Toxicity of targeted therapies and immunotherapy with checkpointinhibitors in Hodgkin lymphoma]. / Toxicité des thérapies ciblées et de l'immunothérapie par inhibiteurs des points de contrôle dans le lymphome de Hodgkin.

TOXICITY OF TARGETED THERAPIES AND IMMUNOTHERAPY WITH CHECKPOINT INHIBITORS IN HODGKIN LYMPHOMA. In patients at increased risk of recurrence or progression after autotransplantation, or in cases of relapse after autotransplantation or after at least two lines of treatment when intensive multidrug therapy is no longer a treatment option, targeted anti-CD30 therapy with brentuximab vedotin may be proposed. Brentuximab vedotin is a monoclonal antibody directed against CD30 and coupled with an anti-microtubule cytotoxic agent, monomethyl auristatin E (MMAE). The main adverse side effect of brentuximab vedotin is peripheral neuropathy. In patients who have relapsed after intensive chemotherapy, including autograft for patients eligible for this treatment, and after failure of brentuximab vedotin, anti-PD1 immunotherapy (nivolumab or pembrolizumab) may be offered. Anti-PD1 (Programmed cell death protein 1) side effects are immune-related, varied and unpredictable (endocrinopathies, rash, colitis, interstitial lung disease). The tolerability profiles of brentuximab vedotin and anti-PD1 and the management of the main undesirable side effects of these treatments are detailed for clinical practice.

TOXICITÉ DES THÉRAPIES CIBLÉES ET DE L'IMMUNOTHÉRAPIE PAR INHIBITEURS DES POINTS DE CONTRÔLE DANS LE LYMPHOME DE HODGKIN. Chez les patients ayant un risque accru de récidive ou de progression après une autogreffe, ou en cas de rechute après autogreffe ou après au moins deux lignes de traitement quand la polychimiothérapie intensive n'est plus une option, un traitement ciblé anti-CD30 par brentuximab vedotin peut être proposé. Le brentuximab vedotin est un anticorps monoclonal dirigé contre le CD30 et couplé à un agent cytotoxique antimicrotubule, la monométhylauristatine E. Le principal effet indésirable du brentuximab vedotin est la neuropathie périphérique. Chez les patients ayant une rechute après chimiothérapie intensive incluant une autogreffe, et après échec de brentuximab vedotin, une immuno­ thérapie anti-PD1 (nivolumab ou pembrolizumab) peut être proposée. Les effets indésirables des anti-PD1 ( programmed cell death protein 1), liés à l'immunité, sont très variés et assez imprévisibles (endocrinopathies, rash, colite, pneumopathies interstitielles). Les profils de tolérance du brentuximab vedotin et des anti-PD1 et la gestion des principaux effets indésirables de ces traitements sont détaillés pour la pratique clinique.

Leprosy rash precipitated by immunotherapy for suspected inflammatory neuropathy.

Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae complex, causing skin and nerve lesions with potential for permanent disability. Leprosy can be overlooked in Western settings, as it is more prevalent in low-income and middle-income countries. We describe a 38-year-old woman with a 4-year history of progressive numbness of the left hand incorrectly diagnosed as multifocal acquired demyelinating sensory and motor neuropathy on the basis of clinical and neurophysiological findings. Treatment with empirical weekly corticosteroid followed by intravenous immunoglobulin resulted in the sudden development of a widespread rash; we then diagnosed borderline lepromatous leprosy on skin biopsy. We postulate that the immune treatments induced a temporary state of immune tolerance followed by a rebound of a T cell-mediated immune response resulting in a type 1 immunological response.

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.

The Effectiveness and Value of Oral Immunotherapy and Viaskin Peanut for Peanut Allergy.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, Commonwealth Fund, California Health Care Foundation, National Institute for Health Care Management (NIHCM), New England States Consortium Systems Organization, Blue Cross Blue Shield of Massachusetts, Harvard Pilgrim Health Care, Kaiser Foundation Health Plan, and Partners HealthCare to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, Allergan, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Cambia Health Services, CVS, Editas, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Herron-Smith and Pearson are employed by ICER, which has a contract with the University of California, San Francisco, to perform work for these analyses. Segal was employed by ICER at the time of this review. Tice and Walsh are employed by the University of California, San Francisco. Gazauskas and Hansen have nothing to disclose.

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.

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.

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.