Chronic use of hydroxychloroquine did not protect against COVID-19 in a large cohort of patients with rheumatic diseases in Brazil

Abstract Background: There is a lack of information on the role of chronic use of hydroxychloroquine during the SARS-CoV-2 outbreak. Our aim was to compare the occurrence of COVID-19 between rheumatic disease patients on hydroxychloroquine with individuals from the same household not taking the drug during the first 8 weeks of community viral transmission in Brazil. Methods: This baseline cross-sectional analysis is part of a 24-week observational multi-center study involving 22 Brazilian academic outpatient centers. All information regarding COVID-19 symptoms, epidemiological, clinical, and demographic data were recorded on a specific web-based platform using telephone calls from physicians and medical students. COVID-19 was defined according to the Brazilian Ministry of Health (BMH) criteria. Mann-Whitney, Chi-square and Exact Fisher tests were used for statistical analysis and two binary Final Logistic Regression Model by Wald test were developed using a backward-stepwise method for the presence of COVID-19. Results: From March 29th to May 17st, 2020, a total of 10,443 participants were enrolled, including 5166 (53.9%) rheumatic disease patients, of whom 82.5% had systemic erythematosus lupus, 7.8% rheumatoid arthritis, 3.7% Sjögren's syndrome and 0.8% systemic sclerosis. In total, 1822 (19.1%) participants reported flu symptoms within the 30 days prior to enrollment, of which 3.1% fulfilled the BMH criteria, but with no significant difference between rheumatic disease patients (4.03%) and controls (3.25%). After adjustments for multiple confounders, the main risk factor significantly associated with a COVID-19 diagnosis was lung disease (OR 1.63; 95% CI 1.03-2.58); and for rheumatic disease patients were diagnosis of systemic sclerosis (OR 2.8; 95% CI 1.19-6.63) and glucocorticoids above 10 mg/ day (OR 2.05; 95% CI 1.31-3.19). In addition, a recent influenza vaccination had a protective effect (OR 0.674; 95% CI 0.46-0.98). Conclusion: Patients with rheumatic disease on hydroxychloroquine presented a similar occurrence of COVID-19 to household cohabitants, suggesting a lack of any protective role against SARS-CoV-2 infection. Trial registration Brazilian Registry of Clinical Trials (ReBEC; RBR - 9KTWX6).

Epidemiological, clinical and immune factors that influence the persistence of antiphospholipid antibodies in leprosy

Abstract Introduction: Antiphospholipid antibodies (aPL) are described in individuals with leprosy without the clinical features of antiphospholipid antibody syndrome (APS), a condition involving thromboembolic phenomena. We have described the persistence of these antibodies for over 5 years in patients with leprosy after specific treatment. Objectives: To determine whether epidemiological, clinical and immunological factors played a role in the longterm persistence of aPL antibodies in leprosy patients after multidrug therapy (MDT) had finished. Methods: The study sample consisted of 38 patients with a diagnosis of leprosy being followed up at the Dermatology and Venereology Outpatient Department at the Alfredo da Matta Foundation (FUAM) in Manaus, AM. ELISA was used to detect anticardiolipin (aCL) and anti-β2 glycoprotein I (anti-β2GPI) antibodies. Patients were reassessed on average of 5 years after specific treatment for the disease (MDT) had been completed. Results: Persistence of aPL antibodies among the 38 leprosy patients was 84% (32/38), and all had the IgM isotype. Mean age was 48.1 ± 15.9 years, and 23 (72.0%) were male. The lepromatous form (LL) of leprosy was the most common (n = 16, 50%). Reactional episodes were observed in three patients (9.4%). Eighteen (47.37%) were still taking medication (prednisone and/or thalidomide). Mean IgM levels were 64 U/mL for aCL and 62 U/mL for anti-β2GPI. In the multivariate binary logistic regression the following variables showed a significant association: age (p = 0.045, OR = 0.91 and CI 95% 0.82-0.98), LL clinical presention (p = 0.034; OR = 0.02 and CI 95% = 0.0-0.76) and bacterial index (p = 0.044; OR = 2.74 and CI 95% = 1.03-7.33). We did not find association between prednisone or thalidomide doses and positivity for aPL (p = 0.504 and p = 0.670, respectively). No differences in the variables vascular thrombosis, pregnancy morbidity, diabetes, smoking and alcoholism were found between aPL-positive and aPL-negative patients. Conclusion: Persistence of positivity for aPL antibodies was influenced by age, clinical presentation and bacterial index. However, further studies are needed to elucidate the reason for this persistence, the role played by aPL antibodies in the disease and the B cell lineages responsible for generation of these antibodies.

Systemic manifestations and ulcerative skin lesions in leprosy: differential diagnosis with rheumatic diseases / Manifestações sistêmicas e ulcerações cutâneas da hanseníase: diagnóstico diferencial com outras doenças reumáticas

A hanseníase apresenta acometimento cutâneo e neurológico característicos; entretanto, as manifestações reumáticas são relativamente comuns sendo, em alguns pacientes, a queixa inicial. O presente relato de caso descreve uma paciente do sexo feminino, com hanseníase borderline, cuja manifestação inicial foi poliartrite simétrica, lesões cutâneas ulceradas em membros inferiores e manifestações sistêmicas simulando doença reumática. Os autores enfatizam a importância do diagnóstico diferencial do comprometimento sistêmico, articular e cutâneo na hanseníase com as doenças reumáticas.

Leprosy is a systemic disease with predominant involvement of skin and nerves; articular manifestations are common and, in some cases, represent the initial complaint. We describe the case of a female patient with borderline leprosy, which manifested, initially, with symmetric polyarthritis, cutaneous ulcerative lesions on the lower limbs, and systemic manifestations mimicking rheumatic disease. The authors emphasize the importance of the differential diagnosis of the systemic, joint and, cutaneous involvement of leprosy with rheumatic diseases.

Vasculite na hanseníase mimetizando doenças reumáticas / Vasculitis in leprosy mimicking rheumatic diseases

Os autores alertam para o múltiplo espectro de apresentação clínica da hanseníase, destacando as lesões cutâneas necrosantes e manifestações articulares simulando doenças reumáticas, confundindo o diagnóstico e o tratamento correto. Nesses aspectos, são relatados dois casos do sexo feminino com hanseníase virchowiana e dimorfa cujas manifestações iniciais foram de lesões eritêmato-violáceas, necróticas e ulceradas, livedo reticular, oligoartrite, poliartralgias, mialgias e edema de membros inferiores, que mimetizaram algumas doenças reumáticas como o lúpus eritematoso sistêmico e a vasculite sistêmica (poliarterite nodosa).

Leprosy has a large spectrum of clinical manifestations, including necrotizing skin lesions and joint complaints that sometimes mimic a primary rheumatic disease, confounding the correct diagnosis and treatment. Herein, the authors report two cases of women with leprosy, respectively virchowian and dimorphic forms, presenting initially with purple-reddish skin lesions, evolving with necrosis and ulceration, livedo reticularis, joint pain, oligoarthritis, myalgia, and leg edema. The differential diagnosis with systemic lupus erythematosus (SLE) and systemic vasculitis such as polyarteritis nodosa (PAN) is discussed.

Tratamento com antiinflamatórios tópicos na osteoartrite de joelho / Topical anti-inflammatory drugs in osteoarthritis of the knee

Os antiinflamatórios não-esteroidais (AINEs) orais são eficazes no alívio da dor na osteoartrite (OA), porém têm o risco de efeitos adversos sistêmicos. Para diminuir a toxicidade é necessário reduzir a concentração plasmática uma vez que os efeitos adversos são dose-dependentes. Os AINEs de uso tópico, em teoria, alcançam altas concentrações nos tecidos-alvo com concentrações plasmáticas baixas, sendo portanto uma alternativa terapêutica, especialmente para pacientes de risco. Nossa revisão dos ensaios clínicos randomizados mostrou que os AINEs tópicos foram mais efetivos que o placebo e tão eficazes quanto os AINEs orais. Porém, o pequeno número de ensaios e falhas na metodologia nos impossibilita de fazer conclusões definitivas, sendo necessários estudos bem desenhados e de maior duração.

Oral non-steroidal anti-inflammatories drugs (NSAIDs) are effective in pain relief in osteoarthritis (OA), but are also associated with risks of adverse systemic side effects. In order to reduce its toxicity, it would be desirable to decrease the plasmatic levels of NSAIDs since those side effects are dose-dependent. Topical NSAIDs would be a therapeutic alternative in theory, because while they reach high levels in local tissues, they also produce low plasmatic levels. Our review analyzed clinical randomized and shown that topical NSAIDs were superior to placebo and have similar efficacy to oral NSAIDs, but due a few number of trials and methodological weaknesses we can't make definitive conclusions. Further well designed, long term studies are required.

Avaliação por imagem do comportamento osteoarticular de nervos periféricos na hanseníase / Imaging methods evaluation in osteoarticular and peripheral nerves involvement in leprosy

Na hanseníase, lesões ósseas por invasão direta do bacilo são de baixa incidência, e os achados radiológicos destas lesões são de osteomielite aguda ou crônica similares aos de outras infecções granulomatosas. As lesões ósseas mais comuns são devidas ao trauma e a infecção secundária nos tecidos denervados. Radiograficamente, são observados vários graus de reabsorção das extremidades distais envolvendo mãos e pés, ocasionando perda dos dígitos e osteoartropatia neuropática de pequenas articulações. Os achados radiográficos são semelhantes às outras condições nas quais há déficit sensorial, como esclerodermia, siringomielia e diabetes mellitus. A ultra-sonografia (US) e a ressonância magnética (RM) podem ser úteis na avaliação do comprometimento dos nervos periféricos auxiliando no diagnóstico das neurites, abscessos e no diagnóstico diferencial das síndromes compressivas.