Prévalence de la maladie fibrosclérosante à IgG4 dans les syndromes secs

La maladie fibrosclérosante à IgG4 (MFS IgG4) est un processus fibrosant caractérisé par sa richesse en plasmocytes sécrétant des IgG4 et pouvant atteindre pratiquement tous les organes. Nous avons mené une étude prospective pendant 2 ans pour déterminer si des stigmates de MFS IgG4 étaient présents chez des patients se plaignant d'un syndrome sec buccal. Parmi 60 patients occidentaux présentant un syndrome sec, 30% semble présenter une atteinte salivaire de la MFS IgG4. Les résultats de notre étude suggèrent qu'il existe certainement d'autres formes cliniques d'atteinte salivaire de la MSF IgG4 que la maladie de Mikulicz ou la tumeur de Küttner chez les patients non asiatiques avec en particulier une faible prévalence du gonflement salivaire. Cette atteinte salivaire est probablement sous estimée dans la pratique quotidienne et constitue vraisemblablement une étiologie de fréquence non négligeable de syndrome sec buccal. Des formes de chevauchement entre syndrome de Gougerot Sjögren (SGS) et maladie fibro-sclérosante à IgG4 semblent exister dans une faible proportion. Au vu de notre étude, il nous semble pertinent d'évoquer une atteinte salivaire de la MFS IgG4 et donc de réaliser un immunomarquage tissulaire avec l'anticorps anti IgG4 sur biopsie de glandes salivaires accessoires, devant un syndrome sec ne répondant pas aux critères de SGS. L'évaluation de l'efficacité de la corticothérapie sur les symptômes de sécheresse des patients présentant une atteinte des glandes salivaires accessoires à IgG4 nécessiterait de plus grands effectifs mais cette option thérapeutique semble licite.CLERMONT FD-BCIU-Santé (631132104) / SudocSudocFranceF

Infectious sacroiliitis: a retrospective, multicentre study of 39 adults

BACKGROUND: Non-brucellar and non-tuberculous infectious sacroiliitis (ISI) is a rare disease, with misleading clinical signs that delay diagnosis. Most observations are based on isolated case reports or small case series. Our aim was to describe the clinical, bacteriological, and radiological characteristics of ISI, as well as the evolution of these arthritis cases under treatment. METHODS: This retrospective study included all ISI cases diagnosed between 1995 and 2011 in eight French rheumatology departments. ISI was diagnosed if sacroiliitis was confirmed bacteriologically or, in the absence of pathogenic agents, if clinical, biological, and radiological data was compatible with this diagnosis and evolution was favourable under antibiotic therapy. RESULTS: Overall, 39 cases of ISI were identified in adults, comprising 23 women and 16 men, with a mean age at diagnosis of 39.7 ± 18.1 years. The left sacroiliac joint (SI) was affected in 59% of cases, with five cases occurring during the post-partum period. Lumbogluteal pain was the most common symptom (36/39). Manipulations of the SI joint were performed in seven patients and were always painful. Mean score for pain using the visual analogue score was 7.3/10 at admission, while 16 patients were febrile at diagnosis. No risk factor was found for 30.7% of patients. A diagnosis of ISI was only suspected in five cases at admission. The mean time to diagnosis was long, being 43.3 ± 69.1 days on average. Mean C-reactive protein was 149.7 ± 115.3 mg/l, and leukocytosis (leukocytes ≥ 10 G/l) was uncommon (n = 15) (mean level of leukocytes 10.4 ± 3.5 G/l). Radiographs (n = 33) were abnormal in 20 cases, revealing lesions of SI, while an abdominopelvic computed tomography (CT) scan (n = 27) was abnormal in 21 cases, suggesting arthritis of the SI joints in 13 cases (48.1%) and a psoas abscess in eight. Bone scans (n = 14) showed hyperfixation of the SI in 13 cases. Magnetic resonance imaging (MRI) (n = 27), when focused on the SI (n = 25), directed towards the diagnosis to ISI in 25 cases. Pathogenic agents were isolated in 33 cases (84.6%) by means of articular puncture (n = 16), blood culture (n = 14), cytobacteriological examination of urine (n = 2), or puncture of the psoas (n = 1). Gram-positive cocci were the mostly isolated common bacteria, with a predominance of staphylococci (n = 21). The most frequently isolated gram-negative bacillus was Pseudomonas aeruginosa (n = 3). Evolution was favourable in 37 out of 39 patients under prolonged antibiotic therapy (mean duration 3.01 ± 1.21 months). CONCLUSION: Our series confirmed that the clinical manifestations of ISI usually lead to delayed diagnosis. Based on our results, we suggest performing an MRI of the spine and SI in clinical situations characterised by lumbogluteal pain and symptoms of an infectious disease, such as fever

Use of biologics to treat relapsing and/or refractory polyarteritis nodosa: data from a European collaborative study

OBJECTIVES: To describe the effectiveness and safety of biologics for the treatment of relapsing and/or refractory polyarteritis nodosa (PAN). METHODS: A retrospective European collaborative study was conducted in patients with PAN who received biologics for relapsing and/or refractory disease. RESULTS: Forty-two patients with PAN received a total of 53 biological courses, including TNF-alpha blockers in 15 cases, rituximab (RTX) in 18 cases, tocilizumab (TCZ) in 10 cases, and other biologics in 10 cases. TNF-alpha blockers and TCZ were mainly used for refractory diseases whereas RTX was mainly initiated for relapsing disease. After a median follow-up of 29 (8-50) months, remission occurred in 40%, partial response in 13%, treatment failure in 40% and treatment discontinuation due to severe adverse events in 7% of patients receiving TNF-alpha blockers, 50%, none, 30% and 20% of TCZ recipients, and 33%, 11%, 56% and none of the RTX recipients, respectively. No remission was noted in patients treated with other biologics. Severe adverse events were observed in 14 (28%) patients without significant differences between the 3 biologics, leading to early biologics discontinuation in only 3 cases. CONCLUSION: These results suggest that TCZ may be effective in relapsing and/or refractory PAN. Our data warrant further study to confirm these findings

Severity of COVID-19 and survival in patients with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 patients

International audienceObjectives: There is little known about the impact of SARS-CoV-2 on patients with inflammatory rheumatic and musculoskeletal diseases (iRMD). We examined epidemiological characteristics associated with severe disease, then with death. We also compared mortality between patients hospitalised for COVID-19 with and without iRMD.Methods: Individuals with suspected iRMD-COVID-19 were included in this French cohort. Logistic regression models adjusted for age and sex were used to estimate adjusted ORs and 95% CIs of severe COVID-19. The most significant clinically relevant factors were analysed by multivariable penalised logistic regression models, using a forward selection method. The death rate of hospitalised patients with iRMD-COVID-19 (moderate-severe) was compared with a subset of patients with non-iRMD-COVID-19 from a French hospital matched for age, sex, and comorbidities.Results: Of 694 adults, 438 (63%) developed mild (not hospitalised), 169 (24%) moderate (hospitalised out of the intensive care unit (ICU) and 87 (13%) severe (patients in ICU/deceased) disease. In multivariable imputed analyses, the variables associated with severe infection were age (OR=1.08, 95% CI: 1.05-1.10), female gender (OR=0.45, 95% CI: 0.25-0.80), body mass index (OR=1.07, 95% CI: 1.02-1.12), hypertension (OR=1.86, 95% CI: 1.01-3.42), and use of corticosteroids (OR=1.97, 95% CI: 1.09-3.54), mycophenolate mofetil (OR=6.6, 95% CI: 1.47-29.62) and rituximab (OR=4.21, 95% CI: 1.61-10.98). Fifty-eight patients died (8% (total) and 23% (hospitalised)). Compared with 175 matched hospitalised patients with non-iRMD-COVID-19, the OR of mortality associated with hospitalised patients with iRMD-COVID-19 was 1.45 (95% CI: 0.87-2.42) (n=175 each group).Conclusions: In the French RMD COVID-19 cohort, as already identified in the general population, older age, male gender, obesity, and hypertension were found to be associated with severe COVID-19. Patients with iRMD on corticosteroids, but not methotrexate, or tumour necrosis factor alpha and interleukin-6 inhibitors, should be considered as more likely to develop severe COVID-19. Unlike common comorbidities such as obesity, and cardiovascular or lung diseases, the risk of death is not significantly increased in patients with iRMD

Severity of COVID-19 and survival in patients with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 patients

International audienceObjectives: There is little known about the impact of SARS-CoV-2 on patients with inflammatory rheumatic and musculoskeletal diseases (iRMD). We examined epidemiological characteristics associated with severe disease, then with death. We also compared mortality between patients hospitalised for COVID-19 with and without iRMD.Methods: Individuals with suspected iRMD-COVID-19 were included in this French cohort. Logistic regression models adjusted for age and sex were used to estimate adjusted ORs and 95% CIs of severe COVID-19. The most significant clinically relevant factors were analysed by multivariable penalised logistic regression models, using a forward selection method. The death rate of hospitalised patients with iRMD-COVID-19 (moderate-severe) was compared with a subset of patients with non-iRMD-COVID-19 from a French hospital matched for age, sex, and comorbidities.Results: Of 694 adults, 438 (63%) developed mild (not hospitalised), 169 (24%) moderate (hospitalised out of the intensive care unit (ICU) and 87 (13%) severe (patients in ICU/deceased) disease. In multivariable imputed analyses, the variables associated with severe infection were age (OR=1.08, 95% CI: 1.05-1.10), female gender (OR=0.45, 95% CI: 0.25-0.80), body mass index (OR=1.07, 95% CI: 1.02-1.12), hypertension (OR=1.86, 95% CI: 1.01-3.42), and use of corticosteroids (OR=1.97, 95% CI: 1.09-3.54), mycophenolate mofetil (OR=6.6, 95% CI: 1.47-29.62) and rituximab (OR=4.21, 95% CI: 1.61-10.98). Fifty-eight patients died (8% (total) and 23% (hospitalised)). Compared with 175 matched hospitalised patients with non-iRMD-COVID-19, the OR of mortality associated with hospitalised patients with iRMD-COVID-19 was 1.45 (95% CI: 0.87-2.42) (n=175 each group).Conclusions: In the French RMD COVID-19 cohort, as already identified in the general population, older age, male gender, obesity, and hypertension were found to be associated with severe COVID-19. Patients with iRMD on corticosteroids, but not methotrexate, or tumour necrosis factor alpha and interleukin-6 inhibitors, should be considered as more likely to develop severe COVID-19. Unlike common comorbidities such as obesity, and cardiovascular or lung diseases, the risk of death is not significantly increased in patients with iRMD

COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases treated with rituximab: a cohort study

International audienceBackground: Various observations have suggested that the course of COVID-19 might be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases receiving rituximab compared with those not receiving rituximab. We aimed to investigate whether treatment with rituximab is associated with severe COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases.Methods: In this cohort study, we analysed data from the French RMD COVID-19 cohort, which included patients aged 18 years or older with inflammatory rheumatic and musculoskeletal diseases and highly suspected or confirmed COVID-19. The primary endpoint was the severity of COVID-19 in patients treated with rituximab (rituximab group) compared with patients who did not receive rituximab (no rituximab group). Severe disease was defined as that requiring admission to an intensive care unit or leading to death. Secondary objectives were to analyse deaths and duration of hospital stay. The inverse probability of treatment weighting propensity score method was used to adjust for potential confounding factors (age, sex, arterial hypertension, diabetes, smoking status, body-mass index, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure, and the underlying disease [rheumatoid arthritis vs others]). Odds ratios and hazard ratios and their 95% CIs were calculated as effect size, by dividing the two population mean differences by their SD. This study is registered with ClinicalTrials.gov, NCT04353609.Findings: Between April 15, 2020, and Nov 20, 2020, data were collected for 1090 patients (mean age 55·2 years [SD 16·4]); 734 (67%) were female and 356 (33%) were male. Of the 1090 patients, 137 (13%) developed severe COVID-19 and 89 (8%) died. After adjusting for potential confounding factors, severe disease was observed more frequently (effect size 3·26, 95% CI 1·66-6·40, p=0·0006) and the duration of hospital stay was markedly longer (0·62, 0·46-0·85, p=0·0024) in the 63 patients in the rituximab group than in the 1027 patients in the no rituximab group. 13 (21%) of 63 patients in the rituximab group died compared with 76 (7%) of 1027 patients in the no rituximab group, but the adjusted risk of death was not significantly increased in the rituximab group (effect size 1·32, 95% CI 0·55-3·19, p=0·53).Interpretation: Rituximab therapy is associated with more severe COVID-19. Rituximab will have to be prescribed with particular caution in patients with inflammatory rheumatic and musculoskeletal diseases

Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry

Objectives: To determine factors associated with COVID-19-related death in people with rheumatic diseases. Methods: Physician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category. Results: Of 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death. Conclusion: Among people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants