Longitudinal follow-up of mixed connective tissue disease and overlapping autoimmune diseases of childhood onset in the Afro-descendant population of the French West Indies.

INTRODUCTION: Overlap autoimmune syndromes (OAS) and mixed connective tissue disease (MCTD) are rare in children. We performed a retrospective, longitudinal and descriptive study of Afro-Caribbean patients from the French West Indies followed for MCTD and OAS to describe their characteristics and outcomes during childhood. METHODS: Retrospective study from January 2000 to 2023. Listings of patients were obtained from multiple sources: computerized hospital archives and national hospital-based surveillance system, registry of pediatricians and adult specialists in internal medicine and the national registry for rare diseases. MCTD was defined according to Kasukawa's criteria. OAS was defined as overlapping features of systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and dermatomyositis/autoimmune myositis (DM/AM). RESULTS: Sixteen patients were included over a 23-year period (10 MCTD and 6 OAS). The incidence was 0.23 per 100,000 children-years. The mean age at diagnosis was 11.9 years old (2.4-17) with median follow up of 7.9 years (2.1-19.6). SLE phenotype was present in the highest, followed by SSc and DM/AM. Patients had an average of three flares during childhood (1-7). A quarter (25%) had symptomatic pulmonary arterial hypertension (PAH). Ninety-four percent received steroids during follow-up and 88% required a corticosteroid-sparing therapy. Three patients (19%) developed SLE after more than 10y of follow-up. There were no death and no chronic organ failure. CONCLUSION: This is the largest pediatric cohort of MCTD and OAS in Afro-descendant patients treated in a country with a high standard of care. The clinical evolution did not differ between MCTD and OAS. The main complication was PAH, more frequent in our cohort.

Juvenile Dermatomyositis in Afro-Caribbean children: a cohort study in the French West Indies.

INTRODUCTION: The epidemiology of Juvenile Dermatomyositis (JDM) in non-Caucasian population is poorly described. We performed a study of patients followed up in the French West Indies for JDM. We aimed to describe clinical and biological specificities during childhood. METHODS: Retrospective study covering the period from Januarys 2000-2023. Listings of patients were obtained from multiple sources, namely computerized hospital archives, registry of referent pediatricians and adult specialists in internal medicine and the French National Registry for rare diseases. JDM and organ involvement were defined according to the international ILAR criteria. RESULTS: Twenty-one patients were included over a 23 year-period. Median age at onset was 8.1 years (Range: 2.5-13.9) with a median follow up of 8 years (Range: 2-19). Two-thirds (14/21) had dysphagia at onset and 33% had respiratory involvement. Thirteen had specific autoantibodies (58%), most frequently anti-Mi-2. The median number of flares during childhood was three (1-9). During childhood, 76% had calcinosis lesions. Clinical evolution seemed to be more aggressive for boys than girls (respectively 4.2 versus 2.2 flares (p = 0.04) and 50% vs 18% needing more than one background therapy, p = 0.03). CONCLUSION: This retrospective study is the largest cohort of pediatric patients of Afro-Caribbean and Black African descent treated for JDM in a high-income health system, and the first to describe the incidence and immunological profile in a population of African descent. They had higher rate of calcinosis and similar respiratory involvement. Overall outcomes during childhood were similar to North America and European countries.

Phenotypic Profiles Among 72 Caucasian and Afro-Caribbean Patients with Antisynthetase Syndrome Involving Anti-PL7 or Anti-PL12 Autoantibodies.

OBJECTIVES: Antisynthetase syndrome (ASyS) is a rare autoimmune disease. We aimed to determine clinical, biological, radiological, and evolutive profiles of ASyS patients with anti-PL7 or anti-PL12 autoantibodies. METHODS: We performed a retrospective study that included adults with overt positivity for anti-PL7/anti-PL12 autoantibodies and at least one Connors' criterion. RESULTS: Among 72 patients, 69% were women, 29 had anti-PL7 and 43 anti-PL12 autoantibodies, median age was 60.3 years, and median follow-up period was 52.2 months. At diagnosis, 76% of patients had interstitial lung disease, 61% had arthritis, 39% myositis, 25% Raynaud's phenomenon, 18% mechanic's hands, and 17% had fever. The most frequent pattern on initial chest computed tomography was non-specific interstitial pneumonia and 67% had fibrosis at last follow-up. During follow-up, 12 patients had pericardial effusion (18%), 19 had pulmonary hypertension (29%), 9 (12.5%) had neoplasms, and 14 (19%) died. Sixty-seven patients (93%) received at least one steroid or immunosuppressive drug. Patients with anti-PL12 autoantibodies were younger (p=0.01) and more frequently exhibited anti-SSA autoantibodies (p=0.01); patients with anti-PL7 autoantibodies had more severe weakness and higher maximum creatine kinase levels (p=0.03 and 0.04, respectively). Initial severe dyspnoea was more common in patients from the West Indies (p=0.009), with lower predicted values of forced vital capacity, forced expiratory volume in 1s, and total lung capacity (p=0.01, p=0.02, p=0.01, respectively) contributing to a more severe 'respiratory' initial presentation. CONCLUSIONS: The high mortality and significant numbers of cardiovascular events, neoplasms and lung fibrosis in anti-PL7/12 patients justify close monitoring and question addition of antifibrotic drugs.

Epidemiology, characteristics, treatments, and outcomes of adult-onset Still's disease in Afro-Caribbeans: Results from a population-based study in Martinique, French West Indies.

OBJECTIVES: To describe the epidemiology, characteristics, response to initial treatment, and outcomes of Adult-Onset Still's disease (AOSD) in the Afro-Caribbean population of Martinique with free and easy access to specialised care. METHODS: We conducted a retrospective study from 2004 to 2022 in the island of Martinique, French West-Indies which total population was 354 800 in 2021. Patients were identified from multiple sources including standardised databases. To be included, patients had to be residents of the island and fulfilled Yamaguchi and/or Fautrel's criteria for AOSD, or have a compatible disease course, without a diagnosis of cancer, auto-immune disease or another auto-inflammatory disorder. Date of diagnosis, clinical and biological characteristics, treatments, and outcomes were collected. RESULTS: The prevalence was 7.6/100 000 inhabitants in 2021. The mean incidence was 0.4/100 000 during study period. Thirty-three patients (70.6% females) with a median follow-up of 35 months [7.5 to 119] were included. Twenty-six patients (78.8%) had a systemic pattern. Patients with a systemic monocyclic pattern had significantly more polyarticular involvement than patients with systemic polycyclic pattern (p = 0.016). Pulmonary involvement occurred in 51.5% of patients at diagnosis and systemic Pouchot score has been identified as an independent predictive factor for pulmonary involvement; OR of 3.29 [CI 95% 1.20; 9.01]. At first flare, all patients but one received oral glucocorticoids, 11 patients (32.4%) received intravenous glucocorticoids pulse and 12 patients (33%) received anti-IL1 therapy. Nineteen patients (57%) relapsed in a median time of 9 months [6 to 12] Three patients (9%) developed hemophagocytosis lymphohistiocytosis, fatal in 1 case. All deceased patients (n = 4, 11.76%) belonged to the systemic polycyclic pattern, with an event-free survival of 13.6 months [IQR 5.7; 29.5] CONCLUSION: AOSD in the Afro-Caribbean population of Martinique shares some similarities with other ethnic groups, but exhibit differences, such as a high proportion of lung involvement. Comparative studies are needed to confirm these results.

Efficacy of plasma exchange in patients with anti-MDA5 rapidly progressive interstitial lung disease.

BACKGROUND: Rapidly progressive interstitial lung disease (RP-ILD) is a frequent and severe manifestation of anti-MDA5 dermatomyositis (MDA5-DM) associated with poor outcome. The optimal treatment regimen for MDA5-DM RP-ILD is yet to be determined. Specifically, the value of adding plasma exchange (PLEX) to corticosteroids and immunosuppressants remains unclear. We aimed to evaluate the effect of PLEX on the outcome of patients with MDA5-DM RP-ILD. METHODS: This French nationwide multicentre retrospective study included all MDA5-DM RP-ILD patients from 2012 to 2021 admitted to 18 centres. The primary endpoint was one-year transplant-free survival. RESULTS: 51 patients with MDA5-DM RP-ILD (female 67%; mean age at disease onset: 51 ± 11.6 years) were included. Thirty-two (63%) patients required mechanical ventilation and twenty-five (49%) received PLEX. One-year mortality or lung transplant occurred in 63% cases after a median follow-up of 77 [38-264] days. The Cox proportional hazards multivariable model only retained mechanical ventilation but not PLEX (p = 0.7) as independent predictor of the primary endpoint. One-year transplant-free survival rates in PLEX + vs. PLEX-were 20% vs. 54% (p = 0.01), respectively. The Kaplan-Meier estimated probabilities of one-year transplant-free survival was statistically higher in PLEX-compared to PLEX + patients (p = 0.05). PLEX + compared to PLEX-patients more frequently received mechanical ventilation and immunosuppressants suggesting PLEX + patients had a more severe disease. CONCLUSION: MDA5-DM RP-ILD is associated with poor rate of one-year transplant-free survival. The use of PLEX was not associated with a better outcome albeit they were mainly given to more severe patients. While our study reports the largest series of MDA5-DM RP-ILD given PLEX, these results needs to be interpreted with caution owing the numerous selection, indication and interpretation bias. Further studies are needed to evaluate their efficacy in this setting.

Systemic lupus of pediatric onset in Afro-Caribbean children: a cohort study in the French West Indies and French Guiana.

BACKGROUND: Systemic diseases of pediatric onset are more frequent in the Afro-Caribbean population. We performed a study of patients followed in the French overseas departments of America (FOAD) for pediatric systemic lupus erythematosus (pSLE). The aims were to describe the clinical and biological specificities during childhood in this population. METHODS: A retrospective study was conducted between January 2000 and September 2021. Patients with pSLE were identified from multiple sources: computerized hospital archives, registry of referring pediatricians, adult specialists in internal medicine and the French National Registry for rare diseases. We studied SLE with pediatric onset defined by international criteria. RESULTS: Overall, 2148 patients were identified, of whom 54 were included. The average follow-up was 8.3 years (range: 0.3-25 years). We observed an increase in new diagnoses over time. At onset, pSLE patients had a median of 10 SLICC criteria (range: 4-12), and the median EULAR/ACR 2019 score was 38 (12-54). At onset, one third of patients had renal involvement, 15% had neurolupus and 41% cardiac involvement. During childhood, 54% had renal involvement, and 26% suffered from neurolupus. Patients suffered a median of 3 flares during childhood, and 26% had more than 5 flares. Patients with younger age at onset had worse outcomes than those who were older at diagnosis, i.e., more flares (median 5, p = 0.02) and requiring an average of 4 background therapies (p = 0.04). CONCLUSION: The outcomes of Afro-Caribbean patients were similar to those in Western population, but with worse disease activity at onset. Further studies should be performed to identify the genetic and environmental factors in this population.

Good Long-Term Prognosis of Lupus Nephritis in the High-Income Afro-Caribbean Population of Martinique with Free Access to Healthcare.

Lupus nephritis (LN) has been described as having worse survival and renal outcomes in African-descent patients than Caucasians. We aimed to provide long-term population-based data in an Afro-descendant cohort of LN with high income and easy and free access to specialized healthcare. STUDY DESIGN: We performed a retrospective population-based analysis using data from 2002-2015 of 1140 renal biopsies at the University Hospital of Martinique (French West Indies). All systemic lupus erythematosus patients with a diagnosis of LN followed for at least 12 months in Martinique or who died during this period were included. RESULTS: A total of 89 patients were included, of whom 68 (76.4%) had proliferative (class III or IV), 17 (19.1%) had membranous (class V), and 4 (4.5%) had class I or II lupus nephritis according to the ISN/RPS classification. At a mean follow-up of 118.3 months, 51.7% of patients were still in remission. The rates of end-stage renal disease were 13.5%, 19.1%, and 21.3% at 10, 15, and 20 years of follow-up, respectively, and mortality rates were 4.5%, 5.6%, and 7.9% at 10, 15, and 20 years of follow-up, respectively. CONCLUSIONS: The good survival of our Afro-descendant LN patients, similar to that observed in Caucasians, shades the burden of ethnicity but rather emphasizes and reinforces the importance of optimizing all modifiable factors associated with poor outcome, especially socioeconomics.

Aseptic Abscess Syndrome: Clinical Characteristics, Associated Diseases, and up to 30 Years' Evolution Data on a 71-Patient Series.

Aseptic abscess (AA) syndrome is a rare type of inflammatory disorder involving polymorphonuclear neutrophils (PMNs), often associated with inflammatory bowel disease (IBD). This study sought to describe the clinical characteristics and evolution of this syndrome in a large cohort. We included all patients included in the French AA syndrome register from 1999 to 2020. All patients fulfilled the criteria outlined by André et al. in 2007. Seventy-one patients were included, 37 of which were men (52.1%), of a mean age of 34.5 ± 17 years. The abscesses were located in the spleen (71.8%), lymph nodes (50.7%), skin (29.5%), liver (28.1%), lung (22.5), and rarer locations (brain, genitals, kidneys, ENT, muscles, or breasts). Of all the patients, 59% presented with an associated disease, primarily IBD (42%). They were treated with colchicine (28.1%), corticosteroids (85.9%), immunosuppressants (61.9%), and biologics (32.3%). A relapse was observed in 62% of cases, mostly in the same organ. Upon multivariate analysis, factors associated with the risk of relapse were: prescription of colchicine (HR 0.52; 95% CI [0.28-0.97]; p = 0.042), associated IBD (HR 0.57; 95% CI [0.32-0.99]; p = 0.047), and hepatic or skin abscesses at diagnosis (HR 2.14; 95% CI [1.35-3.40]; p = 0.001 and HR 1.78; 95% CI [1.07-2.93]; p = 0.024, respectively). No deaths occurred related to this disease. This large retrospective cohort study with long follow up showed that AA syndrome is a relapsing systemic disease that can evolve on its own or be the precursor of an underlying disease, such as IBD. Of all the available treatments, colchicine appeared to be protective against relapse.

Weaning of maintenance immunosuppressive therapy in lupus nephritis (WIN-Lupus): results of a multicentre randomised controlled trial.

OBJECTIVES: Lupus nephritis (LN) is a frequent complication of systemic lupus erythematosus (SLE). Severe (proliferative) forms of LN are treated with induction immunosuppressive therapy (IST), followed by maintenance IST, to target remission and avoid relapses. The optimal duration of maintenance IST is unknown. The WIN-Lupus trial tested whether IST discontinuation after 2‒3 years was non-inferior to IST continuation for two more years in proliferative LN. METHODS: WIN-Lupus was an investigator-initiated multicentre randomised controlled trial. Patients receiving maintenance IST with azathioprine or mycophenolate mofetil for 2-3 years, and hydroxychloroquine, were randomised (1:1) into two groups: (1) IST continuation and (2) IST discontinuation. The primary endpoint was the relapse rate of proliferative LN at 24 months. Main secondary endpoints were the rate of severe SLE flares, survival without renal relapse or severe flare, adverse events. RESULTS: Between 2011 and 2016, 96 patients (out of 200 planned) were randomised in WIN-Lupus: IST continuation group (n=48), IST discontinuation group (n=48). Relapse of proliferative LN occurred in 5/40 (12.5%) patients with IST continuation and in 12/44 (27.3%) patients with IST discontinuation (difference 14.8% (95% CI -1.9 to 31.5)). Non-inferiority was not demonstrated for relapse rate; time to relapse did not differ between the groups. Severe SLE flares (renal or extrarenal) were less frequent in patients with IST continuation (5/40 vs 14/44 patients; p=0.035). Adverse events did not differ between the groups. CONCLUSIONS: Non-inferiority of maintenance IST discontinuation after 2‒3 years was not demonstrated for renal relapse. IST discontinuation was associated with a higher risk of severe SLE flares. TRIAL REGISTRATION NUMBER: NCT01284725.

Health Outcomes of 215 Mothers of Children With Autoimmune Congenital Heart Block: Analysis of the French Neonatal Lupus Syndrome Registry.

OBJECTIVE: Transplacental passage of maternal anti-SSA and anti-SSB antibodies, potentially associated with maternal autoimmune diseases, can cause neonatal lupus syndrome. Given the paucity of data in this setting, we report short- and long-term outcomes of mothers of offspring with congenital heart block (CHB). METHODS: This retrospective study included anti-SSA/SSB antibody-positive mothers of fetuses with high-degree CHB and focused on their health status before pregnancy, at CHB diagnosis, and thereafter. RESULTS: We analyzed 215 women with at least 1 pregnancy with CHB. Prior to this diagnosis, only 52 (24%) mothers had been diagnosed with an autoimmune disease, mainly systemic lupus erythematosus (SLE; n = 26, 12%) and Sjögren syndrome (SS; n = 16, 7%). Six more were diagnosed with an autoimmune disease during the index pregnancy. Of the 157 mothers (73%) with no such diagnosis at childbirth, 77 (49%) developed one after a median follow-up of 11 years (range: 21 days to 54 years). By the end of follow-up, 135 women (63%) had an autoimmune disease diagnosis, mainly SLE (n = 54, 25%) and SS (n = 72, 33%). Three patients with SLE had renal involvement, and only 6 (3%) had required an immunosuppressive drug at any point. The symptoms best predicting autoimmune disease development were arthralgia and myalgia (P < 0.001), dry syndrome (P = 0.01), and parotid swelling (P = 0.05). CONCLUSION: One-quarter of the patients had an autoimmune disease diagnosis at the time of the fetal CHB diagnosis. Nearly half of those without an initial diagnosis progressed during follow-up, most without severe manifestations. Severe diseases such as lupus nephritis were rarely seen, and immunosuppressive drugs were rarely required.

Epidemiology and Characteristics of Spondyloarthritis in the Predominantly Afro-Descendant Population of Martinique, a French Caribbean Island.

(1) Background: The prevalence of Spondyloarthritis (SpA) varies significantly in different regions and ethnic groups due several factors such as heterogeneity in study populations, the diversity of classification criteria used in epidemiological studies, the prevalence variability of HLA-B27 or disparity in healthcare access. To our knowledge, there is no data on SpA in Martinique, a French region in the Caribbean with a predominantly Afro-descendant population and a high level of healthcare. (2) Methods: This was a retrospective study of all SpA patients treated at the Fort de France University Hospital between 1 January 1997 and 1 January 2008. (3) Results: In our cohort of 86 SpA patients, age at diagnosis was late (41 years old), ankylosing spondylitis (AS) was the most frequent sub-type (60.5%), inflammatory bowel disease was the most frequent extra articular feature (23.3%) and no one had personal familial history of the disease. Inflammatory syndrome concerned 55.6% of patients, no one was positive for HIV and HLA-B27 positivity was low (42.2%). However, HLA-B27 was statistically associated with AS. Out of 64 patients, 41 had sacroiliitis. (4) Conclusion: To our knowledge, this is the first comprehensive descriptive study of SpA subtypes in Martinique, a French region in the Caribbean. We report clinical and biological similarities in our SpA cohort with those of sub-Saharan Africa and with SpA subtypes reported in Afro-descendant populations.

The Clinicopathological Spectrum of Kidney Lesions in Chikungunya Fever: A Report of 5 Cases With Kidney Biopsy.

Chikungunya nephropathy is an uncommon etiology of acute kidney injury, associated with the mosquito-borne chikungunya arbovirus (CHIKV). The very limited number of pathologic reports to date have only involved postmortem analyses. We here report 5 cases of acute kidney injury for which kidney biopsies were performed in patients with confirmed acute CHIKV infection, during the recent outbreak of chikungunya disease in the French West Indies. The patients ranged from 42 to 76 years of age. All of the patients developed kidney injury, 3 of whom required short-term dialysis and underwent a kidney biopsy. Analysis of kidney biopsies revealed 2 main histopathologic patterns: acute interstitial nephritis with predominant lymphoid inflammation and acute tubular injury. Epithelioid granulomas were observed in 2 cases. There were no glomerular lesions, except in biopsies from 2 patients, including 1 with a previous known primary focal segmental glomerulosclerosis. CHIKV antigen immunofluorescence microscopy revealed staining in tubular cells. In all of the cases, the short-term outcome was favorable, with recovery of kidney function.

Renal involvement in eosinophilic granulomatosis with polyangiitis (EGPA): a multicentric retrospective study of 63 biopsy-proven cases.

OBJECTIVE: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic small-vessel vasculitis characterized by asthma, hypereosinophilia and ANCA positivity in 40% of patients. Renal involvement is rare and poorly described, leading to this renal biopsy-proven based study in a large EGPA cohort. METHODS: We conducted a retrospective multicentre study including patients fulfilling the 1990 ACR criteria and/or the 2012 revised Chapel Hill Consensus Conference criteria for EGPA and/or the modified criteria of the MIRRA trial, with biopsy-proven nephropathy. RESULTS: Sixty-three patients [27 women, median age 60 years (18-83)] were included. Renal disease was present at vasculitis diagnosis in 54 patients (86%). ANCA were positive in 53 cases (84%) with anti-MPO specificity in 44 (83%). All patients had late-onset asthma. Peripheral neuropathy was present in 29 cases (46%), alveolar haemorrhage in 10 (16%). The most common renal presentation was acute renal failure (75%). Renal biopsy revealed pauci-immune necrotizing GN in 49 cases (78%). Membranous nephropathy (10%) and membranoproliferative GN (3%) were mostly observed in ANCA-negative patients. Pure acute interstitial nephritis was found in six cases (10%); important interstitial inflammation was observed in 28 (44%). All patients received steroids with adjunctive immunosuppression in 54 cases (86%). After a median follow-up of 51 months (1-296), 58 patients (92%) were alive, nine (14%) were on chronic dialysis and two (3%) had undergone kidney transplantation. CONCLUSION: Necrotizing pauci-immune GN is the most common renal presentation in ANCA-positive EGPA. ANCA-negative patients had frequent atypical renal presentation with other glomerulopathies such as membranous nephropathy. An important eosinophilic interstitial infiltration was observed in almost 50% of cases.

Use of Biologics to Treat Relapsing and/or Refractory Eosinophilic Granulomatosis With Polyangiitis: Data From a European Collaborative Study.

OBJECTIVE: To describe the efficacy and safety of biologics for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: A retrospective European collaborative study was conducted in patients with EGPA who received treatment with biologics for refractory and/or relapsing disease. RESULTS: Among the 147 patients with EGPA included in the study, 63 received rituximab (RTX), 51 received mepolizumab (MEPO), and 33 received omalizumab (OMA). At the time of inclusion, the median Birmingham Vasculitis Activity Score (BVAS) was 8.5 (interquartile range [IQR] 5-13) in the RTX group, while the median BVAS in the OMA group was 2 (IQR 1-4.5) and the median BVAS in the MEPO group was 2 (IQR 1-5). In patients receiving RTX, the median BVAS declined both at 6 months (median 1, IQR 0-4.5) and at 12 months (median 0, IQR 0-2), and the frequency of remission, partial response, treatment failure, and stopping treatment due to adverse events was 49%, 24%, 24%, and 3%, respectively. For the treatment of glucocorticoid (GC)-dependent asthma, patients who received MEPO had a much better GC-sparing effect and overall response than did patients who received OMA. The frequency of remission, partial response, treatment failure, and stopping treatment due to adverse events was 15%, 33%, 48%, and 4%, respectively, in the OMA group and 78%, 10%, 8%, and 4%, respectively, in the MEPO group. Remission rates at 12 months were 76% and 82% among patients receiving MEPO at a doses of 100 mg and 300 mg, respectively. CONCLUSION: These results suggest that RTX could be effective in treating relapses of EGPA vasculitis. MEPO is highly effective with a good safety profile in patients with GC-dependent asthma. Our data suggest that 100 mg MEPO monthly could be an acceptable dosage for first-line therapy in selected instances of EGPA, recognizing, however, that this has not been compared to the validated dosage of 300 mg monthly.

Different phenotypes in dermatomyositis associated with anti-MDA5 antibody: Study of 121 cases.

OBJECTIVES: The predominance of extramuscular manifestations (e.g., skin rash, arthralgia, interstitial lung disease [ILD]) as well as the low frequency of muscle signs in anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5+) dermatomyositis caused us to question the term myositis-specific antibody for the anti-MDA5 antibody, as well as the homogeneity of the disease. METHODS: To characterize the anti-MDA5+ phenotype, an unsupervised analysis was performed on anti-MDA5+ patients (n = 83/121) and compared to a group of patients with myositis without anti-MDA5 antibody (anti-MDA5-; n = 190/201) based on selected variables, collected retrospectively, without any missing data. RESULTS: Within anti-MDA5+ patients (n = 83), 3 subgroups were identified. One group (18.1%) corresponded to patients with a rapidly progressive ILD (93.3%; p < 0.0001 across all) and a very high mortality rate. The second subgroup (55.4%) corresponded to patients with pure dermato-rheumatologic symptoms (arthralgia; 82.6%; p < 0.01) and a good prognosis. The third corresponded to patients, mainly male (72.7%; p < 0.0001), with severe skin vasculopathy, frequent signs of myositis (proximal weakness: 68.2%; p < 0.0001), and an intermediate prognosis. Raynaud phenomenon, arthralgia/arthritis, and sex permit the cluster appurtenance (83.3% correct estimation). Nevertheless, an unsupervised analysis confirmed that anti-MDA5 antibody delineates an independent group of patients (e.g., dermatomyositis skin rash, skin ulcers, calcinosis, mechanic's hands, ILD, arthralgia/arthritis, and high mortality rate) distinct from anti-MDA5- patients with myositis. CONCLUSION: Anti-MDA5+ patients have a systemic syndrome distinct from other patients with myositis. Three subgroups with different prognosis exist.

Immune thrombotic thrombocytopenic purpura in older patients: prognosis and long-term survival.

Older age is associated with increased mortality in immune thrombotic thrombocytopenic purpura (iTTP). Yet, data are scarce regarding iTTP occurring among older patients. To assess clinical features and long-term impact of iTTP on mortality in older patients (>60 years old), characteristics and prognoses of adult iTTP patients enrolled in the French Reference Center for Thrombotic Microangiopathies registry between 2000 and 2016 were described according to age (<60 years old or ≥60 years old). Long-term mortality of iTTP older survivors was compared with that of non-iTTP geriatric subjects. Comparing, respectively, older iTTP patients (N = 71) with younger patients (N = 340), time from hospital admission to diagnosis was longer (P < .0001); at diagnosis, delirium (P = .034), behavior impairment (P = .045), renal involvement (P < .0001), and elevated troponin level (P = .025) were more important whereas cytopenias were less profound (platelet count, 22 × 103/mm3 [9-57] vs 13 × 103/mm3 [9-21], respectively [P = .002]; hemoglobin level, 9 g/dL [8-11] vs 8 g/dL [7-10], respectively [P = .0007]). Short- and mid-term mortalities were higher (P < .0001) and increased for every 10 years of age range. Age ≥60 years, cardiac involvement, increased plasma creatinine level, and total plasma exchange volume were independently associated with 1-month mortality. Compared with a non-iTTP geriatric population, older survivors showed an increased long-term mortality (hazard ratio = 3.44; P < .001). In conclusion, older iTTP patients have atypical neurological presentation delaying the diagnosis. Age negatively impacts short-term but also long-term mortality.

Autologous haematopoietic stem cell transplantation (AHSCT) in autoimmune disease adult patients in France: analysis of the long-term outcome from the French Society for Bone Marrow Transplantation and Cellular Therapy (SFGM-TC).

INTRODUCTION: The use of autologous haematopoietic stem cell transplantation (AHSCT) in autoimmune disease (AD) patients has increased progressively worldwide. We retrospectively analysed the long-term outcome of AHSCT for AD reported to the French Society for Bone Marrow Transplantation and Cellular Therapy (SFGM-TC). METHOD: All French AD patients (≥ 18 years at transplant) with a first AHSCT between 1997 and 2013 were included. Primary data were derived from the European Society for Blood and Marrow Transplantation (EBMT) registry, and additional data were obtained through a specific questionnaire designed for the study. Primary end-point was overall survival (OS). Secondary end points were progression-free survival (PFS) and non-relapse mortality (NRM). RESULTS: Ninety-four AD patients were included, of whom 71% suffered from rheumatologic diseases (n = 67, including 56 systemic sclerosis (SSc)), 16% from neurological disease (n = 15, including 14 multiple sclerosis (MS)) and 13% from various other AD (n = 12). After a median (interquartile range, IQR) follow-up of 83 months (38-130), OS at 5 and 10 years were 77% (95% CI 68.5-86.2) and 64% (95% CI 51.7-76.3), and for PFS 51% (95% CI 40.4-61.6) and 44% (95% CI 32.8-55.3), respectively. Overall, NRM was 8.7% (95% CI 4.0-15.5) at day 100, 9.8% (95% CI 4.8-16.9) at 5 years and 13.6% (95% CI 6.9-22.5) at 10 years. CONCLUSIONS: This first SFGM-TC retrospective report shows long-term benefit of AHSCT in AD patients with acceptable toxicity.