Myositis-specific autoantibodies, a cornerstone in immune-mediated necrotizing myopathy.

Over the past few years, myositis-specific autoantibodies played an increasing role in the inflammatory idiopathic myositis definition. They became the critical immunological marker for immune-mediated necrotizing myopathy diagnosis (IMNM) since the paradigm switch from histological to serological criteria. This review is focused on the key role of the anti-signal recognition particle (anti-SRP) and the anti-3-Hydroxy-3-MethylGlutaryl-Coenzyme A Reductase (anti-HMGCR) antibodies in immune-mediated necrotizing myopathy. Anti-SRP and anti-HMGCR antibodies are robust diagnostic tools in case of both the classical subacute form and the slowly progressive form of IMNM that may mimic muscular dystrophy. Anti-SRP and anti-HMGCR patients share clinical, biological and histological features with some antibody-associated specificity. Anti-SRP patients harbour more severe muscle weakness and atrophy with severe muscle damage on magnetic resonance imaging study. Approximately 10-20% of anti-SRP patients develop extramuscular symptoms, especially lung interstitial disease. Conversely, anti-HMGCR patients are often associated with statin exposure. In both cases, patients have a poor outcome with frequent relapse and the use of combined immunotherapy. Of note, various data suggest a direct pathogenic role of these antibodies reinforcing the interest in targeted therapeutic strategy.

Inflammatory disorders associated with trisomy 8-myelodysplastic syndromes: French retrospective case-control study.

OBJECTIVE: We report cases of myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN) with trisomy 8 associated with inflammatory and autoimmune diseases (IADs). METHOD: Data for 21 patients with trisomy 8-MDS/MPN and IADs were analyzed and compared to 103 patients with trisomy 8-MDS/MPN without IADs. RESULTS: The median age of MDS/MPN patients with IADs was 67 [59-80]. The IADs were Behçet's-like disease in 11 (52%) patients, inflammatory arthritis in 4 (19%) and Sjögren's syndrome, autoimmune hemolytic anemia, aseptic abscess, periarteritis nodosa, Sweet's syndrome and unclassified vasculitis in one patient each. Overall, 17/21 (81%) patients with IADs received treatment (88% with steroids), with complete and partial response in 7/17 (35%) and 8/17 (47%), respectively. The effect of MDS treatment on IADs could be assessed in seven patients receiving azacytidine: five achieved remission and two partial response. As compared with the 103 trisomy 8-MDS/MPN cases without IADs, those with IADs were more often non-European (P = 0.005) and had poor karyotype (P < 0.001). We found no difference in overall survival or acute myeloid leukemia progression between trisomy 8-associated MDS/MPN with and without IADs. CONCLUSION: The spectrum of IADs associated with trisomy 8-positive MDS/MPN is dominated by Behçet's-like disease. Steroid therapy is effective, but mostly sparing therapies are necessary. Azacytidine could be an effective alternative.

Gastrointestinal Behcet's-like disease with myelodysplastic neoplasms with trisomy 8: a French case series and literature review.

We report the 11 cases of +8-MDS/MPN associated with Behcet's-like syndrome and compare them with Behcet's disease and Crohn's disease, pool with literature cases for analysis. Data for patients with +8-MDS/MPN and Behçet's-like syndrome were collected from MINHEMON. Eleven patients had Behcet's-like syndrome and +8-MDS/MPN (median age 75 years [IQR 65-87]; M/F ratio 0.8). MDS and Behcet's-like syndrome were diagnosed at the same time (7/11, 64%). By comparison with 63 patients with idiopathic Behcet's disease without associated MDS, those with Behcet's-like syndrome and +8-MDS/MPN were older (median 75 vs 48 years; p = .0003) and had less pseudofolliculitis (11% vs 62%; p = .0045) and ocular impairment (0% vs 52%; p = .0008), but more frequent gastrointestinal involvement (60% vs 13%; p = .0005). By comparison with Crohn's disease, 39 patients with Behcet's-like syndrome and +8-MDS/MPN were significantly older (median 72 [53-78] vs 36 [27-45] years; p = .0002) and more frequently had oral aphtosis (97% vs 5%, p < .0001), skin features (50% vs 10%, p = .0005) and arthralgia (63% vs 20%, p = .03). Median survival did not differ between patients with Behcet's-like syndrome and +8-MDS/MPN and those with +8-MDS/MPN (n = 103) (47 vs 34 months, p = .61). AML-free survival did not differ between patients with MDS/MPN with and without Behcet's-like syndrome (p = .29). MDS/MPN with trisomy 8 can be associated with particular phenotype of ulcerative digestive disease resembling Behcet's or Crohn's disease and should be considered a single disease.