https://orcid.org/0000-0002-5336-4751
Myelodysplastic syndromes are associated in 10–30% to auto-immune diseases (ADs). It has been reported that mutations of the ten-eleven-translocation 2 (TET2) are associated with an increased risk of AD. We described here the case of a necrotizing myopathy associated with a TET2 mutated myelodysplastic syndrome.
Introduction
Myelodysplastic syndromes (MDS) are characterized by a clonal hematopoietic stem cell disorder resulting in ineffective hematopoiesis and cytopenias.
MDS are associated in 10–30% of patients with auto-immune diseases (ADs) such as connective tissue diseases (CTD) or auto-immune thrombocytopenia.1
Inflammatory myopathies are a particular group of CTD. Diagnosis is based on muscle weakness associated with auto-antibodies detection, hyperintensity in muscle magnetic resonance imaging (MRI) and histologic abnormalities depending on the type of myositis.2
Only a few cases of MDS-associated inflammatory myositis have been reported so far, mainly dermatomyositis.3 We report here the occurrence of a severe necrotizing myositis in a 66-year-old patient with multilineage dysplasia (MDS-DML).
Case report
A 66-year-old patient with a history of pulmonary embolism, gastroesophageal reflux and MDS was admitted to our unit, presenting with myalgias, dyspnea and edema.
The patient had been previously diagnosed with MDS-DML with normal karyotype and two mutations of the ten-eleven-translocation 2 (TET2) gene in 2013. He underwent an allogeneic stem cell transplantation, but unfortunately, he presented mixed chimerism and then a secondary graft failure. The hypomethylating agent 5-Azacytidine was administrated for four cycles without hematologic response and then was stopped. Supportive treatment with granulocyte colony-stimulating factor and darbepoetin-alfa was initiated, which were his only treatment at the time of the admission to our department.
Physical examination found fever, no skin lesion, leg edema, diffuse myalgia and severe global muscle weakness. Creatine phosphokinase was 763 IU (N < 170), C-reactive protein 58 mg/l, hemoglobin level 7.5 g/dl, platelets count 282 G/l and white cell count 6.6 G/l.
Bone marrow aspiration found no progressive disease. Antinuclear antibody detection was positive (titer 1/640) with a nucleolar pattern and a specificity for anti-SSA52 and anti-Sm antibodies. Dot-myositis, anti-mitochondria, anti-smooth muscles, anti-Liver and Kidney Microsome (anti-LKM), anti-Soluble Liver Antigen (anti-SLA), anti-Liver Cytosol1 (anti-LC1) and anti-3-Hydroxy-3-MethylGlutaryl-Coenzyme A reductase (anti-HMG CoA reductase) antibodies were negative.
The thoraco-abdominopelvic computed tomography scan showed no signs of neoplasia nor deep infection and the muscle MRI was in favor of a diffuse muscle inflammation. Finally, the muscle biopsy revealed muscle necrosis, an interstitial T-lymphocytes infiltrate without vasculitis, associated with a diffuse class I Human Leucocyte Antigen (HLA) hyperexpression and a few C5b9 depositions (Figure 1). In the light of these results, the patient was diagnosed with immune necrotizing myopathy.
Histologic study of the muscle biopsy from the left quadriceps. (A) Regenerative and necrotic muscle fibers with moderate mononuclear leucocyte in hematoxylin phloxine saffron stain: ×100. (B) T CD8+ lymphocytes in immunolabeling with anti-CD8 antibodies: ×200.
The patient received daily infusions of 250 mg of methylprednisolone for 3 days, followed by oral steroid therapy (1 mg/kg/day). The patient’s clinical condition quickly improved, allowing a decrease of the steroid therapy.
At the 6-month consultation, the patient was in complete clinical remission. There was no sign of relapse 18 months after the beginning of the therapy.
Discussion
We report the case of a patient with a history of MDS-DML with normal karyotype and TET2 mutations, diagnosed with auto-immune necrotizing myopathy. We noticed a particularly good response to steroid therapy.
ADs can be associated with MDS in 10–30% of cases.1 This association might be explained by a proinflammatory environment, especially in low-risk MDS. Indeed, hypersecretion of proinflammatory factors has been reported.4 TET2 is necessary to downregulate Il-1b and Il-6 secretion and macrophages response to Il-6 and Il-8. Consequently, loss-of-function mutations in TET2 increase the proinflammatory bone marrow niche. Interestingly, Oh et al.5 showed that TET2 mutation in MDS was associated with an increased risk of ADs.
On the other hand, association between inflammatory myopathies and solid cancers has been reported, mainly lung and gynecological cancers.6 In contrast, myopathies associated with hematologic neoplasia (mainly non-Hodgkin lymphoma) are quite rare.6 Only a few cases of inflammatory myopathies associated with MDS have been reported.3 Given its low prevalence among myopathies, hemopathy-associated necrotizing myopathies are even more rarely described. Therefore, our case is noteworthy for being an association between a myelodysplastic syndrome and a necrotizing myopathy.
Consent
The patient provides signed consent for the publication. This publication needed no ethical approval.
Authors’ contributions
All authors contributed to the care of the patient and the writing of the manuscript.
Conflict of interest: None declared.
