A comprehensive review of myelodysplastic syndrome patients with autoimmune diseases

Abstract

Primary myelodysplastic syndromes (MDS) are heterogeneous clonal hemopoietic disorders clinically presented with a varying degree of peripheral cytopenias and an increased probability of leukemic evolution. A distinct subset of MDS patients manifests overt autoimmune-inflammatory manifestations, the underlying pathogenesis and prognostic significance of which still remain controversial. In this review we attempt to analyze clinical aspects of MDS-related rheumatoid disease, and discuss pathophysiologic associations between autoimmunity and distorted BM function in preleukemic states in light of recent findings, in vivo and in vitro. We further explore the potential of recent biological and molecular advances to forward therapeutic targeting against both autoimmune and malignant process.

Keywords::

• 5-azacytidine
• autoimmunity
• immunosuppressive treatment
• myelodysplastic syndromes
• signaling inhibition
• vasculitis

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. All authors have read and approved the submission of the manuscript.

No writing assistance was utilized in the production of this manuscript.

Key issues

• A distinct subset of myelodysplastic syndrome (MDS) patients manifests overt autoimmune-inflammatory manifestations (AIMs), the underlying pathogenesis and prognostic significance of which still remain controversial.

• The estimated incidence of AIMs in MDS ranges from 10 to 20% in various studies.

• AIMs in MDS patients have been schematically categorized into five groups, namely acute systemic vasculitis, isolated autoimmune phenomena, classical connective tissue disorders, immune-mediated hematological abnormalities and asymptomatic serological immunologic abnormalities.

• Cutaneous manifestations, mainly leukocytoclastic vasculitis and seronegative oligo-poly arthritis, are the commonest manifestation in MDS patients. Overlapping systemic vasculitic syndromes are rarer, but usually display a worse prognosis.

• AIMs in the MDS context can cause diagnostic pitfalls, especially in patients with subtle hematologic distortion or without a definite MDS diagnosis. The rheumatologist has to consider the possibility of an underlying MDS in patients with vasculitic manifestations or other rheumatic symptoms, specifically in those displaying an impaired hematological profile, unrelated to prior medication.

• A number of studies and case series suggest that immunosuppressive treatment is appropriate for patients in need for therapeutic intervention. Moderate doses of steroids are recommended with quick tapering in the minimum dose required for adequate disease control, in order to avoid unnecessary drug toxicity.

• In the case of acute polysystematic vasculitic syndrome, vigorous protocols with cyclophosphamide and steroids, in doses similar to those used in patients with primary systemic vasculitis, are recommended.