Characteristics and Outcome of Connective Tissue Diseases in Patients with Sickle-Cell Disease: Report of 30 Cases

ObjectivesTo analyze the main characteristics of adults with sickle cell disease (SCD) and concurrent connective tissue disease (CTD).MethodsA retrospective investigational study was performed. CTD was diagnosed according to standard international criteria. Severity of SCD was assessed by a clinical severity score.ResultsThirty patients, 23 women (76%) and 7 men, with hemoglobin S/S (n = 25) or S/C (n = 5) SCD were included. The subtypes of CTD were rheumatoid arthritis (RA) (n = 15), definite systemic lupus erythematosus or “incomplete lupus” requiring treatment (n = 13), primary Sjögren's syndrome with central nervous system involvement (n = 1), and systemic sclerosis (n = 1). Twenty-five of the 30 patients (83%) received steroid treatment, and 15 (50%) received at least 1 immunosuppressive agent (methotrexate in 14 cases) to control CTD. Four RA patients were given antitumor necrosis factor (TNF)α and 1 was treated with rituximab without SCD exacerbation. After a median follow-up of 4.5 years [range: 6 months to 30 years] from CTD diagnosis, 11 of the 25 (44%) patients receiving steroids had at least 1 episode of severe infection (mostly due to Staphylococcus aureus or Escherichia coli). SCD exacerbated in 13 of the 30 (43%) patients after CTD onset; 12 of these patients were receiving prednisone and/or methotrexate. Six patients (20%) had died from sepsis (n = 2), stroke (n = 2), or acute chest syndrome (n = 2).ConclusionsCTD-related clinical manifestations and outcome were not particularly severe in patients with SCD. However, those with active CTD and undergoing steroid ± methotrexate treatment had more serious SCD-related manifestations, a higher rate of severe infections, and an overall patient mortality rate of 20%. Thus, the management of patients with CTD and underlying SCD should consider the risk/benefit ratio of each treatment and steroid-sparing strategies should be implemented.