Impact of Autoimmune Disease and Its Treatment on Adults with Sickle Cell Disease

Background: Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. Within the United States, it affects 1 in 100,000 people and 1 in 365 African American births. Management requires a comprehensive team dedicated to improving quality of life by minimizing the frequency of pain crisis, hospitalizations and infections that ultimately can reduce mortality. Susceptibility to infections among SCD patients is partly attributed to impaired host defense from chronic activation of the alternative complement pathway. This complement pathway dysregulation has also been suggested to predispose SCD patients to an array of autoimmune diseases (AID). It has been reported that the prevalence of AID in SCD teens and adults is 1.8%. The overlapping clinical manifestations and hematological abnormalities represent a challenge in diagnosing a coexisting AID among SCD patients and likely contribute to an under-reporting of its prevalence in the literature. Once coexistence is established, optimizing the management of each disease is challenging as the therapeutic treatment particularly the use of high dose steroids may exacerbate complications of SCD. The aim of this study was to assess the impact of AID and its treatment on SCD outcomes.

Methods: In our retrospective review of 300 adult patients cared for in the adult SCD center from 2016-2021 we identified four patients (1.3%) who met the criteria of SCD and a confirmed diagnosis of an AID. Data that was reviewed included: age, type of SCD, type of AID, treatments of both, number of hospitalizations and ED visits and complications.

Results: Four patients, all women between the ages of 38-42 years at the time of AID diagnosis, were identified. The coexisting SCD type and AID were as follows: HbSS with hereditary persistent of HbF(HPFH) and systemic lupus erythematous (SLE), HbSC and SLE with Sjogren's disease, S beta thalessemia+ and SLE with Raynaud's phenomena and HbSS with rheumatoid arthritis (RA). None of the patients were on hydroxyurea. None of the patients were treated with high dose steroids for their AID.

Patient 1: HbSS/HPFH with infrequent hospitalizations for vasoocclusive pain crisis (VOC) A rash noted during her second pregnancy prompted a skin biopsy, revealing cutaneous SLE for which treatment with hydroxychloroquine (HC) was initiated. She had one admission for VOC pain crisis at 34 weeks of gestation. Her HC was discontinued prior to delivery. She had an elective C-section at 39 weeks and delivered a healthy 7 lb. baby. 6 weeks post partum she developed severe joint pains and fatigue. She experienced symptom relief with resumption of HC and a low dose prednisone (P) 10 mg. No additional immunosuppressive therapy was started as she continues to breast-feed.

Patient 2: HbSC, with SLE and Sjogrens disease with frequent ED visits and admissions for VOC prior to her AID diagnosis. At AID diagnosis she was started on HC and pilocarpine resulting in a prompt reduction in ED visits for pain. She then began to experience worsening arthropathy presumed to be secondary to SLE and was started on methotrexate (MTX). She was hospitalized for community-acquired pneumonia /acute chest syndrome with pleural effusion and pulmonary infiltrates. After no response to antibiotics, she was started on P 30 mg with relief. Because of SLE flare with steroid taper and concern for high dose steroids she was started on rituximab 375 mg/m2 weekly x4. Her pulmonary infiltrates resolved. She continues to have frequent ED/admissions for pain events for VOC.

Patient 3: HbSS with frequent ED/admissions for VOC prior to her diagnosis of RA, AVN and pulmonary hypertension. Her AID was treated with MTX and low dose P. Because of RA progression she started etanercept. She had 1 episode of sepsis and septic arthritis and continues to have frequent VOC.

Patient 4: Sb+thalassemia with infrequent VOC diagnosed with SLE with Raynaud phenomena. She has been treated with HC without VOC but frequent urinary tract infections.

Conclusion: Optimal treatment of adult patients with coexisting SCD and an AID is challenging. In this small group of patients, treatment with a variety of immunosuppressive agents other than high dose steroids, has led to control of the autoimmune disease but no clear improvement of sickle cell pain events and some atypical infections have occurred. Continued tracking of cases of SCD with AID should be done to better understand management and long term outcomes.