Although an association between sickle cell disease (SCD) and some autoimmune diseases (AIDs) has been reported, the diagnosis of AIDs in this context is often described as challenging due to the similarity of the clinical manifestations. Moreover, the pathophysiology of this association may be based on cross-reactivity with triggers and/or activation of particular components and inflammatory markers. However, as the data show, the impact of SCD on joints and muscles may coincide with the clinical manifestations of AID. Accordingly, early detection of AID in SCD and targeted therapy may improve the condition and prevent the severe phenotype of AID and the deterioration of SCD. In essence, there are approximately 80 different associations of AID with SCD that have been well documented.
Previous studies have examined a range of AIDs in the Saudi population. However, to the best of my colleagues' and my knowledge, this is the first retrospective, analytical study designed to examine the frequency of coexistence of AIDS with SCD and factors associated with disease progression.
We have considered the data of 168 patients with SCD who were seen in the outpatient clinic or required hospitalization due to a sickle cell crisis between January 2016 and March 2023. The mean age was 30.66 years (SD ± 11.27), and 54.2% of patients were female. Regarding the frequency of hospitalizations, 61.90% had a history of two or fewer hospitalizations per year, and 38.09% had more than two hospitalizations per year. Diabetes mellitus (DM) and heart disease were equally prevalent (29.7%) and were the most frequently recorded comorbidities.
A proportional analysis (Z-test) was performed to identify positive and negative results between SCD and AIDs: autoimmune hepatitis, inflammatory bowel disease (IBD), multiple sclerosis (MS), mixed connective tissue disease (MCTD), anti-phospholipid syndrome (APS), sarcoidosis, hyperthyroidism, hypothyroidism, and myasthenia gravis (MG). In 84.52% of patients, the association of SCD with AID was negative, and in 15.47% it was positive (p = 0.00001). Of this, systemic lupus erythematosus was present in 4.2%, hypothyroidism in 3.6%, and APS in 3.6%.
In our study, we further found that patients with SCD and a positive diagnosis of AID were more likely to have pulmonary hypertension (100%) and avascular necrosis (AVN) (65%) than patients with a negative diagnosis of AID. We also found a significant correlation between the hospitalization rate of patients with SCD and a positive diagnosis of AIDs and whether they were hospitalized less than twice a year (10.6%) or more than three times a year (23.4%) (p = 0.03).
As research continues into why females are three to four times more likely than males to develop AIDs, we also looked into this. We found that 54.2% of cases occurred in females, which is supported by the high prevalence of most SCD in females compared to males. Some studies suggest hormonal changes as a causal relationship. Therefore, it is suggested that females with SCD in their reproductive years may benefit from additional testing.
One of the proposed explanations for the high frequency of coexistence of ASD and SCD is that SCD may manifest itself as recurrent infections and inflammations caused by the pathology of the body. It is also important to emphasize that the mechanism of development of complications may change over time, increasing the likelihood of recurrence of infection, especially caused by encapsulated pathogens. These factors activate the immune system, which ultimately turns SCD into an autoimmune disease with specific manifestations.
This study was of particular importance for the Saudi and Gulf populations as it was the first of its kind to reveal a high incidence of AIDs in patients with SCD. The results of this study warrant further investigation and highlight the possible need for international guidelines on screening and early detection of the co-occurrence of AIDs and SCD.