Hematological involvement in pediatric systemic lupus erythematosus: A multi-center study

Abstract

Introduction: Systemic lupus erythematosus (SLE) may present with features of several systems, including hematological manifestations. In this study, we aimed to evaluate the characteristics of hematological involvement and assess possible associations and correlations in pediatric SLE patients. Method: This is a retrospective multi-center study. The medical records of pediatric SLE patients followed between January 2000 and June 2020 were analyzed. All children fulfilled the criteria of the Systemic Lupus International Collaborating Clinics. Results: The study included 215 children with SLE, 118 of whom had hematological manifestations. Concomitant renal involvement and low C3 levels were significantly more frequent in patients with hematological involvement ( p = 0.04, p = 0.008, respectively). Also, anti-cardiolipin, anti-beta-2-glycoprotein I (anti-β2 GP1), and anti-Sm antibody positivity, and the presence of lupus anticoagulant were more common in the group with hematological findings ( p = 0.001 for anti-cardiolipin antibody positivity and p < 0.001 for the positivity of anti-β2 GP1 antibody, anti-Sm antibody, and lupus anticoagulant). The most common hematologic abnormality was anemia (n = 88, 74.5%), with autoimmune hemolytic anemia constituting the majority (n = 40). Corticosteroids followed by IVIG were the mainstay of treatment. In patients resistant to corticosteroid and IVIG treatments, the most preferred drug was rituximab. Low levels of C3, high SLEDAI score, high incidence of renal involvement, and positive antiphospholipid antibodies were associated with hematological involvement in the univariate analysis. The presence of antiphospholipid antibodies and high SLEDAI score were independently associated with hematological involvement in multivariate analysis (OR: 4.021; 95% CI: 2.041–7.921; p < 0.001 and OR: 1.136; 95% CI: 1.065–1.212; p < 0.001). Conclusion: Hematological abnormalities are frequently encountered in pediatric SLE. Positive antiphospholipid antibodies and high SLEDAI scores were associated with hematological involvement.

Hematologic manifestations of juvenile systemic lupus erythematosus: An emphasis on anemia

“…Moreover, we found that APLA antibodies were more frequently encountered in patients with AIHA, similar to the results in the literature. 13,20 Our results also showed a moderate negative correlation between hemoglobin levels and SLEDAI score, erythrocyte sedimentation rate, and serum ferritin levels. Similar to our results, a study on adult patients with SLE patients found that inflammatory status was associated with anemia and reported a negative correlation between ferritin and hemoglobin levels.…”

“…Our results showed hematologic involvement in two-thirds of patients at onset, which was similar to previous studies that reported ranges of up to 88%. [10][11][12][13] In addition, anemia was the most frequently observed cytopenia, followed by lymphopenia and leukopenia in our study. Studies with SLE patients often investigated the hematologic findings included in the classification criteria such as AIHA, lymphopenia, leukopenia, and thrombocytopenia.…”

“…19 In addition, a recent meta-analysis reported a 2.8-fold increased risk of AIHA in SLE patients with positive APLA. 20 Akca et al 13 reported that hematologic involvement was associated with higher SLEDAI scores and positive APLA in patients with jSLE. Although our study did not find any significant differences among disease manifestations according to the presence of anemia, patients with anemia had more severe disease reflected by a higher SLEDAI score, erythrocyte sedimentation rate, and rate of positive anti-dsDNA antibody.…”

“…While anemia was the most common type of cytopenia in that study, AIHA was the most common etiology in 45% of the patients, followed by ACD in 40% of the patients. 13 ACD is generated by three major pathophysiologic pathways: iron restriction by the increased activity of hepcidin by the iron retention in macrophages and reduced iron absorption from the gut, suppression of erythropoietin (EPO) activity, and shortened erythrocyte life span with increased erythrophagocytosis. 16 In addition to blunted EPO response in inflammatory conditions, anti-EPO antibodies were not rare in patients with SLE and might be associated with the severity of anemia.…”

Autoimmune hemolytic anemia as an initial presentation in children with systemic lupus erythematosus: two case reports

“… 2 , 3 Hematological abnormalities are common in children with SLE, with an incidence of 34% to 82.7%. 4 Anemia, thrombocytopenia, and leucopenia are common hematological manifestations in pediatric SLE patients. 4 Hematological involvement may result from bone marrow failure or excessive peripheral cell destruction, both of which may be immune-mediated.…”