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Clinical spectrum and therapeutic management of systemic lupus erythematosus-associated macrophage activation syndrome: a study of 20 Moroccan adult patients

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Abstract

Objective

The objective of this study was to describe the clinical and laboratory manifestations, triggers factors, treatment, and outcome of MAS complicating SLE.

Methods

We retrospectively analyzed the medical records of adult patients with SLE for a period of 8 years (2009–2016) and identified patients who had developed MAS. We conducted statistical analysis to identify factors associated with MAS.

Results

Among 208 consecutive lupus patients, 20 patients (19 women) were identified having MAS. The mean age of patients was 35.4 ± 10 years. MAS revealed lupus in 7 patients. In the others, the delay between diagnosis of SLE and MAS was 33,3 months. All cases required hospital admission, and 2 patients were admitted to the intensive care unit. An anemia (hemoglobin < 10 g/dL) was found in all patients. A thrombopenia was observed in 19 (95%) cases. Hypertriglyceridemia and hyperferritinemia were present in all patients. All patients had anti-nuclear antibodies and anti-double-stranded DNA antibodies. Bone marrow aspiration showed hemophagocytosis in 15 (94%) cases. The mean SLEDAI was 20.95 corresponding to an SLE of a very high activity. The mean H-Score was 233.85. MAS was associated with a lupus flare in 13 patients. Documented bacterial infections, viral infections, and a breast cancer were respectively diagnosed in 4, 3, and 1 cases respectively. The corticosteroids were administered in all patients. Intravenous cyclophosphamide was used together with corticosteroids in 6 patients, mycophenolate mofetil in 2 cases and azathioprine in 2 cases. Intravenous immunoglobulin was given in 4 cases, etoposide in one case and rituximab was used as the third line treatment in one patient. All infectious episodes were also treated by broad spectrum antibiotics. All patients had a good outcome without any mortality at the management, with a mean follow-up of 24 months. The clinical parameters significantly associated with MAS were fever (p = 0,001), splenomegaly (p < 0.0001), lymphadenopathy (p < 0.0001), oral and/or nasopharyngeal ulceration (p = 0.04), arthritis (p = 0.017), and pulmonary signs (p = 0.003). Laboratory parameters associated with MAS were anemia (p < 0.0001), thrombopenia (p < 0.0001), hyperferritinemia (p < 0.0001), hypertriglyceridemia (p < 0.0001), SLEDAI (p < 0.0001), and H-Score (p < 0.0001). Receiver operating characteristic (ROC) analysis identified optimal cutoff values of ferritin (> 695 ng/mL) and SLEDAI (> 13.5) to predict the occurrence of MAS in SLE.

Conclusion

MAS was observed in 9.62% Moroccan adult patients with SLE. SLE flare and infection were the common triggers of MAS in our study. Our study indicates that the occurrence of unexplained fever, splenomegaly, lymphadenopathy, profound cytopenia, hyperferritinemia, hypertriglyceridemia, high SLEDAI, and H-Score should raises the possibility of the diagnosis of MAS in SLE patients. Early diagnosis and urgent therapeutic management improves the overall prognosis.

Key Points

• Macrophage activation syndrome (MAS) is an underdiagnosed complication of systemic lupus erythematosus (SLE). The prevalence of this complication in this study is nearly 10%.

• The diagnosis of MAS represents a major challenge for clinicians, as it could mimic a SLE flare up or be confused with infections. Validated diagnostic criteria for MAS in adults secondary to SLE are urgently needed.

• In this study, the H-score calculate the individual risk of adult patients having reactive MAS. The cut-off value for the H-score was 190.5 (sensitivity 96.7%, specificity 97.6%).

• The prognosis of MAS with SLE is good in our study. However, in the literature MAS may be a fatal condition in SLE patients. Prospective studies are necessary to confirm these results.

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Authors and Affiliations

  1. Internal Medicine Department, Unité d’Hématologie Clinique, Ibn Sina Hospital, University Mohamed V of Medicine, Rabat, Morocco

    Ammouri Wafa, Harmouche Hicham, Radi Naoufal, Khibri Hajar, Maamar Mouna, Mezalek Tazi Zoubida & Adnaoui Mohamed

  2. Laboratory of Biostatistics, Epidemiology and Clinical Research, Faculty of Medicine and Pharmacy of Rabat, Mohammed V University, Rabat, Morocco

    Razine Rachid

  3. Laboratoire Central d’Hématologie, Ibn Sina Hospital, Mohammed V University, Rabat, Morocco

    Benkirane Souad

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  1. Ammouri Wafa
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Wafa, A., Hicham, H., Naoufal, R. et al. Clinical spectrum and therapeutic management of systemic lupus erythematosus-associated macrophage activation syndrome: a study of 20 Moroccan adult patients. Clin Rheumatol 41, 2021–2033 (2022). https://doi.org/10.1007/s10067-022-06055-9

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