Macrophage Activation Syndrome (MAS) is a rare but severe hyperinflammatory condition driven by immune dysregulation. While MAS is often secondary to infections or malignancies, its presentation as an inaugural manifestation of systemic lupus erythematosus (SLE) is exceptionally rare, posing significant diagnostic and therapeutic challenges.

Case 1 : A 25-year-old woman with no prior medical history was admitted for febrile pancytopenia associated with a tumoral syndrome. Clinical evaluation revealed, general condition deterioration skin lesions indicative of acute lupus, inflammatory arthralgia. Laboratory findings included pancytopenia, a marked inflammatory syndrome, hyperferritinemia, hypofibrinogenemia, hepatic cytolysis, proteinuria with active urinary sediment (dysmorphic red blood cells), and positive ANA with specific antibodies (anti-DNA, anti-Sm, anti-SSA), along with complement consumption. Bone marrow and lymph node cytology confirmed MAS. MAS diagnosis was based on HLH-2004 criteria (score? 5, H-Score : 203, probability 88–91%) and attributed to SLE (ACR/EULAR 2019 score : 38/10). Treatment with methylprednisolone boluses, oral corticosteroids, immunoglobulins, and hydroxychloroquine led to clinical improvement. Case 2 : A 31-year-old woman, postpartum day five, presented with febrile hepatosplenomegaly and bicytopenia. Laboratory results revealed severe anemia (Coombs negative), thrombocytopenia, significant hyperferritinemia, hepatic cytolysis (ASAT×4N), and proteinuria (2g/24h). Bone marrow aspiration showed hemophagocytosis. Positive ANA with anti-DNA antibodies and complement consumption were noted. MAS was diagnosed based on HLH-2004 criteria (score? 6, H-Score : 228, probability 96–98%) and attributed to SLE (ACR/EULAR 2019 score : 16/10). The patient responded favorably to methylprednisolone boluses, oral corticosteroids, and hydroxychloroquine. Case 3 : A 40-year-old woman was admitted for hepatomegaly and general condition deterioration. Examination revealed lower limb edema, hepatomegaly, and inflammatory polyarthralgia. Laboratory tests showed severe pancytopenia, hyperferritinemia, hypofibrinogenemia, impaired renal function with proteinuria (6.25g/24h), positive ANA with specific antibodies (anti-DNA, anti-Sm, anti-SSA, anti-SSB), and complement consumption. MAS secondary to SLE was diagnosed (HLH-2004 : H-Score 204, probability 88–93%; ACR/EULAR 2019 score : 31/10). Despite treatment with methylprednisolone boluses, oral corticosteroids, and cyclophosphamide, the patient succumbed to massive pulmonary embolism.

These cases underscore the importance of recognizing MAS as a rare but severe inaugural presentation of SLE. Early diagnosis and prompt therapeutic intervention are essential to improving outcomes in this life-threatening condition.