Severe agranulocytosis as the first manifestation of secondary Sjögren’s syndrome masked by iatrogenic Cushing’s: A diagnostic challenge

Abstract

Agranulocytosis is a rare but potentially fatal hematologic condition characterized by a marked reduction in absolute neutrophil count (ANC $<100$ cells//$\mu$L). While most cases are drug-induced, autoimmune etiologies must be considered in refractory or atypical presentations. We report the case of a 54-year-old male with untreated rheumatoid arthritis who presented with persistent fever and was found to have severe agranulocytosis (ANC = 20 cells//$\mu$L) and thrombocytopenia, without an apparent infectious focus. The patient had a history of chronic unsupervised intake of Ardosons (a combination of betamethasone, indomethacin, and methocarbamol), and physical examination revealed cushingoid features suggestive of iatrogenic Cushing’s syndrome. Initial management with empirical broad-spectrum antibiotics and granulocyte-colony stimulating factor failed to improve the cytopenias. Immunologic testing showed high-titer ANA with mixed patterns, strong anti-SSA positivity, and elevated C-reactive protein. The erythrocyte sedimentation rate was undetectable, likely due to steroid suppression. Systemic lupus erythematosus was ruled out based on ACR/EULAR 2019 criteria. A diagnosis of Secondary Sjögren’s syndrome , likely secondary to untreated rheumatoid arthritis, was established by the rheumatology team. The patient responded favorably to high-dose intravenous methylprednisolone followed by immunomodulatory therapy. The patient responded favorably to high-dose intravenous methylprednisolone followed by immunomodulatory therapy. This case highlights the importance of considering autoimmune causes in the differential diagnosis of cytopenias, particularly in patients with underlying connective tissue diseases and chronic glucocorticoid exposure. Functional autoimmune syndromes may present atypically and require high clinical suspicion for timely diagnosis and treatment.