Pancytopenia and Myelofibrosis in Autoimmune Polyglandular Syndrome Type I

Abstract

Autoimmune Polyglandular Syndrome Type I (APS I) is due to a defect in the autoimmune regulator gene (AIRE). Mucocutaneous candidiasis, Addison's disease, hypoparathyroidism, other endocrinopathies, neural ectodermal dysplasia, malabsorption, and autoimmune hepatitis are clinical features of APS I. Immune mediated cytopenias are common. We describe myelofibrosis as an unusual complication of APS I. A 16 year old adolescent female, with clinical diagnosis of APS I, and all attributes described above, including pernicious anemia and neutropenia, presented with pancytopenia. She was DAT positive, hypergammoglobinemic with positive ANA and DsDNA titers. A bone marrow biopsy revealed a mildly hypocellular marrow with myeloid left shift, mild erythroid and megakaryocytic hyperplasia and increased lymphoplasmacytic infiltrate with delicate reticulin fibrosis. There were rare positive CD3 cells and scattered positive CD20, CD34 and CD117 cells. Bone marrow biopsy performed two years earlier demonstrated a cellular marrow with erythroid preponderance and marked megaloblastic and dysplastic changes, presence of giant bands and hypersegmented neutrophils, and scattered CD 117 positive plasma cells without evidence of fibrosis. AIRE encodes a transcription factor that enables negative selection of autoreactive thymocytes and may promote development of the regulatory T-cell subset. Myelofibrosis has been observed in other autoimmune diseases, most notably systemic lupus erythematosus. Additionally, primary autoimmune myelofibrosis was recently characterized as a syndrome associated with lymphocytic infiltration of the bone marrow interstitium. Accordingly, we postulate that myelofibrosis is a manifestation of APS I driven by autoreactive T cells.