A Rare Autoimmune Quartet: Immune Thrombocytopenia in a Patient with Autoimmune Polyglandular Syndrome Type 3

Autoimmune polyglandular syndromes (APS) comprise a group of disorders characterized by the autoimmunemediated dysfunction of multiple endocrine glands.Key endocrine pathologies include hypoparathyroidism, adrenal insufficiency, type-1 diabetes mellitus (DM), and hypothyroidism.Non-endocrine manifestations, such as mucocutaneous candidiasis, alopecia, vitiligo, celiac disease, and autoimmune gastritis (pernicious anemia), are also observed. 1,2However, the coexistence of hematologic autoimmune conditions, such as immune thrombocytopenia or autoimmune hemolytic anemia, is exceedingly rare within the APS spectrum. 3APS is currently categorized into four main types (Table 1). 1,2APS type 3 is defined by the presence of autoimmune thyroid disease in association with another organ-specific autoimmune condition, excluding adrenal insufficiency and hypoparathyroidism.We report a unique case of APS type 3 in a young woman with a history of immune thrombocytopenia, type-1 DM, Hashimoto's thyroiditis, and myasthenia gravis (MG).In addition to the endocrine-based classification, this constellation is also consistent with multiple autoimmune syndrome (MAS) type 3, a category that closely parallels APS type 3 in the literature. 4A 25-year-old woman presented for routine follow-up of immune thrombocytopenia.She had been diagnosed two years earlier and initially treated with corticosteroids.One year ago, during the first month postpartum, she experienced a relapse and received intravenous immunoglobulin (IVIG) along with steroids.Three months after discontinuing steroids, the patient experienced a relapse requiring retreatment.After breastfeeding cessation, a subsequent relapse necessitated four doses of rituximab (375 mg/m/week).Further review of her medical history revealed that she had been diagnosed with type-1 DM and Hashimoto's thyroiditis at the age of 18.Additionally, the diagnosis of MG was established three years ago based on typical clinical findings and compatible electromyographic results, and she was subsequently treated with steroids and IVIG.She remained asymptomatic for MG during rituximab therapy, achieved a complete response for immune thrombocytopenia (platelet count >10010/L at last follow-up), and continued her maintenance therapy for MG thereafter.Her current medications include insulin, levothyroxine, and pyridostigmine.Physical examination was unremarkable, and laboratory findings showed no signs of thrombocytopenia or anemia.The combination of autoimmune thyroiditis, type-1 DM (type 3a), and MG (type 3c) satisfies the diagnostic criteria for APS type 3. Taken together, these findings also place the patient within the expanded framework of MAS type 3.Although rare, her concurrent diagnosis of immune thrombocytopenia requiring second-line therapy further highlights the complexity of her autoimmune profile.Immune thrombocytopenia, usually considered a primary hematologic disorder, can also develop due to identifiable secondary causes such as infections, medications, or systemic disorders, including autoimmune diseases. 5In this context, the coexistence of immune thrombocytopenia with APS, though rare, is a relevant consideration, especially in young patients with multiple autoimmune features.Immune thrombocytopenia accompanying Graves' disease, which does not meet the definition of APS, has been reported rarely. 6,7A previously reported case fulfilling the definition of APS included autoimmune hyperthyroidism and type-1 DM, u n c o r r e c t e d p r o o f along with both immune thrombocytopenia and heparin-induced thrombocytopenia. 3However, our literature search did not identify any previous reports describing the specific combination of type-1 DM, MG, Hashimoto's thyroiditis, and immune thrombocytopenia.Interestingly, our patient, who had type-1 DM (type 3a component), MG (type 3c component without vitiligo), and autoimmune thyroiditis in the absence of adrenal insufficiency, also had a history of immune thrombocytopenia that required second-line treatment.APS-3 and MAS-3 share considerable overlap, although MAS generally encompasses a wider range of non-endocrine autoimmune conditions. 4This constellation fulfills the diagnostic criteria for APS type 3 (3a+3c) and, given the coexistence of additional autoimmune disorders such as immune thrombocytopenia, can also be classified within the spectrum of MAS type 3. Despite its rarity, clinicians should maintain a high index of suspicion for underlying endocrinopathies in patients with immune thrombocytopenia, as it may represent a component of APS or MAS.