Additional autoimmune disorders in patients with acquired autoimmune thrombotic thrombocytopenic purpura
Authors: Ayesha Hassan, Madiha Iqbal, James N. George
Journal: American Journal of Hematology (2019)

Patients with multiple autoimmune diseases have been frequently reported and described as syndromes of polyautoimmunity. Twenty-seven different autoimmune disorders have been reported to occur in clusters. Systemic lupus erythematosus (SLE) and autoimmune thyroid diseases, including Graves' disease, are the most common to occur in clusters.1 Another classification of polyautoimmunity is the autoimmune polyendocrine syndromes, a diverse group of conditions characterized by functional impairment of multiple endocrine glands due to decreased immune tolerance caused by mutations in the thymic autoimmune regulator.2 These syndromes also include nonendocrine autoimmune disorders.2, 3 Among the many autoimmune disorders that occur in the clusters of polyautoimmunity or autoimmune endocrine disorders, thrombotic thrombocytopenic purpura has not been reported. We previously reported that the prevalence of SLE (7%) among Oklahoma Registry patients, 1995-2011, with acquired autoimmune thrombotic thrombocytopenic purpura (TTP, also described as primary immune TTP or iTTP) was significantly greater than the prevalence of SLE (0.3%, P < .001) in the age, race, and gender-matched US population.4 The French Thrombotic Microangiopathies (TMA) Reference Center has reported the same observation: 26 (10%) of 261 patients with acquired autoimmune TTP also had SLE.5 The French TMA Center also documented the occurrence of 14 autoimmune disorders, in addition to SLE, among their TTP patients. Fifty-six (21%) patients had one or more of these 15 autoimmune disorders.5 We reviewed our experience with 90 patients who had acquired autoimmune TTP enrolled in the Oklahoma TTP Registry, 1995-2018. Nearly identical to the French experience, 10 (11%) of the 90 patients have now been diagnosed with SLE (Table 1). Identical to the French experience, 19 (21%) of the 90 patients have been diagnosed with one or more of 14 additional autoimmune disorders, including SLE. Fourteen of these 19 patients had one autoimmune disorder in addition to TTP; 5 had two to four additional autoimmune disorders. Of these 14 autoimmune disorders, 12 have occurred in polyautoimmunity syndromes,1 and 8 have occurred in the autoimmune polyendocrine syndromes.2, 3 Only acquired autoimmune coagulation factor VIII inhibitor, in addition to TTP, has not been previously recognized in either syndromes of polyautoimmunity or autoimmune polyendocrine syndromes. Of these 14 autoimmune disorders, only 3 (SLE, psoriasis, Sjögren's syndrome) were reported to occur in patients with TTP in the French TMA Center patients.5 Systemic lupus erythematosus, the most common additional autoimmune disorder, has multiple similarities to TTP. Both occur predominantly in young, black women; both manifest hemolytic anemia and thrombocytopenia; both have distinct acute episodes, or flares. In two of our patients, SLE was diagnosed 1 and 21 years before the initial diagnosis of TTP. In one patient, the diagnosis of SLE was simultaneous with the diagnosis of the initial episode of TTP. In seven patients, SLE was diagnosed 3 months to 11 years following the initial diagnosis of TTP. Table S1 presents the clinical features and outcomes for the 10 patients with both TTP and SLE. There was no apparent difference between the clinical features of these 10 patients' presentation and course of TTP compared to the other 80 patients who were not also diagnosed with SLE. Table S2 presents the clinical features and outcomes for the nine patients who had additional autoimmune disorders other than SLE. Graves' disease was the second most common additional autoimmune disorder, occurring in four patients. In two patients, Graves' disease occurred 1 and 3 years before the initial episode of TTP; in two patients it occurred 2 and 4 years following TTP. Graves' disease is also the second most common autoimmune disorder involved with polyautoimmunity1 and is a principal manifestation of the autoimmune polyendocrine syndrome type 2.2, 3 Similar to TTP and SLE, Graves' disease occurs predominantly in young, black women.6 Two patients (patients 14 and 15, Table S2) had immune thrombocytopenia (ITP) manifested by persistent asymptomatic mild thrombocytopenia. These patients did not have SLE, otherwise the persistent mild thrombocytopenia would have been attributed to SLE. Two patients had Addison's disease and two patients had an acquired factor VIII inhibitor. Five patients had multiple (two to four) additional autoimmune disorders. The occurrence of Addison's disease, hypothyroidism, hypogonadism, and ITP in patient 15 fulfills the criteria for autoimmune polyendocrine syndrome type 2.2, 3 Of these 14 autoimmune disorders, only TTP and acquired factor VIII inhibitors have not been previously recognized in either the syndromes of polyautoimmunity1 or the autoimmune polyendocrine syndromes.2, 3 This may be because both TTP and acquired factor VIII inhibitors are rare disorders. The incidence of TTP is 2/106 population/year; estimates for the incidence of patients with an acquired factor VIII inhibitor are similar. These observations are important for physicians who care for patients with TTP. Additional autoimmune disorders can precede the initial episode of TTP; they can first occur simultaneously with the initial episode of TTP; they can first occur many years following recovery. With effective treatment for acute episodes of TTP and also for prevention of relapse, issues occurring during long-term follow-up are increasingly important. Recognition of additional autoimmune disorders, possibly multiple additional autoimmune disorders, requires careful follow-up forever of patients who have recovered from TTP. The authors have no conflict with this topic or these data. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.