ARTHRITIS & RHEUMATISM Vol. 42, No. 11, November 1999, pp 2346–2355 © 1999, American College of Rheumatology CLOSE RELATIONSHIP BETWEEN SYSTEMIC LUPUS ERYTHEMATOSUS AND THROMBOTIC THROMBOCYTOPENIC PURPURA IN CHILDHOOD HERMINE I. BRUNNER, MELVIN FREEDMAN, and EARL D. SILVERMAN Objective. To determine the association between childhood-onset thrombotic thrombocytopenic purpura (TTP) and systemic lupus erythematosus (SLE). Methods. The charts of all 5 patients diagnosed with idiopathic TTP at the Hospital for Sick Children (HSC) in Toronto from 1975 to 1998, and all cases of childhood-onset TTP (ages 6–20 years) reported in the literature over the same period were reviewed. Fourteen of the 44 patients identified in the literature were excluded from the analysis for lack of clinical and laboratory information. The remaining 35 patients were grouped into either an SLE/TTP group or a TTP only group, according to the presence or absence of the American College of Rheumatology (ACR) classification criteria for SLE. The groups were compared for differ- ences in clinical or laboratory features. Results. The clinical presentation and initial dis- ease course of pediatric patients with TTP were similar to those observed in adults. Of the 35 patients with childhood-onset TTP included in this review, 9 (26%) fulfilled >4 ACR criteria for SLE and 8 (23%) were found to have incipient SLE. Of the 5 patients initially diagnosed with idiopathic TTP at the HSC, 3 were diagnosed with SLE within 3 years, and the other 2 patients fulfilled 3 ACR classification criteria for SLE within 4 years of disease onset. The clinical syndrome of pediatric TTP presenting with proteinuria, especially with high-grade proteinuria, was significantly associ- ated with the development or coexistence of childhood- onset SLE. Conclusion. TTP in childhood is a rare, but life-threatening, disease. Unlike in adults, TTP in child- hood is commonly associated with SLE. High-grade proteinuria at diagnosis of TTP is the best predictor for the presence or subsequent development of SLE. Thrombotic thrombocytopenic purpura (TTP) was first described by Moschkowitz in 1924 in a 16-year- old girl with malaise, upper extremity weakness, fever, petechiae, anemia, and microscopic hematuria leading to death (1). Postmortem examination revealed hyaline thrombi in the terminal arterioles and capillaries of multiple organs. Despite numerous case reports of TTP in the literature, this disease is rare and has an estimated incidence of up to 1 per million (2,3); fewer than 10% of all cases occur in the pediatric age group (2,4). TTP is diagnosed based on the presence of the characteristic clinical pentad: 1) thrombocytopenia and disseminated platelet aggregation, 2) microangiopathic hemolytic anemia (Coombs-negative reaction) with frag- mented erythrocytes, 3) neurologic abnormalities, 4) fever, and 5) renal disease. The initial prognosis of TTP was reported to be dismal; 90% of patients died within 3 months of onset. Patients who survived the first episode were at a significant risk for relapses (60%). In the late 1970s, plasmapheresis was found to be lifesaving, and today the survival rate is 80–90% (5). Although Moschkowitz had speculated that the lesions seen in TTP were disease-specific, we now know that identical pathologic changes can be seen in combi- nation with other clinically well-defined diseases or during pregnancy (5,6). One of the diseases associated with microangiopathic changes is systemic lupus ery- thematosus (SLE) (7). A recent review of TTP occurring in SLE patients (8) demonstrated that 1) in 73% of cases, SLE was diagnosed before the onset of TTP, 2) in 15% of cases, SLE and TTP were diagnosed concomi- tantly, and 3) in only 12% of cases, TTP preceded the diagnosis of SLE. However, the true percentage of Hermine I. Brunner, MD, Melvin Freedman, MD, FRCPC, Earl D. Silverman, MD, FRCPC: University of Toronto, Toronto, Ontario, Canada. Address reprint requests to Earl D. Silverman, MD, Division of Rheumatology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada. Submitted for publication March 24, 1999; accepted in revised form July 12, 1999. 2346