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SLE: reconciling heterogeneity
  1. Michael D Lockshin1,
  2. Medha Barbhaiya1,
  3. Peter Izmirly2,
  4. Jill P Buyon2 and
  5. Mary K Crow3
  1. 1 Barbara Volcker Center, Hospital for Special Surgery, New York City, New York, USA
  2. 2 Division of Rheumatology, Department of Medicine, New York University School of Medicine, New York City, New York, USA
  3. 3 Mary Kirkland Center for Lupus Research, Hospital for Special Surgery, New York City, New York, USA
  1. Correspondence to Professor Michael D Lockshin; lockshinm{at}

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Patients with SLE experience multiple, varied symptoms and laboratory abnormalities that occur in different combinations, at different points in time.1 A result of the heterogeneity is that studies on SLE employ several, sometimes conflicting, definitions of the illness. Investigators disagree about when SLE begins; how SLE relates to similar and overlapping rheumatic illnesses; whether SLE-like illnesses of known genetic causes count as SLE; and whether the same diagnosis name should apply when investigators describe stratified populations, for instance, SLE with and without renal disease. Inconsistent definitions lead stakeholders—patients, practising physicians, administrators, epidemiologists and investigators—to count different patients and to develop different opinions about the mechanisms and treatment of SLE.

To advocate a consensus vocabulary and conceptual model, in this paper we deconstruct the process of making a diagnosis of SLE by examining its classification and diagnostic criteria, definitions and illness models. We discuss the ways by which stratification biases conclusions and how the purpose for which a stakeholder names a diagnosis determines whom they accept as having this disease.


Classification and diagnostic criteria

When in the mid-19th century Cazenave first used the name lupus erythematosus, SLE was a rare and life-threatening illness.2 3 A century later, as new technologies identified more patients,4–10 physicians found SLE to be more clinically diverse, and often less severe, than they once believed. To improve homogeneity of patient populations identified for clinical studies, investigators developed classification criteria that are specific, binary (SLE is present or not) and time limited (valid only for the extent of a study). The homogeneity of classification criteria is implied but not real. The American College of Rheumatology (ACR) criteria allow 330 different combinations of symptoms and laboratory tests to affirm a diagnosis of SLE.11 Classification criteria are insensitive; they exclude patients who, despite disabling and treatable symptoms, fall below …

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