To the Editor
We read with great interest the article by Grika et al., which was a retrospective analysis of the morbidity, mortality, and organ damage in Antiphospholipid Syndrome (APS) patients with or without Systemic Lupus Erythematosus (SLE)1. The authors conclude that “APS occurs among young individuals and it is a cause of increased morbidity, with one-fourth of the patients progressing to organ damage in a mean time of ten years from disease onset”1. Given that the number of studies analyzing the “organ damage” in APS patients is limited and no “damage index” exists specifically validated for aPL-positive patients, the study is timely and important. Our group also has been interested in assessing and quantifying organ damage in APS patients, and thus we would like to highlight some of the challenges in studying “organ damage” in aPL-positive patients.
The “organ damage” in the study by Grika et al. was evaluated using the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (DI) (the higher SLICC/ACR DI score was associated with increased mortality), which has been designed and validated for SLE patients to capture non-reversible organ damage, not related to active inflammation, lasting at least six months2. In our recent analysis of the utility of the SLICC/ACR DI in aPL-positive patients, we also showed that: a) the SLICC/ACR DI score increases with additional aPL- and/or lupus-related damage; and b) the SLICC/ACR DI captures most, but not all, of aPL-related organ damage3. The top two limitations of SLICC/ACR DI use in aPL-positive patients were: a) not being able to record aPL-related “damage” (livedo reticularis/racemosa, adrenal infarcts requiring chronic treatment, diffuse pulmonary hemorrhage resulting in chronic symptoms, permanent inferior vena cava filter placement, multiple sclerosis-like disease, and/or white matter changes); and b) the definition of the two SLICC/ACR DI items (“venous thrombosis with swelling, ulceration, OR venous stasis for at least six months”; “skin ulceration [excluding thrombosis] for more than six months”). In our analysis, we created an experimental category for aPL-related damage assigning the above "damage" items one point each; we also scored all venous events and skin ulcers as one point.
In another retrospective study, we have previously demonstrated that functional prognosis is poor in an important minority of primary APS patients with more than ten years of disease; one-third of primary APS patients had organ damage and one-fifth were functionally impaired. In this study, we defined “organ damage” as permanent loss of the normal function of an organ system due to a clinical manifestation of APS and “functionally impaired” as any patient who was unable to perform everyday activities self-identified as important to maintain quality of life4.
A recent cross sectional study by Amigo et al. also aimed at the development and validation of a new physician-reported chronic DI in APS patients (DIAPS)5, after an expert panel identified 47 items that reflect irreversible aPL-related damage. The study demonstrated content, criterion, and construct validity; and DIAPS had a good correlation with EuroQol,6 which is a standardized non-disease-specific instrument for describing and valuing health-related quality of life by evaluating various factors (e.g. mobility, self-care, usual activities, pain/discomfort, and anxiety/depression).
Given the significant morbidity as well as social and financial implications associated with increased organ damage in APS patients, it is clear that there is a need for a more accurate way to assess aPL-related organ damage in aPL-positive patients with or without SLE. Meanwhile, physicians should be aware that while the SLICC/ACR DI can provide a crude estimate of APS-related organ damage, in persistently aPL-positive SLE patients, it should be interpreted cautiously as it can overestimate lupus-related, and underestimate aPL-related damage.
Contributor Information
Medha Barbhaiya, Department of Internal Medicine, Weill Cornell Medical Center, 1300 York Ave., New York, New York 10021, USA.
Doruk Erkan, Barbara Volcker Center for Women and Rheumatic Diseases, Hospital for Special Surgery, New York, New York, USA.
References
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