Autonomic disorders have previously been described in association with the antiphospholipid syndrome. The present study aimed to determine the clinical phenotype of patients in whom autonomic dysfunction was the initial manifestation of the antiphospholipid syndrome and to evaluate for autonomic neuropathy in these patients. This was a retrospective study of 22 patients evaluated at the University of Colorado who were found to have a disorder of the autonomic nervous system as the initial manifestation of antiphospholipid syndrome. All patients had persistent antiphospholipid antibody positivity and all patients who underwent skin biopsy were found to have reduced sweat gland nerve fiber density suggestive of an autonomic neuropathy. All patients underwent an extensive evaluation to rule out other causes for their autonomic dysfunction. Patients presented with multiple different autonomic disorders, including postural tachycardia syndrome, gastrointestinal dysmotility, and complex regional pain syndrome. Despite most having low-titer IgM antiphospholipid antibodies, 13 of the 22 patients (59%) suffered one or more thrombotic event, but pregnancy morbidity was minimal. Prothrombin-associated antibodies were helpful in confirming the diagnosis of antiphospholipid syndrome. We conclude that autonomic neuropathy may occur in association with antiphospholipid antibodies and may be the initial manifestation of the syndrome. Increased awareness of this association is important, because it is associated with a significant thrombotic risk and a high degree of disability. In addition, anecdotal experience has suggested that antithrombotic therapy and intravenous immunoglobulin therapy may result in significant clinical improvement in these patients.
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I would like to acknowledge Dr. Graham Hughes as the first to suspect the association of autonomic disease in APS dating back to his earliest descriptions of the syndrome in the 1980s, which have provided valuable insights. I thank Drs. Kathryn Hassell and Graham Hughes for their critical review of the manuscript. I thank Dr. Jennifer Hintzsche for statistical analysis of the data.
The study was approved by the Institutional Review Board of the University of Colorado Anschutz Medical Campus.
Conflict of interest
The author declares that she has no conflict of interest.
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Schofield, J.R. Autonomic neuropathy—in its many guises—as the initial manifestation of the antiphospholipid syndrome. Immunol Res 65, 532–542 (2017). https://doi.org/10.1007/s12026-016-8889-4
- Autonomic neuropathy
- Antiphospholipid syndrome
- Postural tachycardia syndrome
- Gastrointestinal dysmotility
- Complex regional pain syndrome
- Intravenous immunoglobulin