APS: What Rheumatologists Should Know about Hughes Syndrome

I have suggested that part of the initial midwife or obstetrician’s screening should include a simple three-part questionnaire:

1. Have you had a thrombosis?
2. Are you a migraine sufferer?
3. Do you have a family history of autoimmune disease (i.e., lupus, RA, multiple sclerosis, thyroid disease)?

I am sure that such a simple questionnaire might help identify a small at-risk group.

In most centers, once the mother and baby are safely sent home, there is no long-term follow-up. Yet often, APS patients presenting at, say, the age of 40 with a thrombotic problem, give a past history of miscarriage 20 years earlier. In an ideal world, women with recurrent miscarriage deserve regular long-term follow-up. But the world is far from ideal.

Lupus & APS

The early clinical studies of APS were carried out in lupus clinics, and could well have included “lupus features.” Perhaps surprisingly, time has shown little difference between primary APS and the APS associated with lupus. There are, undoubtedly, some classical features of lupus (e.g., Libman Sachs endocarditis, stroke, seizures) that are more likely to be aPL related. It also appears likely that aPL positivity in lupus confers a higher chronicity index.

The passage of time has also revealed one positive finding: It’s very unusual for patients with primary APS to develop lupus in later years.

The Big 3

The association between Hughes syndrome, Sjögren’s and hypothyroidism is so common that I have taken to calling them the big 3. Clinically, it’s an important association because the clinical symptoms of the three conditions—fatigue, cold circulation, aches and pains, and balance and memory problems—are common to all three. Similarly, many of these patients are burdened with the label fibromyalgia.

Each of the three interconnecting syndromes can respond well to treatment—for example, the clinical Sjögren’s to hydroxychloroquine and so on. Many of these patients are on my two trees treatment—willow (aspirin) and cinchona (quinine).

Seronegative APS

I believe that one of the benefits of a trainee clinician’s time spent in the lab is the recognition that many laboratory tests are open to variation. Many, many studies have attempted to assess the importance of titer, immunoglobulin class, triple or double positivity, relevance of “other” aPL such as anti-phosphatidyl-serine etc.^43,44

Broadly, all of these have relevance, but in the clinic, some don’t fit, such as those patients with all of the clinical features of APS whose aPL tests remain doggedly negative.

Some years ago, we wrote a paper introducing the term seronegative APS, calling attention to patients with strong clinical features of APS but with negative tests.⁴⁵ The concept goes back to the early days of seronegative RA and seronegative lupus—both of which labels, although based on clinical observation alone, had important therapeutic and prognostic consequences.