If anything, RA is interesting in that there is never a dull moment as some new adventure waits around every bend. Those adventures may be in the form of a medication that works well, the failure of a medication, new symptoms that appear, etc. Earlier this week I happened to be rubbing my right elbow since it’s been in a lot of pain lately. While rubbing it, I noticed a lump and looked down to see a protuberance that was not there before. I inspected it and compared it to my left elbow determining that it was only presenting on the right side. It was clearly not part of the normal elbow joint. Then it dawned on me, this could be a rheumatoid nodule.
According to the National Rheumatoid Arthritis Society (NRAS) in the UK,
“Rheumatoid nodules are firm lumps that appear subcutaneously (ie under the skin) in about 20% of patients with rheumatoid arthritis. These nodules usually occur over exposed joints that are subject to trauma, such as the fingers joints and elbows, though occasionally they can occur elsewhere such as the back of the heel.”
In a study of almost 800 RA patients in Spain, the most prevalent extra-articular (outside the joint) presentation was nodules appearing in 24.5% of the sample.
According to a dermatological overview on the topic, the nodules consist of inflammatory tissue called necrobiotic granulomas which contains inflammatory cells such as lymphocytes and other white blood cells. The lumps are usually hard and painless and do not typically require any treatment although they may be removed surgically if needed. Nodules are usually benign but sometimes get infected. Nodules tend to be more common with patients with severe and aggressive RA disease symptoms, who are rheumatoid factor (RF) positive, and who display additional extra-articular symptoms including vasculitis (inflammation of blood vessels) and lung disease. Nodules can even develop in the lungs (see this case study).
The exact source of nodules is unknown but some researchers are beginning to argue that rheumatoid nodules may be related to genetic material which originated from the mother during pregnancy – called microchimerism (see this genetic study). According to Dr. Paget at the Hospital for Special Surgery in New York, patients who use high doses of methotrexate are more prone to develop nodules and the reasons for this are unclear (see also this article on MTX induced nodules). But there has been a decline in the presentation of nodules over the past few years probably attributed to the use of biological treatments. However, one group of researchers exhibited cases where increases of lung nodules were seen in patients using TNF blockers which then decreased after stopping the TNF blocker and switching to Rituxan. Supporting this study, other researchers documented that the use of Rituxan effectively treated subcutaneous nodules.
Rheumatoid nodules are an oft neglected area of research (see this recent review on nodules). In a recently published article in the prestigious international journal Rheumatolgy, Highton, Hessian, and Stamp (2007) pointed out that nodules may serve an important role in understanding RA. They stated,
“In conclusion, the rheumatoid nodule is a much-ignored lesion in RA. This is despite the fact that it is a lesion that is destructive of tissue, a key feature shared with the joint lesion. Could this usually peripherally situated lesion be central to understanding which are the core lesions of RA leading to tissue destruction, and which are additional amplification mechanisms? Definition of the seemingly simpler and less diverse inflammatory mechanisms leading to tissue destruction in the rheumatoid nodule might be one way of addressing the increasing complexity of RA pathogenic mechanisms and getting to the centre of the matter.”
While rheumatoid nodules tend to get pushed to the back burner, perhaps more research is needed about their pathology, how they develop, and how they are connected to other aspects of RA.