18th January 2024

Extra-articular features and complications of RA

Persistent, long-standing inflammation can lead to earlier development of cardiovascular and lung diseases and malignancy. Therefore, RA is associated with increased morbidity and premature death. Patients with high titres of Rheumatoid Factor (RF) are most likely to have extra-articular manifestations of RA.

• Skin Manifestations
  • Rheumatoid nodules are the most commonly occurring skin manifestation and are associated with RF positivity. They tend to be seen on extensor surfaces which are exposed to external pressure.
  • Splinter haemorrhages
  • Periungual infarcts
  • Leg ulcers
  • Digital gangrene
  • Pyoderma gangrenosum- rare
• Ocular Manifestations
  • Keratoconjunctivitis sicca is the most frequent ocular manifestation and is often seen together with xerostomia in patients with secondary Sjogren’s syndrome.
  • Episcleritis- inflammation of the layer superficial to the sclera, generally self-limiting and not as painful as scleritis
  • Scleritis – inflammation of the sclera itself- intensely painful
  • Ulcerative keratitis
• Pulmonary manifestations
  • Pleural effusions- these are usually exudative in nature
  • Interstitial lung disease
  • Nodules can also be seen in the lung and are a feature of Caplan syndrome (Rheumatoid pneumoconiosis)- combination of seropositive RA and a characteristic pattern of fibrosis.
  • Airways disease due to chronic inflammation
• Cardiac manifestations
  • Increased risk of atherosclerosis with subsequent complications associated with atherosclerotic disease
  • Pericarditis
  • Myocarditis
  • Myocardial fibrosis can lead to conduction abnormalities
  • Endocarditis with formation of rheumatoid nodules in aortic or mitral valves
• Haematological manifestations
  • Anaemia- multiple causes, including drug-induced, nutritional, Gastrointestinal (GI) bleed, bone marrow suppression and ineffective erythropoiesis
  • Anaemia of chronic disease (normochromic and normocytic) is correlated with disease activity, especially the degree of articular inflammation
  • Eosinophilia- related to disease activity or hypersensitivity to drugs
  • Thrombocytosis- related to the number of active inflamed joints
  • Increased risk of non-Hodgkin’s lymphoma- this risk may be further increased by immunosuppressive agents
  • Felty’s syndrome- the triad of RA, splenomegaly (clinically evident or on US) and neutropenia (<1.8*10/L) on two different occasions where other causes are deemed unlikely.
  • Secondary AA Amyloidosis- as with many other chronic inflammatory diseases. RA can increase the risk of developing secondary amyloidosis. The disease process is increased production of serum amyloid (AA) protein, fibrils of which get deposited in the extracellular tissues of various organs. Amyloidosis can manifest as macroglossia, cardiac failure, chronic kidney disease (usually due to nephrotic syndrome), GI bleeding or malabsorption or as hepatomegaly/ deranged liver function tests. Diagnosis is confirmed via biopsy  (usually fat pad or rectal biopsy), which shows the characteristic findings of red-green birefringence when stained with Congo red. Management is through achieving control.
• GI and renal manifestations are usually iatrogenic and rare
• Neurologically- peripheral neuropathy presenting as diffuse sensorimotor neuropathy or mononeuritis multiplex.