12: Rheumatoid Arthritis

CHAPTER 12
Rheumatoid Arthritis: Clinical Features and Diagnosis


Mohammed Akil1 and Robert Moots2


1 Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK


2 University of Liverpool; Aintree University Hospital, Liverpool, UK


Pathogenesis


Whilst the cause of rheumatoid arthritis (RA) is not fully established, it is clear that there is a complex dysregulated inflammatory process that, in the presence of a yet undefined environmental trigger, develops in genetically predisposed individuals. This leads to the development of an autoimmune synovitis with subsequent hypertrophy that, if inadequately treated, leads to cartilage and bone destruction, progressive joint damage and disability. The inflammatory process also potentially affects many other tissues, including the lungs and cardiovascular system.


Many cells and molecules appear to play central roles in the pathogenesis of RA. T‐cells, which orchestrate the immune response, appear to be important, and biologic drugs that selectively target them are effective, but not in all patients. Similarly, drugs targeting other cells, such as B‐cells, have also proven highly effective. Small soluble immune system messengers, cytokines, also play a crucial role. These include tumour necrosis factor‐alpha (TNF‐α) and interleukin‐6 (IL‐6), both of which are targeted successfully by highly effective biologic drugs. The majority of the genetic predisposition lies in the class II MHC (the ‘shared epitope’ on the hypervariable region of DRB1), the presence of which may also correlate with disease severity.


A possible environmental trigger is smoking. It is thought that this might lead to citrillination of proteins that in turn can act as antigens and trigger the development of an autoimmune response. Indeed, anticitrillinated peptide antibodies, anti‐CCP (also referred to as ACPA), can be used in the diagnosis of RA and may precede onset of symptoms by many years.


Clinical features


The objectives of clinical assessment for RA are to:



  • establish the diagnosis
  • evaluate the disease activity (is the disease active or quiescent?)
  • assess the disease severity (amount of damage and disability)
  • examine for extra‐articular manifestations.

The disease may be insidious in nature, rarely occurring in men younger than 30 years, with gradually rising incidence with advancing age. In women, the incidence steadily increases from the mid‐20s to peak incidence between 45 and 75 years. In the typical presentation, the most common variant, the small joints of the hands and feet are affected in a symmetrical pattern. The joints predominantly involved are the metacarpophalangeal joints, proximal interphalangeal joints and wrists (Figure 12.1); in the feet, the metatarsophalangeal joints and the forefoot joints are typically affected.

Photo of two hands depicting typical changes in the hands in rheumatoid arthritis. The right hand is normal while the left hand has a lump found on the joint of the index finger.

Figure 12.1 Typical changes in the hands in rheumatoid arthritis


Less common forms of presentation are acute monoarticular, palindromic rheumatism and asymmetrical large joint arthritis. Theoretically, any synovial joint can be affected but spine joints other than the cervical spine are very rarely involved.


Extra‐articular manifestations (Figure 12.2) are also varied and may differ in different populations. They can affect almost any system of the body and are mediated by various inflammatory mechanisms, which include immune complex deposition, cytokine production and direct endothelial injury, all of which can mediate distant and local effects. Also, mechanical insults such as synovial hypertrophy and subluxation of joints may cause entrapment of nerves or vessels. The abnormal mechanics and disuse lead to degenerative changes and osteoporosis, compounding disability.

Image described by caption.

Figure 12.2 Large rheumatoid nodules over the elbows


‘Red flags’


As many complications of RA or its treatment can occur, vigilance on the part of clinicians is required to pick them up early and intervene, preventing severe morbidity and even mortality in certain cases; some of these are detailed below.


Atlantoaxial subluxation – This results from involvement of the atlantoaxial joint, which may be clinically asymptomatic until the subluxation develops. Development of pain around the occiput, radiating arm pain, numbness or weakness of the limbs and vertigo on neck movement are warning signs; if not detected, this may lead to sudden death, especially if patients undergo neck manipulation for endotracheal intubation during surgery. It is essential to actively look for this during presurgical evaluation by performing lateral views of the cervical spine in flexion (Figure 12.3) and extension, measuring the distance between the posterior margin of the atlas ring and the anterior surface of the odontoid process.

Image described by caption.

Figure 12.3 Magnetic resonance image of the cervical spine showing atlantoaxial involvement in rheumatoid arthritis


Pericarditis – Onset of central chest pain worsened by lying flat, accompanied by a pericardial rub, merits urgent echocardiogram to confirm and urgent initiation of steroid therapy. Infective causes such as tuberculosis need to be ruled out by aspiration and analysis when suspected.


Monoarticular flare – A single joint worsening should always be viewed with suspicion in RA, and septic arthritis excluded by aspiration. It is prudent to initiate treatment for possible septic arthritis as soon as possible after aspiration, until the results of the joint aspirate rule it out.


Eye involvement – Sudden onset of eye pain and increased lacrimation should alert the clinician to the possibility of scleritis (Figure 12.4); if left untreated, this may lead to full‐thickness involvement of the sclera, with thinning and risk of perforation. Called scleromalacia perforans, this sinister condition is thankfully rare but needs to be looked out for.

Close-up of a person’s eyes with episcleritis.

Figure 12.4 Scleritis in rheumatoid arthritis


Other manifestations of RA are given in Box 12.1.

Nov 5, 2018 | Posted by in RHEUMATOLOGY | Comments Off on 12: Rheumatoid Arthritis

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