Multiple Joint Pain

Differential Diagnosis

Common Diagnoses

Occasional Diagnoses

Rare Diagnoses

  • Sickle-Cell Crisis
  • Amyloidosis
  • Rheumatic Fever
  • Atypical Systemic Infections (e.g. Lyme Disease, Weil’s Disease, Brucellosis, Syphilis [Secondary])
  • Decompression Sickness (the Bends)

Ready Reckoner

Key distinguishing features of the most common diagnoses

RAPsoriasisViralConnective TissueOA
Fever, MalaisePossibleNoYesPossibleNo
Young PatientPossiblePossiblePossiblePossibleNo

Possible Investigations

Likely:FBC, ESR/CRP, autoantibodies.

Possible:Urinalysis, U&E, HLA-B27, joint X-rays, synovial fluid aspiration.

Small Print:Blood film, serology, CXR, bone scan, bronchoscopic biopsy or nodal aspiration.

  • FBC, ESR/CRP, blood film: WCC and ESR/CRP raised in acute inflammation and infection. Anaemia of chronic disease may be seen, and blood film will reveal sickle cell.
  • Autoantibodies: Rheumatoid factor is positive in most cases of RA (if negative, consider measuring anti-CCP), but is also positive in many autoimmune diseases and chronic infections; antinuclear factor is positive in 98% of cases of SLE but a similar result is obtained in 30% of cases of RA and also in many other diseases.
  • Urinalysis: May reveal proteinuria or haematuria if there is renal involvement in connective tissue disease.
  • U&E: To check for renal failure via renal involvement in multisystem connective tissue disease.
  • HLA-B27: A high prevalence in spondoarthritides.
  • Serology: May be useful to diagnose viral, or atypical systemic, infections. ASO titres, if rising, suggest recent streptococcal infection (e.g. in rheumatic fever).
  • Joint X-rays: Hand X-rays may show characteristic features helping to distinguish between RA and psoriatic arthritis; pelvic and lumbar spine X-rays may show the typical changes of ankylosing spondylitis (if negative, and clinical suspicion high, a bone scan may be helpful); X-rays of affected joints may confirm clinical diagnosis of OA.
  • CXR: May reveal lung malignancy.
  • Synovial fluid analysis: Helps distinguish inflammatory from infective and crystal arthropathies.
  • Bronchoscopic biopsy or nodal aspiration: For sarcoidosis.

Top Tips

  • The connective tissue diseases can all affect almost every organ system. Take a full history so as not to miss a clue or complication.
  • Check the skin as this may contribute to the diagnosis (e.g. scaly rash in psoriasis, butterfly rash in SLE, thickening of skin in sclerosis).
  • Don’t overvalue autoimmune blood tests. Most diagnoses of arthritis are clinical, blood tests simply providing confirmatory or prognostic information.

Red Flags

  • Suspect Reiter’s syndrome in a young male with an inflammatory oligoarthritis of the lower limbs.
  • An insidious onset of symmetrical polyarthritis in the 30–50 age range, with early morning stiffness, pain and swelling of hands and feet, suggests RA.
  • Pain in the wrists and ankles of a middle-aged or elderly smoker with clubbing and chest symptoms strongly suggests hypertrophic pulmonary osteoarthropathy caused by underlying lung cancer.
  • Don’t overlook the patient’s occupation as this may be relevant in certain cases – for example, in vets and farm workers, brucellosis and Weil’s disease are possible infective causes.

Published: 2nd August 2022 Updated: 10th April 2024

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