31st January 2024

Fibromyalgia

Given that the cardinal symptom of fibromyalgia is widespread pain, the list of differential diagnoses is broad. Many systemic diseases such as Rheumatoid arthritis (RA), Systemic lupus erythematosus (SLE), Sjögren’s syndrome, spondyloarthropathies or polymyalgia rheumatica (PMR) may initially present similarly. In patients that have prominent symptoms of fatigue and mood or cognitive disturbance, history is vital as there is an extensive list of differentials ranging from endocrine pathologies such as thyroid dysfunction and Addison’s disease to viral infections. Thorough history taking is key, and associated risk factors, including female sex, low household income, middle age, divorce, and low educational status, should be considered. 

Rheumatoid Arthritis 

RA is a chronic systemic inflammatory disease. Patients with RA present with symmetrical joint pain in multiple areas. Mood disturbance, fatigue and symptoms lasting for at least 3 months may all be present in RA, which fits with the diagnostic criteria for fibromyalgia. A defining feature of RA is inflammation. Patients will characteristically have a history of swollen joints with morning stiffness, which is not seen in fibromyalgia. To differentiate these, a careful history and clinical examination should be taken. Blood tests for CRP and ESR should be normal in patients with fibromyalgia. Autoantibodies can also be helpful, particularly rheumatoid factor and anti-CCP, which should be negative. However, it should be noted that autoantibody tests can be positive in healthy individuals. 

Systemic Lupus Erythematosus 

SLE can present with generalised arthralgia, myalgia and fatigue, as seen in fibromyalgia. However, in fibromyalgia patients do not go on to develop the other classical SLE symptoms of rashes, photosensitivity, alopecia, oral ulcers, serositis, synovitis, neurological features, inflammation of the eye or dry mucous membranes. Similarly, a thorough history and examination should be taken to identify any of these features. Laboratory tests can be helpful if there is clinical suspicion of SLE, looking specifically for anaemia suggesting haemolytic anaemia, ANA, Anti-dsDNA, Antiphospholipid antibodies, complement and ENA. 

Spondyloarthropathies 

The spondyloarthropathies are a group of chronic inflammatory conditions, including ankylosing spondylitis (AS), enteric arthropathy, psoriatic arthritis and reactive arthritis. All the spondyloarthropathies can present with widespread pain and fatigue. As with RA, these conditions can be deforming, which is not seen in fibromyalgia. These are seronegative conditions; therefore, laboratory investigations are less helpful. Although many patients will be HLA-B27 positive. Diagnosis of AS is clinical and supported by imaging. Most patients are male with low back pain and morning stiffness improving throughout the day. This differs from fibromyalgia, where there are at least 7 pain areas and no prolonged morning stiffness. Enthesitis, iritis, aortic valve incompetence and pulmonary fibrosis are associated AS features and not classically seen in fibromyalgia. Enteric arthropathy should be differentiated from fibromyalgia by the presence of inflammatory bowel or coeliac symptoms. Psoriatic arthritis should be considered in any patient with joint pains and psoriasis. Radiology will show erosive changes, which are not seen in fibromyalgia. Finally, reactive arthritis is less likely to be a differential for fibromyalgia given the unilateral monoarthritis it tends to present with. 

Polymyalgia Rheumatica

PMR is a condition with a similar presentation to fibromyalgia. There is bilateral aching, tenderness in shoulders, hips, proximal limbs and often fatigue and depression. Patients tend to be older, with stiffness as opposed to pain as the primary complaint. Additionally, PMR is associated with giant cell arteritis. Typically, there is a raised CRP and ESR in these patients, differentiating it from fibromyalgia. 

Inflammatory myositis 

Polymyositis, dermatomyositis, and inclusion body myositis can all present with myalgia and fatigue; however, pain is a less common symptom. These conditions can be differentiated from fibromyalgia due to the presence of muscle weakness and raised creatinine kinase on blood tests. Furthermore, there are characteristic electromyography and muscle biopsy findings. 

Drug-induced myositis 

Statins can cause myositis, and patients present with widespread muscle discomfort. Interestingly, patients with fibromyalgia are more likely to develop statin-induced muscle pain. With statin-induced myositis, the temporal relationship between treatment with statin and the elevation in muscle enzymes distinguishes these diagnoses. 

Thyroid Disease 

Hypothyroidism can present with a myriad of symptoms. Similar symptoms to fibromyalgia include tiredness, low mood, impaired cognition or memory and myalgia. However, cold intolerance, non-pitting oedema of legs, myopathy and goitre are more specific to hypothyroidism. Thyroid function tests will differentiate the diagnoses. 

Addison’s Disease

Addison’s disease tends to cause myalgia, arthralgia, mood disturbance and gastrointestinal upset. Features specific to adrenal insufficiency include pigmented palmar creases, postural hypotension, and vitiligo. The condition is less commonly associated with widespread pain. 

Viral Infections 

Viral infections such as hepatitis, chikungunya, CMV, EBV and lyme disease are associated with arthralgias and myalgias. These can be distinguished from fibromyalgia based on the history, including travel history, illness duration and lack of positive serology.