Fibromyalgia is a medical condition characterized by chronic and widespread pain, fatigue, sleep disturbance, and memory and cognitive problems. It is often co-morbid with one of more mental disorders, such as depression, anxiety, personality disorder, obsessive-compulsive disorder, or post-traumatic stress disorder.
Given the similarity of symptoms with other pain-causing diseases, fibromyalgia is often misdiagnosed clinically. According to the 2010 guidelines of the American College of Rheumatology, physicians sometimes diagnose fibromyalgia by excluding other disorders that can be responsible for the pain and other symptoms.
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Differential diagnosis of fibromyalgia
Chronic widespread pain and fatigue are common symptoms of many diseases, including rheumatic, inflammatory, and endocrine disorders. Therefore, presence of these symptoms can mislead the clinical diagnosis of fibromyalgia.
The common differential diagnoses of fibromyalgia include hypothyroidism, rheumatic diseases, myofascial pain syndrome, and chronic fatigue syndrome. Other potential causes of patient symptoms must be excluded before giving a diagnosis of fibrmyalgia.
Hypothyroidism – people with hypothyroidism may exhibit symptoms of fibromyalgia, such as fatigue, depression, and muscle or joint pain. Hashimoto thyroiditis is an autoimmune disease and the most common cause of hypothyroidism. Fibromyalgia is prevalent among 30 - 40% among people with Hashimoto thyroiditis.
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The prevalence of primary and secondary hypothyroidism among fibromyalgia patients is 10 - 44% and 44%, respectively. Studies have found that the presence of autoantibodies against thyroglobulin and thyroid peroxidase is two times higher among fibromyalgia patients than healthy individuals. Interestingly, fibromyalgia patients with fully functional thyroid gland also have a higher level of thyroid peroxidase autoantibodies in blood. This observation suggests that fibromyalgia pathogenesis may be supported by thyroid autoimmunity.
Another connection between hypothyroidism and fibromyalgia is that the characteristics of pain experienced by fibromyalgia patients are positively and negatively correlated with hypothyroidism and intracellular T3 level, respectively. In addition, reduced T3 level induces nociceptive afferent neurons to secrete more substance P, which is a neuropeptide responsible for pain signaling and often associated with fibromyalgia pain.
Regarding emotional distress associated with fibromyalgia, it is hypothesized scientifically that fibromyalgia-related anxiety and depression can significantly alter blood cortisol level, decrease cellular T4 uptake, and reduce the conversion of T4 to T3.
Rheumatic diseases – prevalence of fibromyalgia in patients with various rheumatic diseases (rheumatoid arthritis, lupus, ankylosing spondylitis, Sjögren's syndrome, and polymyalgia rheumatica, psoriatic arthritis) is higher than in the general population. The most common symptoms between fibromyalgia and rheumatic diseases are long-lasting pain and fatigue. Although rheumatic pain is generally nociceptive and caused by inflamed joints, it can eventually become centralized or widespread, leading to the development of fibromyalgia-like symptoms.
Increased activity of rheumatic diseases is believed to be one of the triggering factors for widespread pain, physical limitation, and fatigue in fibromyalgia. Studies have found that disease activity scores for patients with rheumatic diseases are significantly higher among patients with fibromyalgia. Therefore, while diagnosing fibromyalgia, physicians should consider the incidences of rheumatic diseases for better clinical outcomes.
The association of fibromyalgia with various rheumatic diseases is as follows:
Fibromyalgia and rheumatic arthritis – it is believed that the conversion of rheumatic arthritis-related acute peripheral pain into fibromyalgia-related chronic centralized pain is mainly triggered by long-lasting exposure to inflammation and pain. People who are exposed to increased systemic inflammation for long time generally have lower pain threshold. However, the connection between inflammation and pain amplification is not fully understood.
Although rheumatic arthritis and fibromyalgia often coexist, acute inflammatory markers (erythrocyte sedimentation rate, C-reactive protein, and swollen joint count), which are used in the evaluation of rheumatic arthritis, are not abnormal in the diagnosis of fibromyalgia. In contrast, moderate to severe pain associated with rheumatic condition may be the main player for pain sensitization in the central nervous system, leading to the onset of fibromyalgia.
Fibromyalgia and systemic lupus erythematosus (SLE) – the incidence of fibromyalgia is higher among patients with SLE as compared to the general population. The most common symptoms between fibromyalgia and SLE are musculoskeletal pain, fatigue and stiffness, cold induced vasospasm, cognitive problems, and depression. One possible connection between these two conditions is the presence of auto-antibodies against N-methyl-d-aspartate (NMDA) receptors (NR2A and NR2B subunits) in the serum and cerebrospinal fluid of SLE patients. Because of the dense presence of NMDA receptors in the central and peripheral nervous systems, these auto-antibodies can alter various important functions, including pain sensation, cognition, and emotional behaviors.
Despite being a confound condition, fibromyalgia is not associated with SLE-related organ damage and disease activity. However, it is believed that auto-antibody positive fibromyalgia patients are at higher risk of developing SLE.
SLE patients undergoing long-term steroid therapy generally have increased tenderness at the tender points, and withdrawal of steroid therapy often mimics fibromyalgia-like symptoms. Thus, it is important for a physician to thoroughly consider the medical history of a patient while diagnosing fibromyalgia.
Fibromyalgia syndrome and Sjögren’s syndrome (SS) – prevalence of fibromyalgia is about 15% in patients with primary SS. Patients who suffer from both fibromyalgia and SS demonstrate higher symptom intensity and SS activity. Studies have found that fibromyalgia is associated with higher intensity of certain symptoms (dryness, limb pain, and fatigue) as well as more severe depression in primary SS patients.
Fibromyalgia and ankylosing spondylitis (AS) – average prevalence of fibromyalgia among AS patients is 13% (range: 4 – 25%). Studies have found that fibromyalgia is significantly correlated with higher AS disease activity. The most common symptoms between fibromyalgia and AS are fatigue and sleep problems. Although pain is experienced in both the conditions, the nature and origin of pain is different.
Diagnosis of AS is mainly confirmed by inflammation of the sacroiliac joint, increased erythrocyte sedimentation rate, positive HLA-B27 test, and inflammation of the eye (uveitis). In addition, AS patients mostly have pain in the sacroiliac, hip, and shoulder joints. In general, physicians suspect the presence of fibromyalgia if AS patients have pain beyond the spine that affects the knees, thighs, elbows, and shoulders.
Fibromyalgia and polymyalgia rheumatica (PR) – since both the conditions are associated with muscular pain, PR can often be misdiagnosed as fibromyalgia. However, there are differences between fibromyalgia and PR. The pain and stiffness associated with PS are generally localized to the muscles of the neck, shoulders, and hip areas. The pain is not chronic in nature and usually lasts for around 2 years. Laboratory tests can indicate abnormalities in patients with PR but not fibromyalgia.
In contrast, fibromyalgia pain is distributed all over the body and generally long-lasting (chronic).
Myofascial pain syndrome (MPS) – MPS is often misdiagnosed as fibromyalgia as both the conditions are associated with chronic pain sensation. However, the nature of the pain differs between fibromyalgia and MPS. While MPS is related to muscular pain arising from localized trigger/tender points (painful areas of tight fibers formed within a muscle), fibromyalgia pain is diffuse and migratory and involves both muscles and joints.
Moreover, other common symptoms of fibromyalgia, such as extreme fatigue, sleep disturbance, and irritable bowel syndrome, are not frequently associated with MPS.
Chronic fatigue syndrome (CFS) – although fibromyalgia and CFS are interrelated conditions, some differences do exist. The most common symptoms between these two conditions include pain, fatigue, sleep disturbance, dizziness, memory problems, digestive problems, and anxiety and depression.
The major difference between these two conditions is that pain is the predominant symptom in fibromyalgia, whereas fatigue is predominant in CFS. The chronic and widespread pain in fibromyalgia should be present for at least 6 months to be diagnosed with fibromyalgia.
In contrast, the major criterion for diagnosing CFS is the presence of fatigue for more than 6 months together with sore throat, enlarged lymph nodes, muscle or joint pain, and other symptoms of systemic disorders.
Fibromyalgia and other related conditions
Fibromyalgia is related to many diseases that are otherwise clinically distinct entities. These are as follows:
Fibromyalgia and diabetes mellitus (DM) – both the conditions are interlinked. The likelihood of developing fibromyalgia is higher in DM patients with uncontrolled glucose level. Studies have found that patients suffering from both fibromyalgia and DM have significantly higher levels of HbA (1c), indicating a poor control of blood glucose level. Such patients also have increased numbers of tender points and higher pain sensation, sleep disturbance, fatigue, and headache than those without fibromyalgia.
Fibromyalgia and obesity – the prevalence of obesity and overweight is higher among fibromyalgia patients. The obesity-related predisposing factors for fibromyalgia are impaired physical activity, cognitive problem, sleep disturbances, anxiety and depression, thyroid gland malfunctioning, impaired growth hormone/insulin-like growth factor-1 signaling, and disruption of the endogenous opioid system.
Fibromyalgia and carpal tunnel syndrome (CTS) – epidemiological data have shown that the prevalence of CTS is high among fibromyalgia patients. The most prevalent symptoms of CTS in fibromyalgia patients are paresthesia in the hands and sensory and motor deficits.
Studies have found that severity of CTS is highly correlated with the functional impairment in patients with fibromyalgia, and moderate CTS is the most common form in fibromyalgia patients.
Fibromyalgia and temporomandibular disorder (TMD) – although clinically distinct entities, the prevalence of TMD is higher in patients with fibromyalgia. The most common symptoms between these two conditions are pain, sleep disturbance, lack of attention, articular sounds, and movement limitation.
In contrast to the centralized pain in fibromyalgia, TMD is associated with orofacial pains in the masticatory muscles, which originates from the tender points. The pain often migrates toward the neck and shoulder areas.