Differentials
Rheumatoid arthritis (RA)
SIGNS / SYMPTOMS
As with other rheumatologic conditions, fibromyalgia may coexist with RA, making the diagnosis challenging.
Patients with RA will have not only widespread body pain and arthralgias but should also have signs of active synovitis on physical exam.
Differential features of RA include predominantly joint pain, usually symmetrical small joints; inflammatory joint pain (significant stiffness which improves with movement); joint line tenderness, synovitis on exam.
If a patient with RA also has widespread pain and soft-tissue tenderness, fibromyalgia is likely. If the patient is treated for RA with subsequent resolution of synovitis and markers of inflammation, yet the patient still has widespread pain and fatigue, the most likely cause is fibromyalgia.
INVESTIGATIONS
RF or anti-cyclic citrullinated protein (CCP) antibody is usually positive. Plain films of the hands and feet may show erosive joint changes.
Markers of systemic inflammation (erythrocyte sedimentation rate, CRP) are typically elevated.
Polymyalgia rheumatica (PMR)
SIGNS / SYMPTOMS
Patients are typically older (>55 years of age) on presentation than those with fibromyalgia.
Differentiating features of PMR include hip and shoulder pain/stiffness, described as both muscular and joint pain, rather than widespread pain, morning stiffness that lasts more than an hour; significant stiffness after a period of inactivity; neck pain; unexplained weight loss.
May also present with temporal arteritis, that is jaw claudication, headache, visual changes (diplopia, amaurosis fugax, vision loss), scalp tenderness, artery changes (prominence, tenderness, nodularity), and blood pressure disparity in the arms.
PMR responds rapidly to corticosteroids, whereas people with fibromyalgia do not improve with corticosteroid treatment.
INVESTIGATIONS
Erythrocyte sedimentation rate, CRP, or other markers of inflammation are usually elevated.
Systemic lupus erythematosus (SLE)
SIGNS / SYMPTOMS
SLE and fibromyalgia may coexist.
Differentiating features of SLE include multisystem involvement; muscle and joint pain (inflammatory); serositis (pleural effusion, pericardial effusion); glomerulonephritis; fever and rash; photosensitivity; mucositis; Raynaud phenomena; uveitis; thrombotic, pregnancy complications.
INVESTIGATIONS
Strict criteria for the diagnosis of SLE must be met; an isolated positive antinuclear antibody (ANA) test is not enough to establish the diagnosis of SLE in a patient with widespread pain as ANA is positive in up to 10% of the general population.
Further testing with anti-DNA antibody, autoantibodies to extractable nuclear antigens, and complement levels should be considered to confirm a diagnosis of SLE.
Polyarticular osteoarthritis
SIGNS / SYMPTOMS
Joint swelling and inflammation are possible in osteoarthritis (OA), but not in fibromyalgia unless it is a concomitant diagnosis. OA presents predominantly in the joints rather than myalgia, with crepitus, Bouchard/Heberdeen nodes on exam.
INVESTIGATIONS
Radiographs are characteristic: joint space narrowing, subchondral sclerosis, osteophytes, subchondral cysts.
Ankylosing spondylitis
SIGNS / SYMPTOMS
Patients have limited range of movement of the spine; spine movement in fibromyalgia is typically maintained.
Differentiating features of ankylosing spondylitis include restricted spinal motions, inflammatory spine pain (worse in the morning, improving with activity), prolonged morning stiffness, and are more symptomatic after inactivity.
INVESTIGATIONS
Radiographic features are characteristic: erosions and osteitis at the ischial tuberosities, iliac crest, symphysis pubis, and femoral trochanter.
Myositis (dermatomyositis and other inflammatory myopathies)
SIGNS / SYMPTOMS
Weakness and muscle fatigue are present (and more common than pain) in patients with a primary muscle inflammatory condition.
INVESTIGATIONS
Creatine kinase or aldolase levels are elevated.
Osteomalacia
SIGNS / SYMPTOMS
Osteomalacia can present with widespread bone pain, fatigue, and malaise. However, they often have a history of fracture and proximal myopathy.
INVESTIGATIONS
Physical exam.
X-rays may show low bone mineral density or characteristic findings of longstanding secondary hyperparathyroidism; Looser pseudofractures are pathognomic.
Creatinine kinase likely elevated.
Neuropathy
SIGNS / SYMPTOMS
Differentiating symptoms of neuropathy include burning and/or shooting pain, numbness/tingling, and weakness.
INVESTIGATIONS
Electromyogram; quantitative sensory testing; nerve biopsy.
Myofascial pain syndrome (MPS)
SIGNS / SYMPTOMS
Myalgia is localized, typically to an extremity and the attached truncal musculature.
In contrast to the tender points of fibromyalgia, trigger points are the hallmark of MPS, with pressure over these areas not only reported as tender but causing radiation and reproduction of the pain.
Some experts consider MPS to be a localized form of fibromyalgia.
INVESTIGATIONS
Patients with localized MPS do not have evidence of widespread central sensitization.
Multiple sclerosis
SIGNS / SYMPTOMS
Differentiating symptoms of multiple sclerosis (MS) include visual changes (e.g., double vision, unilateral, partial, or complete loss), ascending numbness in leg or bandlike truncal numbness, and slurred speech.
MS is also associated with postexercise muscle fatigue, as well as generalized fatigue, which may be experienced by patients with fibromyalgia. However, chronic, widespread pain is unusual.
INVESTIGATIONS
MRI brain, cervical spine, thoracic spine; lumbar puncture.
Myasthenia gravis
SIGNS / SYMPTOMS
Primarily weakness and pain are the differentiating symptoms of myasthenia gravis.
INVESTIGATIONS
Muscle acetylcholine receptor (AChR) binding antibody; muscle-specific receptor tyrosine kinase (MuSK) antibodies; electromyogram.
Lyme disease
SIGNS / SYMPTOMS
Differentiating symptoms of Lyme disease include the characteristic rash and joint swelling.
INVESTIGATIONS
Serologic tests.
Hyperthyroidism
SIGNS / SYMPTOMS
Increased thirst or urination, decreased appetite, constipation, nausea/vomiting, kidney stones, and thinning bones are the differential symptoms for hyperthyroidism.
INVESTIGATIONS
Thyroid-stimulating hormone is typically suppressed and free T4 is high.
Hypothyroidism
SIGNS / SYMPTOMS
Patients with hypothyroidism may have muscular aching and prominent fatigue that improves on replacement of thyroid hormone.
A routine thyroid-stimulating hormone (TSH) test is recommended for patients presenting with suspicion of fibromyalgia. Fibromyalgia and hypothyroidism may coexist.
INVESTIGATIONS
TSH is elevated and free T4 is low.
Hyperparathyroidism
SIGNS / SYMPTOMS
Symptoms may mimic those of fibromyalgia, for example poor sleep, myalgia, fatigue, memory loss.
INVESTIGATIONS
Elevated serum parathyroid hormone and calcium.
Cortisol excess
SIGNS / SYMPTOMS
The differentiating symptoms of cortisol excess include hypertension, diabetes, weight gain, moon faces, and hirsutism.
INVESTIGATIONS
Dexamethasone suppression test; evening salivary cortisol test; 24-hour urine cortisol collection.
Adrenal insufficiency
SIGNS / SYMPTOMS
Postural hypotension, nausea/vomiting, weight loss, and skin pigmentation are differential symptoms of adrenal insufficiency.
INVESTIGATIONS
Morning cortisol collection; adrenocorticotropic hormone stimulation test.
Vitamin D deficiency
SIGNS / SYMPTOMS
Low vitamin D levels are associated with widespread body pain; however, this may not be causal but may instead be due to low outdoor activity and sunlight exposure in people with chronic pain.
INVESTIGATIONS
Serum 25-hydroxyvitamin D level is low.
Iatrogenic effects
SIGNS / SYMPTOMS
Some medications can be associated with widespread musculoskeletal pain, for example, statins, aromatase inhibitors, bisphosphonates, opioid-induced hyperalgesia (controversial).
INVESTIGATIONS
Interrupting the medications to look for improvement and recurrence with reintroduction is a possible way to investigate their relationship with their pain.
Chronic fatigue syndrome (CFS)
SIGNS / SYMPTOMS
Myalgic encephalomyelitis (ME)/CFS is characterized by a sudden or gradual onset of persistent disabling fatigue, postexertional malaise, unrefreshing sleep, cognitive and autonomic dysfunction, myalgia, arthralgia, headaches, and sore throat and tender lymph nodes (without palpable lymphadenopathy), with symptoms lasting at least 6 months.[117]
There is considerable overlap between fibromyalgia (FM) and CFS, and it is often challenging to differentiate the two. A large portion of patients with FM meet criteria for CFS/ME, including the postexertional malaise. In practice treatment should focus on the predominant phenotype, that is if pain is the predominant issue and fatigue seems like a passenger address as FM. If patients appear more tender, but have significant fatigue, the treatment approach should be from a CFS/ME perspective.
INVESTIGATIONS
No differentiating tests.
Chronic liver disease
SIGNS / SYMPTOMS
Patients with liver disease, most notably hepatitis C, often have myalgias.
INVESTIGATIONS
Elevated liver function tests; presence of hepatitis C antibody.
Iron deficiency anemia
SIGNS / SYMPTOMS
Patients with myalgias and iron deficiency often report improvement in symptoms with iron replacement.
INVESTIGATIONS
Low serum iron levels, low transferrin saturation; low ferritin.
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