Contributor: Jason Kolfenbach, MD
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Diffuse Soft Tissue Pain
A 38 year-old accountant notes persistent joint pain and fatigue that have worsened over the past several months. She has had similar but milder pain for the past 4-5 years. She notes pain in her neck, shoulders, arms, back and knees. The pain interferes with her sleep most nights and she never awakens feeling rested. She has trouble making it through a full day at work because she is so tired. She has tried various over-the-counter non-steroidal anti-inflammatory therapies along with sleep aids, all without significant improvement. She denies depression but does admit to a fair amount of stress at work trying to keep up with the work load. The only past medical history is a prior diagnosis of irritable bowel syndrome. The rest of her review of systems is negative.
On joint exam, there is no synovitis or joint deformity. She has full range of motion of all extremities and passive joint movement does not reproduce her pain. On palpation though, she displays increased tenderness over multiple juxta-articular muscle groups including over her upper trapezius, posterior cervical muscles, lumbar, paraspinous, greater trochanter, medial knees and lateral epicondyles. There is discomfort with examiner resistance during strength testing, but normal strength of the upper and lower extremity muscles throughout. The rest of her examination is normal including head and neck, skin, cardiac, pulmonary, abdominal, and neurologic testing.
Laboratory evaluation is notable for CBC, CMP, ESR, thyroid studies and vitamin D levels that are normal. Hepatitis B and C testing is negative.
This patient’s presentation and clinical findings are consistent with a diagnosis of fibromyalgia as the cause of her widespread chronic pain and fatigue.
In addition to fibromyalgia, what other disorders might present with chronic widespread pain and fatigue?
The differential for diffuse pain is broad. Rheumatologic causes include polymyalgia rheumatica, lupus, rheumatoid arthritis, myositis, vasculitis and scleroderma. Infectious entities that can cause chronic widespread pain include hepatitis C and HIV. Endocrinopathies such as hypothyroidism and hyperparathyroidism should be considered. Drug toxicity as a cause is best exemplified by the muscle pain complicating statin therapy.
Other considerations include malignancy, neurologic disorders, sleep apnea and psychogenic pain from mood disorders.
What clinical and/or laboratory features from above are most helpful in identifying the diagnosis?
The presence of widespread tender points, along with a concurrent history of irritable bowel syndrome (IBS), is suggestive of fibromyalgia. Concurrent functional disorders such as IBS, interstitial cystitis, and TMJ syndrome may be present. In addition, there is a high prevalence of comorbid depression among patients with fibromyalgia. The syndrome can develop without a precipitating event, but has been reported following injury/trauma as well as in the setting of physical/emotional abuse (highlighting the importance of a full history during the initial encounter).
The lack of joint swelling, muscle weakness or other objective exam findings, coupled with lack of end-organ disease by lab testing, suggest a diagnosis other than a systemic inflammatory process. In general, the absence of clinical, radiographic and laboratory evidence of an inflammatory process after > 2 years of symptoms suggests a non-inflammatory etiology. The utility of laboratory testing is to rule out other etiologies. How extensive this testing should be is debatable.
Preliminary diagnostic criteria for fibromyalgia were updated in 2010 and do not include reliance upon tender points on exam. A useful case-based approach to the patient presenting with chronic widespread pain can be found in the High Impact Rheumatology Curriculum.
The patient returns to review the results of her studies. Extra time is spent counseling her on the diagnosis of fibromyalgia, explaining what it is and how it can be managed. She is reassured that this is not a progressively destructive or life-threatening illness. The need for regular, daily exercise and lifestyle modification is stressed. The diagnosis and treatment of any barriers to sleep is also essential, and referral to a sleep physician may be warranted. Therapeutic options are discussed and a trial of low dose, nighttime amitriptyline is begun.
The patient from the case above returns for follow-up 3 months later. Sleep has improved ‘somewhat’ since initiation of amitriptyline, but she continues to suffer from daytime fatigue, widespread muscle pain and malaise. No focal joint issues have arisen and outside of her chronic IBS she has no other symptom complaints. She has some continued anxiety revolving around her job, but denies depression.
Her exam is similar to the prior evaluation, with diffuse muscle tenderness in response to examiner palpation, no active synovitis, and no signs of localized organ abnormality.
During discussion with the patient she expresses frustration: “I don’t understand why my lab tests are normal. I have been told that amitriptyline is an anti-depressant. This isn’t just ‘all in my head’. Can you tell me what caused this to happen?”.
What is the current evidence behind the pathophysiology of fibromyalgia, and how can you use this information to provide patient-level counseling?
Counseling on the above is provided. It is explained that patients with fibromyalgia have dysfunctional pain processing pathways in which the ‘volume is inappropriately turned up’. The patient expresses thanks for explaining hercondition, but wonders if there are other treatment options other than amitriptyline.
Describe pharmacologic and non-pharmacologic approaches to the treatment of fibromyalgia?
Non-pharmacologic therapies include: patient education, exercise and cognitive behavioral therapy. Pharmacologic therapies should be tailored to individual patient symptoms such as concurrent depression, insomnia, soft tissue pain, and/or comorbid conditions such as IBS.
Pharmacologic options may include: gabapentin and pregabalin (which may exert effect through reduction of neurotransmitters such as substance P and glutamate), tramadol (with opioid receptor activity, but also dual serotonin/norepinephrine reuptake inhibition-SNRI), tricyclic agents (SNRI activity), cyclobenzaprine (muscle relaxant and SNRI activity), venlafazine (SNRI activity) and newer agents such as duloxetine, milnacipran and desvenlafaxine.
Regional Soft Tissue Pain
A 68 year-old female is evaluated for several months of left hip pain. She has multiple medical problems including diabetes, hypertension, coronary artery disease and osteoarthritis. She has known degenerative disease of her knees and has used a cane for ambulation for several years. Five years ago she underwent lumbar surgery for degenerative disc disease. She takes 2-3 hydrocodone-acetaminophen tablets a day for the back and knee pain.
The hip pain is new for the past 2-3 months. She localizes the pain to the upper outer thigh overlying the greater trochanter. The pain is particularly problematic when she lies on her left side and it interferes with her sleeping. She does not note any increased pain with walking. Her knee and back symptoms are unchanged. The pain does not radiate down the leg. She denies any numbness to the area of the pain.
What is the differential for hip pain that localizes to the lateral thigh/hip region?
The first step in the evaluation of musculoskeletal pain is attempting to localize the site of pain: articular, periarticular, regional (bone or muscle), and referred sources. Developing a systemic approach to the patient presenting with acute musculoskeletal symptoms is important, and several review articles offer excellent summaries on the approach of patients with regional and diffuse musculoskeletal complaints. [8, 9]
The differential of hip pain should include articular abnormalities of the hip, bursa and tendon disorders, neurologic disorders, referred pain from the knee, and bone disorders. Pain from disorders of the hip articulation such as osteoarthritis and avascular necrosis generally are noted in the groin but pain may be more diffuse. Trochanteric bursitis pain is localized over the greater trochanter with tenderness elicited in that area. Meralgia paresthetica causes paresthesias and numbness over the lateral thigh. The iliotibial band syndrome, a syndrome most commonly seen in runners, causes lateral but typically distal thigh pain. Lumbar spine disease with nerve root entrapment especially involving L2 to L4 may cause pain described as in the hip and thigh, while lumbar spinal stenosis typically produces bilateral leg pain with walking. Bone abnormalities including primary bone malignancies, metastatic bone lesions, occult fractures and Paget’s may present with localized hip and leg pain. Inter-abdominal abnormalities causing referred pain include abscesses, renal stones and hernias.
How does the positional nature of the pain aid in localizing the source of the pain?
Pain occurring with palpation or pressure over the greater trochanter would be most characteristic of trochanteric bursitis. Local bone abnormalities should also be considered. Unlikely in this scenario would be referred pain from an intra-abdominal or lumbar spine process.
On exam, the patient is 5’2’’ and weighs 180 lbs. She is stiff on arising and walks with a cane. There is no tenderness over her spine nor back. There is increased tenderness to palpation over the left greater trochanter but not on the right side. Rotation, flexion and abduction of the left hip are normal but she notes pain in her left lateral thigh with adduction of the left hip. On knee exam there is crepitus bilaterally but no effusion. Range of motion of the knee does not reproduce the pain. Neurologic exam of the lower extremities is intact and there is no loss of sensation elicited over the lateral left thigh.
A diagnosis of trochanteric bursitis is made on the basis of the history and exam findings.
Are any additional studies warranted at this time?
No further studies are warranted giving the typical nature of the history and exam findings.
What history and exam findings would have been characteristic for degenerative hip disease, radicular pain from degenerative back disease, metastatic bone pain, referred pain from the knee and meralgia paresthetica?
Degenerative hip disease would typically cause pain with weight bearing and ambulation, and be relieved with recumbency; pain is often reproduced with active or passive range of motion testing of the hip articulation. Radicular pain from the lumbar spine should not cause localized tenderness in the hip or thigh but would instead be associated with abnormalities on neurologic testing. Metastatic bone lesions classically cause constant pain which is not positional. Meralgia paresthetica causes numbness and paresthesia over the lateral thigh.
What other potential diagnoses are in the differential? What clinical and/or exam features make these less likely?
What treatment options are available for trochanteric bursitis?
Using sterile technique and 25 gauge 1 ½ inch needle, 2 cc of local anesthetic and 40 mg of injectible corticosteroid preparation are injected deep in the area of greatest tenderness overlying the left greater trochanter. Immediately following the procedure, the patient relates significant improvement in the pain when palpated.
Regional Musculoskeletal Disorders:
Keywords: Fibromyalgia, Complex Regional Pain Syndrome, Neuropathic joint, Joint pain, Widespread pain, Regional pain, Tendinopathy, Bursitis, Joint Injection, Arthrocentesis
(Answer questions 1 – 6 on a piece a paper. Find Answer Key at the bottom on the page.)
A 70 year old man presents to clinic for progressive shoulder pain. He complains of mild bilateral shoulder discomfort for the past ‘few years’, but has had progressive worsening at the right shoulder for three months. There is no history of recent or prior trauma to this area. He has chronic lower back pain from degenerative arthritis, but outside of this area and the involved shoulders there are no new sites of joint nor muscle pain. He describes both pain and stiffness. He is uncertain if activity improves his symptoms as he has avoided overhead activity secondary to pain, and he is also not engaged in regular exercise due to his chronic back symptoms. He localizes the pain to the upper and outer portion of the right shoulder in the deltoid region.
A review of systems is otherwise negative.
Joint examination reveals normal range of motion without swelling nor tenderness at the fingers, wrists and elbows bilaterally. The right and left shoulders are without obvious effusion. There is normal passive range of motion with external rotation bilaterally, with slightly limited range of motion with internal rotation on the right. Additional shoulder examinations were performed in an effort to localize the source of pain.
Joint examination of the lower extremities was normal other than mild limitation in range of motion at the hips and discomfort at the lumbar spine through active flexion and extension.
The rest of the physical examination is normal.
1) Which of the following clinical tests is not designed to identify pathology in the subacromial space?
Provocation testing of the right shoulder revealed discomfort with Hawkins test and Neer sign, as well as during painful arc testing. Drop arm testing on the right was normal. Formal strength testing of the right shoulder revealed 5/5 strength in resisted abduction, with breakaway weakness secondary to pain. Strength was normal in internal and external rotation on the right, with discomfort noted by the patient during the examination.
Subacromial bursitis is suspected based upon the clinical and examination findings. Non-steroidal anti-inflammatory medications are recommended, along with modification of activities and rest.
2) Strengthening which of the muscles below would be most likely to provide benefit for this condition?
The patient returns for follow up three months later, but unfortunately has not improved despite good compliance with home exercises and anti-inflammatory medications. He continues to have discomfort with Hawkins, Neer, and painful arc testing, with normal strength in abduction as well as internal and external rotation. Internal rotation at the right shoulder continues to be moderately limited. A decision is made to perform a subacromial steroid injection, along with a referral to physical therapy. Upon return to clinic 4 weeks later he reports only mild, temporary improvement in his symptoms, which after 3 weeks returned to his baseline level of pain. A plain radiograph if the shoulder is obtained.
3) What finding on X-ray likely account for the patients continued symptoms?
A 38 year old accountant presents with symptoms of worsening anxiety and restlessness for two months. She has noticed perspiration even while at rest, with the onset coinciding with her increase in anxiety. She has a history of IBS, and believes the frequency of her loose stools has increased during this time period as well. She does not recall recent sick contacts and has not noticed fevers nor chills. She has not traveled outside of the city for the past several years.
PMH: IBS; Fibromyalgia; Mild anxiety disorder
Medications: Dicyclomine 20mg three times daily; Amitriptyline 20mg at night; venlafaxine 150mg twice daily; tramadol 100mg three times daily as needed
Exam: VS: Temperature 38.1, HR 100, RR 26, BP 135/80
Musculoskeletal exam: joint examination is normal without synovitis nor deformity.
Neuro exam: she does not exhibit involuntary movement, although a slight resting tremor at the bilateral hands is noted on exam. Muscular strength is normal. Deep tendon reflexes: patellar reflex 3+ bilaterally, Achilles 3+ bilaterally, biceps 4+ bilaterally, brachioradialis 3+ bilaterally.
The rest of her cardiovascular, pulmonary, gastrointestinal, and skin exam are normal.
Lab orders are placed: CBC, comprehensive metabolic panel, urinalysis, TSH, urine toxicology screen (to identify ingestion of illicits such as cocaine or amphetamines).
4) In conjunction with this laboratory testing, which of the options below best describes the additional work-up/management that is needed at this visit?
A 55 year old female presents with joint and muscle pain for the past 5 years that has been progressively worse. She describes diffuse pain in her hands, hips, and shoulders. There has been no obvious joint swelling, and the discomfort is described as being generalized to the entire region of her hip and shoulder girdle, as well as the entire hand. Pain is the predominant symptom, with report of stiffness as well. She is unable to engage in exercise or other significant physical activity because of her symptoms.
Review of systems: periodic areas of numbness in limbs, present for past year; progressive, ‘disabling’ fatigue; poor sleep attributed to pain and anxiety; poorly controlled depression (not on therapy secondary to intolerance and/or weight gain on agents in past); memory issues, complaint of ‘mental slowing’
Prior lab testing that is brought with her to the appointment:
CBC, CMP & UA normal; ESR, CRP normal: 1 month prior
TSH and Vitamin D level normal: 3 months prior
ANA 1:80, with negative ‘reflex panel’; ESR, CRP normal; TSH, Vitamin B12, folate all normal: 1 year prior
ESR, CRP normal: 2 years prior
On joint exam there is no synovitis, with full range of motion of all extremities. Muscle strength testing of the upper and lower extremities is normal. On palpation, she describes pain upon light pressure over the superior aspect of the posterior cervical muscles, trapezius, and deltoid area bilaterally. On examination of the lower body she displays similar discomfort to palpation of the gluteal and greater trochanteric region, as well as the anterior quadriceps muscle bilaterally. Palpation of regions at the anterior cervical spine and chest, as well as regions in the distal arms and legs bilaterally, did not elicit painful response. The rest of her physical examination is normal.
5) Based upon the clinical scenario above, which of the following statements best describes the suspected diagnosis?
A 56 year old man comes in for evaluation of right hand pain, stiffness, and swelling for two months. The pain is located diffusely across the hand from his finger tips to his wrist. He describes this as 9/10 in intensity, sharp in quality. There is a mild dull ache to the forearm and upper arm, without swelling. There is no prior history of joint swelling or stiffness. He denies trauma, as well as recent sick contacts nor recent travel. Outside of his right hand and arm symptoms, he denies other joint issues.
Past medical history: Hypertension; carpal tunnel syndrome, with surgical release 3 months ago
Review of systems: negative outside of current symptoms
On exam there are no signs of infection nor poor wound healing at the post-surgical site. The right hand is slightly cool to touch throughout, tender to touch, with diffuse soft tissue swelling. Examination of the skin reveals brisk capillary refill. There are no skin ulcerations or signs of infarct at the fingertips. Joint examination outside of the right hand is normal. The rest of the physical exam is normal.
6) Which of the following diagnostic studies is most likely to help choose the appropriate medical therapy?
1) The correct answer is C.
In the evaluation of shoulder pain, it is important to remember that the majority of etiologies arise from periarticular structures rather than intracapsular disease. Pain that is worsened with active (rather than passive) range of motion testing is suggestive of a muscle or tendon source of pain. Having the patient identify the location of maximal pain, along with provocation testing, can often localize the site of pathology.
Yergason testing is performed in the evaluation of suspected biceps tendonitis. It is not designed to identify pathology arising from the subacromial space (supraspinatus tendinitis or tear, subacromial bursitis, impingement syndrome). Patients with biceps tendonitis often localize discomfort to the anterior aspect of the shoulder, rather than the lateral aspect as in this case. Biceps tendonitis should not cause significant pain with overhead activity.
Hawkins testing, Neer sign, and painful arc testing all evaluate for pathology in the subacromial space. The description of pain with overhead activity raises suspicion of a disorder in this region and should prompt further evaluation with these tests.
Hawkins testing and Neer sign are very sensitive tests to localize injury to the subacroimial space (roughly 80%), but specificity can be poor (30%). As such, a negative test is helpful in ruling out disease in this area.
Painful arc testing is performed by the examiner stabilizing the shoulder with one hand while passively abducting the arm. A positive report of pain between 60 to 120 degrees is consistent with disease in the subacromial space (specificity 80%). Pain during the arc beyond 120 degrees may be a sign of acromioclavicular disease.
2) The correction answer C.
Subacromial bursitis and rotator cuff tendinitis (often supraspinatus tendinitis when referring to conditions localized to the subacromial space) often result from impingement of those structures between the undersurface of the acromion and the humeral head. This occurs when the interval between the acromion and humeral head is narrowed.
The deltoid is the major abductor of the arm, and also serves to pull the humeral head superiorly. The rotator cuff muscles are involved with internal and external rotation at the shoulder, as well as shoulder abduction. In addition, they exert a downward pull on the humeral head, acting as stabilizer to keep the humeral head down in the glenoid fossa as the arm is abducted. Exercises to strengthen the rotator cuff will help ‘open’ the space between the acromion and humeral head in individuals with weak rotator cuff muscles who have an imbalance between the deltoid and rotator cuff muscles.
The trapezius muscle elevates the scapula, while the biceps radialis serves to flex the arm at the elbow and supinate the arm. Strengthening of these muscles would not serve to relieve impingement in the subacromial space.
3) The correct answer is D.
A humeral head fracture can cause significant shoulder pain, but the absence of trauma and lack of evidence for an occult fracture on plain films rule out this etiology.
Calcific tendinitis and chronic rotator cuff tear (with subsequent weakening of the rotator cuff and development of the so-called ‘high riding shoulder’) are both conditions which can lead to recurrent or prolonged symptoms stemming from subacromial bursitis. The radiograph from this patient does not show evidence of either of these conditions (1, 2).
The radiograph shows evidence of a large osteophyte on the undersurface of the acromion. This decreases the space which the supraspinatus and subacromial bursae occupy. Despite adequate exercises to strengthen the rotator cuff, the interval may still be narrowed secondary to the presence of a large bone spur; referral to orthopedics should be discussed with the patient.
4) The correct answer is C.
Serotonin-syndrome results from excessive serotonergic activity in the central nervous system, and commonly is the result of medication use/medication interaction. Clinicians who manage depression and other mood disorders, as well as fibromyalgia, need to be aware of this syndrome given that many of the medications used to treat these conditions can raise levels of serotonin. Selective serotonin reuptake inhibitors (SSRIs) are well known to increase serotonin levels, but many other medications can be culprits as well, including trazodone, amitriptyline, and tramadol. Concurrent use of multiple medications may elevate the risk for development of serotonin syndrome.
The syndrome classically consists of changes in mental status (anxiety, delirium, restlessness), autonomic hyperactivity (increased heart rate, increased temperature, sweating, elevation in blood pressure, diarrhea), and neuromuscular hyperactivity (tremor, increased deep tendon reflexes, myoclonus and muscle rigidity). The syndrome represents a clinical spectrum spanning from milder to more severe presentations, with more severe forms thought to be reflective of the degree of serotonergic activity. Treatment consists of stoppage of the medications that are increasing serotonin levels. Whether all such medications need to be stopped simultaneously and immediately depends on the severity of the presentation. Additional intervention such as temporary use of benzodiazepines has been described, and more severe cases may require hospital admission for monitoring and additional management.
Brain MRI and EMG/NCV are not immediately necessary in this case. Hyperreflexia is present diffusely, with no localizing disease, which is reassuring that a focal lesion is not driving current symptomatology. As such a search for a more generalized process should begin first. CSF culture is not likely necessary at this time given lack of signs of infection (no symptoms of headache, neck stiffness, or mention on exam of neck stiffness).
Close monitoring during withdrawal of medications will be necessary; if symptoms persist then consideration should be given to these and other diagnostic tests.
5) The correct answer is C.
While prior classification criteria for fibromyalgia included reliance upon specific tender points on exam, more recent understanding of the syndrome places an emphasis on widespread pain and presence of associated symptoms such as sleep disturbance, mood disorder, bowel and bladder irritability, and multiple somatic complaints. As such, the failure to reach > 11/18 tender points is not thought to rule out the diagnosis of fibromyalgia.
Additional testing for an inflammatory rheumatic disease is not likely necessary based upon the clinical symptoms and work-up to date. The lack of joint swelling, muscle weakness or other objective exam findings, coupled with lack of end-organ disease by lab testing only 1 month prior, suggest a diagnosis other than a systemic inflammatory process. In general, the absence of clinical, radiographic and laboratory evidence of an inflammatory process after > 2 years of symptoms suggests a non-inflammatory etiology.
Research has identified objective abnormalities on functional brain MRI and in CSF neurotransmitter levels in patients with fibromyalgia. While providing valuable insight in to the pathophysiology of pain processing, they are considered a research tool and are not used in the clinical evaluation of suspected fibromyalgia.
6) The correct answer is A.
The clinical history and appearance on examination of the right hand are consistent with a diagnosis of complex regional pain syndrome (CRPS). This syndrome may follow a precipitating event, and an association with surgical procedures such as carpal tunnel release has been seen. A bone scan can be helpful in CRPS to help confirm the diagnosis, and it may help in predicting response to prednisone as well. Early in disease, diffuse uptake is seen across the finger and wrist joints. Later in disease, the sensitivity of bone scan drops significantly. As such, a negative study does not rule out disease, but may suggest a low likelihood of response to prednisone.
Nailfold capillaroscopy can be a useful tool to aid in the diagnosis of systemic sclerosis and other rheumatic conditions. Early onset systemic sclerosis may present with bilateral finger puffiness. The unilateral swelling in this case would be highly atypical of systemic sclerosis. In addition, the brisk capillary refill is also not consistent with the vasculopathy seen in scleroderma, and is suggestive of a hyperemic state.
Rheumatoid factor, anti-CCP, and ANA testing are unlikely to help direct medical therapy based upon lack of clinical or exam evidence of rheumatoid arthritis or another rheumatic condition at this time.
Last updated February 2015.