Polymyalgia Rheumatica

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Incidence increases with age
Average age of onset ¢ ¼70 years

Pediatric Considerations

Rare in patients <50 years of age; peak incidence between 70 and 80 years of age (2)

EPIDEMIOLOGY

Incidence

Incidence increases after 50. Incidence of PMR is 50/100,000 and incidence of giant cell arteritis (GCA) is 18/100,000 people in the United States.
Predominant sex: female > male (2 to 3:1) (3)
Most common in Caucasians, especially those of northern European ancestry

Prevalence
Prevalence in population >50 years old: 700/100,000

ETIOLOGY AND PATHOPHYSIOLOGY

Unknown. Symptoms appear to be related to enhanced immune system activity and periarticular inflammatory activity.
Pathogenesis
- Polygenic; multiple environmental and genetic factors contribute
- Histologic evidence of GCA and parvovirus B19 DNA in temporal artery specimen

Genetics
Associated with human leukocyte antigen determinants (HLA-DRB1*04 and DRB1*01 alleles) (4)

RISK FACTORS

Age >50 years
Presence of GCA

COMMONLY ASSOCIATED CONDITIONS

GCA (temporal arteritis) may occur in 15 " 30% of patients; more common in females than males with PMR.

DIAGNOSIS

HISTORY

Suspect PMR in elderly patients with new onset of proximal limb pain and stiffness (neck, shoulder, hip).
Difficulty rising from chair or combing hair are signs of proximal muscle involvement.
Nighttime pain
Difficulty arising from a chair or raising the arms
Systemic symptoms in ¢ ¼25% (fatigue, weight loss, low-grade fever)

PHYSICAL EXAM

Decreased range of motion (ROM) of shoulders, neck, and hips
Muscle strength is usually normal, although it may be limited by pain and/or stiffness.
Muscle tenderness
Disuse atrophy
Synovitis of the small joints and tenosynovitis
Coexisting carpal tunnel syndrome

DIFFERENTIAL DIAGNOSIS

Rheumatoid arthritis
Palindromic rheumatism
Late-onset seronegative spondyloarthropathies (e.g., psoriatic arthritis, ankylosing spondylitis)
Systemic lupus erythematosus; Sj ¶gren syndrome; fibromyalgia
Polymyositis/dermatomyositis (check creatine phosphokinase, aldolase)
Thyroid disease
Hyperparathyroidism, hypoparathyroidism
Hypovitaminosis D
Viral myalgia
Osteoarthritis
Rotator cuff syndrome; adhesive capsulitis
Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome
Occult infection or malignancy (e.g., lymphoma, leukemia, myeloma, solid tumor)
Myopathy (e.g., steroid, alcohol, electrolyte depletion)
Depression

DIAGNOSTIC TESTS & INTERPRETATION

Consider PMR in patients >50 years of age with proximal muscle pain and stiffness.

Temporal artery biopsy if symptoms of GCA are present
ESR (Westergren) elevation >40 mm/hr
- ESR is typically elevated, sometimes >100 mm/hr
- ESR normal (<40 mm/hr) in 7 " 22% of patients
Elevated C-reactive protein
Normochromic/normocytic anemia
Anticyclic citrullinated peptide (anti-CCP) antibodies usually negative (in contrast to elderly-onset rheumatoid arthritis [RA])
Rheumatoid factor: usually negative (5 " 10% of patients >60 years of age will have positive rheumatoid factor without RA)
Mild elevations in liver function tests, especially alkaline phosphatase
Antibodies to ferritin peptide
Drugs that may alter lab results: prednisone
Disorders that may alter lab results: other disorders causing elevation of the sedimentation rate (e.g., infection, neoplasm, renal failure)
Normal EMG
Normal muscle histology

Initial Tests (lab, imaging)

ESR (usually >40 mm/hr); C-reactive protein; CBC
MRI is not necessary for diagnosis but may show periarticular inflammation, tenosynovitis, and bursitis.
US may show bursitis, tendinitis, and synovitis.
MRI, PET, and temporal artery US may all play a role in diagnosis of PMR.

Diagnostic Procedures/Other
A temporal artery biopsy is indicated in patients with symptoms suggestive of GCA. Treat empirically pending biopsy results.
Test Interpretation
Scoring algorithm: morning stiffness >45 minutes (2 points), hip pain/limited ROM (1 point), absence of rheumatoid factor and anti-citrullinated protein antibody (ACPA) (2 points), and absence of peripheral joint pain (1 point). A score of >4 has 68% sensitivity and 78% specificity which increase with a positive temporal artery US.

TREATMENT

GENERAL MEASURES

Address risk of steroid-induced osteoporosis.
- Obtain dual energy x-ray absorptiometry and check 25-OH vitamin D levels if necessary.
- Consider antiresorptive therapies (bisphosphonates) based on recommendations for treatment of corticosteroid-induced osteoporosis.
Encourage adequate calcium (1,500 mg/day) and vitamin D (800 to 1,000 U/day) supplementation.
Physical therapy for ROM exercises, if needed

MEDICATION

First Line

Prednisone: 10 to 20 mg/day PO initially; expect a dramatic (diagnostic) response within days. 15 mg/day is an effective dose in most patients.
- Increase to 20 mg/day if no immediate response.
- If no response to 10 to 20 mg/day within a week, reconsider diagnosis.
Divided-dose steroids (BID or TID) may be helpful (especially if symptoms recur in the afternoon).
Consider using delayed-release prednisone at bedtime (may be more efficient in treating morning stiffness)
Begin slow taper by 2.5 mg decrements every 2 to 4 weeks to a dose of 7.5 to 10 mg/day. Below this dose, taper by 1 mg/month to prevent relapse.
Increase prednisone for recurrence of symptoms (relapse common).
Corticosteroid treatment often lasts at least 1 to 2 years.
May stop steroids at 6 to 12 months if patient is symptom-free and there is a normal ESR
Contraindications
- Use steroids with caution in patients with chronic heart failure, diabetes mellitus, immunocompromised conditions, and with systemic fungal or bacterial infection.
- Treat infections concurrently.
Precautions
- Long-term steroid use (>2 years) is associated with sodium and water retention, exacerbation of chronic heart failure, hypokalemia, increased susceptibility to infection, osteoporosis, fractures, hypertension, cataracts, glaucoma, avascular necrosis, depression, and weight gain
- Patients may develop temporal arteritis while on low-dose corticosteroid treatment for PMR. This requires an increase in dose to 40 to 60 mg.
- Alternate-day steroids are not effective.

Second Line

NSAIDs usually are not adequate for pain relief.
Methotrexate has a modest effect in reducing relapse rate and lowering the cumulative dose of steroid therapy.
There is conflicting evidence for antitumor necrosis factor agents (anti-TNF) (infliximab, etanercept) regarding steroid-sparing effects.
Anti-interleukin (anti-IL) 6 therapy is under investigation for future use (5).
Corticosteroid injections may reduce pain and stiffness and allow for increased levels of activity.

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Patient Monitoring

Evaluate patients monthly initially and during medication taper; every 3 months otherwise.
Follow ESR as steroids are tapered; both ESR and CRP should decline as symptoms improve.
Follow-up for symptoms of GCA (e.g., headache, visual loss, and diplopia) and report immediately.
Monitor side effects of corticosteroid therapy such as osteoporosis, hypertension, and hyperglycemia.
Do not treat elevated ESR (do not increase the steroid dose to normalize the ESR If patient is asymptomatic).

DIET

Regular diet
Aim for adequate calcium and vitamin D.

PATIENT EDUCATION

Review adverse effects of corticosteroids.
Discuss the symptoms of GCA and instruct the patient to report them immediately should any occur.
Contact physician if symptoms recur during steroid taper.
Instruct patients to not discontinue steroids abruptly.
Counsel patients on calcium and vitamin D requirements.
Resources for patients
- Arthritis Foundation: http://www.arthritis.org/
- American College of Rheumatology: http://www..rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Polymyalgia-Rheumatica

PROGNOSIS

Most patients require at least 2 years of corticosteroid treatment.
Prognosis is very good with proper treatment.
Relapse is common (in 25 " 50% of patients), particularly if steroids are tapered too quickly.
Higher age at diagnosis, female sex, high baseline ESR, increased plasma viscosity, increased levels of soluble IL-6 receptor, or high initial steroid dose have been associated with a prolonged disease course and greater number of disease flares.

COMPLICATIONS

Complications related to chronic steroid use
Exacerbation of disease with taper of steroids; development of GCA (may occur when PMR is being treated adequately)

REFERENCES

11 Mackie SL, Hughes R, Walsh M, et al. "An impediment to living life " : why and how should we measure stiffness in polymyalgia rheumatica? PLoS One. 2015;10(5):e0126758.22 Salvarani C, Gabriel SE, O 'Fallon WM, et al. Epidemiology of polymyalgia rheumatica in Olmsted County, Minnesota, 1970-1991. Arthritis Rheum. 1995;38(3):369 " 373.33 Liozon E, Ouattara B, Rhaiem K, et al. Familial aggregation in giant cell arteritis and polymyalgia rheumatica: a comprehensive literature review including 4 new families. Clin Exp Rheumatol. 2009;27(1 Suppl 52):S89 " S94.44 Weyand CM, Hunder NN, Hicok KC, et al. HLA-DRB1 alleles in polymyalgia rheumatica, giant cell arteritis, and rheumatoid arthritis. Arthritis Rheum. 1994;37(4):514 " 520.55 Seitz M. Polymyalgia rheumatica: what is the current status? Z Rheumatol. 2015;74(6):507 " 510.

ADDITIONAL READING

Aikawa NE, Pereira RM, Lage L, et al. Anti-TNF therapy for polymyalgia rheumatica: report of 99 cases and review of the literature. Clin Rheumatol. 2012;31(3):575 " 579.
Buttgereit F, Gibofsky A. Delayed-release prednisone " a new approach to an old therapy. Expert Opin Pharmacother. 2013;14(8):1097 " 1106.
Camellino D, Cimmino MA. Imaging of polymyalgia rheumatica: indications on its pathogenesis, diagnosis and prognosis. Rheumatology (Oxford). 2012;51(1):77 " 86.
Dasgupta B, Borg FA, Hassan N, et al. BSR and BHPR guidelines for the management of polymyalgia rheumatica. Rheumatology (Oxford). 2010;49(1):186 " 190.
Dasgupta B, Cimmino MA, Maradit-Kremers H, et al. 2012 provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Ann Rheum Dis. 2012;71(4):484 " 492.
Hern ¡ndez-Rodr ez J, Cid MC, L ³pez-Soto A, et al. Treatment of polymyalgia rheumatica: a systematic review. Arch Intern Med. 2009;169(20):1839 " 1850.
Kreiner F, Galbo H. Effect of etanercept in polymyalgia rheumatica: a randomized controlled trial. Arthritis Res Ther. 2010;12(5):R176.
Michet CJ, Matteson EL. Polymyalgia rheumatica. BMJ. 2008;336(7647):765 " 769.
Rent A, Ly KH, Blet A, et al. Contribution of antiferritin antibodies to diagnosis of giant cell arteritis. Ann Rheum Dis. 2013;72(7):1269 " 1270.
Spies CM, Burmester GR, Buttgereit F. Methotrexate treatment in large vessel vasculitis and polymyalgia rheumatica. Clin Exp Rheumatol. 2010;28(5 Suppl 61):S172 " S177.

CODES

ICD10

M35.3 Polymyalgia rheumatica
M31.5 Giant cell arteritis with polymyalgia rheumatica

ICD9

725 Polymyalgia rheumatica
446.5 Giant cell arteritis

SNOMED

65323003 Polymyalgia rheumatica (disorder)
239938009 Giant cell arteritis with polymyalgia rheumatica (disorder)

CLINICAL PEARLS

Consider PMR in patients >50 years of age presenting with proximal limb (hip, neck, shoulder) pain and stiffness.
A normal ESR does not exclude PMR.
If there is not a dramatic and rapid response to steroids, reconsider the diagnosis.
Adjust steroid dosing according to patient symptoms, not the ESR.

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