BOTTOM LINE

Polymyalgia Rheumatica (PMR) is a peri-arthritis of shoulders and hips presenting as subacute symmetrical morning stiffness in older adults usually around or above the age of 70 with a predilection for Caucasian women. Patients have a high ESR and CRP. Patients should be exquisitely responsive to 15-20mg of daily prednisone and clinically normalize within 24-72 hours; if not exquisitely responsive, consider other inflammatory arthritis or other diagnoses. [🕑 5 minute read]

EPIDEMIOLOGY

• Annual incidence: ~13-113/100,000 people. Prevalence ~700-900/100,000 people
• Age:
  • 70-80 years; does not happen under age of 50. If presenting at younger ages (ex: 50-65), carefully consider other diagnoses like seronegative RA
• Sex:
  • Female > Males, ~2:1
• Ethnicity:
  • Highest incidence in northern European/Scandinavian descent. Uncommon in Asian, African, Latin descent.

CLINICAL MANIFESTATIONS

—History

• Patient:
  • Old (mean age 70s) F > M ~2:1
• Onset: 
  • Subacute (<2 weeks)
• Pattern:
  • Symmetrical proximal shoulders (70-95%) and hip girdle (groin 50-70%)
• Local:
  • AM stiffness in shoulders and hips. Shoulder impingement. No joint swelling.
  • May localize pain to head of humerus (site of insertion for rotator cuff tendons)
• Systemic:
  • Constitutional symptoms, GCA
• Treatment response:
  • Near resolution of symptoms withing 24-72 hours of prednisone 15-25mg daily

PMR does not cause objective “weakness” or myopathy; muscles are normal in PMR.
· Formal strength testing on exam is normal (patients give way due to pain)
· CK is normal, muscle biopsies are normal
· The “myalgia” term in PMR is an antiquated term

Always screen PMR patients for GCA (ex: headache, scalp tenderness, vision changes, jaw/limb claudication)
· PMR patients who get GCA: ~15%
· GCA patients who present with PMR: 40-60%

—Exam

• Painful ROM in shoulders and Hips; shoulder impingement.
• Neurological exam: normal strength (gives way due to pain)
• Screen for joint swelling and perform cardiac and peripheral vascular exam to screen for GCA
  • peripheral and temporal pulses, bilateral brachial blood pressures, auscultation for bruits in chest, neck, and abdomen

INVESTIGATIONS

• CBC: Neutrophilia or thrombocytosis may reflect inflammation
• Chemistries: ALT, Creatinine CK normal.
• ESR should be >40mm/h (though can be lower in 7-20% of patients)
• CRP should be elevated

ESR

• To measure ESR, a patients blood is placed in an upright tube and allowed to sediment for 1-hour.
• Erythrocytes carry a positively charge; proteins made during inflammation (like CRP) carry a negative charge
• During acute inflammation, more negatively charged proteins are made which bind to the positively charged erythrocytes — thus sedimenting faster and increasing ESR. Hence, ESR is reported in units of mm/h.

DIAGNOSIS

Polymyalgia rheumatica should be suspected in patients (typically around the age of 70) presenting with subacute symmetrical morning stiffness in their shoulders and sometimes hip girdle with signs of shoulder impingement on exam. Review and exam should include a screen for features of Giant Cell Arteritis (ex: temporal headache, jaw/limb claudication, vision changes, scalp tenderness, abnormal cardio/vascular exam) or rheumatoid arthritis (peripheral symmetrical small-joint swelling). ESR and CRP should be elevated and patients should respond exquisitely to prednisone 15-20mg/day.

—DIFFERENTIAL DIAGNOSIS

• Consider an alternate diagnosis if:
  • Young (ex: 50-65 years); never happens <50 years old
  • Male
  • No exquisite response to prednisone 15-20mg/d after 24-48 hours
  • Symptoms distal to elbows and knees
  • Presence of Joint swelling
  • ESR not very high, or ESR <<< CRP

• Rheumatoid arthritis:
  • Elderly-onset RA often presents with PMR-like presentation and is seronegative
• RS3PE:
  • Relapsing Seronegative Symmetrical Synovitis with Pitting Edema): look for pitting hand edema and occult malignancy
• Localized repetitive strain:
  • Is there a history of repetitive use? Asymmetrical symptoms? Normal ESR?
• Other
  • Cancer: widespread bony metastases and myeloma
  • Drugs: statin myopathy
  • Hypothyroidism
  • Psoriatic arthritis: up to 30% of psoriasis patients can get psoriatic arthritis
  • Infection: HIV, TB, SBE
  • Fibromyalgia: diffuse generalized tenderness on exam

CLASSIFICATION CRITERIA

—2012 EULAR/ACR CLASSIFICATION CRITERIA

TREATMENT

• Prednisone
  • Prednisone 15-25mg daily; patients should have near resolution of symptoms within 24-72 hours
  • Taper prednisone to 10mg/d within 4-8 weeks, then taper by 1mg monthly until off
  • Monitoring: re-measure ESR and CRP monthly during initial taper, can spread out to q3 months if stable
• Prophylaxis
  • Consider bisphosphonate depending on risk factors and arrange a BMD
  • Consider PPI for ulcer prophylaxis
• Refractory: if worsening symptoms during prednisone taper, first consider:
  • Is it a true flare of PMR (concordant proximal morning stiffness with elevated ESR)?
  • Is it an alternate diagnosis, such as rheumatoid arthritis (see differential above)?
  • Is it osteoarthritis and or other localized pathology symptomatic with prednisone taper?

Increased pain with a prednisone taper should be evaluated carefully before assuming a flare of PMR. Prednisone has anti-prostaglandin effects and can provide general analgesia like an NSAID; has evidence for use in treating osteoarthritis.

• If truly refractory PMR, can consider
  • Methotrexate, combination csDMARDs
  • IL-6 inhibition
    • Sarilumab: approved in United States to decrease flare rate and steroid requirement in PMR
    • Tocilizumab: small studies showing improvement in PMR activity and steroid requirement in PMR

PROGNOSIS

• Morbidity: No erosive or structural damage to joints; morbidity is related to prolonged steroid exposure
• Mortality: no difference in mortality compared to general population

REFERENCES

Dasgupta, B., Cimmino, M. A., Maradit-Kremers, H., Schmidt, W. A., Schirmer, M., Salvarani, C., Bachta, A., Dejaco, C., Duftner, C., Jensen, H. S., Duhaut, P., Poór, G., Kaposi, N. P., Mandl, P., Balint, P. V., Schmidt, Z., Iagnocco, A., Nannini, C., Cantini, F., Macchioni, P., … Matteson, E. L. (2012). 2012 provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Annals of the rheumatic diseases, 71(4), 484–492. https://doi.org/10.1136/annrheumdis-2011-200329

Devauchelle-Pensec, V., Carvajal-Alegria, G., Dernis, E., Richez, C., Truchetet, M. E., Wendling, D., Toussirot, E., Perdriger, A., Gottenberg, J. E., Felten, R., Fautrel, B. J., Chiche, L., Hilliquin, P., Le Henaff, C., Dervieux, B., Direz, G., Chary-Valckenaere, I., Cornec, D., Guellec, D., Marhadour, T., … Saraux, A. (2022). Effect of Tocilizumab on Disease Activity in Patients With Active Polymyalgia Rheumatica Receiving Glucocorticoid Therapy: A Randomized Clinical Trial. JAMA, 328(11), 1053–1062. https://doi.org/10.1001/jama.2022.15459

Dejaco, C., Singh, Y. P., Perel, P., Hutchings, A., Camellino, D., Mackie, S., Abril, A., Bachta, A., Balint, P., Barraclough, K., Bianconi, L., Buttgereit, F., Carsons, S., Ching, D., Cid, M., Cimmino, M., Diamantopoulos, A., Docken, W., Duftner, C., Fashanu, B., … American College of Rheumatology (2015). 2015 recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Arthritis & rheumatology (Hoboken, N.J.), 67(10), 2569–2580. https://doi.org/10.1002/art.39333

Doran, M. F., Crowson, C. S., O’Fallon, W. M., Hunder, G. G., & Gabriel, S. E. (2002). Trends in the incidence of polymyalgia rheumatica over a 30 year period in Olmsted County, Minnesota, USA. The Journal of rheumatology, 29(8), 1694–1697.

González-Gay, M. A., Matteson, E. L., & Castañeda, S. (2017). Polymyalgia rheumatica. Lancet (London, England), 390(10103), 1700–1712. https://doi.org/10.1016/S0140-6736(17)31825-1

Kobza Black, A., Greaves, M. W., & Hensby, C. N. (1982). The effect of systemic prednisolone on arachidonic acid, and prostaglandin E2 and F2 alpha levels in human cutaneous inflammation. British journal of clinical pharmacology, 14(3), 391–394. https://doi.org/10.1111/j.1365-2125.1982.tb01996.x

Kroon, F. P. B., Kortekaas, M. C., Boonen, A., Böhringer, S., Reijnierse, M., Rosendaal, F. R., Riyazi, N., Starmans, M., Turkstra, F., van Zeben, J., Allaart, C. F., & Kloppenburg, M. (2019). Results of a 6-week treatment with 10 mg prednisolone in patients with hand osteoarthritis (HOPE): a double-blind, randomised, placebo-controlled trial. Lancet (London, England), 394(10213), 1993–2001. https://doi.org/10.1016/S0140-6736(19)32489-4

Spiera R, et al. (2022). Sarilumab in Patients with Relapsing Polymyalgia Rheumatica: A Phase 3, Multicenter, Randomized, Double Blind, Placebo Controlled Trial (SAPHYR).  Arthritis Rheumatol. 2022;74S:ACR #1676.