Polymyalgia Rheumatica & Giant-cell Arteritis Bill Cayley MD

Learning Objectives Participants will have medical knowledge to describe Pathophysiology of Polymyalgia Rheumatica (PMR) and Giant-cell Arteritis (GCA) Evaluation for PMR and GCA Management of PMR and GCA

Diane Z Diane is an 85 year old woman who had “the flu” 6 months ago, and proximal muscle weakness since then. She is fatigued and her gait is a bit unsteady. Review of systems is otherwise normal. PMH is significant only for Bell’s Palsy and PSVT. FH is unremarkable. No history of rheumatologic disease. SH indicates she lives alone but has family involved with care. What else do you want to know? Notes for instructor: Ask participants what additional items of the history they would pursue

Diane Z Physical Examination WD WN older female in NAD. Weight is 152 # (stable). HEENT: PERRLA, EOMI, Neck supple, no LA or TM. Cardiac Regular, no murmurs or rubs. Chest Clear with good air entry. Abdomen soft, normal bowel sounds Neuro and MSK exams normal. What else do you want to know? Notes for instructor: Ask participants what additional items of the physical exam they would pursue

Diane Z Labs: Hemoglobin 12.7 TSH .82 Lyme negative ESR 33 What is your diagnosis? Why? Notes for instructor: Ask participants what their final diagnosis would be and why

Jane T 46 year old woman with headaches, stabbing “all over the head”, some starting from top of head, others from left temporal region which is tender when she touches it. Requests ESR. PMH: GERD, Depression, DM, Htn, OSA. SH indicates she is single, lives alone, works at local factory ROS includes occasional heartburn, occasional leg swelling. Blood sugars are stable. No skin lesions. What else do you want to know? Notes for instructor: Ask participants what additional items of the history they would pursue

Jane T Physical Examination WD WN female in NAD. Wt 309 (stable). HEENT: PERRLA, EOMI. Left temporal region tender on palpation. Oropharynx benign. Cardiac Regular, Lungs Clear, Abdomen Soft. What else do you want to know? Notes for instructor: Ask participants what additional items of the physical exam they would pursue

Jane T Labs: A1C 5.2 K 3.8 Cr 0.7 ESR 44 What is your diagnosis? What’s next? Notes for instructor: Ask participants what their final diagnosis would be and why

Jane T Temporal Artery Biopsy: Negative! Notes for instructor: Ask participants how this affects their differential or final diagnosis

Overview Polymyalgia Rheumatica & Giant-cell Arteritis Inflammatory disorders. Constitutional symptoms with increased acute phase reactants. The syndromes are considered to be different manifestations of inflammatory vasculitis. PMR Pain and stiffness in girdle muscles GCA Unilateral headache and temporal artery tenderness Polymyalgia Rheumatica (PMR) & Giant-cell Arteritis (GCA) are interrelated inflammatory disorders. Both are characterized by consitutional symptoms with increased acute-phase reactants. PMR usually presents with severe stiffness and pain in the girdle muscles; true muscle weakness is generally not present, rather activity is limited by the discomfort associated with movement. GCA usually presents with unilateral headache and tenderness over the temporal artery. Both syndromes are thought to be common manifestations of a common underlying inflammatory process. Source: Unwin B, Williams CM, Gilliland W. Polymyalgia rheumatica and giant cell arteritis. Am Fam Physician. 2006 Nov 1;74(9):1547-54. PMID: 17111894 (http://www.aafp.org/afp/20061101/1547.html)

Epidemiology Polymyalgia Rheumatica & Giant-cell Arteritis Generally affect people over 50 One patient may have both 50% with GCA have PMR 10% with PMR have GCA Incidence GCA: 18 cases per 100,000 over 50 Men: 8/100,000 Women: 24/100,000 PMR: 500 cases per 100,000 over 50 Polymyalgia Rheumatica (PMR) & Giant-cell Arteritis (GCA) generally affect those over 50 years old. Up to 50 percent of patients with GCA may also have PMR, and 10 percent of patients with PMR may also have GCA. Peak incidence for both disorders is between age 70 and 80, and both are more common in northern latitudes. Source: Unwin B, Williams CM, Gilliland W. Polymyalgia rheumatica and giant cell arteritis. Am Fam Physician. 2006 Nov 1;74(9):1547-54. PMID: 17111894 (http://www.aafp.org/afp/20061101/1547.html)

Pathophysiology Activation of cellular immunity? Immune complexes deposited in arteries? Speculative Influenza, Hep B, B Burgdorferi GCA Vasculitis of head & neck large arteries PMR Vasculitis may or may not be present The pathophysiology of GCA and PMR is unclear. Both are characterized by activation of cellular immunity, and inflammation may be due to immune complex deposition in arteries. Speculation has included influenza viruses, hepatitis B, and borrelia burgdorferi as possible inciting agents, but none of these agents has been conclusively linked to PMR or GCA. GCA is due to vasculitis of head and neck large arteries, while in PMR vasculitis may or may not be present. Sources: Epperly, TD, Moore KE, Harrover JD. Polymyalgia Rheumatica and Temporal Arteritis. Am Fam Physician 2000;62:789-96,801. (http://www.aafp.org/afp/20000815/789.html)

Clinical Features of GCA History Consitutional symptoms: Fever, night sweats, depression, malaise Temporal or occipital headache Jaw claudication, tongue pain Mandibular or dental discomfort Painless vision loss, amaurosis fugax, diplopia Tinnitus, vertigo Features of the clinical history suggesting GCA include constitutional symptoms such as fever, night sweats, depression, or malaise. Patient may also have a temporal or occipital headaache, and complain of jaw claudication, tongue pain, or dental discomfort with chewing. Visual symptoms include painless vision loss, amaurosis fugax, or diplopia, and patients may also have tinnitus or vertigo. Source: Unwin B, Williams CM, Gilliland W. Polymyalgia rheumatica and giant cell arteritis. Am Fam Physician. 2006 Nov 1;74(9):1547-54. PMID: 17111894 (http://www.aafp.org/afp/20061101/1547.html)

Clinical Features of GCA Examination and labs Temporal or occipital scalp tenderness Swollen temporal artery Anemia ESR greater than 50 mm/hour Physical examination findings suggesting GCA include temporal or occipital scalp tenderness, and a swollen or “beaded” temporal artery. Patients may have anemia, or a sedimentation rate greater than 50 mm/hr. Source: Unwin B, Williams CM, Gilliland W. Polymyalgia rheumatica and giant cell arteritis. Am Fam Physician. 2006 Nov 1;74(9):1547-54. PMID: 17111894 (http://www.aafp.org/afp/20061101/1547.html)

GCA: History, Exam and Lab Finding LR (+) LR (-) Jaw Claudication 4.2 .72 Diplopia 3.4 .95 Temporal Artery – “Beaded” 4.6 .93 Temporal Artery – Prominent 4.3 .67 Temporal Artery – Absent Pulse 2.7 .71 Temporal Artery – Tender 2.6 .82 ESR abnormal 1.1 .2 ESR > 100 1.9 .8 This chart lists the performance characteristics of individual elements of the history and physical examination for diagnosis of temporal arteritis. Adapted from: Smetana GW, Shmerling RH. Does this patient have temporal arteritis? JAMA. 2002 Jan 2;287(1):92-101. PMID: 11754714 (http://jama.ama-assn.org/cgi/content/full/287/1/92)

Clinical Features of PMR History Consitutional symptoms: Fever, night sweats, depression, malaise Pain and stiffness in shoulder and/or pelvic girdle Morning stiffness of 45 minutes or more Difficulty getting up, doing ADLs Clinical findings suggestive of PMR include constitutional symptoms such as fever, night sweats, depression, or malaise. Patients typically have pain or stiffness in the shoulder or hip girdle muscles, morning stiffness of 45 minutes duration or more, and difficulty getting up and about and doing ADLs. Source: Michet CJ, Matteson EL. Polymyalgia rheumatica. BMJ. 2008 Apr 5;336(7647):765-9. PMID: 18390527 (http://www.bmj.com/cgi/content/full/336/7647/765)

Clinical Features of PMR Exam Affected muscle groups TENDER but not WEAK Laboratory investigations ESR > 40 mm/hour On physical examination, patients with PMR typically have TENDERNESS in the shoulder or hip girdle muscles, but not true weakness. Laboratory investigations usually show an elevated sedimentation rate. Source: Michet CJ, Matteson EL. Polymyalgia rheumatica. BMJ. 2008 Apr 5;336(7647):765-9. PMID: 18390527 (http://www.bmj.com/cgi/content/full/336/7647/765)

Differential Diagnoses Giant-cell Arteritis Dental conditions Trigeminal neuralgia Sinus disease Otological conditions Retinal vascular accident Polymyalgia Rheumatica Neoplastic disease Cervical spondylosis Rheumatoid arthritis Connective tissue dz Myeloma Leukaemia Osteomyelitis Hypothyroidism Miliary tuberculosis Typical differential diagnoses to also consider when evaluating for GCA or PMR Sources: Meskimen S, Cook TD, Blake RL. Management of Giant Cell Arteritis and Polymyalgia Rheumatica. Am Fam Physician 2000;61:2061-8,2073. (http://www.aafp.org/afp/20000401/2061.html) Epperly, TD, Moore KE, Harrover JD. Polymyalgia Rheumatica and Temporal Arteritis. Am Fam Physician 2000;62:789-96,801. (http://www.aafp.org/afp/20000815/789.html) Swannell AJ. Polymyalgia rheumatica and temporal arteritis: diagnosis and management. BMJ. 1997 May 3;314(7090):1329-32. PMID: 9158471 (http://bmj.bmjjournals.com/cgi/content/full/314/7090/1329)

Laboratory Investigations Erythrocyte Sedimentation Rate (ESR) GCA May be > 100 Sometimes only 40-50 Rarely normal PMR Generally > 40 Up to 20 % of patients may have normal ESR Sources: Meskimen S, Cook TD, Blake RL. Management of Giant Cell Arteritis and Polymyalgia Rheumatica. Am Fam Physician 2000;61:2061-8,2073. (http://www.aafp.org/afp/20000401/2061.html) Epperly, TD, Moore KE, Harrover JD. Polymyalgia Rheumatica and Temporal Arteritis. Am Fam Physician 2000;62:789-96,801. (http://www.aafp.org/afp/20000815/789.html) Swannell AJ. Polymyalgia rheumatica and temporal arteritis: diagnosis and management. BMJ. 1997 May 3;314(7090):1329-32. PMID: 9158471 (http://bmj.bmjjournals.com/cgi/content/full/314/7090/1329)

Erythrocyte Sedimentation Rate The height of the layer of RBCs that settle in a tube of anticoagulated blood in one hour. Normals Men: Age/2 Women: (Age +10)/2 Inflammatory disorders produce abnormal proteins which bind to RBCs and make them "stick" together and settle out of the plasma more rapidly Source: Unwin B, Williams CM, Gilliland W. Polymyalgia rheumatica and giant cell arteritis. Am Fam Physician. 2006 Nov 1;74(9):1547-54. PMID: 17111894 (http://www.aafp.org/afp/20061101/1547.html) Brigden ML. Clinical utility of the erythrocyte sedimentation rate. Am Fam Physician. 1999 Oct 1;60(5):1443-50. PMID: 10524488 (www.aafp.org/afp/991001ap/1443.html)

Laboratory Investigations Other tests to consider Chemistries, glucose & liver enzymes CBC - Normocytic anemia may be present Rhematoid Factor & ANA (r/o RA) TSH (r/o hypothyroidism) Blood Cx (r/o endocarditis) CPK (r/o polymyositis) SPEP (r/o myeloma) Other testing to consider when evaluating for GCA or PMR to rule out differential diagnoses. Sources: Michet CJ, Matteson EL. Polymyalgia rheumatica. BMJ. 2008 Apr 5;336(7647):765-9. PMID: 18390527 (http://www.bmj.com/cgi/content/full/336/7647/765) Meskimen S, Cook TD, Blake RL. Management of Giant Cell Arteritis and Polymyalgia Rheumatica. Am Fam Physician 2000;61:2061-8,2073. (http://www.aafp.org/afp/20000401/2061.html) Epperly, TD, Moore KE, Harrover JD. Polymyalgia Rheumatica and Temporal Arteritis. Am Fam Physician 2000;62:789-96,801. (http://www.aafp.org/afp/20000815/789.html) Swannell AJ. Polymyalgia rheumatica and temporal arteritis: diagnosis and management. BMJ. 1997 May 3;314(7090):1329-32. PMID: 9158471 (http://bmj.bmjjournals.com/cgi/content/full/314/7090/1329)

Biopsy for Giant-cell Arteritis Biopsy shows Severe intimal thickening Reduction in vessel lumen Internal elastic lamina is disrupted with fragmentation and sometimes destruction. Normal biopsy appearances do not exclude the diagnosis because of possible skip lesions. Temporal artery biopsy samples Positive in 60-80% of patients with giant cell arteritis Positive in only 15-20% of patients with PMR Temporal artery biopsy for GCA may show severe intima thickening with reduction in the vessel lumen. However, a normal biopsy does not completely exclude the diagnosis of GCA. Additionally, while temporal artery biopsy may be positive in only 60-80% of patients with GCA, it may also be positive in up to 15-20% of patients with PMR. Source: Epperly, TD, Moore KE, Harrover JD. Polymyalgia Rheumatica and Temporal Arteritis. Am Fam Physician 2000;62:789-96,801. (http://www.aafp.org/afp/20000815/789.html)

Diagnostic Criteria Diagnosis of GCA (ACR) Three or more of: Age 50 years of age or older New localized headache Temporal artery abnormal tenderness or decreased temporal artery pulse ESR 50 mm/hr or greater Abnormal temporal artery biopsy Sensitivity: 93.5% Specificity: 91.2% Diagnosis of PMR Age 50 years or older 1 month aching & morning stiffness in at least two of : Shoulders & upper arms Hips & thighs Neck & torso ESR 40 mm/hr or greater Exclusion of other disease Sources: Hunder GG, Bloch DA, Michel BA, Stevens MB, Arend WP, Calabrese LH, et al. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum 1990;33:1122-8 (see http://www.rheumatology.org/publications/classification/tca.asp?aud=mem) Evans JM, Hunder GG. Polymyalgia rheumatica and giant cell arteritis. Clin Geriatr Med 1998;14:455-73

Management Corticosteroids are primary therapy To prevent bone loss For GCA steroids should not be delayed to wait for biopsy Temporal artery biopsy in GCA will remain abnormal for up to four weeks after starting steroids. To prevent bone loss Calcium w/ Vitamin D Bisphosphonates Corticosteroids are the primary therapy for PMR and GCA. For suspect, GCA steroids should not be delayed to wait for biopsy, since temporal artery biopsy specimens in GCA will remain abnormal for up to four weeks after starting steroids. To prevent bone loss from long-term steroids, patients should be advised to use Calcium w/ Vitamin D as well as bisphosphonates. Source: Unwin B, Williams CM, Gilliland W. Polymyalgia rheumatica and giant cell arteritis. Am Fam Physician. 2006 Nov 1;74(9):1547-54. PMID: 17111894 (http://www.aafp.org/afp/20061101/1547.html)

Management - GCA Start with Prednisone 40-60 mg daily If visual symptoms, give Solu-medrol 250 mg Q 6hrs for 3-5 days, then oral steroids Once symptoms resolve and ESR normal (usually 2-4 weeks) begin slow taper Reduce dose 10 % of daily dose every 2 weeks Monitor symptoms and ESR for relapse If relapse, hold taper until Sx/ESR normalize then resume slower taper. Taper to 5 mg daily, then SLOW taper (18-24 mo) For treatment of GCA, start prednisone 40-60 mg daily. If the patient has visual symptoms, give Solu-medrol 250 mg Q 6hrs for 3-5 days, then change to oral steroids. Once symptoms resolve and the ESR is normal (usually 2-4 weeks) begin slow taper of steroids. Sources: Unwin B, Williams CM, Gilliland W. Polymyalgia rheumatica and giant cell arteritis. Am Fam Physician. 2006 Nov 1;74(9):1547-54. PMID: 17111894 (http://www.aafp.org/afp/20061101/1547.html) Meskimen S, Cook TD, Blake RL. Management of Giant Cell Arteritis and Polymyalgia Rheumatica. Am Fam Physician 2000;61:2061-8,2073. (http://www.aafp.org/afp/20000401/2061.html) Epperly, TD, Moore KE, Harrover JD. Polymyalgia Rheumatica and Temporal Arteritis. Am Fam Physician 2000;62:789-96,801. (http://www.aafp.org/afp/20000815/789.html)

Management - PMR Corticosteroids usually provide immediate relief Start Prednisone 15-20 mg daily Do not use higher doses Absence of response suggests alternate diagnosis Taper once Sx & ESR are stable 2-4 weeks Then taper by 2.5 mg every 2-4 weeks to 10 mg daily Then taper by 1 mg every 2-4 weeks to 5 mg daily Then SLOW taper till off (18-24 mo) Corticosteroids usually provide immediate relief of PMR. Start Prednisone at a dose of 15-20 mg daily. Do not use higher doses of steroids, as absence of response to low-dose prednisone suggests an alternate diagnosis. Begin tapering prednisone once symtoms and ESR are stable for 2-4 weeks. Sources: Michet CJ, Matteson EL. Polymyalgia rheumatica. BMJ. 2008 Apr 5;336(7647):765-9. PMID: 18390527 (http://www.bmj.com/cgi/content/full/336/7647/765) Unwin B, Williams CM, Gilliland W. Polymyalgia rheumatica and giant cell arteritis. Am Fam Physician. 2006 Nov 1;74(9):1547-54. PMID: 17111894 (http://www.aafp.org/afp/20061101/1547.html) Meskimen S, Cook TD, Blake RL. Management of Giant Cell Arteritis and Polymyalgia Rheumatica. Am Fam Physician 2000;61:2061-8,2073. (http://www.aafp.org/afp/20000401/2061.html) Epperly, TD, Moore KE, Harrover JD. Polymyalgia Rheumatica and Temporal Arteritis. Am Fam Physician 2000;62:789-96,801. (http://www.aafp.org/afp/20000815/789.html)

Long-Term Prognosis GCA & PMR tend to be self-limited GCA PMR Steroids Relapse rates up to 25% GCA Blindness – 10% of untreated GCA Increased risk of macrovascular disease - aortic aneurysms & dissection, stroke PMR Generally no long-term effects Steroids DM, Osteoporosis, Vertebral and Hip Fractures GCA and PMR tend to be self-limited, though relapse rates up are up to 25%. Patients with GCA are at risk for blindness (rates as high as 10% if GCA is untreated). Patients with GCA are also at increased risk of macrovascular disease, including aortic aneurysms and dissection, and stroke. PMR generally has no long-term effects. Steroid therapy for GCA and PMR places patients at increased risk of diabetes, osteoporosis, and vertebral and hip fractures. Sources: Michet CJ, Matteson EL. Polymyalgia rheumatica. BMJ. 2008 Apr 5;336(7647):765-9. PMID: 18390527 (http://www.bmj.com/cgi/content/full/336/7647/765) Unwin B, Williams CM, Gilliland W. Polymyalgia rheumatica and giant cell arteritis. Am Fam Physician. 2006 Nov 1;74(9):1547-54. PMID: 17111894 (http://www.aafp.org/afp/20061101/1547.html) Meskimen S, Cook TD, Blake RL. Management of Giant Cell Arteritis and Polymyalgia Rheumatica. Am Fam Physician 2000;61:2061-8,2073. (http://www.aafp.org/afp/20000401/2061.html) Epperly, TD, Moore KE, Harrover JD. Polymyalgia Rheumatica and Temporal Arteritis. Am Fam Physician 2000;62:789-96,801. (http://www.aafp.org/afp/20000815/789.html)

Follow-up – Diane Z Diagnosis of PMR Age 50 years or older YES Aching & stiffness Shoulders and upper arms YES Hips and thighs YES Neck and torso ESR > 40 NO Exclusion of other disease YES Did not meet all dx criteria, but did have good response to Prednisone started at 15 mg daily and slowly tapered.

Follow-up – Jane T Diagnosis of TA Diagnosed as no TA Three or more of the following: Age 50 years of age or older NO New onset of localized headache YES? Temporal artery tenderness YES ESR > 50 mm/hr NO Abnormal temporal artery biopsy NO Diagnosed as no TA Tried Amitryptiline for chronic daily headache

Patient education FamilyDoctor.org http://familydoctor.org/online/famdocen/home /common/pain/disorders/567.html Patient UK http://www.patient.co.uk/showdoc/23068806/ http://www.patient.co.uk/showdoc/23068836/

Selected References and Resources Michet CJ, Matteson EL. Polymyalgia rheumatica. BMJ. 2008 Apr 5;336(7647):765-9. PMID: 18390527 (http://www.bmj.com/cgi/content/full/336/7647/765) Unwin B, Williams CM, Gilliland W. Polymyalgia rheumatica and giant cell arteritis. Am Fam Physician. 2006 Nov 1;74(9):1547-54. PMID: 17111894 (http://www.aafp.org/afp/20061101/1547.html) Weyand CM, Goronzy JJ. Giant-cell arteritis and polymyalgia rheumatica. Ann Intern Med. 2003 Sep 16;139(6):505-15. PMID: 13679329 (http://www.annals.org/cgi/reprint/139/6/505) Puttick MP. Rheumatology: 11. Evaluation of the patient with pain all over. CMAJ. 2001 Jan 23;164(2):223-7. PMID: 11332320 (http://www.cmaj.ca/cgi/content/full/164/2/223) Smetana GW, Shmerling RH. Does this patient have temporal arteritis? JAMA. 2002 Jan 2;287(1):92-101. PMID: 11754714 (http://jama.ama- assn.org/cgi/content/full/287/1/92) Resources: Michet CJ, Matteson EL. Polymyalgia rheumatica. BMJ. 2008 Apr 5;336(7647):765-9. PMID: 18390527 (http://www.bmj.com/cgi/content/full/336/7647/765) Unwin B, Williams CM, Gilliland W. Polymyalgia rheumatica and giant cell arteritis. Am Fam Physician. 2006 Nov 1;74(9):1547-54. PMID: 17111894 (http://www.aafp.org/afp/20061101/1547.html) Weyand CM, Goronzy JJ. Giant-cell arteritis and polymyalgia rheumatica. Ann Intern Med. 2003 Sep 16;139(6):505-15. PMID: 13679329 (http://www.annals.org/cgi/reprint/139/6/505) Puttick MP. Rheumatology: 11. Evaluation of the patient with pain all over. CMAJ. 2001 Jan 23;164(2):223-7. PMID: 11332320 (http://www.cmaj.ca/cgi/content/full/164/2/223) Smetana GW, Shmerling RH. Does this patient have temporal arteritis? JAMA. 2002 Jan 2;287(1):92-101. PMID: 11754714 (http://jama.ama-assn.org/cgi/content/full/287/1/92) Meskimen S, Cook TD, Blake RL. Management of Giant Cell Arteritis and Polymyalgia Rheumatica. Am Fam Physician 2000;61:2061-8,2073. (http://www.aafp.org/afp/20000401/2061.html) Epperly, TD, Moore KE, Harrover JD. Polymyalgia Rheumatica and Temporal Arteritis. Am Fam Physician 2000;62:789-96,801. (http://www.aafp.org/afp/20000815/789.html) Swannell AJ. Polymyalgia rheumatica and temporal arteritis: diagnosis and management. BMJ. 1997 May 3;314(7090):1329-32. PMID: 9158471 (http://bmj.bmjjournals.com/cgi/content/full/314/7090/1329)