Atypical Polymyalgia Rheumatica

A Case Report

• NG is a 47 year old female who developed severe shoulder and upper arm pain bilaterally as well as hip pain , wrist pain and severe morning stiffness in March 2011. She denied ever experiencing anything like this before. She did admit to losing 30 pounds intentionally after completing the HCG diet one month prior.

• She denied fever, night sweats, rash, mucosal ulcers, strenuous activity, visual changes, jaw claudication, small joint pain, swelling and respiratory symptoms.

Review of Systems

• General : see above• HEENT: no new headache• Endocrine: no cold intolerance, polydipsia or

polyuria• Hematologic: no bruising or bleeding• Skin: no rash• Respiratory : no cough or dyspnea

ROS Continued

• Cardiovascular: No chest pain, palpitations, or claudication

• Gastrointestinal: No nausea, vomiting, diarrhea , constipation, or change in stools

• Genitourinary: No change in menses, dysuria, frequency, hematuria, or foamy urine

• Musculoskeletal: no active synovitis , but severe pain with ROM of shoulders

ROM Continued

• Neurologic: No motor weakness, numbness, paresthesias, cognitive symptoms

• Psychiatric: recent discontinuation of Zoloft which she had used since 2004

Allergies

• None

Medications

• HCTZ 25 mg po daily• Metoprolol 12.5 po BID• KCL 10 meq po daily• Recent HCG injections completed one month

ago • Ibuprofen 200mg po QID

Past Medical History

• Hypertension• Depression • Migraine• Obesity

Past Surgical History

• Knee surgery bilaterally• Cholecystectomy• Foot surgery• Breast cyst aspiration

Social History

• No smoking• Rare social alcohol• No illicit drug abuse• Lesbian• Works as a manager at Petsmart

Family History

• Unknown ( Adopted )

Physical Examination

• Vital signs: BP 131/89, Temp 97.6, Weight 201.8, Height 5 feet 2 inches

• Head : normal, No temporal artery tenderness• Eyes: normal• ENT: normal• Lymphatic : no nodes• Skin: normal

PE Continued

• Chest: Clear to A & P• Cardiovascular : Normal ( no murmurs or rubs

and pedal pulses normal)• Abdomen : obese ,non tender , no mass, or

organomegaly• Back: No significant findings• Neurologic : normal

PE Continued

• Musculoskeletal : Severe pain with ROM of the shoulders and hips bilaterally. Some tenderness of the wrists but no active synovitis, and no synovitis of the hands, or feet, or knees

Laboratory

• CMP : normal except AST 64• Magnesium : normal 2.2• Phosphate : normal 3.6• CBC : normal WBC 10.4, Hgb 14, PLT 131• WSR : 28• CPK : 53• TSH : 2.66

Lab Continued

• Vitamin D : 31• CCP : <1• RF: <5• ANA reflex : negative• CRP : 18.1

Clinical Course

• The patient was empirically treated with Prednisone 20 mg po daily . She had a “miraculous” response after the first dose. On her follow up visit she was asymptomatic and her CRP fell to 2.2 . Her prednisone has been slowly tapered subsequently and she continues to do well.

Differential Diagnosis

• Polymyalgia rheumatica• Seronegative rheumatoid arthritis• Bursitis / tendonitis• RS3PE syndrome ( Remitting seronegative

symmetrical synovitis with pitting edema )• Spondyloartropathy

Differential Diagnosis Continued

• CPPD disease ( calcium pyrophosphate deposition disease )

• Fibromyalgia• Hypothyroidism• Paraneoplastic syndrome• Infective endocarditis• Inflammatory Myopathy

Differential Diagnosis Continued

• Vasculitis• Miscellaneous ( Parkinson’s disease

Hyperparathyroidism, Drug induced-HCG, Depression)

Seronegative Rheumatoid Arthritis

• Symmetric polyarthritis of small joints of hands and feet

• Does not respond to low dose steroids• Can mimic Polymyalgia rheumatica• Lower WSR and CRP than PMR

Bursitis

• Not bilateral• Usually does not have elevated WSR or CRP

RS3PE Syndrome

• Remitting seronegative symmetrical synovitis with pitting edema

• Sudden onset of polyarthitis• Negative rheumatoid factor• Distal joint involvent• Some response to steroids• May be paraneoplastic

Spondyloarthropathy

• Proximal symptoms• Elevated WSR• Axial skeletal involvement• Edema• Constitutional symptoms• Enthesitis

Spondyloarthropathy Continued

• Uveitis• Sacroillitis• HLA –B27

CPPD Disease

• Calcium pyrophoshate deposition disease• Characteristic crystals on joint aspiration• Chondrocalcinosis

Fibromyalgia

• Tender points• Widespread musculoskeletal pain• Aching • Fatigue• Normal WSR and CRP

Hypothyroidism

• Aching• Stiffness• Arthralgias• Elevated TSH

Paraneoplastic Syndrome

• Diffuse muscle and joint pain• Does not respond to steroids

Infective Endocarditis

• Persistent fever• Heart murmur• Diffuse aching

Inflammatory Myopathy

• Dermatomyositis or polymyositis• Proximal muscle weakness• Elevated CPK• Abnormal EMG• Myositis on biopsy

Vasculitis

• Can mimic PMR• Positive ANCA• Upper respiratory involvement• Pulmonary hemorrhage• Renal disease• Neuropathy

Miscellaneous

• Parkinsons• Hyperparathyroidism• Drug induced • Depression

HCG

• No clinical reports linking HCG to rheumatologic syndromes

• HCG diets are popular currently• No clinical evidence that HCG is better than

placebo in curbing appetite

Polymyalgia rheumatica

• Aching in shoulders neck and hip girdle• Severe morning stiffness• Can be associated with giant cell arteritis

PMR

• 15-30% of cases develop GCA

PMR

• Usually occurs in adults greater than 50 years old

• Average age of patients is 70

PMR

• Prevalance is 700 per 100,000 over the age of 50

• Women are effected 2-3 times more than men

PMR

• Incidence is higher in northern regions• 113/100,000 in Norway• 13/100,000 in Italy

Pathogenesis

• PMR is associated with specific alleles of HLA DR4

• Macrophages and CD4 T lymphocytes are found in synovial membranes

Clinical Manifestations

• At least 30 minutes of stiffness in the morning• Trouble dressing and rising from or turning in

bed• Pain in shoulders in 70-95% of patients• Pain in hips and neck in 50-70% of patients• The pain worsens with movement

Clinical Manifestations Continued

• Synovitis and bursitis• 50% of patients have distal synovitis in knees

and wrists• Swelling and tenosynovitis can be seen in

hands wrists and ankles• Carpal tunnel syndrome can be seen in 10-

15% of patients

Clinical manifestations Continued

• Decreased ROM in shoulders neck and hips• Muscle tenderness in not a prominent feature• Shoulder tenderness is more due to synovial

or bursal inflammation• Subjective weakness

Clinical Manifestations Continued

• Systemic signs and symptoms in 40%• Malaise• Fatigue• Depression • Weight loss• Fever

Laboratory

• WSR greater than 40 in 78-93%• Elevated CRP is more common than elevated

WSR• CRP is greater than 5 in 99%• 90% of patients with a normal WSR had an

elevated CRP

Laboratory Continued

• Normocytic anemia can be seen• Negative ANA• Negative rheumatoid factor• Negative CCP• Elevated alkaline phosphatase can be seen

Imaging

• MRI shows inflammation of extra-articular synovial structures:

• Tenosynovial sheaths and bursas• Subacromial and subdeltoid bursitis• Ultrasound shows the same in 96% of patients

Diagnosis

• Age greater than 50• Bilateral aching and morning stiffness greater

than 30 minutes• WSR greater than 40• Prompt response to steroids ( 50-70% of

patients are better in 3 days )

Atypical Presentations

• Age 40-50 years • WSR less than 40

Treatment

• Baseline lab testing ( glucose ,UA ,creatinine, alkaline phosphatase and calcium )

• Dexa scan

Treatment Continued

• 15 mg prednisone daily ( range 10-20 mg )• Improvement can be noted after the first dose• 50-70% reduction in pain and stiffness within

3 days• Doses greater than 15mg daily are associated

with more side effects• If no response consider GCA

Maintenance Therapy

• Maintain dose for 2-4 weeks that suppressed symptoms

• If on greater than 15 mg daily of prednisone taper in 5mg daily decrements every 2-4 weeks

• If on 15mg daily taper in 2.5 mg daily decrements every 2-4 weeks

Maintenance Therapy Continued

• When at a daily dose of 10 mg reduce the dose no faster than 1mg monthly

• This approach allows therapy for one year

Monitoring Response to Therapy

• WSR and CRP generally normalize with prednisone therapy

• If they do not consider GCA or malignancy• Monitor WSR and CRP every 2-3 months

Relapse

• Occurs in 25-50% of patients• If off steroids resume dose at original dose of

steroids that control was achieved with• If on prednisone increase the dose to the

lowest dose that controlled the symptoms ( a 1-2 mg increase may be adequate )

• In patients who relapse multiple times the dose reduction interval should be every 2-3 months

Relapse Continued

• Distinguish recurrent symptoms of PMR from those secondary to prednisone taper alone:

• Rest increases stiffness and aching in PMR• Rest improves symptoms in steroid withdrawal

Relapse Continued

• An alternative approach to relapse is methylprednisolone 40-120 mg im

Steroid Treatment Side Effects

• Osteoporosis• Glucose intolerance• Hypertension

Management of Steroid Side Efects

• Dexa scan• Calcium and Vitamin D therapy• Prophylactic bisphosphonates in some cases• Monitor blood pressure , glucose, and A1C

levels

Alternative Therapies

• No agent has been proven effective as a steroid sparring agent when used in combination

• Methotrexate has been used in combination with high dose prednisone in patients with GCA , but this is controversial

• TNF inhibitors and infliximab were not helpful

Alternative Therapies Continued

• Etanercept therapy shows some benefit but there is no evidence that it can be a substitute for prednisone

• In patients who could not reduce prednisone below 7.5-10 mg daily or had severe steroid side effects one small study ( 6 pts ) used Etanercept 25 mg twice weekly for 24 weeks with good results

Other Therapy

• Physical therapy• Low dose NSAIDs with PPIs for concurrent

osteoarthritis

Prognosis

• Most patients have a self limited course that lasts from months to a few years

• Some require therapy for 2-3 years• 10% will relapse within 10 years following a

course of therapy• There is no increase in mortality from PMR

itself