What is the best course of action for a patient with a history of polymyalgia rheumatica (PMR) on prednisone, hypothyroidism on Synthroid (levothyroxine), who is experiencing intermittent episodes of weakness, bilateral leg weakness, and increased fatigue after tapering off prednisone?

Evaluation and Management of Post-Prednisone Taper Weakness in PMR

Immediate Priority: Rule Out PMR Relapse vs. Alternative Diagnoses

This patient requires urgent evaluation for PMR relapse, steroid withdrawal syndrome, hypothyroidism exacerbation, and inflammatory myositis—with the most critical step being assessment of inflammatory markers (ESR/CRP) and creatine kinase to differentiate between PMR relapse (pain without true weakness, elevated ESR/CRP, normal CK) and myositis (true weakness, elevated CK). 1, 2

Critical Diagnostic Distinctions

PMR Relapse vs. Myositis

The key clinical distinction is pain versus weakness:

• PMR relapse presents with severe myalgia and fatigue resembling weakness, but patients retain actual muscle strength—they have pain with movement, not true motor weakness. Inflammatory markers are highly elevated, but CK remains normal. 1

• Inflammatory myositis presents with true proximal muscle weakness (difficulty standing from chair, lifting arms overhead) with or without pain. CK is elevated, and EMG/MRI show muscle inflammation. This can be severe and even fatal if myocarditis develops. 1

Immediate Laboratory Workup Required

• ESR and CRP (expect elevation >40 mm/hr in PMR relapse) 1, 2
• Creatine kinase (normal in PMR, elevated in myositis) 1
• TSH and free T4 (given hypothyroidism history and fatigue) 2
• Complete metabolic panel (assess adrenal insufficiency risk post-taper) 2

Most Likely Diagnosis: PMR Relapse

Given the temporal relationship (symptoms started shortly after completing prednisone taper), bilateral leg involvement, fatigue, and PMR history, this most likely represents PMR relapse, which occurs in 26-97% of patients and can develop up to 9 years after initial presentation. 3, 4

Risk Factors Present in This Patient

• Female sex (increases relapse risk) 5
• Recent glucocorticoid discontinuation (highest risk period) 1, 2

Treatment Algorithm for PMR Relapse

Step 1: Restart Prednisone at Pre-Relapse Dose

Immediately restart prednisone at the dose that previously controlled symptoms (likely 10-15 mg daily based on standard tapering protocols). 1, 2

• Do not start at initial diagnosis doses (12.5-25 mg) unless symptoms are severe 1
• Expect symptom improvement within 2 weeks; if no response, increase to 25 mg daily and reconsider diagnosis 1

Step 2: Slower Taper Protocol

Once remission is re-established (typically within 4-8 weeks):

• Reduce to the dose at which relapse occurred over 4-8 weeks 1, 2
• Then taper by 1 mg every 4 weeks (or alternate-day schedules like 10/7.5 mg) 1, 2
• This is slower than the initial taper to prevent repeat relapse 1

Step 3: Add Methotrexate as Steroid-Sparing Agent

Given this patient has already relapsed once, strongly consider adding methotrexate 7.5-10 mg weekly to reduce future relapse risk and cumulative glucocorticoid burden. 1, 2, 6

Methotrexate is specifically indicated for:

• Patients who have experienced relapse 1, 2
• Those requiring prolonged therapy 1, 2
• Patients with glucocorticoid-related comorbidities (this patient has hypothyroidism) 1

Alternative Diagnoses to Exclude

Adrenal Insufficiency

After prolonged prednisone use, abrupt discontinuation can cause adrenal crisis. However, the patient completed a "long taper," which should have allowed HPA axis recovery. 7

• If symptoms include hypotension, nausea, or severe fatigue disproportionate to PMR, consider morning cortisol level 7

Hypothyroidism Exacerbation

Fatigue and weakness can indicate inadequate thyroid replacement. 8

• Check TSH—adjust levothyroxine if elevated 2
• Note: Hypothyroidism alone does not cause the acute bilateral leg weakness pattern described

Inflammatory Myositis (Critical to Exclude)

If CK is elevated or true weakness (not just pain) is confirmed on examination:

• Urgent rheumatology referral 2, 5
• Consider EMG and muscle MRI 1
• High-dose glucocorticoids (not low-dose PMR treatment) required 1

Monitoring Plan

Follow-up Schedule

• Every 4-8 weeks during first year after relapse 1, 2, 5
• Monitor ESR/CRP, symptoms, and glucocorticoid adverse effects at each visit 2, 5

Red Flags Requiring Urgent Evaluation

• Visual symptoms (PMR can progress to giant cell arteritis with vision loss in 26% of cases, particularly in relapsing patients) 3
• Headache, jaw claudication, scalp tenderness (GCA symptoms) 3
• Progressive true weakness (myositis) 1

Common Pitfalls to Avoid

• Do not assume symptoms are "just deconditioning" after steroid taper—PMR relapse is extremely common and requires prompt treatment 3, 4
• Do not restart at initial diagnosis doses unless symptoms are refractory—use pre-relapse dose 1
• Do not taper at the same rate that caused relapse—slower tapering (1 mg/month maximum) is essential 1, 2
• Do not ignore the diarrhea history—while now resolved, consider whether this was a viral trigger for relapse or unrelated 1