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15 Articles in Volume 20, Issue #6
20/20 with Mark Wallace: Where Cannabis Fits into Pain Practice
A Commentary on Opioid Stewardship: Fentanyl, Sufentanil, and Perioperative Pain
Adherence and Relapse – How to Maintain Long-Term Gains in Patients with Chronic Conditions
Advanced Practice Matters with Theresa & Jeremy: COVID, Pain, and Power
Analgesics of the Future: Inside the Potential of Janus Kinase Inhibitors
Application Note: Using Photobiomodulation to Treat Trigeminal Neuralgia
Case Report: Quadratus Lumborum Block for Managing Pathologic Pain to the Hip
Chronic Pain and the Short-term Effects of Medical Cannabis
Differential Diagnosis: Polymyalgia Rheumatica or Rheumatoid Arthritis
Genicular Nerve Blocks: Field Tips on Prognostic Value and Technical Considerations
Guideline Update: ACR Promotes Pharmacologic Treatment for Osteoarthritis
Navigating New York's Medical Marijuana Program: A Patient Handout
Person-Centered Care: Lessons from the VA’s Whole Health Model
Psychedelics for Chronic Pain: Is It Time?
Resident’s Corner: What Pain Medicine Education is Missing in the COVID Era

Differential Diagnosis: Polymyalgia Rheumatica or Rheumatoid Arthritis

Diagnosing the two most common systemic rheumatic diseases in adults becomes even more complicated in older patients, as the presented case studies illustrate.

Rheumatoid arthritis and polymyalgia rheumatica are the two most common systemic rheumatic diseases in adults. Polymyalgia rheumatica (PMR) occurs exclusively in people over the age of 50 years, in contrast to rheumatoid arthritis (RA) with typical onset between 30 and 50 years of age.  However, other symptom characteristics often overlap, making differential diagnoses difficult to decipher. Below are two hypothetical patient cases, followed by a discussion of how to diagnose – and treat – each based on what is known to date about each condition.

 

Case 1

A 62-year-old female had been in generally good health until she began experiencing pain and stiffness in her neck and shoulders, as well as in her hips and lower back, over the previous 3 weeks. Her symptoms have gradually worsened and now interfere with her sleep and ability to conduct daily activities. The stiffness is especially bad in the morning and she reports that “it takes me an hour to loosen up and make breakfast.” She has not had any fever, skin rash, or other systemic symptoms but does report feeling exhausted. Her appetite has been poor over the past month and she has lost 5 pounds. The only medication that she has been on is an antihypertensive. For the past few weeks, she has been taking two or three OTC ibuprofen about three times daily with slight improvement in her symptoms.

The general physical examination was unremarkable. The musculoskeletal (MSK) examination demonstrated no obvious swelling or warmth in the extremities. There was decreased range of motion in the patient’s neck, shoulders, and hips and tenderness over her shoulders. The neurologic examination was normal.

Laboratory findings included a hematocrit of 33 but otherwise the CBC and chemistry profile were normal. The ESR was 68 mm/hr and the CRP was elevated. Rheumatoid factor and antinuclear antibody tests came back negative.

 

Case 2

A 65-year-old female has been experiencing intermittent pain and stiffness in her knees, wrists, and shoulders for the past 3 to 4 months. At first,  her symptoms would come and go but for the past 3 weeks she has been in constant pain somewhere in her body. She thinks that her knees and hands are swollen and reports feeling very stiff for hours in the morning. Her appetite has been poor, and she notes, “I am constantly exhausted.” There have been no rashes and no other systemic symptoms. Her general health is good although she is modestly overweight.

The general physical examination is unremarkable. The MSK examination reveals warmth, tenderness, and possible swelling over both wrists, knees, and ankles. Her strength and the neurologic examination are normal. Laboratory tests reveal a hematocrit of 31, an elevated platelet count and normal WBC, an elevated ESR of 50, an elevated CRP, and a negative rheumatoid factor and antinuclear antibody.

 

Initial Clinical Assessment: What Is the Most Likely Diagnosis in Case 1 and 2?

The primary differential diagnosis in the two presented cases is polymyalgia rheumatica or rheumatoid arthritis. There are many similar features in both patient cases. Both are women, around the same age, and in generally good health. They each present with diffuse MSK pain, considerable stiffness, and fatigue. The pain and stiffness are very prominent in the morning and increase with rest or prolonged inactivity.  The 3-week to 3-month duration of these symptoms excludes the possibility of infectious arthritis or crystal-induced arthritis (gout or pseudogout) and greatly lessens the possibility of a cancer-associated arthropathy (paraneoplastic syndrome).

Both patients also report decreased appetite. One-half to one-third of patients with either PMR and RA will experience systemic symptoms including fatigue, malaise, anorexia, weight loss, or low-grade fever.The laboratory test results are also very similar with both cases showing modest anemia, thrombocytosis, elevated acute phase reactants (including both the ESR and CRP), and negative serologic tests. These all represent non-specific markers of chronic inflammation, prominent in both PMR and RA.

The most important differentiating feature between these two patients is the joint swelling and inflammation involving the knees, wrists, and ankles reported in Case 2. Multiple joint inflammation is very unusual in PMR but is characteristic of RA.

PMR almost always presents with a symmetrical soreness and stiffness in the proximal muscles of the neck, shoulders, and hip girdle. The joints involved in Case 1 (neck, shoulders, hips) suggest PMR; whereas knees, wrists, and ankles in Case 2 suggest RA.

In Case 2, the joint symptoms were more episodic initially, which also favors the diagnosis of RA. PMR typically begins more abruptly, over days or weeks. Both cases likely would demonstrate a limited range of motion (ROM) in the involved joints, but in PMR, passive ROM is usually maintained. Positive serology – that is, either rheumatoid factor or anti-CCP antibody – would have suggested RA but these results are negative in 20% to 40% of RA patients.

 

Consider Giant Cell Arteritis in PMR Patients

In any patient with suspected polymyalgia rheumatica, it is essential to consider coexistent giant cell (temporal) arteritis (GCA). GCA, with its potential for acute blindness, aortitis, and other neurovascular complications, occurs in 10% to 20% of patients with PMR.1 GCA may occur concurrently with PMR but may also occur later in the course of PMR disease.

Every patient with PMR needs to be questioned about new onset-headache, visual symptoms, and jaw or extremity claudication and should be carefully examined for scalp tenderness, bruits, or absent pulses. If there is a strong concern about GCA, prompt referral to a rheumatologist, and sometimes an ophthalmologist and/or neurologist, should be made and head/neck vascular imaging and temporal artery biopsy should be considered (see Figure 1).

How to Further Evaluate and Manage the Patients

There are no additional laboratory tests to help differentiate RA from PMR in patients. An anti-CCP antibody, more sensitive and specific than the rheumatoid factor, could be ordered in Case 2 and plain radiographs of the hands and wrists would be appropriate, although joint X-rays at 3 months are often unremarkable. In Case 1, the symmetrical proximal muscle pain might be consistent with a myopathy, although the muscle strength and neurologic evaluation were unremarkable. Nevertheless, muscle enzymes, including a CPK, might be considered.

Since the evidence is strong that PMR is the likeliest diagnosis in Case 1, a trial of 10 to 20 mg of prednisone once daily in the morning should be started. The response to low dose prednisone in PMR is generally so dramatic that it can be utilized to confirm a clinical diagnosis. Most patients with PMR feel much better and their ESR and CRP rates generally decrease significantly within a week.

Case 2, with a likely diagnosis of RA, should be referred to a rheumatologist for diagnostic confirmation and to begin disease-modifying medications.

 

Characteristic Features that Help Distinguish Polymyalgia Rheumatica from Rheumatoid Arthritis

Both RA and PMR are more common in women, but RA typically begins in the age range of 30 to 50 years. PMR almost never occurs in people under age 50, and the usual age of onset is 60 to 80   years. Classically, RA involves the small joints of the hands and feet but also frequently involves the knees, wrists, and ankles. PMR typically involves the neck, shoulders, and hips and never involves the feet. Table I further differentiates symptom characteristics.

The most helpful distinguishing feature, as in the two cases presented herein, is the presence of joint inflammation (synovitis) in RA. However, 10% to 30% of patients with PMR may have small joint effusions, such as in the knees. Any joint swelling or inflammation tends to be mild and self-limited in PMR. Erosive small joint arthritis, the hallmark of RA, never occurs in PMR. The stiffness and pain around the shoulders and hips in PMR is secondary to subdeltoid/subacromial and pelvic girdle bursitis and tendonitis, rather than from synovitis.2

Subcutaneous nodules, usually around the elbows and forearms, are virtually pathognomonic for RA but are present in only 20% of cases. Extra-articular manifestations of RA, including lung or neurologic involvement, occur in about 10% of patients and also are not part of the clinical picture of PMR. A positive rheumatoid factor or anti-CCP antibody is present in 50% to 70% of patients with RA and not present in PMR. As discussed above, the response to low-dose prednisone is so dramatic and rapid that it can be used for diagnostic purposes in PMR.3,4

Elderly-Onset RA or PMR

Making a differential diagnosis of PMR or RA becomes more complicated when RA begins in older patients. About 30% of patients with RA first develop symptoms when they are over age 60 years.5

Back in 1985, I was involved in one of the early studies of what we termed elderly-onset rheumatoid arthritis (EORA), defined as RA beginning after age 60.6 In comparing EORA to younger onset RA (YORA), we found more abrupt disease onset, less small joint disease, and fewer subcutaneous nodules or positive tests for rheumatoid factor. One-quarter of EORA had a clinical picture nearly indistinguishable from PMR (see Table II).

Since then, a number of studies have confirmed our findings of a more PMR-type presentation and a better prognosis in EORA compared to YORA.7 However, many patients with EORA have a clinical presentation identical to that in younger patients, including seropositivity.8

 

Which Therapeutic Approach to Take for PMR and RA?

Polymyalgia Rheumatica First-Line Treatments

Since PMR responds so well to low dose corticosteroids, primary care physicians are encouraged to begin such a diagnostic challenge when PMR is strongly considered. Doses between 10 mg to 20 mg once daily in the morning are recommended and patients should experience a marked reduction in their symptoms with a significant fall in the ESR/CRP within a few weeks. Usually, the dose is tapered to 10 mg/day within 4 to 8 weeks and then slowly by 1 mg every 4 weeks until discontinued. Most patients with PMR can be tapered off completely within one year.

GCA Factors

If the diagnosis is less certain or if GCA is considered, the patient should be referred to a rheumatologist and the referral should be considered a relative medical emergency in view of potential blindness or irreversible loss of function. Patients with suspected GCA are usually started on high doses of corticosteroids, such as 60 mg/day of prednisone, while awaiting more definitive tests, such as biopsy and imaging studies.

Rheumatoid Arthritis First-Line Treatments

Any patient with probable RA should be referred to a rheumatologist, ideally within a few weeks of the suspected diagnosis. There is strong evidence that timely referral to a rheumatologist is important for patient outcome in RA.

Patients with a confirmed diagnosis of RA are typically started on a disease-modifying medication and rapid initiation of potent therapy is important in optimal outcome.

 

Conclusion

The most important finding to help clinicians differentiate between polymyalgia rheumatica and rheumatoid arthritis is the patient’s history and physical examination suggesting joint swelling and inflammation, which is not a prominent feature in PMR.

Other features not present in PMR but that may be present in RA cases are:

  • multiple small joint involvement
  • subcutaneous nodules
  • positive rheumatoid factor and/or anti-CCP antibody

It is especially difficult to differentiate PMR from RA that begins in elderly patients and both often present with severe joint stiffness and fatigue. Note that elevated acute phase reactants tend to be similar in patients with PMR and RA. Finally, any patient under age 50 to 55 is very unlikely to have PMR.

Keeping these important differences in mind when assessing patients can help providers make the correct diagnoses and set patients on an effective treatment path.

 

See also, highlights from the ACR 2020 Meeting on managing rheumatoid disease in adults and children.

Continue Reading:
How Clinicians Can Manage Rheumatic and Immune Diseases During COVID-19
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