polymyalgia rheumatica

REQUEST AN APPOINTMENT OR BOOK A CONSULANT – Sargam.dange.18@gmail.com

Polymyalgia rheumatica is an inflammatory disorder that causes muscle pain and stiffness, especially in the shoulders and hips. Signs and symptoms of polymyalgia rheumatica (pol-e-my-AL-juh rue-MAT-ih-kuh) usually begin quickly and are worse in the morning.

Most people who develop polymyalgia rheumatica are older than 65. It rarely affects people under 50.

This condition is related to another inflammatory condition called giant cell arteritis. Giant cell arteritis can cause headaches, vision difficulties, jaw pain and scalp tenderness. It’s possible to have both conditions together.

Polymyalgia rheumatica (PMR) is a relatively common chronic inflammatory condition of unknown etiology that affects elderly individuals. It is characterized by proximal myalgia of the hip and shoulder girdles with accompanying morning stiffness that lasts for more than 1 hour.  Approximately 15% of patients with PMR develop giant cell arteritis (GCA), and 40-50% of patients with GCA have associated PMR. Despite the similarities of age at onset and some of the clinical manifestations, the relationship between GCA and PMR is not yet clearly established. 

Pathophysiology

The cause of polymyalgia rheumatica (PMR) is unknown. PMR is closely linked to giant cell arteritis (GCA, temporal arteritis), although it is controversial whether GCA and PMR are two separate diseases or part of the same spectrum of disease. One hypothesis is that in a genetically predisposed patient, an environmental factor, possibly a virus, causes monocyte activation, which helps determine the production of cytokines that induce manifestations characteristic of PMR and GCA. However, although several infectious agents have been investigated as possible triggers, results are inconclusive. 

Immunogenetic studies support a polygenic basis for GCA and PMR. Occurrence in siblings and increased prevalence in those of Northern European heritage suggest a genetic role in the pathophysiology of the disease. Although most studies confirm an association between HLA-DRB1*04 alleles and GCA, the strength of this association with PMR varies between different populations. Interleukin (IL)–1 and tumor necrosis factor–alpha (TNF-α) gene polymorphisms have weak association with GCA and PMR. In Spain, an IL-6 polymorphism was associated with the expression of PMR symptoms in GCA patients. Additionally, in this Spanish population, the RANTES polymorphism was associated with PMR and not GCA. 

Pathologically, GCA and PMR are similar, except that significant vascular involvement does not occur in pure PMR. Synovitis, bursitis, and tenosynovitis around the joints, especially the shoulders, hips, knees, metacarpal phalangeal joints, and wrists, are seen in PMR. Inflammation is thought to start within the synovium and bursae, with recognition of an unknown antigen by dendritic cells or macrophages.

Systemic macrophage and T-cell activation are characteristic of both GCA and PMR. Patients often have an elevated IL-6 level, which is likely responsible for the systemic inflammatory response in both GCA and PMR. Most studies in PMR show that a decrease in the level of circulating IL-6 correlates with remission of clinical symptoms. Data on other circulating cytokines (eg, IL-1, IL-2, TNF-α, IL-10) are too scant to draw any conclusions. However, studies do show that interferon-gamma (IFN-γ) is expressed in nearly 70% of temporal artery biopsy samples from patients with GCA but is not detected in patients with isolated PMR, suggesting IFN-γ may be crucial to the development of GCA. 

Although PMR causes severe pain and stiffness in the proximal muscle groups, no evidence of disease is present on muscle biopsy. Muscle strength and electromyographic findings are normal. Instead, the inflammation is at the level of the synovium and bursae, with MRI studies revealing periarticular inflammation as well as bursitis in the bursae associated with both the shoulder and hip girdles. 

Some evidence suggests the presence of cell-mediated injury to the elastic lamina in the blood vessels in the affected muscle groups. A prospective study of 35 patients with isolated PMR noted vascular (¹⁸F) fluorodeoxyglucose positron emission tomography (FDG-PET) imaging at diagnosis in 31% of patients, predominantly at the subclavian arteries, but at a much lower intensity than in GCA patients. Increased FDG uptake in the shoulders was seen in 95% of the patients, in the hips in 89%, and in the spinous processes of the cervical and lumbar vertebrae (correlating with interspinous bursitis) of 51% of the patients with isolated PMR. 

A study of circadian variation in PMR found that plasma concentrations of IL-6, IL-8, TNF-α, and IL-4 peaked between 4 and 8 am in both untreated patients and controls, although levels of those cytokines were higher throughout the day in patients. The peak in cytokines matched the early-morning peak of pain and stiffness in untreated patients. In addition, melatonin levels were consistently higher in patients than in controls and varied with time, peaking around 2 am, suggesting that melatonin stimulates cytokine production, which in turn accounts at least partly for PMR symptoms. 

PMR is a clinical diagnosis based on the complex of presenting symptoms and the exclusion of the other potential diseases . Corticosteroids are considered the treatment of choice, and a rapid response to low-dose corticosteroids is considered pathognomonic. Patients who are at risk for relapse, have steroid-related adverse effects, or need prolonged steroid therapy may benefit from the addition of methotrexate or tocilizumab. 

REQUEST AN APPOINTMENT OR BOOK A CONSULANT – Sargam.dange.18@gmail.com

Etiology

The exact cause (or causes) of polymyalgia rheumatica (PMR) is unknown. The disease is more common among northern Europeans, which may indicate a genetic predisposition. Other risk factors for PMR are an age of 50 years or older and the presence of GCA. PMR has been reported as a rare complication of cancer therapy with immune checkpoint inhibitors (eg, nivolumab).

An autoimmune process may play a role in PMR development. PMR is associated with the HLA-DR4 haplotype. A high level of IL-6 is associated with increased disease activity.

History

Patients with polymyalgia rheumatica (PMR) were often in good health prior to disease onset, which is abrupt in about 50% of patients. In most patients, symptoms appear first in the shoulder girdle. In the remainder, the hip or neck are involved at onset. At presentation, symptoms may be unilateral but they usually become bilateral within a few weeks.

The symptoms include pain and stiffness of the shoulder and hip girdle. The stiffness may be so severe that the patient may have a great difficulty rising from a chair, turning over in bed, or raising the arms above shoulder height. Stiffness after periods of rest (gel phenomenon) as well as morning stiffness of more than 1 hour typically occurs.

Muscle weakness is not a feature of PMR. However, this can be difficult to assess in the setting of pain, especially if symptoms are protracted and untreated, resulting in disuse atrophy.

Patients may also describe distal peripheral joint swelling or, more rarely, limb edema. Carpal tunnel syndrome can occur in some patients. Most patients report systemic features as listed below.

Several diagnostic criteria for PMR exist. One set of diagnostic criteria is as follows  :

• Age of onset 50 years or older
• Erythrocyte sedimentation rate ≥40 mm/h
• Pain persisting for ≥1 month and involving 2 of the following areas: neck, shoulders, and pelvic girdle
• Absence of other diseases capable of causing the same musculoskeletal symptoms
• Morning stiffness lasting ≥1 hour
• Rapid response to prednisone (≤20 mg)

In 2012, the European League Against Rheumatism and the American College of Rheumatology published new provisional classification criteria for PMR in patients aged 50 or older with bilateral shoulder aching and elevated inflammatory markers. These are not diagnostic criteria, but rather are designed for enrolling patients into clinical trials of new treatments for PMR. This collaborative initiative resulted in a scoring algorithm based on the following criteria:

• Morning stiffness >45 minutes (2 points)
• Hip pain/limited range of motion (1 point)
• Absence of rheumatoid factor and/or anti–citrullinated protein antibody (anti-CCP) (2 points)
• Absence of peripheral joint pain (1 point)

A score of ≥4 points has a 68% sensitivity and 78% specificity for discriminating PMR from other comparison patients. There is also an additional ultrasound criteria (1 point if positive findings), which can add up to a score of ≥5 points that is associated with a 66% sensitivity and 81% specificity for PMR. 

Systemic findings in more than 50% of patients are as follows:

• Low-grade fever and weight loss
• Malaise, fatigue, and depression
• Difficulty rising from bed in the morning
• Difficulty getting up from the toilet or out of a chair
• Difficulty completing daily life activitiesHigh, spiking fevers (rare, should prompt evaluation for underlying infection, malignancy, or vasculitis)

Musculoskeletal findings are as follows  :

• Morning stiffness for ≥1 hour, often more prolonged
• Muscle stiffness after prolonged inactivity
• Synovitis of proximal joints and periarticular structures
• Peripheral arthritis (in 25% of patients)
• Carpal tunnel syndrome (in about 15% of patients)
• Distal extremity swelling (in approximately 12%)
• Possible development of arthralgia and myalgia up to 6 months after onset of systemic symptoms

Many investigators believe that nonerosive synovitis and tenosynovitis are responsible for many symptoms of PMR.

Physical Examination

PMR is a clinical diagnosis based on the complex of the presenting symptoms and exclusion of the other potential diseases. The symptoms and signs of PMR are nonspecific, and objective findings on physical examination are often lacking.

General symptoms are as follows:

• Fatigued appearance
• Low-grade temperature
• Distal extremity swelling with pitting edema

Musculoskeletal findings are as follows:

• Normal muscle strength; no muscle atrophy typically present at initial presentation
• Pain in the shoulder and hip with movement; active range of motion may be decreased because of pain
• Transient synovitis of the knee, wrist, and sternoclavicular joints; a more peripheral nonerosive arthritis may be seen in some cases
• Tenderness to palpation with decreased active range of motion in the musculature of the proximal hip/leg and/or shoulder/arm girdle

In later stages, disuse muscle atrophy with proximal muscle weakness may occur. Contractures of the shoulder capsule may lead to limitation of passive and active movements.

REQUEST AN APPOINTMENT OR BOOK A CONSULANT – Sargam.dange.18@gmail.com

Symptoms

The signs and symptoms of polymyalgia rheumatica usually occur on both sides of the body and might include:

• Aches or pain in your shoulders
• Aches or pain in your neck, upper arms, buttocks, hips or thighs
• Stiffness in affected areas, particularly in the morning or after being inactive for a time
• Limited range of motion in affected areas
• Pain or stiffness in your wrists, elbows or knees

You might also have more-general signs and symptoms, including:

• Mild fever
• Fatigue
• A general feeling of not being well (malaise)
• Loss of appetite
• Unintended weight loss
• Depression

Risk factors

Risk factors for polymyalgia rheumatica include:

• Age. Polymyalgia rheumatica affects older adults almost exclusively. It most often occurs between ages 70 and 80.
• Sex. Women are about two to three times more likely to develop the disorder.
• Race. Polymyalgia rheumatica is most common among white people whose ancestors were from Scandinavia or northern Europe.

Complications

Symptoms of polymyalgia rheumatica can greatly affect your ability to perform everyday activities, such as:

• Getting out of bed, standing up from a chair or getting out of a car
• Combing your hair or bathing
• Getting dressed

Diagnosis

A physical exam, including joint and neurological exams, and test results can help your doctor determine the cause of your pain and stiffness. During the exam, he or she might gently move your head and limbs to assess your range of motion.

Your doctor might reassess your diagnosis as your treatment progresses. Some people initially given a diagnosis of polymyalgia rheumatica are later reclassified as having rheumatoid arthritis.

Tests your doctor might recommend include:

• Blood tests. Besides checking your complete blood counts, your doctor will look for two indicators of inflammation — erythrocyte sedimentation rate (sed rate) and C-reactive protein. However, in some people with polymyalgia rheumatica, these tests are normal or only slightly high.
• Imaging tests. Increasingly, ultrasound is being used to distinguish polymyalgia rheumatica from other conditions that cause similar symptoms. MRI can also identify other causes of shoulder pain, such as joint changes.

Monitoring for giant cell arteritis

Your doctor will monitor you for signs and symptoms that can indicate the onset of giant cell arteritis. Talk to your doctor immediately if you have any of the following:

• New, unusual or persistent headaches
• Jaw pain or tenderness
• Blurred or double vision or visual loss
• Scalp tenderness

If your doctor suspects you might have giant cell arteritis, he or she will likely order a biopsy of the artery in one of your temples. This procedure, performed during local anesthesia, involves removing a small sample of the artery, which is then examined for inflammation.

Treatment

Treatment usually involves medications to help ease your signs and symptoms. Relapses are common.

Medications

• Corticosteroids. Polymyalgia rheumatica is usually treated with a low dose of an oral corticosteroid, such as prednisone (Rayos). You’ll likely start to feel relief from pain and stiffness within the first two or three days.After the first two to four weeks of treatment, your doctor might begin to gradually decrease your dosage depending on your symptoms and the results of blood tests. Because of potential side effects, the goal is to keep you on as low a dose as possible without triggering a relapse in your symptoms.Most people with polymyalgia rheumatica need to continue the corticosteroid treatment for a year or more. You’ll need frequent follow-up visits with your doctor to monitor how the treatment is working and whether you have side effects.Long-term use of corticosteroids can result in serious side effects, including weight gain, loss of bone density, high blood pressure, diabetes and cataracts. Your doctor will monitor you closely for problems. He or she might adjust your dose and prescribe treatments to manage reactions to corticosteroid treatment.
• Calcium and vitamin D. Your doctor will likely prescribe daily doses of calcium and vitamin D supplements to help prevent bone loss as a result of corticosteroid treatment. The American College of Rheumatology recommends 1,000 to 1,200 milligrams of calcium supplements and 600 to 800 international units of vitamin D supplements for anyone taking corticosteroids for three months or more.
• Methotrexate. Joint guidelines from the American College of Rheumatology and the European League Against Rheumatism suggest using methotrexate (Trexall) with corticosteroids in some patients. This is an immune-suppressing medication that’s taken by mouth. It might be useful early in the course of treatment or later, if you relapse or don’t respond to corticosteroids.

Medication Summary

The goals of therapy in polymyalgia rheumatica (PMR) are to control painful myalgia, to improve muscle stiffness, and to resolve constitutional features of the disease. Oral corticosteroids are the first line of treatment. Nonsteroidal anti-inflammatory drugs (NSAIDs) may be helpful as adjuncts to corticosteroids during tapering, or alone in mild cases; however, because they are associated with increased drug-related morbidity, they should be used with caution, especially in elderly patients. Steroid-sparing agents may be beneficial.

The interleukin-6 receptor antagonist tocilizumab is approved for use in giant cell arteritis and has demonstrated benefit for PMR in several case series and retrospective studies.  However, controlled trials are needed to fully establish the efficacy of tocilizumab in PMR, and it has not yet been approved for this indication by the US Food and Drug Administration.

Physical therapy

Most people who take corticosteroids for polymyalgia rheumatic return to their previous levels of activity. However, if you’ve had a long stretch of limited activity, you might benefit from physical therapy. Talk with your doctor about whether physical therapy is a good option for you.

REQUEST AN APPOINTMENT OR BOOK A CONSULANT – Sargam.dange.18@gmail.com