Polymyalgia rheumatica

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Ayesha A. Khan, MD[3] Ujjwal Rastogi, MBBS [4]; Rim Halaby, M.D. [5]; Ahmed Elsaiey, MBBCH [6]

Polymyalgia rheumatica (PMR) is a chronic inflammatory disease that involves the articular and periarticular parts of the cervical region, shoulder girdle and pelvic girdle. PMR affects subjects over the age of 50 years and it is characterized by pain and stiffness in the neck, shoulders, upper arms, hip, and thighs. Although myalgia is one of the symptoms of PMR, there is no inflammation of the muscles; instead, PMR is a disease of the joint that causes synovitis. The diagnosis of PMR relies on the clinical findings and laboratory evidence of systemic inflammation. PMR is associated with giant cell arteritis. The cause of PMR is unknown but it has been suggested that both genetic and environmental factors are implicated. The mainstay of treatment of PMR is steroid therapy.

Polymyalgia rheumatica was first described in 1888 by Bruce William as “senile rheumatic gout”. The disease was referred to as “polymyalgia rheumatica” by Stuart Barber in 1957 in his article entitled “myalgic syndrome with constitutional effects; polymyalgia rheumatica”.

There is no established system for the classification of polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is a chronic inflammatory disease of the articular and periarticular structures of the cervical region, shoulder girdle and hip girdle. The underlying pathophysiology of PMR remains unknown. It has been hypothesized that genetic and environmental factors are implicated, particularly due to the seasonal and geographical differences in the prevalence of this disease. It has also been hypothesized that PMR is associated with infections such as parainfluenza virus type 1, mycoplasma pneumoniae, chlamydia pneumoniae, and parvovirus B19. In addition, histological examinations of synovial biopsies of affected individuals reveal mild synovitis with predominance of CD4 T cells and macrophages. Although myalgia is a symptom of PMR, there is no inflammation of the muscles.The senescence of the immune systems as demonstrated by the loss of the CD28 on CD4+ T senescent cells may be responsible for aberrant immune responses in PMR. Adaptive immune alterations also occurs in PMR mainly represented by the activation of Th17 cells, mainly driven by the increased IL-6 levels. An altered distribution and phenotype of B cells also occurs in PMR even in the absence of a clear autoimmune response. Local activation of myeloid and endothelial cells has been also demonstrated in the non-inflamed arteries and inflamed synovial tissues of PMR patients.

There is no specific cause for polymyalgia rheumatica. However, there are possible theories about the causes which include inflammatory joint lining attack, viral infections, and genetic inheritance of HLA-DR4.

PMR must be differentiated from other conditions such as late onset rheumatoid arthritis, polymyositis, dermatomyositis, fibromyalgia, and remitting seronegative symmetrical synovitis with pitting edema.

Polymyalgia rheumatica (PMR) affects mostly subjects who are more than 50 years of age. The prevalence of PMR is highest among subjects from Scandinavian countries and those from northern European origin.

Age, female sex, Scandinavia and northern Europe origin are risk factors for polymyalgia rheumatica. Other risk factors include smoking, sun exposure, infections, and nulliparity.

There is insufficient evidence to recommend routine screening for polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) affects the quality of life of the patients. The pain and stiffness in the proximal joints might lead to sleep disturbance as well as an inability to do regular daily activities such as getting dressed and getting out of a chair. The symptoms begin rapidly and last for weeks. Once the steroid treatment is initiated, the symptoms resolve rapidly within few days. In fact, the rapid resolution of symptoms with the steroid therapy reinforces the diagnosis of PMR. The steroid treatment can be associated with complications such as weight gain and bone fracture. Approximately 40 to 50% of subjects experience a relapse of the symptoms. PMR is associated with giant cell arteritis.

The diagnosis of polymyalgia rheumatica (PMR) is mostly clinical and it is supported with specific findings on laboratory tests and ultrasound of the affected joints. The European League Against Rheumatism/American College of Rheumatology collaborative initiative developed a provisional classification criteria for PMR. The following criteria are required for the diagnosis of PMR: age more than 50 years, bilateral shoulder pain, and elevated C-reactive protein (CRP) and/or erythrocyte sedimentation rate (ESR).

Polymyalgia rheumatica (PMR) is typically characterized by symmetrical pain and morning stiffness in the proximal joints and limbs, including the neck, the shoulder girdle, the pelvic girdle, the lower back, and the thighs. In some patients, there is involvement of the distal parts of the body such as peripheral synovitis or arthritis. Constitutional symptoms can also be present, and they include fever, fatigue, loss of appetite, and weight loss. There is an association between PMR and giant cell arteritis which can present with one or more of the following symptoms that include headaches, scalp tenderness, jaw claudication, fever, or distorted vision.

Physical examination of patients with polymyalgia rheumatica reveals limitation of the active and passive range of motion of the affected joint. There is no true muscle weakness. There are no changes in the joints. Ophthalmoscopic exams in patients with polymyalgia rheumatica associated with giant cell arteritis might be abnormal.

Polymyalgia rheumatica (PMR) is a clinical diagnosis that is supported by laboratory tests. Elevation of C-reactive protein (CRP) and/or erythrocyte sedimentation rate (ESR) is essential for the diagnosis of PMR.

There are no EKG findings associated with polymyalgia rheumatica.

There are no x ray findings associated with polymyalgia rheumatica.

There are no echocardiography findings associated with polymyalgia rheumatica. Ultrasound exam is important for the diagnosis of polymyalgia rheumatica (PMR). It can reveal evidence of bursitis, synovitis or tenosynovitis in the affected areas.

There are no CT findings associated with polymyalgia rheumatica.

MRI is used for the assessment of bursitis, synovitis, and tenosynovitis among patients with polymyalgia rheumatica (PMR). MRI is more sensitive than ultrasonography for the evaluation of iliopsoas bursitis and hip synovitis. A study has demonstrated that MRI of the shoulders facilitates the proper diagnosis in patients with the typical proximal symptoms of PMR with normal ESR values.

There are no other imaging findings associated with polymyalgia rheumatica.

A muscle biopsy might be performed to differentiate polymyalgia rheumatica (PMR) from other diseases. In addition, temporal artery biopsy is required when a subject with PMR have symptoms suggestive of giant cell arteritis.

The mainstay of treatment of polymyalgia rheumatica (PMR) is low dose glucocorticoids, typically prednisone or prednisolone. The starting dose of the glucocorticoid treatment is 12.5-15 mg daily for 2 to 4 weeks after which the treatment should be slowly tapered. The average duration of the treatment with glucocorticoids is 1 to 2 years; nevertheless, longer corticosteroids regimens might be necessary among patients who experience relapse of the symptoms. Prophylaxis for osteoporosis with calcium and vitamin D should be started with the steroid therapy.

Surgical intervention is not recommended for the management of polymyalgia rheumatica.

There are no established measures for the primary prevention of polymyalgia rheumatica.

There are no established measures for the secondary prevention of polymyalgia rheumatica.

• Polymyalgia Rheumatica – The Arthritis Society
• Patient Education – Polymyalgia Rheumatica – American College of Rheumatology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2]

Polymyalgia rheumatica was first described in 1888 by Bruce William as “senile rheumatic gout”. The disease was referred to as “polymyalgia rheumatica” by Stuart Barber in 1957 in his article entitled “mylagic syndrome with constitutional effects; polymyalgia rheumatica”.

• In 1888, the syndrome of polymyalgia rheumatica was described for the first time by Bruce William.^[1]
• In 1957, the disease was referred to as “polymyalgia rheumatica” by Stuart Barber. In his article entitled “mylagic syndrome with constitutional effects; polymyalgia rheumatica”, Barber described the disease as a widespread muscle pain involving the neck, shoulder, lower back, pelvic girdle, and thighs in the absence of any objective changes of the joints. Barber noted the presence of constitutional symptoms and an elevated ESR among patients with these symptoms.^[2]
• In 1963, Bagratuni referred to polymyalgia rheumatica as an “anarthritic rheumatoid syndrome” and described it as a disease that resembles the prodrome symptomatic phase of rheumatoid arthritis.^[3]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]

There is no established system for the classification of polymyalgia rheumatica.

There is no established system for the classification of polymyalgia rheumatica.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2]

Polymyalgia rheumatica (PMR) is a chronic inflammatory disease of the articular and periarticular structures of the cervical region, shoulder girdle and hip girdle. The underlying pathophysiology of PMR remains unknown. It has been hypothesized that genetic and environmental factors are implicated, particularly due to the seasonal and geographical differences in the prevalence of this disease. It has also been hypothesized that PMR is associated with infections such as parainfluenza virus type 1, mycoplasma pneumoniae, chlamydia pneumoniae, and parvovirus B19. In addition, histological examinations of synovial biopsies of affected individuals reveal mild synovitis with predominance of CD4 T cells and macrophages. Although myalgia is a symptom of PMR, there is no inflammation of the muscles.

• PMR is a chronic inflammatory disease of the articular and periarticular structures of the cervical region, shoulder girdle and hip girdle.
• The cause of PMR remains unknown; however, there is evidence in the literature of possible involvement of genetic and environmental factors.^[1]
• This hypothesis is supported by the seasonal and geographical variations of the prevalence of PMR. In fact, the prevalence of PMR is the highest among patients from northern European descent and Scandinavian countries, which suggests a genetic and/or environmental role in the pathophysiology of PMR.^[2][3][4]
• Several genes have been reported to be involved in PMR, such as:^{[5][6][7][3][8]}
  • HLA DRB1
  • Interleukin 6
  • Interleukin 1 receptor antagonist
  • Tumor necrosis factor 3b (TNFb3)

• Moreover, the association between PMR and infections is another hypothesis for the development of PMR through viral stimulation of the immune system. This hypothesis is supported by the highest incidence of PMR in the time of some infection epidemics. Some of the infections that have been linked to PMR are:^[9][10]
  • Parainfluenza virus type 1
  • Mycoplasma pneumoniae
  • Chlamydia pneumoniae
  • Parvovirus B19

• In addition to the previous hypotheses, it has been postulated that PMR can be explained by an age related dysregulation in the hypothalamus, pituitary gland and gonads. This disturbance leads to adrenal insufficiency and decrement in dehydroepiandrosterone or androstenedione.^[11]

• Imaging studies such as ultrasound and MRI reveal inflammation in the articular and periarticular regions. The examination of histopathological specimens demonstrates mild synovitis with a predominance of T helper cells and macrophages.^[12]

• Polymyalgia rheumatica may be associated with the following conditions:^[13][14]
  • Giant cell arteritis (temporal arteritis)
  • Systemic lupus erythematosus
  • Rheumatoid arthritis

• In cases the polymyalgia rheumatica associated with giant cell arteritis, microscopic histopathological analysis will show the following findings of arteritis:^[15][16][17]
  • Skip lesions and normal intervening segments
  • Intimal thickening, with prominent cellular infiltration
  • Lymphocytes in the internal or external elastic lamina or adventitia
  • Areas of necrosis may be present in the arterial wall
  • Granulomas containing multinucleated histiocytic and foreign body giant cells, helper T-cell lymphocytes, plasma cells, and fibroblasts^[18]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]

There is no specific cause for polymyalgia rheumatica. However, there are possible theories about the causes which include inflammatory joint lining attack, viral infections, and genetic inheritance of HLA-DR4.

• The specific cause of polymyalgia rheumatica is unknown or not well understood.
• Possible theories about the causes include the following:^[1]
  • Inflammatory attack of the joints’ lining
  • Viral infection (eg, Adenovirus) stimulating the immune system causing autoimmune attack to the joints
  • Genetic inheritance of HLA-DR4 subtype

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]

Polymyalgia rheumatica (PMR) must be differentiated from other conditions such as late onset rheumatoid arthritis, polymyositis, dermatomyositis, fibromyalgia, and remitting seronegative symmetrical synovitis with pitting edema.

Polymyalgia rheumatica (PMR) must be differentiated from other conditions such as late onset rheumatoid arthritis, polymyositis, dermatomyositis, fibromyalgia, and remitting seronegative symmetrical synovitis with pitting edema.^[1][2][3][4]

Disease	Differentiating signs and symptoms	Diagnostic findings
Polymyalgia rheumatica	Older at onset Generalized stiffness	Elevated ESR or CRP Response to corticosteroids
Fibromyalgia	Symptoms have been present at a similar level for at least 3 months. Chronic musculoskeletal pain with multiple tender points Stiffness, numbness, and fatigue Headaches Sleep disorder	All lab tests are normal
Rheumatoid arthritis	Multiple joint swelling Morning stiffness Rheumatoid nodules	Positive RF or anti-cyclic citrullinated protein (CCP) antibody Elevated ESR or CRP
SLE	Maculopapular rash Multi-system involvement	Positive anti-Smith antibodies
Chronic fatigue syndrome	Fatigue plus 4 of the following symptoms: Short-term memory loss Sore throat Tender lymph nodes in the neck or armpit Muscle pain Joint pain without swelling or redness Headaches Insomnia Malaise	Diagnosis of exclusions Symptoms must present for more than 6 months
Spondyloarthritis	Axial skeletal pain and stiffness Restricted spinal motion	Elevated ESR or CRP Negative RF Bamboo spine on x-ray
Osteoarthritis	Localized joint pain Restricted to affect joints Older at onset	Degenerative joint changes on x-ray
Hypothyroidism	Systemic symptoms such as weight gain, constipation, dry skin Muscular aching Prominent fatigue	Elevated TSH Low free T4
Polymyositis and dermatomyositis	Pelvic and shoulder girdle muscle weakness Rash	Muscle biopsy confirms the diagnosis Elevated CPK enzyme
Neuropathy	Numbness and tingling Paresthesia	Abnormal EMG

Organ system	Disease	Symptoms												History	Physical Examination	Diagnosis
		Age of onset	Muscle weakness	Fever	Myalgia	Contractures	Gait abnormality	Neuropathy	Atrophy	Stiffness	Myoglobinuria	Other features	Laboratory Findings			Creatine Kinase	Muscle Biopsy	Electromyogram
Inflammatory/ Rheumatologic	Polymyalgia Rheumatica[5]	50s	Diffuse	+	+	−	−	−	−	+	−	Weight loss	History of joints stiffness, worse in the morning	Restricted shoulder motion	↑↑ ESR ↑↑ CRP	Normal	Normal	Normal
	Dermatomyositis[6]	40s−50s Can affect children	Proximal	+	+	−	−	−	−	+	−	Rash Dyspnea Weight loss Cough	Viral infections Cancer	Heliotrope rash on face and hands Telangiectasia Erythema Mechanic’s hands Gottron’s sign ( violaceous scaly eruption )	↑↑ ESR ↑↑ CRP	↑↑	Perimysial mononuclear infiltrate	Myopathic
	Polymyositis[7]	> 18 years	Proximal	+	+	−	−	−	−	+	−	Similar to dermatomyositis without mucous and skin involvement	N/A	N/A	↑↑ ESR ↑↑ CRP	↑↑	Endomysial mononuclear infiltrate Patchy necrosis
	Inclusion body myositis[8]	50s	Proximal & distal	−	−	−	−	−	−	−	−	Dysphagia Asymmetric weakness	Retrovirus (most common)	N/A	Antibodies to cytoplasmic 5’−nucleotidase	↑↑	Inflammatory cells Invading muscle cells Vacuolar degeneration Inclusions or plaques	Neurogenic
	Fibromyalgia[9]	40−50s	Generalized	−	−	−	−	+	−	−	−	Anxiety or depression features Fatigue Sleep disturbance Numbness Muscle spasms	History of depression	Tenderness in the soft tissue anatomical location	Normal	Normal	Normal	Normal
Organ system	Disease	Age of onset	Muscle weakness	Fever	Myalgia	Contractures	Gait abnormality	Neuropathy	Atrophy	Stiffness	Myoglobinuria	Other features	History	Physical Examination	Laboratory Findings	Creatine Kinase	Muscle Biopsy	Electromyogram

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2]

Polymyalgia rheumatica (PMR) affects mostly subjects who are more than 50 years of age. The prevalence of PMR is highest among subjects from Scandanavian countries and those from northern European origin.

• There is an association between PMR and giant cell arteritis. While 40 to 60% of patients with giant cell arteritis have PMR, 16 to 21% of patients with PMR develop giant cell arteritis.^[1][2][3]
• The annual incidence of PMR is 64 per 100,000 population ages> 50 years.^[4]

• PMR affects more than 700,000 subjects in the United States.^[5]

• Mortality rate among individuals with PMR is similar to the general population.^[4]

• The incidence of polymyalgia rheumatica increases with age.
• PMR mostly affects people who are older than 50 years of age.^[6][7]
• The mean age for the occurrence of PMR is 74 years.

• Polymyalgia rheumatica occurs more among subjects from Scandinavian countries and those from northern European origin.^[7][8]

• Females are more affected with polymyalgia rheumatica than men. ^[6]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]

Age, female sex, Scandinavia and northern Europe origin are risk factors for polymyalgia rheumatica. Other risk factors include smoking, sun exposure, infections, and nulliparity.

• Common risk factors of polymyalgia rheumatica include the following:^[1][2][3]
  • Age
  • Female sex
  • Scandinavia and northern Europe origin
  • Smoking
  • Sun exposure
  • Infections
  • Nulliparity

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]

There is insufficient evidence to recommend routine screening for polymyalgia rheumatica.

There is insufficient evidence to recommend routine screening for polymyalgia rheumatica.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2]

Polymyalgia rheumatica (PMR) affects the quality of life of the patients. The pain and stiffness in the proximal joints might lead to sleep disturbance as well as an inability to do regular daily activities such as getting dressed and getting out of a chair. The symptoms begin rapidly and last for weeks. Once the steroid treatment is initiated, the symptoms resolve rapidly within few days. In fact, the rapid resolution of symptoms with the steroid therapy reinforces the diagnosis of PMR. The steroid treatment can be associated with complications such as weight gain and bone fracture. Approximately 40 to 50% of subjects experience relapse of the symptoms. PMR is associated with giant cell arteritis.

• If left untreated, PMR affects the quality of life of the patients.
• The pain and stiffness in the proximal joints might lead to sleep disturbance as well as an inability to do regular daily activities such as getting dressed and getting out of a chair.
• The symptoms begin rapidly and last for weeks.

• PMR is associated with following complications:
  • Giant cell arteritis
    • While 40 to 60% of patients with giant cell arteritis have PMR, 16 to 21% of patients with PMR develop giant cell arteritis.^[1][2][3]
    • Some symptoms of temporal arteritis include
      • Severe headaches
      • Scalp tenderness
      • jaw claudication
      • Fever
      • Distorted vision that might lead to blindness
      • Aching in the limbs caused by decreased blood flow
      • fatigue
  • Corticosteroid related complications such as:^[4]
    • Weight gain
    • Bone fracture
  • Cardiac complications such as:^[5]
    • Myocardial inflammation
    • Left ventricular dyskinesia
    • Reduced systolic function

• Once the steroid treatment of PMR is initiated, the symptoms resolve rapidly within few days. In fact, the rapid resolution of symptoms with the steroid therapy reinforces the diagnosis of PMR.
• Approximately 40 to 50% of subjects experience relapse of the symptoms, which requires longer duration of glucocorticoid treatment.^[4]
• Factors that are associated with relapse are:
  • Female sex
  • Initial high dose glucocorticoid therapy
  • Fast tapering of the glucocorticoid therapy^[4]