Differentiating Polymyalgia rheumatica from other diseases

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

Overview

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.

Differentiating Polymyalgia Rheumatica from other Diseases

PMR must be differentiated from the following conditions:

Rheumatoid arthritis: PMR and late onset rheumatoid arthritis (RA) can initially present with similar clinical features like synovitis. These patients are treated initially as PMR with glucocorticoids. RA treatment is started when there is no improvement or when it evolves into characteristic RA or when there is a persistently raised plasma viscosity.^[1] ^[2]

Polymyositis and dermatomyositis: Patients with dermatomyositis or polymyositis present with tenderness and weakness of proximal muscles, while PMR patients present with pain and stiffness. This differentiation between these entities may be difficult in elderly patients. Proper history, complete physical examination, ESR, creatine kinase levels and muscle biopsy help in establishing the proper diagnosis.^[3] ^[4]

Malignancy (such as myeloma): Patients with malignancy sometimes present with PMR like symptoms and have poor response to steroid therapy.^[5] This is in fact paraneoplastic syndrome presenting as PMR.^[6]

Fibromyalgia: Fibromyalgia occurs in age groups 20-50 years. Patients have characteristic tender points. Unlike PMR, the active phase proteins and ESR are normal.

Hyperparathyroidism: Hyperparathyroidism presents with proximal stiffness and bone pain with elevated parathyroid hormone levels and often raised calcium levels without elevation of ESR levels.

Chronic infection (subacute bacterial endocarditis (SBE)): Rheumatologic symptoms seen in infective endocarditis can present as a clinical picture suggestive of polymyalgia rheumatica hindering the correct diagnosis.^[7]

Hypothyroidism: Patients with hypothyroidism muscle and joint pain and weakness similar to PMR. Delayed relaxation of deep tendon reflexes is seen in hypothyroidism with elevated TSH levels and low T4 levels.

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE): RS3PE presents with symmetrical synovitis and pitting edema, usually in patients over 50 years of age and lack rheumatoid factor. Unlike PMR, the symptoms commonly manifest distally.

Differentiating polymyalgia rheumatica on the basis of fatigue and chronic pain

Disease	Differentiating signs and symptoms	Diagnostic findings
Polymyalgia rheumatica	Older at onset Generalized stiffness	An elevated erythrocyte sedimentation rate (ESR) OR C-reactive protein (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	RF or anti-cyclic citrullinated protein (CCP) antibody is positive. Markers of systemic inflammation (ESR, CRP) are typically elevated.
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	X-ray of the involved joints demonstrate degenerative changes
Hypothyroidism	Systemic symptoms such as weight gain, constipation, dry skin Muscular aching and prominent fatigue that improves on replacement of thyroid hormone.	TSH is elevated and free T4 is low.
Myopathaies (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

Differentiating polymyalgia rheumatica from other causes of myopathy

Organ system	Disease	Symptoms												History	Physical Examination	Diagnosis
Organ system	Disease	Age of onset	Muscle weakness	Fever	Myalgia	Contractures	Gait abnormality	Neuropathy	Atrophy	Stiffness	Myoglobinuria	Other features	Laboratory Findings	History	Physical Examination	Creatine Kinase	Muscle Biopsy	Electromyogram
Medication−induced	Corticosteroids^[8]	Variable	Proximal	−	+	−	−	−	+	−	−	Central obesity Excessive sweating Insomnia Reduced libido Amenorrhea Infertility Psychological disturbances	Positive h/o medications	Facial and sphincter muscles are usually spared	Positive ACTH stimulation test 24-hour urine cortisol Low dose dexamethasone suppression test	Normal	Normal	Normal
	Statins^[9]	60+	Proximal	−	+	−	−	−	−	−	−/+(Rhabdomyolysis)	N/A	Positive h/o medications H/o other medication use	Tenderness Muscle aches	↑↑ Liver enzymes	↑↑	Necrosis Degeneration, and regeneration of fibers Phagocytic infiltration	Normal
	Alcohol^[10]	Variable	Proximal	−	−	−	+	+/−	−	−	−	Swelling Tender Erythema and induration	Alcohol intoxication	Change in mental status Telangiectasia Peripheral neuropathy	Monspecific and are normal in many patients	Normal or ↑↑	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
Endocrine	Cushing's disease^[11]	25 −45	Proximal	−	−	−	−	−	+	−	−	Decreased libido Obesity/weight gain Plethora Round face Menstrual changes Hirsutism Hypertension Ecchymoses Lethargy Depression Dorsal fat pad Abnormal glucose tolerance	N/A	Facial and sphincter muscles are usually spared Overweight Straie Moon face HTN Hyperpigmentation	Positive ACTH stimulation test 24-hour urine cortisol Low dose dexamethasone suppression test	Normal	Atrophy of type 2 muscle fibers, especially type 2B	Normal
	Adrenal insufficiency^[12]	30−50 years	Proximal	−	+	−	−	−	−	+	−	Signs of glucocorticoid, mineralocorticoid, and, androgen deficiency	Signs of postural hypotension History of tuberculosis History of malignancy History of other autoimmune disease	Hypotension Hyperpigmentation Auricular−cartilage calcification Vitiligo	Electrolyte abnormalities Hypoglycemia	Normal	Normal	Normal
	Hyperaldosteronism with myopathy^[13]	50	Proximal & distal	−	−	−	−	−	−	−	+ Rhabdomyolysis	Palpitations Hypertension	Episodes of increased heart beats	Hyperpigmentation	Hypokalemia	Normal	Normal	Normal
	Hyperthyroidism^[14]	40	Proximal	−	−	−	−	−	+	+	+	Signs of hyperthyroidism	H/o of weight loss	Sweating Tremor Neck swelling	Decreased TSH	↑↑	Non specific	Myotonic
	Hypothyroidism^[15]	55	Proximal	−	+	+	−	−	+	+	+ Rhabdomyolysis	Signs of hypothyroidism	H/o weight gain	Myxoedema Muscle pseudohypertrophy	Increased TSH	↑↑	Nonspecific	Normal
	Diabetic infraction^[16]	45	Proximal	+	+	−	−	+	+	−	−	Cramps Sudden onset of pain Anterior thigh muscles are most commonly involved	H/O long standing diabetes	Swelling Tenderness	Elevated ESR Leukocytosis	Normal	Necrosis Edema	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
Inflammatory/ Rheumatologic	Dermatomyositis^[17]	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^[18]	> 18 years	Proximal	+	+	−	−	−	−	+	−	Similar to dermatomyositis without mucous and skin involvement	N/A	N/A	↑↑ ESR ↑↑ CRP	↑↑	Endomysial mononuclear infiltrate Patchy necrosis	Myopathic
	Inclusion body myositis^[19]	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^[20]	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
	Polymyalgia Rheumatica^[21]	50s	Diffuse	+	+	−	−	−	−	+	−	Weight loss	History of joints stiffness, worse in the morning	Restricted shoulder motion	↑↑ ESR ↑↑ CRP	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
Genetic	Becker muscular dystrophy^[22]	<13yrs	Proximal	−	−	+	+	−	+	−	−	Milder form of Duchenne	Growth delay Age of onset of symptoms is much delayed than duchenne	Positive Grower sign	Decreased amount of dystrophin.	↑↑	Muscle fibril degeneration, regeneration Isolated fiber hypertrophy Muscle replacement with fat and connective tissue	Myopathic
	Duchenne muscular dystrophy^[23]	<13 yrs	Proximal	−	−	+	+	−	+	−	−	Calf psedohypertrophy Cardiomyopathy Kyphoscoliosis Cognitive impairment	Early onset	Positive Grower sign	Errors in the Xp21 gene. Absence of dystrophin.	↑↑		Myopathic
	Limb−girdle muscular dystrophies^[24]	<15 yrs	Proximal	−	+	+	+	−	+	−	−	Calf hypertrophy Scapular winging Cardiomyopathy Cardiac arrhythmias Respiratory muscle weakness	Autosomal dominant Deterioration of ability to run/walk	Muscle weakness is generally symmetric	LMNA gene CAV3 gene	↑↑	N/A	Myopathic
	Myotonic dystrophy^[25]	<18 years	Proximal & distal	−	−	+	+	−	−	+	−	Myotonia Cataracts Diabetes mellitus Frontal balding Cardiac arrhythmias Cholecystitis Pregnancy Eyelid ptosis	Positive family history	Muscles often contract and are unable to relax	Mutations in the DMPK gene	N/A	N/A	Myopathic
	Glycogen storage disease^[26]	Variable	Proximal	−	−	−	−	−	+	−	−	AR Faituge Hypoglycemia	Exercise intolerance	Hypotonia Hepatomegaly	Lactic acidosis Elevated liver enzymes Ketosis	↑↑	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
Infectious	Lyme disease^[27]	Variable	Proximal	+	+	−	+/−	+	−	−	−	Erythema Migrans Flu−like symptoms Lyme arthritis Neurological manifestations	H/o tick bite Hiking trip	Target−like lesions HSM	Clinical diagnosis +Serology	N/A	N/A	N/A
	Influenza^[28]	Variable	Proximal and Distal	+	+	−	+	−	−	−	+	Fever Malaise Rhinorrhea Muscle pain worse with movement	Cold weather H/o Ill contacts	Muscle weakness, tenderness, and swelling.	↑↑ Liver enzymes Positive PCR	↑↑	N/A	N/A
	Polio^[29]	<5 yrs	Proximal	−	−	−	+	+	+	−	−	Asymmetrical paralysis Muscle atrophy Tremors Skeletal deformities	History of skipped immunization.	Normal Meningeal signs Asymmetrical flaccid paralysis Pharyngeal paralysis	Isolation from pharyngealsecretions, CSF Positive serology	N/A	N/A	Neurological pattern
	Syphilis^[30]	Variable	Negative	−	−	−	+	+	−	−	−	Chancre Lymphadenopathy Condylomata lata Neuro syphilis Cardiovascular syphilis	History of risk factors (MSM, unprotected sex, multiple sex partners)	Non−tender chancre in primary syphilis. Followed by rash Generalized lymphadenopathy in secondary syphilis	Darkfield examinations VDRL RPR FTA−ABS	N/A	N/A	N/A
	Pyomyositis^[31]	Variable	Proximal & Distal	+	+	−	−	−	−	+	−	Fever Malaise Psoas abscess	Immunocompromised	Muscles are painful, swollen, tender, and indurated. Depending on the site of involvement, it may mimic appendicitis (psoas muscle), septic arthritis of the hip (iliacus muscle), or epidural abscess (piriformis muscle).	Leukocytosis Elevated ESR	N/A	N/A	N/A
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
Neurologic	ALS^[32]	>35	Proximal & Distal Distal	−	−	−	−	+	+	+	−	Dysphagia Spasticity Hyperreflexia Babinski's +	N/A	Both upper and lower motor neuron signs	Clinical diagnosis	Normal	Nonspecific findings of chronic denervation with reinnervation	Neuropathic
	Stroke^[33]	>65	Proximal & distal	−	−	−	+	+	+	−	−	Dysphagia Unilateral/Bilateral weakness	H/o HTN, dyslipidaemia DM	Weakness of the involved arm	Head CT	Normal	Normal	Neuropathic
	GBS^[34]	18 −350	Proximal	−	−	−	+	−	−	+	−	Ascending paralysis	Precedes a gastrointestinal disease	Weakness of lower extremities followed by upper extremities	Cytologic albumin ratio	Normal	Normal	Neuropathic
	Multiple Sclerosis^[35]	30's	Proximal & distal	−	−	−	+	+	−	−	−	Ocular findings Urinary incontinence Problems with speech or swallowing	Attacks or exacerbation	Localized weakness Focal sensory disturbances Hyper reactive reflexes Increased tone or stiffness	Head CT ologo−clonal bands	Normal	N/A	Neuropathic
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
Neuromuscular	Botulinum^[36]	Variable	Distal	−	−	−	+	−	−	+	−	Double vision Blurred vision Drooping eyelids Slurred speech Difficulty swallowing	H/O food exposure	Hyporeflexia Decreased strength	+Toxin	Normal	N/A	Myopathic
	Lambert−Eaton syndrome^[37]	Variable	Distal	−	−	+	+	−	−	+	−	Weakness of the bulbar muscles Ocular Limb weakness	Weaknessa is often relieved temporarily after exertion or physical exercise.		Antibodies against voltage−gated calcium channels
	Myasthenia gravis^[38]	Variable	Proximal	−	−	+	+	−	−	+	−	Ocular Bulbar Limb weakness Isolated neck, limbs and respiratory weakness	Weakness often worsens with activity		Antibodies that block or destroy nicotinic acetylcholine receptors

References

↑ Pease CT, Haugeberg G, Montague B; et al. (2009). "Polymyalgia rheumatica can be distinguished from late onset rheumatoid arthritis at baseline: results of a 5-yr prospective study". Rheumatology (Oxford). 48 (2): 123–7. doi:10.1093/rheumatology/ken343. PMID 18980958. Unknown parameter |month= ignored (help)
↑ Pease CT, Haugeberg G, Morgan AW, Montague B, Hensor EM, Bhakta BB (2005). "Diagnosing late onset rheumatoid arthritis, polymyalgia rheumatica, and temporal arteritis in patients presenting with polymyalgic symptoms. A prospective longterm evaluation". J. Rheumatol. 32 (6): 1043–6. PMID 15940765. Unknown parameter |month= ignored (help)
↑ Sørensen CD, Hansen LH, Hørslev-Petersen K (2010). "[Myositis as differential diagnosis in polymyalgia rheumatica]". Ugeskr. Laeg. (in Danish). 172 (42): 2899–900. PMID 21040663. Unknown parameter |month= ignored (help)
↑ Hopkinson ND, Shawe DJ, Gumpel JM (1991). "Polymyositis, not polymyalgia rheumatica". Ann. Rheum. Dis. 50 (5): 321–2. PMC 1004419. PMID 2042988. Unknown parameter |month= ignored (help)
↑ Manganelli P, Borghi L, Coruzzi P, Novarini A, Ambanelli U (1986). "[Paraneoplastic polymyalgia rheumatica. Case contribution]". Minerva Med. (in Italian). 77 (38): 1739–41. PMID 3774196. Unknown parameter |month= ignored (help)
↑ Kwiatkowska B, Filipowicz-Sosnowska A (2008). "[Polymyalgia rheumatica mimicking neoplastic disease--significant problem in elderly patients]". Pol. Arch. Med. Wewn. (in Polish). 118 Suppl: 47–9. PMID 19562970.
↑ Auzary C, Le Thi Huong D, Delarbre X; et al. (2006). "Subacute bacterial endocarditis presenting as polymyalgia rheumatica or giant cell arteritis". Clin. Exp. Rheumatol. 24 (2 Suppl 41): S38–40. PMID 16859595.
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Template:WH Template:WS

[pmid18980958-1] Pease CT, Haugeberg G, Montague B; et al. (2009). "Polymyalgia rheumatica can be distinguished from late onset rheumatoid arthritis at baseline: results of a 5-yr prospective study". Rheumatology (Oxford). 48 (2): 123–7. doi:10.1093/rheumatology/ken343. PMID 18980958. Unknown parameter |month= ignored (help)

[pmid15940765-2] Pease CT, Haugeberg G, Morgan AW, Montague B, Hensor EM, Bhakta BB (2005). "Diagnosing late onset rheumatoid arthritis, polymyalgia rheumatica, and temporal arteritis in patients presenting with polymyalgic symptoms. A prospective longterm evaluation". J. Rheumatol. 32 (6): 1043–6. PMID 15940765. Unknown parameter |month= ignored (help)

[pmid21040663-3] Sørensen CD, Hansen LH, Hørslev-Petersen K (2010). "[Myositis as differential diagnosis in polymyalgia rheumatica]". Ugeskr. Laeg. (in Danish). 172 (42): 2899–900. PMID 21040663. Unknown parameter |month= ignored (help)

[pmid2042988-4] Hopkinson ND, Shawe DJ, Gumpel JM (1991). "Polymyositis, not polymyalgia rheumatica". Ann. Rheum. Dis. 50 (5): 321–2. PMC 1004419. PMID 2042988. Unknown parameter |month= ignored (help)

[pmid3774196-5] Manganelli P, Borghi L, Coruzzi P, Novarini A, Ambanelli U (1986). "[Paraneoplastic polymyalgia rheumatica. Case contribution]". Minerva Med. (in Italian). 77 (38): 1739–41. PMID 3774196. Unknown parameter |month= ignored (help)

[pmid19562970-6] Kwiatkowska B, Filipowicz-Sosnowska A (2008). "[Polymyalgia rheumatica mimicking neoplastic disease--significant problem in elderly patients]". Pol. Arch. Med. Wewn. (in Polish). 118 Suppl: 47–9. PMID 19562970.

[pmid16859595-7] Auzary C, Le Thi Huong D, Delarbre X; et al. (2006). "Subacute bacterial endocarditis presenting as polymyalgia rheumatica or giant cell arteritis". Clin. Exp. Rheumatol. 24 (2 Suppl 41): S38–40. PMID 16859595.

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Differentiating Polymyalgia rheumatica from other diseases

Overview

Differentiating Polymyalgia Rheumatica from other Diseases

Differentiating polymyalgia rheumatica on the basis of fatigue and chronic pain

Differentiating polymyalgia rheumatica from other causes of myopathy

References

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