Differentiating Polymyalgia rheumatica from other diseases

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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.

• 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.

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

• 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.

• 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 Various Muscle Weakness

Disease	Symptoms									History	Physical Examination	Diagnosis
	Age of onset	Muscle weakness		Fever	Muscle pain	Gait abnormality	Neuropathy	Myoglobinuria	Other features			Laboratory Findings	Creatine Kinase	Muscle Biopsy	Electromyogram
		Proximal	DIstal
Medications
Corticosteroids	Variable	+	-	-	+	-	-	-	Central obesity Excessive sweating Insomnia Reduced libido  Amenorrhea Infertility  Psychological disturbances	+ History of medications	Facial and sphincter muscles usually are spared	+ ACTH Stimulation test 24-hour urine cortisol Low dose dexamethasone suppression test	-	-	-
Statins	60+	+	-	-	+	-	-	-/+(rhabdomyolysis)	N/A	Positive medication history	Tenderness Muscle aches	↑↑ liver enzymes	↑↑	Necrosis Degeneration, and regeneration of fibers Phagocytic infiltration	-
Alcohol	Variable	+	-	-	-	+	+/-	-	Swelling Tender Erythema and induration	Alcohol intoxication	Change in mental status Telangiectasia Peripheral neuropathy	nonspecific and are normal in many patients	Normal or ↑↑	Normal	Normal
Endocrine
Cushing's disease	25 -45	+	-	-	-	-	-	-	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 usually are spared Overweight Straie Moon face HTN Hyperpigmentation	+ 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	30-50 years	+	-	-	-	-	-	-	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	50	+	+	-	-	-	-	+ Rhabdomyolysis	Palpitations Hypertension	Episodes of heart beats	Hyperpigmentation	Hypokalemia	Normal	Normal	Normal
Hyperthyroidism	40	+	-	-	-	-	-	+	Signs of hyperthyroidism	Sweating Tremor' H/o of weight loss	Sweating Tremor' Swelling on neck examination	Decreased TSH	↑↑	Non specific	Myotonic
Hypothyroidism	>55	+	-	-	+	-	-	+ Rhabdomyolysis	Signs of hypothyroidism	H/o weight gain	Myoedema  Muscle pseudohypertrophy	Increased TSH	↑↑	Nonspecific	Normal
Diabetic infraction	45	+	-	+	+	-	+	-	Cramps Sudden onset of pain Anterior thigh muscles are most commonly involved	H/O long standing diabetes	Swelling Tenderness	Elevation of the erythrocyte sedimentation rate Leukocytosis	Normal	Necrosis Edema	Normal
Inflammatory / Rheumatologic
Dermatomyositis	40s-50s Can affect childreen	+	-	+	+	-	-	-	Rash Dyspnea Weight loss Cough		Heliotrope rash on face and hands Telangectasia Erythema Mechanic's hands Gottron's sign ( violaceous scaly eruption )	↑↑ ESR ↑↑ CRP	↑↑	Perimysial mononuclear infiltrate	Muscle inflammation and damage
Polymyositis	> 18 years	+	-	+	+	-	-	-	Similar to dermatomyositis without mucous and skin involvement	N/A	N/A		↑↑	Endomysial mononuclear infiltrate Patchy necrosis
Inclusion body myositis	50s	+	+										↑↑
Fibomyalgia	40-50s	+	-	-	-	-	++	-	Anxiety or depression features Fatigue Sleep disturbance Numbness Muscle spasms	History of depressive disorder	Tenderness in the soft tissue anatomical location	Normal	Normal	Normal	Normal
Polymyalgia Rheumatica	50s	+	-	+	+	-	-	-	Weight loss	History of joints stiffness which is worse in the morning	Restricted shoulder motion	↑ CRP ↑ ESR	Normal	Normal	Normal
Genetic
Becker muscular dystrophy	<13yrs	+	-	-	-	+	-	-	Milder form of Duchenne	Growth delay Age of onset of symptoms is much delayed than duchenne		Decreased amount of dystrophin.	↑↑	Muscle fibril degeneration, regeneration Isolated fiber hypertrophy Muscle replacement with fat and connective tissue	Myopathic changes
Duchenne muscular dystrophy	<13 yrs	+	-	-	-	+	-	-	Calf psedohypertrophy Cardiomyopathy Kyphoscoliosis Cognitive impairment	Early onset	+Grower sign	Errors in the Xp21 gene. Absence of dystrophin.	↑↑
Limb-girdle muscular dystrophies	<15 yrs	+	-	-	+	+	-	-	Calf hypertrophy Scapular winging Cardiomyopathy Cardiac arrhythmias Respiratory muscle weakness	Autosomal dominant		LMNA gene CAV3 gene	↑↑	-
Myotonic dystrophy type 1		+	+	-	-	+	-	-	Myotonia Cataracts Diabetes mellitus Frontal balding Cardiac arrhythmias Cholecystitis Pregnancy Eyelid ptosis
Infectious
Lyme disease	Variable	+	-	+	+	+/-	+	-	Erythema Migrans Flu-like symptoms Lyme arthritis Neurological manifestations	+ Tick bite Hiking/Tip	Target-like lesions HSM	Clinical diagnosis +Serology	-	-	-
Infulenza	Variable	-	-	+	+	+	-	+	Fever Malaise Rhinorrhea Muscle pain worse with movement		Muscle weakness, tenderness, and swelling.	↑↑ Liver enzymes +PCR	↑↑	-	-
Polio	<5 yrs	+	-	-	-	+	+	-	Asymmetrical paralysis Muscle atrophy Tremors Skeletal deformities		Normal Meningeal signs Asymmetrical flaccid paralysis Pharyngeal paralysis	Isolation from pharyngealsecretions, CSF +Serology	-	-	Neurological pattern
Syphilis	Variable	-	-	-	-	+	+	-	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	-	-	-
Pyomyositis	Variable	+/-	+/-	+	+	-	-	-	Fever Malaise Psoas abscess	Immunocopmprimised	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	-	-	-
Neurologic
ALS											Both upper and lower motor neuron signs		Normal	Nonspecific findings of chronic denervation with reinnervation	Neuropathic
Stroke	>65	+	+	-	-	+	+	-	Dysphagia Unilateral/Bilateral weakness	H/o HTN, dyslipedemia DM	Weakness of the involved arm		Normal	Normal	Neuropathic
GBS	18 -350	-	+	-	-	+	-	-	Ascending paralysis	Precedes a gastrointestinal disease	Weakness of lower extremities followed by upper extremities	Cytologic albumin ratio	Normal	Normal	Neuropathic
Multiple Sclerosis
Neuro-muscular
Botulisim		-	+							H/0 Food exposure and air
Lambert-Eaton myaes		+	+
Myasthenia gravis		+	+						Ocular Bulbar  Limb weakness Isolated neck, limbs and respiratory weakness
Paraneoplastic
Metabolic
Glycogen storage disease	Variable	+	-	-	-	-	-	-	AR Faituge Hypoglycemia	Exercise intolerance	Hypotonia Hepatomeagly	Lactic acidosis Elevated liver enzymes Ketosis	↑↑	Normal	Normal