Differentiating rheumatoid arthritis from other diseases

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

Differentiating Rheumatoid arthritis from other Diseases

• Osteoarthritis (OA):
  • Signs and symptoms of osteoarthritis are usually minimal and spares the wrist joint and the metacarpophalangeal joint. It typically affects the distal inter-phalangeal joint and frequently associated with Heberden's nodes.
  • Joint stiffness is usually minimal in OA and lasts less than one hour. In contrast, joint stiffness is a very prominent symptom of RA and should last more than an hour for atleast 6 weeks in order to fulfill the criteria for diagnosis defined by The American College of Rheumatology.
• Systemic lupus erythematosus (SLE):
  • Symptoms specific to SLE like butterfly malar rash, Discoid lupus erythromatosus, photosensitivity, myositis, nephritis are not seen in RA.
  • The C reactive protein levels are often normal or mildly elevated in SLE, whereas it is always elevated in RA. However, the erythrocyte sedimentation rate is found to be elevated in both.
• Septic arthritis
  • Bacterial cause: Characterized by fever, chills, joint swelling and tenderness, demonstration of causative organism in the aspirated joint fluid by gram staining or microbial culture.
  • Viral cause: rubella, parvovirus B19, hepatitis B virus, hepatitis C virus are the most common responsible etiologic agents. The syndrome is often self limiting, lasting for a few weeks, and rarely beyond 6 weeks. Serology can help identifying HBV, HCV, parvovirus B19. Anti-CCP antibody is more specific than Rheumatoid factor for establishing a diagnosis of RA, as Rheumatoid factor levels may be raised in HCV infection.
  • Lyme Arthritis: It is characterized by intermittent, persistent or migratory pattern of arthritis, often involving large joints like knee, shoulder, ankle, elbow, wrist and temporomandibular joint in the decreasing order of incidence. Involvement of small joints of the hand is not common with Lyme disease. Diagnosis is made by serology. Other clues include residing in an endemic area, antecedent history of erythema chronicum migrans.
• Gout:
  • Chronic gout can assume a polyarticular pattern and can be confused with RA. However, demonstration of urate crystals in the aspirated joint fluid and presence of tophi on physical examination can help establish diagnosis.
• Polymyalgia rheumatica:
  • It often asymmetric, seen in those above 50 years of age, involves proximal muscles of shoulder and hip, and tends to have a milder course.
  • Stiffness involves the axial muscles more often than the small joints of hand that predominates RA.
  • They are typically seronegative or have only a mild elevation of Rheumatoid factor and respond dramatically to glucocorticoids.
• Paraneoplastic syndromes:
  • Hypertrophic pulmonary osteoarthropathy]]: Characterized by clubbing of digits, joint pain (deep and nagging type) and periosteal reaction.
  • Myelodysplastic syndrome: Patients with myelodysplastic syndrome often present with various autoimmune diseases including polyarthritis which could be confused with RA.
• Other differentials:
  • Fibromyalgia
  • Polychondritis
  • Psoriatic arthritis
  • Sarcoidosis
  • Sjogren syndrome

Differential diagnosis

Arthritis Type	Clinical Features							Body Distribution				Key Signs				Laboratory Abnormalities
	History of Psoriasis	Symmetric joint involvement	Asymmetric joint involvement	Enthesopathy	Dactylitis	Nail Dystrophy	Human immunodeficiency virus association	Upper extremity-hands	Lower extremity	Sacroiliac joints	Spine	Osteopenia	Joint Space	Ankylosis	Periostitis	Soft tissue swelling	ESR	Rheumatoid factor (RF)	HLA-B27
Psoriatic arthritis	+	+	++	+	+	+	+	+++ (DIP/PIP)	+++	++ (Unilateral)	++	-	++ (Widening)	++	+++ (Fluffy)	++	+	-	30-75%
Rheumatoid arthritis	-	++	+	-	-	-	-	+++ (MCP/wrist)	+++	+ (Unilateral)	++(Cervical)	+++	+++ (Narrowing)	+	+ (Linear)	+++	+++	+++	6-8%
Ankylosing spondylitis	-	+++	-	+	-	-	-	+	+	+++ (Bilateral)	+++	+++	++ (Narrowing)	+++	+++ (Fluffy)	+	+++	-	90%
Reactive arthritis (Reiter's syndrome)	-	+++	-	+	+	-	-	++	+++	++ (Unilateral)	+	+	+ (Narrowing)	-	+++ (Fluffy)	++	++	-	75%

Key:+ : Infrequently present, ++ : Frequently present, +++ : Always present, - : Absent

Disease	Differentiating signs and symptoms	Diagnostic findings
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
Polymyalgia rheumatica	Older at onset Generalized stiffness	An elevated erythrocyte sedimentation rate (ESR) OR C-reactive protein (CRP) Response to corticosteroids
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

Causes of lung cavities	Differentiating Features	Differentiating radiological findings	Diagnosis confirmation
Malignancy (Primary lung cancer)	Elderly male or female Chronic smokers Presents with a low-grade fever, absence of leukocytosis, systemic complaints weight loss, fatigue Absence of factors that predispose to gastric content aspiration, no response to antibiotics within 10 days Hemoptysis is commonly associated with bronchogenic carcinoma	A coin-shaped lesion with thick wall(>15mm) is seen on CXR with less ground glass opacities Bronchoalveolar lavage cytology shows malignant cells	Biopsy of lung
Pulmonary Tuberculosis	Mostly in endemic areas Symptoms include productive cough,night sweats, fever and weight loss	CXR and CT demonstrates cavities in the upper lobe of the lung	Sputum smear positive for acid-fast bacilli and nucleic acid amplification tests (NAAT) is used on sputum or any sterile fluid for rapid diagnosis and is positive for mycobacteria.
Necrotizing Pneumonia	Any age group Acute, fulminant life threating complication of prior infection >100.4F fever, with hemodynamic instability Worsening pneumonia-like symptoms	CXR demonstrates multiple cavitary lesions Pleural effusion and empyema are common findings	CBC is positive for causative organism
Loculated empyema	Children and elderly are at risk Pleuritic chest pain, dry cough, fever with chills Dullness to percussion decreased breath sounds, and reduced vocal resonance on examination	Empyema appears lenticular in shape and has a thin wall with smooth luminal margins	Thoracocentesis
Granulomatosis with polyangiitis (Wegener's)	Women are more commonly effected than man. Kidneys are also involved Upper respiratory tract symptoms , perforation of nasal septum, chronic sinusitis, otitis media, mastoiditis. Lower respiratory tract symptoms, hemoptysis, cough, dyspnea. Renal symptoms, hematuria, red cell casts	Pulmonary nodules with cavities and infiltrates are a frequent manifestation on CXR	Positive for P-ANCA Biopsy of the tissue involved shows necrotizing granulomas
Rheumatoid nodule	Elderly females of 40-50 age group Manifestation of rheumatoid arthritis Presents with other systemic symptoms including symmetric arthritis of the small joints of the hands and feet with morning stiffness are common manifestations.	Pulmonary nodules with cavitation are located in the upper lobe (Caplan syndrome) on Xray.	Positive for both rheumatoid factor and anticyclic citrullinated peptide antibody.
Sarcoidosis	More common in African-American females Often asymptomatic except for enlarged lymph nodes Associated with restrictive lung disease Erythema nodosum Lupus pernio (skin lesions on face resembling lupus) Bell palsy Epithelioid granulomas containing microscopic Schaumann and asteroid bodies	On CXR bilateral adenopathy and coarse reticular opacities are seen. CT of the chest demonstrates extensive hilar and mediastinal adenopathy Additional findings on CT include fibrosis (honeycomb, linear, or associated with bronchial distortion), pleural thickening, and ground-glass opacities.	Biopsy of lung shows non-caseating granuloma
Bronchiolitis obliterans (Cryptogenic organizing pneumonia)	Rare condition and mimics asthma, pneumonia and emphysema It is caused by drug or toxin exposure, autoimmune diseases, viral infections, or radiation injury People working in industries are at high risk Presents with fever, cough, wheezing and shortness of breath over weeks to months,	Common appearance on CT is patchy consolidation,often accompanied by ground-glass opacities and nodules.	Biopsy of the lung Pulmonary function tests demonstrate low fev1/fvc
Langerhans cell Histiocytosis	Exclusively afflicts smokers, with a peak age of onset of between 20 and 40 years. Clinical presentation varies, but symptoms generally include months of dry cough, fever, night sweats and weight loss. Skin is involved in 80% of the cases, scaly erythematous rash is typical.	Thin-walled cystic cavities are the usual radiographic manifestation, observed in over 50% of patients by either CXR or CT scans.	Biopsy of the lung

Arthritis Type	Clinical Features							Body Distribution				Key Signs				Laboratory Abnormalities
	History of Psoriasis	Symmetric joint involvement	Asymmetric joint involvement	Enthesopathy	Dactylitis	Nail Dystrophy	Human immunodeficiency virus association	Upper extremity-hands	Lower extremity	Sacroiliac joints	Spine	Osteopenia	Joint Space	Ankylosis	Periostitis	Soft tissue swelling	ESR	Rheumatoid factor (RF)	HLA-B27
Psoriatic arthritis	+	+	++	+	+	+	+	+++ (DIP/PIP)	+++	++ (Unilateral)	++	-	++ (Widening)	++	+++ (Fluffy)	++	+	-	30-75%
Rheumatoid arthritis	-	++	+	-	-	-	-	+++ (MCP/wrist)	+++	+ (Unilateral)	++(Cervical)	+++	+++ (Narrowing)	+	+ (Linear)	+++	+++	+++	6-8%
Ankylosing spondylitis	-	+++	-	+	-	-	-	+	+	+++ (Bilateral)	+++	+++	++ (Narrowing)	+++	+++ (Fluffy)	+	+++	-	90%
Reactive arthritis (Reiter's syndrome)	-	+++	-	+	+	-	-	++	+++	++ (Unilateral)	+	+	+ (Narrowing)	-	+++ (Fluffy)	++	++	-	75%

Key:+ : Infrequently present, ++ : Frequently present, +++ : Always present, - : Absent

Disease	Differentiating signs and symptoms	Diagnostic findings
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
Polymyalgia rheumatica	Older at onset Generalized stiffness	An elevated erythrocyte sedimentation rate (ESR) OR C-reactive protein (CRP) Response to corticosteroids
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

References