Arthritis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2], Cafer Zorkun, M.D., Ph.D. [3]

Overview

Arthritis (from Greek arthro-, joint + -itis, inflammation; plural: arthritides) could be defined as painful joint damage. It might be as part of a systemic disorder or a single joint involvement. Arthritis may present as joint pain (arthralgia), swelling, erythema, warmness, and limitation of movement. It could be classified according to the number of involved joints, presence of inflammation, or duration of symptoms. Osteoarthritis (also known as degenerative joint disease) is the most common form of arthritis in the United States which involves up to 10% of population older than 60 years. Inflammatory arthritis is common in systemic autoimmune disorders, such as rheumatoid arthritis and systemic lupus erythematosus (SLE) and is part of diagnostic criteria for this spectrum of diseases. Disease course in systemic disorders is usually chronic and multiple joints (polyarticular) are involved. In the other hand, infectious conditions like septic arthritis are acute in nature and they usually involve single joints (monoarticular). Crystal induced arthropathies may result in inflammatory joint(s) involvement, mainly are due to uric acid crystal deposition (gout) in articular space. Although, disease course and presence of other systemic manifestations are important for diagnosis but the gold standard method for diagnosis is joint aspiration, fluid analysis, and microscopic evaluation. Imaging might be helpful in certain condition to find the disease chronicity and structural changes in articular and periarticular structures. Prompt treatment is necessary specially for septic and inflammatory conditions to prevent structural joint damage and deformities.

Classification

Primary Forms of Arthritis:

• Osteoarthritis
• Rheumatoid arthritis
• Septic arthritis
• Gout and pseudogout
• Juvenile idiopathic arthritis
• Still's disease
• Ankylosing spondylitis

Differential Diagnosis

Differential Diagnosis of Monoarthritis

Differentiating the diseases that can cause monoathritis:

To review the differential diagnosis of monoarthritis with joint swelling, click here.

To review the differential diagnosis of monoarthritis with fever, click here.

To review the differential diagnosis of monoarthritis with weight loss, click here.

To review the differential diagnosis of monoarthritis with claudication, click here.

To review the differential diagnosis of monoarthritis with morning stiffness, click here.

To review the differential diagnosis of monoarthritis with local erythema, click here.

To review the differential diagnosis of monoarthritis with joint swelling and fever, click here.

To review the differential diagnosis of monoarthritis with joint swelling, fever, and weight loss, click here.

Diseases			Clinical manifestations							Para-clinical findings								Gold standard	Additional findings
			Symptoms				Physical examination
										Lab Findings				Imaging			Histopathology
			Joint Swelling	Fever	Weight loss	Claudication	Morning stiffness	Local erythema	Skin manifestation	CBC	ESR	Synovial fluid	Other	X-ray	CT scan	Other
Monoarthritis	Osteoarthritis		+	-	-	-	-	-	Heberden nodes	Anemia	-	Noninflammatory joint fluid	Urinary pyridinium cross-links	Joint-space loss, subchondral bony sclerosis, cyst formation	Malalignment of the patellofemoral joint	Early diagnosis of osteoarthritis of the hand with bone scan	-	Clinical findings	Microfracture, bone pain
	Trauma		+	-	-	-	-	+	Wound or laceration	-	-	Hemarthrosis	-	Severe joint effusion, Fracture	Fracture, Synovial tear	-	-	X-ray	Deformity, Severe pain
	Neoplasms		+	-	+	+/-	-	-	Rash	Normocytic normochromic anemia	↑	High WBC count (10,000-40,000/µL)	Hypercalcemia, Hyperphosphatemia	Peri-articular osteoblastic or osteoclastic lesion	Elevation of the periosteum	Intense radionuclide uptake in bone scan	Spindle-shaped and atypical stromal cells, with irregular nuclei	Clinical findings and imaging	Nocturnal pain, Pathologic fractures
	Infection	Gonococcal infection	+	+	-	-	-	+	Maculopapular, Pustular, Vesicular lesions on an erythematous base	Leukocytosis	↑	Purulent with cell count > 50,000 WBC/µL (with PMNs > 90%)	Blood and synovial fluid culture	Minor articular damage	-	-	Dermal vasculitis with perivascular neutrophils	Nucleic acid amplification tests (NAATs)	Dermatitis, Tenosynovitis
		Nongonococcal bacterial infections	+	+	-	-	-	+	Local erythema	Leukocytosis	↑	Purulent with cell count > 50,000 WBC/µL (with PMNs > 90%)	Blood and synovial fluid culture	Joint effusion, Cartilage destruction, Joint space narrowing	Sternoclavicular or sacroiliac joint infections	Periarticular osteomyelitis in MRI	-	Synovial fluid culture	Limping, Malaise
		Mycobacterial infection	-	+	+	+	+/-	-	Local erythema	Leukocytosis, Normocytic normochromic anemia	↑	Moderately elevated WBC counts (neutrophilic predominance), low glucose, and increased protein	PPD	Tissue swelling, Bone destruction with normal joint space, Osteopenia	Vertebral anterior portion collapse	Complicated effusion with partial joint destruction and erosion in MRI	Granulomatous inflammation	Synovial fluid culture	Limping, Malaise, Chronic cough
		Fungal infection	-	+/-	-	-	-	+/-	Local eczema, Local erythema	Eosinophilia, Leukocytosis	↑	WBC counts range from 9,000-43,000/µL (PMNs predominance)	Direct microscopy	Joint effusion, Dislocation of the joint, Metaphyseal irregularities and punched out lesions	Articular erosion	-	Villonodular synovitis, Typical pannus, Non-caseating granulomas, Spherules containing coccidioidal endospores	Synovial histopathology	Malaise, Tenderness
		Lyme disease	+	+	+/-	+/-	-	-	Erythema migrans	Leukopenia, Thrombocytopenia	-	Cell counts 500-98,000/µL	Microscopic hematuria, Proteinuria, ↑ALT or AST	Knee joint effusion. Intra-articular edema	-	Unspecific effusion, Synovial thickening or enhancement in MRI	Fibrosis of the deeper dermis and hyalinization of collagen bundles	Serologic tests	Erythema migrans
	Crystal-induced arthritis	Gout	+	+/-	-	-	-	+	Local swelling and erythema	Leukocytosis	↑	Needle shaped urate crystals, WBC count > 2000/µL	Urinary uric acid (>1100 mg in 24h)	Punched-out erosions or lyticareas with overhanging edges	Complementary for recognizing erosions	Tophi or edema in MRI	Large pale pink acellular areas (urate crystals), surrounded by histiocytes and multinucleated giant cells	Synovial fluid microscopy	Conjunctival nodules
		Pseudo-gout	+	-	-	-	-	+/-	Local swelling and erythema	Leukocytosis	↑	Rod shaped CPPD crystals, WBC count > 2000/µL	Hypercalcemia, Hypercalciuria	Radiodense lines paralleling the articular surface and calcification (chondrocalcinosis)	Calcific mass with a lobulated configuration in the ligamentum flavum or the joint capsule	Synovitis and calcific deposits in ultrasonography	Synovial calcium pyrophosphate crystals	Synovial fluid microscopy	Tenderness
	Systemic disorders	Reactive arthritis	+/-	+/-	-	-	-	-	Genital ulceration	Normocytic normochromic anemia	↑	High WBC count (10,000-40,000/µL)	HLA-B27 test	Periosteal reaction and proliferation of tendon insertion site	Sacroiliitis	Enthesitis in ultrasonography	Keratoderma blennorrhagicum,Balanitis circinata	Spondyloarthritis and unequivocal demonstration of preceding infection	Conjunctivitis, Uveitis
		Psoriatic arthritis	+	-	-	-	-	+	Scaly erythematous plaques, Guttate lesions, Lakes of pus, Erythroderma	Normal	↑	High WBC count (5000-15,000/µL) with >50% of PMN leukocytes	↑RF, ANA, IgA	Joint-space narrowing, Fluffy periostitis	Pencil-in-cup deformity, Early signs of synovitis	Sacroiliitic synovitis, Enthesitis in MRI	Lack of intrasynovial Igand RF, Greater propensity for fibrous ankylosis, osseous resorption, and heterotopic bone formation	Clinical findings	Onycholysis, Splinter hemorrhages
		Inflammatory bowel disease-associated arthritis	+	+	-	-	+	+/-	Pyoderma gangrenosum(ulcerative colitis),Erythema nodosum(Crohn disease)	Iron deficiency anemia, Leukocytosis, Thrombocytosis	↑	Mild to moderate inflammatory fluid, PMNpredominance	↑RF, Antiendomysial Ab,Antitransglutaminase Ab	Bilateral sacroiliitis, Syndesmophytes and apophyseal joint involvement in spine	-	Early detection of spinal and sacroiliac lesions in MRI	-	Clinical findings and history	Acute anterior uveitis
		Sarcoid periarthritis	+	-	-	-	-	-	Mild papules and nodules	Mild anemia	↑	Cell count < 25% PMNs (non-inflammatory)	IL-2 and IFN-γ, ↑ACE, ↑1, 25-dihydroxyvitamin D	Bilateral hilar adenopathy	Active alveolitis or fibrosis	Hepatosplenomegaly in ultrasonography	Noncaseating granulomas (NCGs)	Histological confirmation	Heart block, Ocular lesion
		Rheumatoid arthritis	+	-	+	+	+	-	Rheumatoid nodules	Anemia, Thrombocytosis	↑	WBC count >2000/µL (generally 5000-50,000/µL), with neutrophilpredominance (60-80%)	Anti-CCP Ab, Hyperuricemia	Joint-space narrowing	Microfractures	Synovitis in MRI	Influx of inflammatory cells into the synovial membrane, withangiogenesis	Clinical findings coupled anti-CCP antibody	Rheumatoid nodules
		Myelodysplastic and leukemic disorders	+	+	+	+/-	-	-	Petechia and purpura	Anemia, Leukocytosis, Thrombocytopenia	↑	WBC count >2000/µL (inflammatory), with neutrophilpredominance	LDH, Uric acid	Articular surface erosion, Synovial effusion	Thickened synovium	Synovitis in MRI	Inflammatory cells infiltration in synovial tissue	Bone marrow biopsy	Fatigue, Nausea, Recurrent infections

Differential Diagnosis of Diseases That Cause Polyarthritis

Differentiating the diseases that can cause polyarthritis:

To review the differential diagnosis of polyarthritis with joint swelling, click here.

To review the differential diagnosis of polyarthritis with fever, click here.

To review the differential diagnosis of polyarthritis with weight loss, click here.

To review the differential diagnosis of polyarthritis with claudication, click here.

To review the differential diagnosis of polyarthritis with morning stiffness, click here.

To review the differential diagnosis of polyarthritis with local erythema, click here.

To review the differential diagnosis of polyarthritis with joint swelling and fever, click here.

To review the differential diagnosis of polyarthritis with joint swelling, fever, and weight loss, click here.

Diseases			Clinical manifestations							Para-clinical findings								Gold standard	Additional findings
			Symptoms				Physical examination
										Lab Findings				Imaging			Histopathology
			Joint Swelling	Fever	Weight loss	Claudication	Morning stiffness	Local erythema	Skin manifestation	CBC	ESR	Synovial fluid	Other	X-ray	CT scan	Other
Polyarthritis	Infectious arthritis	Lyme disease	+	+	+/-	+/-	-	-	Erythema migrans	Leukopenia, Thrombocytopenia	-	Cell counts 500-98,000/µL	Microscopic hematuria, Proteinuria, ↑ALT or AST	-	-	-	Fibrosis of the deeper dermis and hyalinization of collagen bundles	Serologic tests	Erythema migrans
		Bacterial endocarditis	+	+	+	-	-	+/-	Janeway lesions, Osler nodes, Roth spots	Normochromic-normocytic anemia	↑	↑WBC, S. aureus in culture	Hyperglobulinemia, Cryoglobulinemia	Joint erosion and effusion	-	-	Vegetation or intracardiac abscess demonstrating active endocarditis	Echocardiography (TTE)	Vertebral osteomyelitis
	Postinfectious (reactive) arthritis	Rheumatic fever	+	+	-	-	-	+/-	Erythema marginatum rheumaticum	Leukocytosis	↑	Sterile inflammatory reaction with cells<20,000/μL	Streptococcal antibody titer	Cardiomegaly	Valvular or pericardial calcification	Echocardiographic changes in heart valves	Edema, Fibrinoid necrosis, Mononuclear cell infiltrate	Echocardiography	Chorea, Carditis
		Reactive arthritis	+/-	+/-	-	-	-	-	Genital ulceration	Normocytic normochromic anemia	↑	High WBC count (10,000-40,000/µL)	HLA-B27 test	Periosteal reaction and proliferation of tendon insertion site	Sacroiliitis	Enthesitis in ultrasonography	Keratoderma blennorrhagicum, Balanitis circinata	Spondyloarthritis and unequivocal demonstration of preceding infection	Conjunctivitis, Uveitis
		Enteric infection	-	+	-	-	-	-	Keratoderma and psoriaform lesions, Erythema nodosum	Neutrophilia	↑	PCR of causative organism	Stool exam and culture	-	-	-	Neutrophilic infiltration in synovial tissues	PCR of causative organism in synovial fluid	Diarrhea, Enthesopathy
	Other seronegative spondyloarthritides	Ankylosing spondylitis	+	-	+/-	+/-	+	-	Dactylitis (sausage digit)	Normocytic normochromic anemia	↑	High WBC count (lymphocyte predominance)	↑Alkaline phosphatase (ALP)	Bony erosions and sclerosis of the joints	Early sacroiliitis, erosions, and enthesitis	Possible cauda equina syndrome secondary to spinal stenosis in MRI	Chronic inflammation with CD4+ and CD8+ T lymphocytes and macrophages	Plain x-rays	Peripheral enthesitis, Uveitis
		Psoriatic arthritis	+	-	-	-	-	+	Scaly erythematous plaques, Guttate lesions, Lakes of pus, Erythroderma	Normal	↑	High WBC count (5000-15,000/µL) with >50% of PMN leukocytes	↑RF, ANA, IgA	Joint-space narrowing, Fluffy periostitis	Pencil-in-cup deformity, Early signs of synovitis	Sacroiliitic synovitis, Enthesitis in MRI	Lack of intrasynovial Ig and RF, Greater propensity for fibrous ankylosis, osseous resorption, and heterotopic bone formation	Clinical findings	Onycholysis, Splinter hemorrhages
		Inflammatory bowel disease	+	+	-	-	+	+/-	Pyoderma gangrenosum (ulcerative colitis), Erythema nodosum (Crohn disease)	Iron deficiency anemia, Leukocytosis, Thrombocytosis	↑	Mild to moderate inflammatory fluid, PMN predominance	↑RF, Antiendomysial Ab, Antitransglutaminase Ab	Bilateral sacroiliitis, Syndesmophytes and apophyseal joint involvement in spine	-	Early detection of spinal and sacroiliac lesions in MRI	-	Clinical findings and history	Acute anterior uveitis
	Rheumatoid arthritis		+	-	+	+	+	-	Rheumatoid nodules	Anemia, Thrombocytosis	↑	WBC count >2000/µL (generally 5000-50,000/µL), with neutrophil predominance (60-80%)	Anti-CCP Ab, Hyperuricemia	Joint-space narrowing	Microfractures	Synovitis in MRI	Influx of inflammatory cells into the synovial membrane, with angiogenesis	Clinical findings coupled anti-CCP antibody	Rheumatoid nodules
	Crystal-induced arthritis		+	+/-	-	-	-	+	Joint erythema	Leukocytosis	↑	Needle shaped urate crystals, WBC count > 2000/µL	Urinary uric acid (>1100 mg in 24h)	Punched-out erosions or lytic areas with overhanging edges	Complementary for recognizing erosions	Tophi or edema in MRI	Large pale pink acellular areas (urate crystals), surrounded by histiocytes and multinucleated giant cells	Synovial fluid assay	Conjunctival nodules
	Systemic rheumatic illnesses	Systemic lupus erythematosus	+	-	+/-	-	-	+	Malar rash, Photosensitivity, Discoid lupus	Leukopenia, Lymphopenia, Anemia, Thrombocytopenia	↑	Cell count from < 25% PMNs (non-inflammatory effusions) to > 50% PMNs (inflammatory effusions)	Creatine kinase, LFT, ANA, Anti-dsDNA, Anti-Sm, Lupus anticoagulant	Periarticular osteopenia and soft-tissue swelling without erosions	Interstitial lung disease, Pneumonitis, Pulmonary emboli, Alveolar hemorrhage	Pericardial effusion, Pulmonary hypertension, Verrucous Libman-Sacks endocarditis in echocardiography	Inflammatory infiltrates at the dermoepidermal junction and vacuolar change in the basal columnar cells	Anti-dsDNA	Rheumatoid arthritis, Serositis, Oral ulcers
		Systemic vasculitis	-	-	+/-	+	-	-	Petechia, Purpura	Anemia, Thrombocytosis	↑	-	P-ANCA, C-ANCA, ANA	Soft tissue swelling with mild erosions	Focal regions of infarction or hemorrhage	Multiple microaneurysms,Hemorrhage due to focal rupture, Occlusion in angiography	Acute destruction of the media by neutrophils, with loss of elastic fibers	Angiography	Peripheral neuropathy, Livedo reticularis
		Systemic sclerosis	-	-	+/-	-	-	-	3 phases of (1) Edematous, (2) Indurative, and (3) Atrophic	Thrombocytopenia	↑	Cell count < 25% PMNs (non-inflammatory)	Hypergammaglobulinemia, Creatine phosphokinase	Juxta-articular osteoporosis, Joint space narrowing, Frank erosions	Synovial inflammation	Synovial vascularity in doppler ultrasonography	Epidermal skin appendages atrophy, Broad and hyalinized collagen fibers in the reticular dermis	Histopathology	Raynaud phenomenon, Tendon friction rubs
		Polymyositis/dermatomyositis	-	-	+/-	-	-	+	Heliotrope rash, Gottron papules, Poikiloderma	Normocytic normochromic anemia	↑	Predominantly mononuclear cells and large macrophage-like cells	Anti–Mi-2 antibodies, Anti–Jo-1 antibodies, Creatine kinase, ANA	Marginal erosions and periarticular calcification	-	-	Vacuolar changes of the columnar epithelium and lymphocytic infiltrates	Muscle biopsy	Dysphagia
		Still's disease	-	-	+/-	-	+/-	+	Mild papules and nodules	Anemia, Thrombocytosis	↑	High WBC count (5000-15,000/µL) with >50% of PMN leukocytes	ANA, RF	Soft tissue swelling, Osteopenia, Joint-space narrowing	Synovial inflammation	Inflamed synovium in ultrasonography	Inflammatory infiltration in synovium	Clinical findings and synovial fluid analysis	Ocular involvement
		Behçet's syndrome	+	-	-	-	-	-	Erythema nodosum	Normocytic normochromic anemia	↑	Cell count < 25% PMNs (non-inflammatory)	Serum complement levels, Human leukocyte antigen (HLA)-B51	Soft tissue swelling	Non-erosive synovitis	-	Dermal vessels infiltration with lymphocytes and plasma cells, Immune deposits of immunoglobulin M (IgM) and C3	Clinical findings	Oral ulcer, Mucosal erosion
		Relapsing polychondritis	+	-	-	-	-	-	-	Leukocytosis, Anemia	-	Cell count < 25% PMNs (non-inflammatory)	Cryoglobulins, ANA, C-ANCA	Tracheal stenosis in CXR	Calcification of cartilaginous structures	Aortic root dilatation and degree of aortic regurgitation in echocardiography	Chondrolysis, Chondritis, Perichondritis	Clinical findings coupled with imaging	Ear pain and redness, Polyarthritis
	Other systemic illnesses	Sarcoidosis	+	-	-	-	-	-	Mild papules and nodules	Mild anemia	↑	Cell count < 25% PMNs (non-inflammatory)	IL-2 and IFN-γ, ↑ACE, ↑1, 25-dihydroxyvitamin D	Bilateral hilar adenopathy	Active alveolitis or fibrosis	Hepatosplenomegaly in ultrasonography	Noncaseating granulomas (NCGs)	Histological confirmation	Heart block, Ocular lesion
		Palindromic rheumatism	+	-	-	+/-	+	-	Rheumatoid nodules	Anemia	↑	High WBC count (5000-15,000/µL) with >50% of PMN leukocytes	RF, Anti-CCP antibody, ↑Cr or BUN, ↑ALT or AST, ANA	Effusions in joints	Microfractures	Basilar invagination with cranial migration of an eroded odontoid peg in MRI	Influx of inflammatory cells into the synovial membrane, withangiogenesis, proliferation of chronic inflammatory cells	Clinical findings coupled anti-CCP antibody	Rheumatoid nodules
		Familial Mediterranean fever	-	+	-	-	-	-	A well-demarcated, erythematous, warm rash, particularly below the knee	Leukocytosis	↑	Cell counts as high as 100,000/µL	CRP, Amyloid A protein, Fibrinogen	Synovial effusions	Pleural effusions	Air-fluid levels in MRI	Massive amyloid infiltration of the blood vessels and endothelial side of the glomerular basement membrane	Clinical findings	Abdominal pain, Severe myalgia, Scrotal attacks
		Hyperlipoproteinemias	-	-	-	-	-	-	Xanthelasma	Leukocytosis	↑	Xanthochromic fluid with mononuclear cells predominance	CRP, Hyperlipidemia	Joint space narrowing	Achilles tendon enthesitis	Retrocalcaneal bursitis and ill-defined edema in posterosuperior corner of the calcaneus	Inflammatory infiltration	Laboratory findings	Atherosclerosis
Polyarticular pain	Viral arthritis	Hepatitis B and C	-	+	+	-	-	-	Urticarial and maculopapular eruptions	Leukocytosis	↑	Cell counts < 100,000/µL	LFT, HBsAg	Joint space narrowing	-	-	Deposition of immune complexes, Cryoprecipitates containing HBsAg and complements	HBsAg	Liver failure, Icterus
		Rubella	-	+	+/-	-	-	-	Acute maculopapular rash	Leukocytosis	↑	Rubella virus antigen	LFT, CRP	Joint space narrowing	-	-	proliferation of the synovial lining cells, without inflammatory cells	Serological evidence	Headache, Malaise
		Parvovirus	+	+	+/-	-	-	-	Fifth disease/ Erythema infectiosum	Aplastic crisis	↑	Normal	ANA, RF, CRP	Joint swelling	-	-	Immune complex deposition	Parvovirus IgM antibody	Transient aplastic crisis, Fetal infection
	Fibromyalgia		-	-	-	+/-	+/-	-	Maculopapular rash	Normal	-	Normal	-	-	-	-	Mild inflammation	Clinical findings	Muscle pain
	Soft tissue abnormalities		+	-	-	-	-	+/-	Maculopapular rash	Normal	-	Cell count < 25% PMNs (non-inflammatory)	CRP, Ca	Joint swelling	Synovial edema and thickness	Mild joint effusion in ultrasonography	Mild inflammation	Clinical findings	Mucositis, Enthesitis
	Hypothyroidism		-	-	-	-	-	-	Dry and coarse skin	Anemia	-	Clear yellow fluid with normal cell counts	TSH, T4, T3	Peri-articular demineralization	Destructive changes in the cartilage and bone	High-signal fluid in the joint space in MRI	Physeal growth plate with little evidence of cartilage cellular proliferation	TSH, T4, T3	Decreased DTR, Fatigue
	Neuropathic pain		-	-	-	-	-	-	Livedo reticularis	Normal	-	Normal	Hyperglycemia, Hypokalemia, Hypocalcemia	-	-	-	-	Neurologic examination	Paresthesia, Dysesthesia
	Metabolic bone disease		-	-	-	-	-	-	Hyperpigmentation	Mild anemia	↑	Cell count < 25% PMNs (non-inflammatory)	Vitamin D, PTH	Peri-articular demineralization	Microfractures	Subperiosteal reaction	Decrease mineralization of bone matrix	Laboratory findings	Bone pain, Constipation
	Depression		-	-	+	-	-	-	-	Normal	-	Normal	Normal	-	-	-	-	Psychological interview	Slow psychomotor, Muscle pain

References

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