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Differentrial Diagnosis

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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]


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.


Primary Forms of Arthritis:

Differential Diagnosis

Differential Diagnosis of Monoarthritis

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[1] + - - - - - 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[2] + - - - - + Wound or laceration - - Hemarthrosis - Severe joint effusion, fracture Fracture, synovial tear - - X-ray Deformity, severe pain
Neoplasms[3] + - + +/- - - 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[4] + + - - - + 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) Dermatitistenosynovitis
Nongonococcal bacterial infections[5] + + - - - + 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[6] - + + + +/- - 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[7] - +/- - - - +/- Local eczema, local erythema Eosinophilia, leukocytosis WBC = 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[8] + + +/- +/- - - 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[9] + +/- - - - + Local swelling and 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 microscopy Conjunctival nodules
Pseudo-gout[10] + - - - - +/- 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[11] +/- +/- - - - - 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 Conjunctivitisuveitis
Psoriatic arthritis[12] + - - - - + Scaly erythematous plaques, guttate lesions, lack of pus, erythroderma Normal High WBC count (5000-15,000/µL) with >50% of PMN leukocytes RFANAIgA Joint-space narrowing, fluffy periostitis Pencil-in-cup deformity, early signs of synovitis Sacroiliitic synovitisenthesitis in MRI Lack of intrasynovial Ig A and RF, greater propensity for fibrous ankylosisosseous resorption, and heterotopic bone formation Clinical findings Onycholysissplinter hemorrhages
Inflammatory bowel disease-associated arthritis[13] + + - - + +/- Pyoderma gangrenosum (ulcerative colitis), erythema nodosum (Crohn disease) Iron deficiency anemialeukocytosisthrombocytosis Mild to moderate inflammatory fluidPMN predominance RFantiendomysial 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[14] + - - - - - 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 Non-caseating granulomas Histological confirmation Heart blockocular lesion
Rheumatoid arthritis[15] + - + + + - Rheumatoid nodules Anemiathrombocytosis WBC count >2000/µL (generally 5000-50,000/µL), with neutrophil predominance (60-80%) Anti-CCP Abhyperuricemia Joint space narrowing Microfractures Synovitis in MRI Influx of inflammatory cells into the synovial membrane, with angiogenesis Clinical findings and positive anti-CCP antibody Rheumatoid nodules
Myelodysplastic and leukemic disorders[16] + + + +/- - - Petechia and purpura Anemia, leukocytosis, thrombocytopenia WBC count >2000/µL (inflammatory), with neutrophil predominance 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[17] + + +/- +/- - - 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[18] + + + - - +/- 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[19] + + - - - +/- 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[11] +/- +/- - - - - 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[20] - + - - - - 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[21] + - +/- +/- + - 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[12] + - - - - + Scaly erythematous plaques,

Guttate lesions, Lakes of pus,


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[13] + + - - + +/- 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[15] + - + + + - 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[9] + +/- - - - + 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[22] + - +/- - - + 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[23] - - +/- + - - 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 ruptureOcclusion in angiography Acute destruction of the media by neutrophils, with loss of elastic fibers Angiography Peripheral neuropathyLivedo reticularis
Systemic sclerosis[24] - - +/- - - - 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[25] - - +/- - - + 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[26] - - +/- - +/- + Mild papules and nodules Anemia, Thrombocytosis High WBC count (5000-15,000/µL) with >50% of PMN leukocytes ANA, RF Soft tissue swelling,


Joint-space narrowing

Synovial inflammation Inflamed synovium in ultrasonography Inflammatory infiltration in synovium Clinical findings and synovial fluid analysis Ocular involvement
Behçet's syndrome[27] + - - - - - 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[28] + - - - - - - LeukocytosisAnemia - Cell count < 25% PMNs (non-inflammatory) CryoglobulinsANAC-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[14] + - - - - - 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 blockOcular lesion
Palindromic rheumatism[29] + - - +/- + - Rheumatoid nodules Anemia High WBC count (5000-15,000/µL) with >50% of PMN leukocytes RFAnti-CCP antibody, ↑Cr or BUN,


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[30] - + - - - - 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[31] - - - - - - 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[32] - + + - - - 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[33] - + +/- - - - Acute maculopapular rash Leukocytosis Rubella virus antigen LFT, CRP Joint space narrowing - - proliferation of the synovial lining cells, without inflammatory


Serological evidence Headache, Malaise
Parvovirus[34] + + +/- - - - Fifth disease/ Erythema infectiosum Aplastic crisis Normal ANA, RF, CRP Joint swelling - - Immune complex deposition Parvovirus IgM antibody Transient aplastic crisis, Fetal infection
Fibromyalgia[35] - - - +/- +/- - 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[36] - - - - - - 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[37] - - - - - - Livedo reticularis Normal - Normal Hyperglycemia, Hypokalemia, Hypocalcemia - - - - Neurologic examination Paresthesia, Dysesthesia
Metabolic bone disease[38] - - - - - - 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[39] - - + - - - - Normal - Normal Normal - - - - Psychological interview Slow psychomotor, Muscle pain


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