Psoriatic arthritis

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

Psoriatic arthritis is a systemic, immune- mediated inflammatory arthritis, associated with psoriasis. The etiology is not clearly understood. It may be caused by complex interaction between genetic, immunologic and environmental mechanisms which act as triggers for the disease development. Both psoriatic arthritis and psoriasis have been shown to have strong familial predisposition. Psoriatic arthritis present with pain and stiffness in the affected joints. According to Moll and Wright criteria, joint involvement pattern in psoriatic arthritis include distal arthritis usually involving distal interphalangeal joints, asymmetric oligoarthritis, symmetric polyarthritis, arthritis mutilans, spondylitis, and sacroiliitis. Other symptoms include enthesitis (pain and tenderness at the insertion of tendons and ligaments to the bone), dactylitis ( sausage like finger or toe swelling), psoriatic skin plaques, nail changes (pitting, hyperkeratosis, and nail destruction). The pathophysiology of psoriatic arthritis consists of interactions between cytokines, dendritic cells, and T lymphocytes. Psoriatic arthritis must be differntiated from other inflammatory arthritides including rheumatoid arthritis, ankylosing spondylitis, reactive arthritis, gout, pseudogout, osteoarthritis, arthritis associated with inflammatory bowel disease. The prevalence of psoriatic arthritis in general population ranges from 60 – 250 cases per 100,000 individuals and the prevalence of psoriatic arthritis among psoriasis patients is 11,000 per 100,000 individuals. The mainstay of therapy for psoriatic arthritis NSAIDs, conventional DMARDs (eg, methotrexate, sulfasalazine, cyclosporine) and biologic DMARDs (eg, TNF inhibitors), anti IL therapy (eg, secukinumab, ustekinumab). Other treatment options include physiotherapy, patient education about disease and joint preservation and surgery. Psoriatic arthritis is associated with a number of comorbid conditions due to circulating immunoglobulins, antibodies including metabolic syndrome, increased insulin resistance, atherosclerosis, stroke, hypertension, uveitis, osteoporosis and depression. Patients are monitored regularly for disease activity, drug efficacy, adverse effects and associated comorbid conditions.

The association between psoriasis and psoriatic arthritis was first described by Dr. Alibert in 1822. It was considered as a variant of rheumatoid arthritis before the discovery of rheumatoid factor. In 1948, Dr. Wright described it as a different entity from rheumatoid arthritis.

According to the severity of the disease, psoriatic arthritis may be classified into mild, moderate, and severe arthritis.

The pathogenesis of psoriatic arthritis involves prominent T-lymphocytic infiltrate, particularly CD4 cells in the skin and joints. The elevated levels of TNF leads to a high number of osteoclast precursor cells circulating in the blood which ultimately leads to joint destruction. High levels of tumor necrosis factor alpha (TNF), IL-8, IL-6, IL-1, IL-10, and matrix metalloproteinases are present in the synovial fluid of patients with early psoriatic arthritis.

There are no established causes of psoriatic arthritis. The occurrence of psoriatic arthritis is secondary to a combination of genes, immune mechanisms and exposure to specific external factors or triggers, which increase an individual’s risk of developing psoriatic arthritis. These risk factors lead to complex interactions between the genetics, immune system, and the environment.

Psoriatic arthritis must be differentiated from other arthritides including rheumatoid arthritis, reactive arthritis, ankylosing spondylitis, arthritis associated with inflammatory bowel disease, osteoarthritis, gout, and Pseudogout.

The prevalence of psoriatic arthritis in general population ranges from 60 – 250 cases per 100,000 individuals in United states. Incidence of psoriatic arthritis is approximately 6 per 100,000 individuals. The prevalence among psoriasis patients is 11,000 per 100,000 individuals. Psoriatic arthritis may commonly occur in age groups 40-50 yrs with mean age at diagnosis is 40.7 years.

Genetic factors (eg, increased expression of HLA-B, HLA-C, single nucleotide polymorphisms involving various genes), immune mediators (eg, dendritic cells, T lymphocytes), and environmental agents(eg, infections, physical trauma) may act as a risk factors for the development of psoriatic arthritis.

Various screening tools have been proposed to screen psoriatic arthritis such as Psoriatic Arthritis Screening and Evaluation tool (PASE), Psoriasis Epidemiology Screening Tool (PES), and Toronto Psoriatic Arthritis Screen (ToPAS).

If left untreated psoriatic arthritis may lead to severe joint destruction and deformity resulting in loss of physical function and reduced quality of life. Psoriatic arthritis is associated with various comorbid conditions including cardiovascular disease ( increased risk of atherosclerosis, myocardial infarction, heart failure), metabolic syndrome, liver disease, diabetes mellitus, depressionand osteoporosis. Prognosis is good with early diagnosis and treatment. Overall survival rate also depends on management of comorbid conditions along with arthritis treatment.

The diagnosis of psoriatic arthritis is easily confirmed when the cutaneous manifestations of psoriasis coexist with arthritis. There is no definitive diagnostic test for psoriatic arthritis. It must be differentiated from other arthritides based on the joint involvement patterns, clinical features, imaging and laboratory studies. The CASPAR criteria (ClASsification criteria for Psoriatic ARthritis) has been propsed to diagnose psoriatic arthritis using point scoring system. The specificity of this criteria is approximately 98.7% and sensitivity is approximately 91.4%.

Psoriatic arthritis is a chronic inflammatory arthritis which is progressive. Patients with psoriatic arthritis usually have a positive history of joint pain and stiffness involving both peripheral and axial joints. Common symptoms include joint pain, swelling, morning stiffness, decreased range of motion, fatigue, dactylitis due to inflammation and swelling of the entire digit, enthesopathy,skin lesions, and dystrophic nails.  

Common physical examination findings of patients with psoriatic arthritis include peripheral and axial joint inflammation and tenderness, enthesis, dactylitis, scaly, erythematous papules and plaques on the skin and dystrophic nail changes.

There are no specific diagnostic laboratory findings associated with psoriatic arthritis. There are certain blood tests that can check for markers of inflammation. Patients with psoriatic arthritis are usually tested for the gene associations includes HLA-B27, HLA-C*06, rheumatoid factor, and autoantibodies. Other laboratory findings consistent with psoriatic arthritis include CBC, ESRand CRP levels, and synovial fluid analysis.

An x-ray may be helpful in the diagnosis of psoriatic arthritis. Findings on an x-ray suggestive psoriatic arthritis include bone erosion, characteristic “pencil-in-cup” deformities and proliferative changes. Psoriatic arthritis may also lead to periostitis, dactylitis, or arthritis mutilans.

There are no ECG findings associated with psoriatic arthritis. ECG may be helpful in the evaluation of cardiovascular disease associated with psoriatic arthritis.

Ultrasonography may be helpful in the diagnosis of psoriatic arthritis. Findings on an ultrasonography suggestive of psoriatic arthritis include synovitis, thickening of the joint capsule, joint effusions, and widening of joint space. 

CT scan of patients with psoriatic arthritis involving spinal column and sacroiliac joints may show erosions, synovitis, sacroiliitis and bone ankylosis.

MRI of hands of patients with psoriatic arthritis may show periostitis, erosions, enthesitis, synovitis, ankylosis, and edema of bone marrow.

There are no other imaging findings associated with psoriatic arthritis.

Bone mineral density testing may show decreased bone density in psoriatic arthritis.

Pharmacologic therapy for psoriatic arthritis includes nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs, tumor necrosis factor (TNF) inhibitors, and interleukin 17 (IL-17) inhibitors, interleukin IL-12/23 inhibitors, and topical glucocorticoid injections. Psoriatic arthritis is a chronic inflammatory arthritis which is manifested as peripheral and axial arthritis, dactylitis, enthesitis and skin and nail involvement. Non – pharmacologic therapy including patient education, weight reduction, and physical therapy may also play an important role in disease management. While treating the patients the primary goal is to maximize the long-term health-related quality of life.

Surgery may not be the first-line treatment for patients with psoriatic arthritis. Surgical options, such as the knee surgery, hip replacements, and surgery involving hand joints may be recommended in patients with severe joint damage and deformity.

Effective measures for the primary prevention of include patient education, exercise, physical, and behavioral therapies.

Essential measures for the secondary prevention of psoriatic arthritis include calcium and vitamin D supplementation to prevent drug associated osteoporosis. To decrease the risk of cardiovascular complications and to prevent recurrent episodes effective measures include exercise, smoking cessation, and dietary control.

Template:WH Template:WS

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

The association between psoriasis and psoriatic arthritis was first described by Dr. Alibert in 1822. It was considered as a variant of rheumatoid arthritis before the discovery of rheumatoid factor. In 1948, Dr. Wright described it as a different entity from rheumatoid arthritis.

• In 1822, the association between psoriasis and psoriatic arthritis was noticed by Dr. Alibert.
• In 1948 after the discovery of rheumatoid factor, psoriatic arthritis was considered as a separate entity from rheumatoid arthritis by UK physician Wright.^[1]

Template:WH Template:WS

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

According to the severity of the disease, psoriatic arthritis may be classified into mild, moderate, and severe form of arthritis.

• Based on the severity, psoriatic arthritis may be classified into following categories:^[1]
  • Mild
  • Moderate
  • Severe

Organ system involvement	Mild psoriatic arthritis	Moderate psoriatic arthritis	Severe psoriatic arthritis
Peripheral arthritis	<5 joints involvement No damage can be seen on x-ray No loss of physical function Minimal impact on patient’s quality of life	⩾5 joints involvement Damage can be visible on x-ray Non-responsive to NSAIDs Moderate impact on patient’s quality of life	⩾5 joints involvement Severe damage may be seen on x-ray Nonresponsive to NSAIDs, standard DMARDs Severe impact on patient’s quality of life
Axial joint involvement	Mild pain present No loss of physical function	Loss of physical function Bath Ankylosing Spondylitis Disability Activity Index (BASDAI) >4	Failure of response
Skin	Body Surface Area ( BSA) <5 Psoriasis area and severity index (PASI) <5	Resistant to topical therapy Dermatology Life Quality Index (DLQI)<10 PASI<10	BSA>10, DLQI>10PASI>10
Dactylitis	+/- Pain Normal activity/ function	Presence of erosive disease or loss of physical function	Failure of response to NSAIDs and conventional DMARDs
Enthesitis	Number of sites involved:1–2 No loss of physical function	Number of sites involved >2 or Loss of function	Loss of function >2 sites involvement and failure of response

Template:WH Template:WS

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

The pathogenesis of psoriatic arthritis involves prominent T-lymphocytic infiltrate, particularly CD4 cells in the skin and joints. High levels of tumor necrosis factor alpha (TNF), IL-8, IL-6, IL-1, IL-10, and matrix metalloproteinases are present in the synovial fluid of patients with early psoriatic arthritis.The elevated levels of TNF and various interleukins lead to a high number of osteoclast precursor cells circulating in the blood which ultimately leads to joint destruction.

The pathogenesis of psoriatic arthritis (PsA) involves the following events:^[1]

• In joints there is a prominent lymphocytic infiltrate, limited to the dermal papillae in skin and to the underlying stroma.
• T lymphocytes, particularly CD4 cells, are the most common inflammatory cells in the skin and joints, with a CD4/CD8 ratio of 2:1.
• High levels of tumor necrosis factor alpha (TNF), IL-8, IL-6, IL-1, IL-10, and matrix metalloproteinases are present in the joint fluid of patients with early PsA.
• Collagenase mediated degradation of cartilage collagen begins in early phases of the disease and may be the result of the proteases produced as a result of above mentioned cytokines.

• The elevated levels of TNF leads to a high number of osteoclast precursor cells circulating in the blood.
• Osteoclast precursors migrate to the joint where they encounter increased expression of receptor activator of nuclear factor kappa B ligand ( NF-κB), which favors the differentiation and activation of osteoclasts.
• Osteoclasts eventually lead to the joint destruction seen in psoriatic arthritis.

Template:WH Template:WS

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

The exact etiology of psoriatic arthritis is not known. Genetics, environmental factors, and immune mechanisms act as triggers for the disease development and progression.

• There are no established causes of psoriatic arthritis.
• The occurrence of psoriatic arthritis is secondary to a combination of genes, immune mechanisms and exposure to specific external factors or triggers, which increase an individual’s risk of developing psoriatic arthritis.
• These risk factors lead to complex interactions between the genetics, immune system, and the environment.^[1]

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chandrakala Yannam, MD [2], Mehrian Jafarizade, M.D [3], Eiman Ghaffarpasand, M.D. [4]

Psoriatic arthritis must be differentiated from other arthritides including rheumatoid arthritis, reactive arthritis, ankylosing spondylitis, arthritis associated with inflammatory bowel disease, osteoarthritis, gout, and Pseudogout.

• Psoriatic arthritis must be differentiated from other arthritides including^[1][2][3][4]
  • Rheumatoid arthritis
  • Reactive arthritis
  • Ankylosing spondylitis
  • Arthritis associated with inflammatory bowel disease
  • Osteoarthritis
  • Gout
  • Pseudogout

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[5]	+	+	+/-	+/-	–	–	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[6]	+	+	+	–	–	+/-	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[7]	+	+	–	–	–	+/-	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[8]	+/-	+/-	–	–	–	–	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[9]	–	+	–	–	–	–	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[10]	+	–	+/-	+/-	+	–	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[11]	+	–	–	–	–	+	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[12]	+	+	–	–	+	+/-	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[13]		+	–	+	+	+	–	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[14]		+	+/-	–	–	–	+	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[15]	+	–	+/-	–	–	+	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[16]	–	–	+/-	+	–	–	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[17]	–	–	+/-	–	–	–	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[18]	–	–	+/-	–	–	+	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[19]	–	–	+/-	–	+/-	+	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[20]	+	–	–	–	–	–	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[21]	+	–	–	–	–	–	–	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[22]	+	–	–	–	–	–	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[23]	+	–	–	+/-	+	–	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[24]	–	+	–	–	–	–	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[25]	–	–	–	–	–	–	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[26]	–	+	+	–	–	–	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[27]	–	+	+/-	–	–	–	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[28]	+	+	+/-	–	–	–	Fifth disease/ Erythema infectiosum	Aplastic crisis	↑	Normal	ANA, RF, CRP	Joint swelling	–	–	Immune complex deposition	Parvovirus IgM antibody	Transient aplastic crisis, Fetal infection
	Fibromyalgia[29]		–	–	–	+/-	+/-	–	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[30]		–	–	–	–	–	–	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[31]		–	–	–	–	–	–	Livedo reticularis	Normal	–	Normal	Hyperglycemia, Hypokalemia, Hypocalcemia	–	–	–	–	Neurologic examination	Paresthesia, Dysesthesia
	Metabolic bone disease[32]		–	–	–	–	–	–	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[33]		–	–	+	–	–	–	–	Normal	–	Normal	Normal	–	–	–	–	Psychological interview	Slow psychomotor, Muscle pain

Template:WH Template:WS

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

The prevalence of psoriatic arthritis in general population ranges from 60 – 250 cases per 100,000 individuals in United states. Incidence of psoriatic arthritis is approximately 6 per 100,000 individuals. The prevalence among psoriasis patients is high and approximately 11,000 per 100,000 individuals. Psoriatic arthritis may commonly occur in age groups 40-50 yrs with mean age at diagnosis is 40.7 years.

• The prevalence of psoriatic arthritis in general population ranges from 60 – 250 cases per 100,000 individuals in United states.^[1]
• The prevalence ranges in genreal population from 50 – 210 cases per 100,000 individuals in Europe.^[2]
• The prevalence among psoriasis patients is 11,000 per 100,000 individuals.
• Incidence of psoriatic arthritis is approximately 6 per 100,000 individuals.^[3]

• Psoriatic arthritis may commonly occur in age groups 40-50 yrs with mean age at diagnosis is 40.7 years.^[3]

• In general, there is no gender predilection to psoriatic arthritis.^[4]

• There is insufficient data to support the racial dominance of psoriatic arthritis.

Template:WH Template:WS

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

Genetic factors (eg, increased expression of HLA-B, HLA-C, single nucleotide polymorphisms involving various genes), immune mediators (eg, dendritic cells, T lymphocytes), and environmental agents(eg, infections, physical trauma) may act as a risk factors for the development of psoriatic arthritis.

• Genetic factors:^[1][2][3]
  • Both psoriasis and psoriatic arthritis have been shown to have strong familial distribution among first degree relatives.
  • psoriatic arthritis is frequently associated with HLA-B alleles than with HLA-C alleles, when compared to psoriasis.
  • In patients with psoriatic arthritis when compared to general population, HLA antigens that are expressed more oftenly including HLA-B13, HLA-B17, HLA-B57, and HLA-Cw*0602.
  • HLA CLASS 1 antigens that are related to psoriatic arthritis include HLA-B13, HLA-B38, HLA-B27, HLA-B39, and HLA-B57.
  • HLA-B38 and HLA-B39 have a strong association with peripheral inflammatory articular disease, while HLA-B27 is strongly associated with spondylitis.
  • HLA class 2 antigens that are associated with psoriatic arthritis including HLA-DRB1*04 and HLA-DRB1*07.
  • HLA antigens, HLA-B27 along with HLA-DR7, HLA-DQ3 and in the absence of HLA-DR7, and HLA-B39 may be considered as predictors for disease progression. HLA-B22 antigen is protective for psoriatic arthritis.^[4]
  • Increased risk for both psoriatic arthritis and psoriasis may be associated with following gene polymorphisms:
    • TNF-alpha polymorphisms^[5]
    • CARD15 gene on chrosome 16q: Pleiotropic autoimmune gene. It is the first non-MHC gene that can be associated with psoriatic arthritis.^[6]
    • Polymorphisms involving IL-23 receptor and IL-12 beta genes.^[7]
    • Interleukin 2 (IL2) and interleukin 21 (IL21)
    • MHC class I chain-related gene A (MICA)^[8]
    • IL-1 gene cluster polymorphism
    • IL-13 polymorphism
  • Increased risk for deveoping poriatic arthritis may also be related to interactions between certain HLA-class I alleles and killer inhibitory receptors (KIRs) located on chromosome 19. Psoriatic arthritis susceptibility is correlated with the presence of KIR2DS1 and/or KIR2DS2, and HLA-Cw alleles.^[9]
• Immune mechanisms:^[10][11][12]
  • Presence of increased levels immunoglobulins and antinuclear antibodies in the serum may be found in patients with psoriatic arthritis.
  • In patients with psoriatic arthritis, the synovial fluid contains reactive dendritic cells, which lead to activation of T lymphocytes by presenting an unknown antigen to CD4 positive T cells.
  • Cytokines produced as a result of T cell activation and activation of other inflammatory precursors lead to proliferation and activation of synovial and epidermal fibroblasts.
  • Excessively proliferated fibroblasts from epiderm and synovium may produce excess IL-1, IL-6, and platelet-derived growth factors.
  • T lymphocytes may express HLA-DR and IL-2 receptor, and receptors to several adhesive molecules and cytokines particularly IL-6.
  • Synovial fluid of patients with psoriatic arthritis will show increased levels of tumor necrosis factor (TNF)-alpha, IL-1, IL-6, and IL-8.
  • Elevated concentrations of serum interleukins including IL-10, IL-13, interferons particularly INF- alpha, chemokines such as CCL19, vascular endothelial growth factor, fibroblast growth factor, and decreased levels of granulocyte-colony stimulating factor may be found.

• Environmental factors:
  • Trauma: Koebner’s phenomenon^[13]
  • Infections:^[14][15]
    • Bacterial (eg, streptococcus)
    • Viral (eg, HIV)^[16]
  • Smoking: May have inverse relation with psoriatic arthritis among psoriasis patients.^[17]

Template:WH Template:WS

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

Various screening tools have been proposed to screen psoriatic arthritis such as Psoriatic Arthritis Screening and Evaluation tool (PASE), Psoriasis Epidemiology Screening Tool (PES), and Toronto Psoriatic Arthritis Screen (ToPAS).

• Various screening tools have been proposed to screen psoriatic arthritis:^[1]
  • Psoriatic Arthritis Screening and Evaluation tool (PASE)
  • Psoriasis Epidemiology Screening Tool (PES)
  • Toronto Psoriatic Arthritis Screen (ToPAS)

Template:WH Template:WS

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

If left untreated psoriatic arthritis may lead to severe joint destruction and deformity resulting in loss of physical function and reduced quality of life. Psoriatic arthritis is associated with various comorbid conditions including cardiovascular disease ( increased risk of atherosclerosis, myocardial infarction, heart failure), metabolic syndrome, liver disease, diabetes mellitus, depression and osteoporosis. Prognosis is good with early diagnosis and treatment. Overall survival rate also depends on management of comorbid conditions along with arthritis treatment.

• If left untreated psoriatic arthritis may lead to severe joint destruction and deformity resulting in loss of physical function and reduced quality of life.
• Common complications or comorbid conditions associated with psoriatic arthritis include:^{[1][2][3][4][5][6][7]}
  • Metabolic syndrome
  • Progressive joint destruction and deformity
  • Hypertension
  • Increase insulin resistance and diabetes mellitus
  • Dyslipidemia
  • Increased atherosclerotic risk
  • Myocardial infarction
  • Congestive heart failure
  • Arrythmias
  • Stroke
  • Inflammatory bowel disease
  • Osteoporosis
  • Depression
  • Increased risk for malignancy (breast, prostate, and lung)
  • uveitis
  • Non alcoholic fatty liver disease
  • Decreased quality of life
• Prognosis is generally good with early diagnosis and treatment with DMARDs and TNF inhibitors. Overall survival rate also depends on management of comorbid conditions along with arthritis treatment.^[8][9]

Template:WH Template:WS