Psoriatic arthritis

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

Historical Perspective

• [Disease name] was first discovered by [scientist name], a [nationality + occupation], in [year] during/following [event].
• In [year], [gene] mutations were first identified in the pathogenesis of [disease name].
• In [year], the first [discovery] was developed by [scientist] to treat/diagnose [disease name].

Classification

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

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 xray 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

Causes

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.

Differentiating psoriatic arthritis from other Diseases

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

Epidemiology and Demographics

• The prevalence of psoriatic arthritis in general population ranges from 60 - 250 cases per 100,000 individuals in United states.
• The prevalence of psoriatic arthritis ranges in genreal population from 50 - 210 cases per 100,000 individuals in Europe.
• The prevalence of psoriatic arthritis among psoriasis patients is 11,000 per 100,000 individuals.
• The incidence of psoriatic arthritis is 3.6-6 per 100,000 individuals.

Age

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

Gender

• In general, there is no gender predilection to psoriatic arthritis.

Race

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

Risk Factors

• Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

Natural History, Complications and Prognosis

• The majority of patients with [disease name] remain asymptomatic for [duration/years].
• Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
• If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
• Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
• Prognosis is generally [excellent/good/poor], and the [1/5/10­year mortality/survival rate] of patients with [disease name] is approximately [#%].

Diagnosis

Diagnostic Criteria

• The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:

• [criterion 1]
• [criterion 2]
• [criterion 3]
• [criterion 4]

Symptoms

• Common symptom may be associated with psoriatic arthritis include:
  • Joint pain and swelling
  • Joint stiffness
  • Morning stiffness: May lasts more than 30 mins. It is aggravated by prolonged rest and relieved by physical activity.
  • Decreased range of motion and quality of life depending on the severity of the disease.
  • Enthesitis: Pain can be felt in areas where tendons, ligaments, and synovium attach to bones.
    • Common locations include:
      • Achilles tendinitis
      • Plantar fasciitis
  • Dactylitis: Sausage-like swelling of the entire finger or toe.
  • Skin lesions: Scaly, erythematous papules and plaques
  • Dystrophic nails
  • Ocular symptoms include redness and tearing due to conjunctivitis, blepharitis, and uveitis.
  • Fatigue

Physical Examination

• Patients with psoriatic arthritis usually appear normal.
• Physical examination of a patient with psoriatic arthritis may include:
• Joint involvement:
  • Joint tenderness
  • Joint swelling may or may not be present
  • Patterns of joint involvement in psoriatic arthritis may include according to moll and wright :
    • Distal arthritis: Involving mostly DIP joints, may be symmetric or asymmetric. It may involve multiple joints or only few joints.
    • Asymmetric oligoarthritis: Most common pattern can be seen in psoriatic arthritis. It is characterized by asymmetric involvement of less than 5 small or large joints.
    • Symmetric polyarthritis
    • Arthritis mutilans: Resorption of phalanges, metatarsals and, metacarpals.
    • Spondylitis
    • Sacroiliitis
  • Joint effusion
• Achilles tendinitis
• Dactylitis: sausage digit due to swelling of the whole finger or toe.
• Skin:
  • Psoriatic arthritis may occur after the onset of psoriasis in most of the patients. However, in some cases, arthritis precede psoriasis. The phenotypes of skin psoriasis that are associated with an increased risk of psoriatic arthritis are the lesions in the scalp, nail, intergluteal, and perianal regions.
    • Scaly, erythematous papules and plaques
    • Pustular lesions
    • Guttate lesions
    • Auspitz sign: Small bleeding points seen upon disruption of a psoriatic scale.
• Nails:
  • Nail pits
  • Onycholysis
  • Subungual hyperkeratosis
  • Splinter hemorrhages
  • Beau lines
  • Leukonychia
  • Oil drop patches
  • Nail crumbling
  • Nail destruction
• Involvement of eyes:
  • conjunctivitis
  • Uveitis
  • Iritis
• Edema of hands or feet: Swelling of hands and feet which is asymmetrical with pitting edema may be found in some cases.

Laboratory Findings

• There are no specific laboratory findings associated with psoriatic arthritis and most the tests are non-specific.
• However, there are certain laboratory tests that can check for markers of inflammation and to exclude other diseases. These include:
  • CBC with differential count
    • Leukocytosis
    • Anaemia
  • Elevated ESR
  • Elevated CRP (C- reactive protein)
  • Autoantibodies: The following autoantibodies may be found in patients with psoriatic arthritis.
    • Rheumatoid factor
    • ANA (Antinuclear antibodies)
    • Anti-citrullinated peptide antibodies (ACPA)
  • Genetic markers:
    • HLA-B27
    • HLA-C*06
  • Synovial fluid analysis: Elevated WBC count suggestive of inflammation.

Imaging Findings

• X-ray of digits:
  • Bone destructive changes including formation of subchondral cyst and erosions
  • Fluffy periostitis
  • Ankylosis
  • Phalangeal tuft acroosteolysis
  • New bone formation: Perisoteal and endosteal bone formation may result in increased bone density of an entire phalanx resulting in so called ivory phalanx.
  • Pencil-in-cup deformity (osteolytic lesions) usually involving DIP joints but also affects PIP joints
  • Osteolysis and ankylosis both coexists in the same joints of hands and foot
  • Enthesitis
  • Dactylitis (sausage digit)
  • Gross finger deformity
  • Arthritis mutilans: It may lead to "telescoping of fingers" caused by marked bony resorption and the subsequent collapse of soft tissue
  • Asymmetrical sacroiliitis
  • Spondylitis: Asymmetric paravertebral ossifications and relative sparing of the facet joints

Psoriatic-arthritis of hands showing pencil-in-cup deformity - By Case courtesy of Dr Jeremy Jones, <a href="https://radiopaedia.org/">Radiopaedia.org</a>. From the case <a href="https://radiopaedia.org/cases/8798">rID: 8798</a>

• MRI: MRI may reveal the following findings:
  • enthesitis
  • Periostitis
  • Joint erosions
  • Synovitis (articular or flexor tendon sheath)
  • Ankylosis
  • Edema of bone marrow
• Ultrasonography: Ultrasonography may reveal following findings.
  • Joint effusions and widening of joint space
  • Synovitis (articular and flexor tenosynovitis)
  • Dactylitis
  • Thickening of the joint capsule

Other Diagnostic Studies

• Bone mineral density (BMD) testing: Bone density may be decreased in psoriatic arthritis resulting in osteoporosis and increased risk for fractures.

Treatment

Medical Therapy

• Medical therapy for psoriatic arthritis is according to the guidelines proposed by
  • European League Against Rheumatism (EULAR): Guidelines were first proposed in 2012 and they were updated in 2015.
  • Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)
  • American College of Rheumatology (ACR)
  • National Psoriasis Foundation (NPF)
  • American Academy of Dermatology (AAD) Psoriasis Guidelines of Care
  • British Society of Rheumatology (BSR)
• Pharmacologic therapy for psoriatic arthritis include, non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic DMARDs (eg, methotrexate, sulfasalazine, cyclosporin A, leflunomide), biologicDMARDs including, TNF inhibitors (eg, etanercept, infliximab, adalimumab, golimumab), phosphodiesterase (PDE) inhibitors (eg, apremilast), interleukin(IL) inhibitors (eg, secukinumab, ixekizumab, abatacept) and intraarticular glucocorticoid injections.
• Peripheral arthritis:
  • Mild disease: Nonsteroidal antiinflammatory drugs (NSAIDs) are the most commonly used drugs for the management of mild active psoriatic arthritis.
    • Preferred regimen (1): Naproxen: 375-500 mg/twice a day
    • Preferred regimen (2): Celecoxib: 200 mg/twice a day
    • Preferred regimen (3): Nimesulide: 200 and 400 mg/day
    • Preferred regimen (4): Ibuprofen: Max dose of up to 2400 mg/day
      • Adverse effects of non-steroidal anti-inflammatory drugs include increased cardiovascular risk, gastritis, ulcers and low renal clearance.
  • Moderate to severe disease: Conventional synthetic disease-modifying antirheumatic drugs (DMARDs) may be considered in patients with moderate to severe active peripheral arthritis. These are also considered in patients who are resistant or not responding to NSAIDs, and local corticosteroid injections.
    • Preferred regimen (1): Methotrexate: 15 to 25 mg/week
      • Adverse effects of methotrexate: Liver toxicity, immunosuppression, interstitial pneumonitis, increased infection risk.
      • Folic acid supplementation should be given to all patients taking methotrexate.
    • Preferred regimen (2): Leflunomide: 20 mg/day
      • Adverse effects of Leflunomide: Liver toxicity, diarrhea, rash, alopecia, pneumonitis.
    • Preferred regimen (3): Sulfasalazine: 2-3 gms/day
      • Adverse effects of sulfasalazine: Nausea, diarrhea, abdominal pain, rash, and neutropenia.
    • Preferred regimen (4): Cyclosporine A: 3.5 mg/kg per day
      • Adverse effects of Cyclosporine A: Hypertension, kidney damage.
  • Severe disease and the presence of adverse prognostic factors: TNF inhibitors (eg, etanercept, infliximab, adalimumab, golimumab), interleukin(IL) inhibitors (eg, secukinumab, ixekizumab, abatacept).
    • Biologic DMARDs are considered for patients who fail to respond or contraindication to conventional synthetic DMARDs. It is also administered in patients with presence of poor prognosis factors, even if they have not failed a standard DMARDs therapy.
      • TNF inhibitors:
        • Preferred regimen (1): Adalimumab: It is a human anti-TNF alpha monoclonal antibody. Dosage: 40 mg can be given s.c every 2 weeks
        • Preferred regimen (2): Etanercept: It is a TNF receptor p75-IgG1 fusion protein. Dosage: 50 mg can be given s.c every week.
        • Preferred regimen (3): Infliximab: It is a chimeric monoclonal antibody against TNF alpha. Dosage: 5 mg/kg at weeks 0, 2, and 6 and after that 5 mg/kg every 6-8 weeks.
        • Preferred regimen (4): Golimumab: it is a human IgG1k anti-TNF alpha antibody. Dosage: 50 mg can be given s.c and monthly.
        • Preferred regimen (5): Certolizumab pegol: It is a Fab fragment of anti-TNF alpha monoclonal antibody. Dosage: 400 mg at 0, 2, and 4 weeks can be given s.c and then 200 mg every 2 weeks sub cutaneously.
          • Adverse effects: Reactivation of latent tuberculosis, increased risk for infections including bacterial and opportunistic infection. Therefore, before starting treatment with TNF inhibitors screening for TB, Hepatitis B, and C should be done.
      • IL inhibitor therapy: This is considered in patients with severe peripheral arthritis, where TNF therapy is contraindicated or not responding even after switching to different TNF inhibitor.
        • Anti-IL-17 therapies :
          • Preferred regimen (1): Secukinumab: It is a monoclonal antibody against IL-17A. Dosage: 150 mg at weeks 0, 1, 2, 3, and 4 and then every 4 weeks can be given subcutaneously.
          • Preferred regimen (2): Ixekizumab : Dosage: 160 mg initially, then 80 mg every two or four weeks can be given subcutaneously.
        • Anti-IL-12/23 therapy:
          • Ustekinumab: It is a IgG1 monoclonal antibody against the shared P40 subunit of human IL-12 and IL-23. Dosage: 45 mg at weeks 0 and 4 and then for every 12 weeks can be given subcutaneously.
      • Abatacept: It is a costimulatory T-cell molecule, blocking signal activation of the CD28 receptor on the T cell inhibiting T-cell activation. Dosage: 125 mg can be given subcutaneously once in a week.
• Axial disease/ spondylitis:
  • Mild disease: Non-steroidal anti-inflammatory drugs (NSAIDs), local corticosteroid injections, patient education, exercise and physiotherapy may be recommended to treat mild axial involvement.
    • Preferred regimen (1): Naproxen: 375-500 mg/twice a day
    • Preferred regimen (2): Celecoxib: 200 mg/twice a day
  • Moderate to severe disease: TNF inhibitors
• Skin disease:
  • Phototherapy: First line of treatment including UVB, PUVA.
  • Fumeric esters, retinols, calcipotriol
  • Conventional DMARDs and TNF inhibitors, and retinoic acid derivatives (eg, acitretin) may be used in combinatination with phototherapy.
• Nail disease:
  • Topical corticosteroids, calcipotriol creams, DMARDs and TNF inhibitors may be helpful.

• Enthesitis:
  • Mild disease: NSAIDs, local corticosteroid injection, physical therapy may be helpful.
  • Moderate to severe disease: TNF inhibitors
• Dactylitis:
  • NSAIDs, steroid injections, conventional DMARDs and TNF inhibitors can be helpful.
  • Biologic DMARDs can be considered for treatment of dactylitis if, therapy with NSAIDs, steroid injections, conventional DMARDs fails.
• Non pharmacologic therapy:
  • Exercise
  • Weight reduction
  • Physical therapy
  • Occupational therapy
  • Educating the patient about disease course, joint protection and comorbid conditions.
  • Orthotics

Surgery

• Surgery may be indicated in patients of psoriatic arthritis with severe joint damage that limit mobility.
• Common procedures include hand joint surgery involving PIP and DIP joints, hip or knee surgery.

Prevention

• There are no established preventive measures for psoriatic arthritis.
• Patients are monitored regularly for disease activity, drug efficacy, adverse effects and associated comorbid conditions.