psoriatic arthritis

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Psoriatic arthritis is a chronic inflammatory form of arthritis that affects some people with psoriasis. It causes joint pain, stiffness, and swelling. Here is an in-depth explanation of psoriatic arthritis:

Key facts about psoriatic arthritis:

• Psoriatic arthritis occurs in about 30% of people with psoriasis. It develops when the immune system attacks healthy cells and tissue, leading to inflammation of the joints and overproduction of skin cells. The underlying cause is not fully understood but involves a combination of genetic and environmental factors.
• Symptoms include joint pain, swelling, and stiffness, especially in the fingers and toes. In most cases, the condition develops gradually with periods of flare-ups and remission. It can cause permanent joint damage if not treated.
• The disease can affect any joint, but often impacts joints of fingers and toes, as well as knees, ankles, elbows, wrists, and spine. Inflammation where ligaments and tendons attach to bones can also cause pain at joints or localized pain in areas like heels.
• Five types of psoriatic arthritis have been identified:
• Asymmetric: Affects joints on one side or a few digits. Most common.
• Symmetric: Affects same joints on each side of body. Resembles rheumatoid arthritis.
• Distal Interphalangeal Predominant (DIP): Affects joints closest to nails. Can cause "sausage digit".
• Spondylitis: Inflammation of spine, sacroiliac joints, and sites where tendons attach to bone. Can lead to spinal fusion.
• Arthritis mutilans: Rare but most severe. Causes severe inflammation and deformity of small joints in hands and feet.
• Diagnosis is based on symptoms, physical exam, and medical tests like blood work, x-rays or MRI to detect inflammation and joint damage.

Treatment options for psoriatic arthritis:

• Disease-modifying antirheumatic drugs (DMARDs) like methotrexate to slow progression.
• Biologic response modifiers (biologics) to target specific parts of the immune system.
• Steroids to reduce inflammation. Oral or injected corticosteroids are often used during flare-ups.
• NSAIDs for milder cases. Nonsteroidal anti-inflammatory drugs reduce pain and swelling.
• Physical therapy and lifestyle changes (exercise, applying heat/ice, joint protection) provide relief and improve mobility.
• For severe joint damage, surgery may be recommended to repair or replace damaged joints.

Treatment usually requires trial and error to find the most effective therapy or combination of therapies for each patient. Early diagnosis and aggressive treatment helps minimize joint damage and long term disability.

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Topic Highlights:-

• Psoriatic arthritis (PsA) is an inflammatory arthritis occurring in individuals with psoriasis, resulting in functional impairment.
• This visual presentation focuses on types of psoriatic arthritis, the epidemiology, clinical diagnosis, immunopathogenesis, traditional systemic therapies, biological agents for PsA and other potential treatments that focus on more aggressive treatment to improve the outlook for patients with PsA.

Transcript:-
Psoriatic arthritis (PsA), an aspect of psoriasis , is a chronic, autoimmune disease characterized by inflammation of the skin and joints. Psoriasis affects approximately 2-3% of the general population and the prevalence of PsA in psoriasis patients is between 6% and 39%. Most patients experience a change in signs and symptoms as the disease progresses. The intensity of pain ranges from mild to severe. Psoriatic arthritis can occur at any age and affects men and women equally .

Focus on more aggressive treatment of patients with progressive disease, both with traditional disease modifying drugs and emerging biologics has improved the outlook for patients with PsA regarding control of symptoms in the joints, enthesium, and skin, inhibition of progressive joint destruction, improvement of function and quality of life. It is also possible that the condition remains generally under diagnosed, related to lack of awareness by both the patient and physician.

Five types of psoriatic arthritis have been defined, that can coexist but tend to occur separately in most cases: Asymmetric arthritis , mildest form of psoriatic arthritis, affects any joint such as the knee, hip, ankle or wrist. Inflamed joints are often tender and red. When hands and feet are involved, swelling and inflammation in the tendons can cause the fingers and toes to resemble small sausages ( dactylitis ).

Symmetric arthritis , the second most common form of psoriatic arthritis, resembles rheumatoid arthritis but with a negative rheumatoid factor . Symptoms often occur in the same joints on both sides of the body. Though milder than rheumatoid arthritis, it can cause disabling joint damage.

Distal interphalangeal predominant (DIP) , a less common form of psoriatic arthritis, affects distal joints of the fingers and toes. DIP is sometimes confused with osteoarthritis, but psoriatic arthritis usually causes nail changes.

Spondylitis , this form of psoriatic arthritis causes inflammation with stiffness of the neck, lower back, sacroiliac or spinal vertebrae . With disease progression, movement tends to become increasingly painful and difficult.

Arthritis mutilans , a rare but often debilitating and destructive form of psoriatic arthritis, affects the small joints of the hands and feet, sometimes affecting the neck and lower back.

The CASPAR (ClASsification criteria for Psoriatic ARthritis) study group has developed formal classification criteria for categorizing PsA. The criteria consisted of established inflammatory articular disease with at least three of the following features – current psoriasis, a history of psoriasis, a family history of psoriasis, dactylitis, juxta articular new bone formation, rheumatoid factor negativity, and nail dystrophy .

Evidence now exists documenting the central role of tumor necrosis factor alpha (TNFa) in both PsA and psoriasis. High levels of TNF-a are found in psoriatic skin lesions and in the synovial fluid, serum, and synovial tissue of patients with PsA. In joints, TNF-a mediates biological processes that can result in cartilage and bone damage, including: expression of cartilage destroying metalloproteinases by fibroblasts and chondrocytes , maturation and activation of bone eroding osteoclasts from monocytic stem cells, and angiogenesis . In both the joints and the skin, TNFa induces the expression of endothelial , keratinocyte and dendritic cell surface adhesion molecules, which attract immune cells to sites of inflammation. In addition to stimulating pro-inflammatory cells and cytokines in the skin, a key role played by TNFα is promotion of keratinocyte hyperproliferation and survival, which is important in the psoriatic lesion.

Other key cytokines, which are increased, and thus potential targets for therapy, include IL-1, IL-6, IL-12, IL-15, and IL-18. T cell activity is significantly upregulated, thus inhibition of T cell activation via blockade of second signal pathways is also a promising therapeutic approach, as may be inhibition of intracellular signaling pathways.

Synovial biopsy studies have documented the similarity of immunohistology of various spondyloarthritis (SpA) subsets, including PsA and ankylosing spondylitis (AS), and distinction of these from rheumatoid arthritis (RA). Some distinguishing features of the spondyloarthritides include decreased quantity of cellular infiltrate yet more vascularity than seen in RA, infiltration with polymorphonuclear cells and CD163+ macrophages, and upregulation of toll-like receptors 2 and 4. Angiogenesis is prominent in both the synovium and psoriatic skin lesions, induced by angiogenic growth factors such as vascular endothelial growth factor (VEGF), transforming growth factor β (TGFβ), and angiopoietins . There is an increased interest in the bone and enthesial pathology of PsA. Recent histologic and MRI studies demonstrate inflammatory infiltrate in the subendosteal region of the bone adjacent to the cartilage, often corresponding to bone edema on MRI, and at enthesial insertion sites, not typically seen in RA.

The exact cause of PsA is not known. A combination of abnormal immune response, genetic and environmental factors are said to play a role in disease development. Other factors that can trigger psoriatic arthritis include skin injury, stress, severe sunburn, alcohol, poor nutrition, certain medications and infections, especially streptococcal infection. HIV/AIDS leads to flaring of psoriatic arthritis.

Some of the symptoms of psoriatic arthritis include: scaly skin patches on some areas of the body , joint pain and tenderness, swelling of fingers or toes, morning stiffness and fatigue, eye inflammations like conjunctivitis or iritis , nail abnormalities such as discoloration, pitting or lifting of the nails. Pleuritis and aortitis are the other symptoms that could be observed in patients with PsA.

The skin lesions of psoriasis typically appear before arthritis manifestations, often by as long as 10 years. Questioning the psoriasis patient about sustained pain and possible swelling in joints or whole digits (dactylitis); the presence of prolonged morning stiffness; persistent pain at tendon and ligament insertion sites (enthesitis); back and/or buttock pain (spine and sacroiliac inflammation); and fatigue, can help establish the diagnosis, and distinguish the condition from osteoarthritis and injury-induced tendonitis.

Laboratory tests are often unhelpful. Acute phase reactants such as sed rate or CRP may be normal and rheumatoid factor is usually negative.

As the disease advances, distinctive radiographic features begin to appear that can help differentiate the condition from other forms of arthritis. MRI and ultrasound may be even more sensitive imaging studies, which can detect inflammation at an early stage.

A challenge of PsA therapy is addressing the multiple clinical domains involved in the disease: arthritis, enthesitis, dactylitis, spine disease, skin, and the significant impairment in function and the patient’s quality of life. In patients with milder disease, non-steroidal anti-inflammatory drugs (NSAIDs) may be adequate for arthritis, while topical ointments like steroid or Vitamin D, or forms of light therapy may be adequate for skin disease. However, moderate to severe manifestations in these domains often requires systemic therapy. Drugs such as sulfasalazine or methotrexate may substantially help arthritis, but not always the disease of skin, nails, and entheses. Agents such as cyclosporine may help the skin but not adequately the joints, and none of these traditional disease-modifying therapies may help the spine. Thus, advances in targeted therapy with the newer biologic agents, especially the TNF antagonists, appear to address all domains with significant effectiveness.

Non-medication approaches to PsA therapy are a fundamental backdrop to medication therapy. These include patient and family education, regular exercise, physical and occupational therapy.

Biologic medications are proteins, which mimic natural biological processes and target specific pro-inflammatory molecules and/or cellular receptors. As complex proteins, they must be administered parenterally either subcutaneously, intramuscularly, or intravenously. Biologic agents currently approved for treatment of PsA include the anti-tumor necrosis factor alpha (TNF-a) compounds, example: etanercept , which mimics the natural TNF receptor, and infliximab and adalimumab , both monoclonal antibodies, the former chimeric (combination of mouse and human) and the latter humanized.

The anti-TNFα medications have shown the greatest efficacy of any treatment to date in the various clinical aspects of PsA. Highly significant improvements in composite assessments of joint disease, pain and function were demonstrated in clinical trials with each of the agents. Trials with anti-TNF agents, which measured dactylitis and enthesitis response, showed significant benefit. Fatigue significantly improved. Serial radiographs of hands and feet showed inhibition of progressive joint damage. Skin disease significantly improved with all treatments, although typically substantial clearing of the skin lesions took longer than joint improvement.

Significant efficacy of anti-TNF treatment of inflammatory spine symptoms and signs has been demonstrated in a closely related disease, ankylosing spondylitis, with some adverse effects. The most significant is a slight increase in serious bacterial or opportunistic infections. Administration reactions, either infusion reactions with the intravenous drug infliximab, or injections site reactions with the subcutaneously administered medicines may occur. Administration reactions are most often mild and self-limited. Other rare reactions, including drug-induced autoimmune conditions, which will resolve with discontinuation of the medicine, may also occur. Thus, appropriate patient education about and monitoring for such adverse events should be done.

Controlled phase 2 trials have been completed with the co-stimulatory blockade agents alefacept . Pilot trials with other biologics in development have been completed or are underway, involving agents that are either approved or in development for RA and psoriasis.

Alefacept is a fully human fusion protein that blocks interaction between lymphocyte function-associated antigen 3 ( LFA-3 ) on the antigen-presenting cell and CD2 on the T cell, or attracts natural killer lymphocytes to interact with CD2 to yield apoptosis of particular T cell clones. It is FDA approved for treatment of psoriasis and is administered weekly as a 15 mg intramuscular injection, in an alternating 12 weeks on, 12 weeks off regimen in order to allow return of depleted CD4 cells in the off period. Modest efficacy for arthritis was noted in a controlled trial.

Abatacept , a cytotoxic T lymphocyte antigen 4 immunoglobulin (CTLA4-Ig), is a recombinant human fusion protein that binds to the CD80 / 86 receptor on an antigen presenting cell, thus blocking the second signal activation of the CD28 receptor on the T-cell. It is administered intravenously once per month and has been approved for use in RA and not for PsA.

Some of the other biological agents considered for PsA therapy include Inhibitors of IL-12 / 23 , anti- IL-15 , monoclonal antibodies directed towards inhibition of the IL-6 receptor (MRA). Modulators of intracellular signaling pathways, like JAK-3 inhibitors, which interrupt intracellular signaling induced by multiple pro-inflammatory cytokines in psoriasis and RA, are also potential targets for therapy in both joints and skin.

Healthy diet, healthy weight, regular exercise, use of cold and hot packs to minimize pain and swelling, relaxation techniques, maintaining correct posture to avoid further damage to the affected joints, and moderate exposure to sunlight alleviate symptoms of psoriasis.

Numerous studies have increased our understanding of the basic pathophysiology of PsA, providing support for the clinical effects of targeted therapy. The consequent emerging treatments for PsA have demonstrated a significant benefit for clinical signs and symptoms in the joints, enthesium, skin, and inhibition of joint damage. Observation of the effectiveness of new therapeutic agents has helped elucidate the pathogenesis of PsA and psoriasis, which, in turn, may lead to more novel and effective interventions.