Psoriatic arthritis

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis. The classic features of psoriatic arthritis include enthesitis (inflammation of the entheses), synovitis (inflammation of the joint membrane), and dactylitis (sausage-like swelling of the fingers). It particularly affects the peripheral joints, the spine, and the sacroiliac joints. PsA also often presents with nail lesions, which may include small depressions in the nail (pitting), thickening of the nails, and detachment of the nail from the nailbed. and about 20-30% of patients with psoriasis develop PsA. It is not clear if the two diseases are distinct disease entities or one disease.

PsA is classified as a type of seronegative spondyloarthropathy, and is a clinical diagnosis. There are no reliable tests for PsA.

Genetics are thought to be strongly involved in the development of psoriatic arthritis.

PsA occurs in both children and adults, and affects men and women equally. Psoriatic arthritis is inflammatory, and affected joints are generally red or warm to the touch.

Sausage-like swelling in the fingers or toes, known as dactylitis, occurs in about 40% of PsA cases.

PsA may cause shoulder pain, most commonly felt in the front of the shoulder or the upper part of the arm. It is usually felt when moving the arm and may only be noticed in certain movements. In addition, many people find it painful when lying on the sore side in bed at night.

Axial skeleton (spine)

Approximately 25–70% of PsA patients have inflammation of the axial skeleton. There are also post inflammatory changes. The changes in the nails may only be very minimal, such as minor pits of the nail surface. The nails may be discolored (e.g., "oil spots").

Enthesitis

Enthesitis is inflammation of an enthesis (the site where a tendon or ligament attaches to a bone). In PsA, enthesitis most often occurs at the attachment of the calcaneal tendon (Achilles tendon). It is sometimes described as extreme exhaustion that does not go away with adequate rest. The fatigue may be caused directly by the disease itself, or be a secondary effect of other factors.

Poor sleep quality is common among people with psoriatic arthritis.

Psychological

PsA is associated with anxiety and depression. People with the condition may have reduced participation in social activities and become socially isolated.

Pattern of disease activity

Psoriatic arthritis may remain mild or progress to destructive joint disease. Periods of active disease, or flares, will typically alternate with periods of remission. In severe forms, psoriatic arthritis may progress to arthritis mutilans which on X-ray gives a "pencil-in-cup" appearance.

Causes

Psoriatic arthritis is an inheritable polygenic disease, with many genes known or theorized to contribute to its clinical presentation (or lack thereof). When someone with the genes for psoriatic arthritis comes into contact with certain substances, these substances may induce an autoimmune reaction, causing the immune system to target normal tissues in the body. The exact strength, location, and clinical effects of this reaction depend on which genes are involved for each individual. The substance that triggers the reaction is typically not known. If the genes are functioning abnormally, then the immune system has a higher risk of attacking normal tissues.

HLA-B27

Approximately 40–50% of individuals with psoriatic arthritis have the HLA-B27 genotype. For instance in the US HLA-B27 incidence is 6–8%,

Risk factors

Health and environmental factors known to be associated with psoriatic arthritis include: which are visible in doppler ultrasound and MRI.

Ridging or pitting of fingernails or toenails (onycholysis), which is associated with psoriasis and psoriatic arthritis.
Radiologic images demonstrating degenerative joint damage. PsA presents with both erosions and new bone growth, whereas rheumatoid arthritis only causes erosions.

Other symptoms that are more typical of psoriatic arthritis than other forms of arthritis include enthesitis (inflammation in the Achilles tendon (at the back of the heel) or the plantar fascia (bottom of the feet)), and dactylitis (sausage-like swelling of the fingers or toes). Enthesitis also occurs in axial spondyloarthritis.

Comorbidities may help differential diagnosis.

The underlying process in psoriatic arthritis is inflammation; therefore, treatments are directed at reducing and controlling inflammation. The first-line initial treatment for most patients is a TNF inhibitor-type biological disease-modifying anti-rheumatic drug (DMARD).

Biological DMARDs

Biologics (also called biological response modifiers) are a class of therapeutics developed using recombinant DNA technology. Biologic medications are derived from living cells cultured in a laboratory. Unlike traditional DMARDs that affect the entire immune system, biologics target specific parts of the immune system. They are given by injection or intravenous (IV) infusion.

Biologics prescribed for psoriatic arthritis are TNF-α inhibitors, including infliximab, etanercept, golimumab, certolizumab pegol and adalimumab, as well as the IL-12/IL-23 inhibitor ustekinumab, and the IL-23 inhibitor risankizumab.

Biologics may increase the risk of minor and serious infections. More rarely, they may be associated with nervous system disorders, blood disorders or certain types of cancer. People with psoriasis who are treated with biologics do not have a higher risk of cancer. Coxibs (COX-2 inhibitors) e.g. celecoxib or etoricoxib, are associated with a statistically significant 50 to 66% relative risk reduction in gastrointestinal ulcers and bleeding complications compared to traditional NSAIDs, but carry an increased rate of cardiovascular events such as myocardial infarction (MI) or heart attack, and stroke. Both COX-2 inhibitors and other non-selective NSAIDs have potential adverse effects that include damage to the kidneys.

Conventional synthetic disease-modifying antirheumatic drugs

Oral small molecules such as methotrexate, leflunomide, cyclosporin, azathioprine, and sulfasalazine are used in persistent symptomatic cases without exacerbation. Rather than just reducing pain and inflammation, this class of drugs helps slow down or halt the progression of the disease, and therefore limits the amount of joint damage that occurs. Most DMARDs act slowly and may take weeks or even months to take full effect. According to a recent Cochrane review, low-dose oral methotrexate was slightly more effective than placebos. Immunosuppressant drugs can also reduce psoriasis skin symptoms but can lead to liver and kidney problems and an increased risk of serious infection.

Phosphodiesterase-4 inhibitors

A first-in-class treatment option for the management of psoriatic arthritis is apremilast, a small molecule phosphodiesterase-4 inhibitor approved for use by the FDA in 2014. By inhibiting PDE4, an enzyme that breaks down cyclic adenosine monophosphate, cAMP levels rise, resulting in the down-regulation of various pro-inflammatory factors including TNF-α, interleukin 17 and interleukin 23, as well as the up-regulation of anti-inflammatory factor interleukin 10.

It is given in tablet form and taken by mouth. Side effects include headaches, back pain, nausea, diarrhea, fatigue, nasopharyngitis, and upper respiratory tract infections, as well as depression and weight loss.

It was patented in 2014 and manufactured by Celgene. There is no current generic equivalent available on the market.

JAK inhibitors

The JAK1 inhibitors tofacitinib (Xeljanz) and upadacitinib (Rinvoq) are approved for the use in active psoriatic arthritis. The TYK2 inhibitor deucravacitinib (Sotyktu), which has been approved for plaque psoriasis, is currently undergoing a Phase II clinical trial to evaluate the efficacy and safety on psoriatic arthritis. The Takeda TYK2 inhibitor TAK-279 recently demonstrated a 20% improvement in signs and symptoms of disease at week 12 as compared to placebo in a Phase II clinical trial. Takeda has also initiated a Phase III, Multicenter, Randomized, trial to evaluate the efficacy and safety of TAK-279 in subjects with Moderate-to-Severe Plaque Psoriasis.

Other treatments

A review found tentative evidence of benefit of low level laser therapy and concluded that it could be considered for relief of pain and stiffness associated RA.

Photochemotherapy with methoxsalen and long-wave ultraviolet light (PUVA therapy) is used for severe skin lesions. Doctors may use joint injections with corticosteroids in cases where one joint is severely affected. In psoriatic arthritis patients with severe joint damage, orthopedic surgery may be implemented to correct joint destruction, usually with the use of a joint replacement. Surgery is effective for pain alleviation, correcting joint disfigurement, and reinforcing joint usefulness and strength.

Management of fatigue

Changes in lifestyle may help manage fatigue.

Prognosis

The condition can be disabling, People with PsA may have reduced ability to work. Reported prevalence ranges from 0.1 to 1% of the general population. Some people with PsA never get psoriasis.

Psoriatic arthritis can develop in people who have any level of severity of psoriatic skin disease, ranging from mild to very severe. Studies have found that obesity is a significant risk factor and predictor of disease outcome. Other risk factors associated with an increased risk of developing psoriatic arthritis include severe psoriasis, nail psoriasis, scalp psoriasis, inverse psoriasis, and having a first-degree relative with psoriatic arthritis.

More than 80% of patients with psoriatic arthritis will have psoriatic nail lesions characterized by nail pitting, separation of the nail from the underlying nail bed, ridging and cracking, or, more severely, loss of the nail itself (onycholysis).

References

External links

Psoriatic Arthritis at Patient.info
Guidelines of care for the management of psoriasis and psoriatic arthritis—National Guideline Clearinghouse
US National Institute of Arthritis and Musculoskeletal and Skin Diseases