Psoriatic Arthritis – Causes, Symptoms, Diagnosis, Treatment Psoriatic arthritis (also arthritis psoriatic, arthropathic psoriasis, or psoriatic arthropathy) is a chronic, progressive, heterogeneous inflammatory arthritis that may affect peripheral and axial joints, entheses, skin and nails, and other organs and may develop in between 6 and 42% of people who have chronic skin conditions psoriasis. It is long-term inflammatory arthritis that occurs in people affected by the autoimmune disease psoriasis. [rx],[rx] The classic feature of psoriatic arthritis is swelling of entire fingers and toes with a sausage-like appearance. This often happens in association with changes to the nails such as small depressions in the nail (pitting), thickening of the nails, and detachment of the nail from the nail bed. Skin changes consistent with psoriasis (e.g., red, scaly, and itchy plaques) frequently occur before the onset of psoriatic arthritis but psoriatic arthritis can precede the rash in 15% of affected individuals. It is classified as a type of seronegative spondyloarthropathy. [dropshadowbox align=”none” effect=”lifted-both” width=”auto” height=”” background_color=”#ffffff” border_width=”1″ border_color=”#dddddd” ] Summary of key differences in PsA and RA Psoriatic Arthritis Rheumatoid Arthritis Clinical/anatomical ▸ DIP joint and axial arthritis ▸ Often asymmetrical ▸ Enthesitis common ▸ MCP and wrist joints ▸ Predominantly symmetrical Genetic ▸ HLA Cw6 and B27 ▸ IL23 receptor ▸ HLA DRB1 Pathogenesis ▸ Absence of circulating autoantibodies ▸ Distinct vascular pathology ▸ T-lymphocyte predominance ▸ Early expression of vascular growth factors ▸ Circulating autoantibodies RF/ACPA ▸ T-lymphocyte and B-lymphocyte infiltrate ▸ Late expression of vascular growth factors Response to therapy ▸ DMARDs, eg, methotrexate ▸ TNF inhibitors ▸ Abatacept ▸ Ustekinumab ▸ Secukinumab ▸ DMARDs, eg, methotrexate ▸ TNF inhibitors ▸ Abatacept ▸ Rituximab ▸ Tocilizumab ACPA, anticitrullinated protein antibodies; DIP, distal interphalangeal; DMARDs, disease-modifying anti-rheumatic drugs; HLA, human leukocyte antigen; IL, interleukin; MCP, metacarpophalangeal; RF, rheumatoid factor; TNF, tumor necrosis factor. [/dropshadowbox] Types of Psoriatic Arthritis Symmetric psoriatic arthritis – affects several joints in pairs on both sides of your body, like both elbows or both knees. It can be mild to severe. It destroys your joints over time, and they may stop working. That’s why you need treatment. For about half of people with this type, it can be disabling. The symptoms of symmetric psoriatic arthritis looks like rheumatoid arthritis. Asymmetric psoriatic arthritis – typically affects only a few joints. They can be large or small and anywhere in your body. Fingers and toes may swell like sausages. Distal interphalangeal predominant (DIP) psoriatic arthritis – mainly affects small joints at the ends of the fingers and toes, as well as the nails. Sometimes it’s confused with osteoarthritis, what most people think of when they hear “arthritis,” when the cartilage and bone in the joints wear away. Spondylitis – affects the backbone. It can cause inflammation and stiffness between your vertebrae — the bones of your neck, spine, lower back, and pelvis. Spondylitis can also attack ligaments that connect muscles to bones and other connective tissue. Arthritis mutilans – is the most severe and destructive form of psoriatic arthritis. Fortunately, it’s rare. It damages the small joints in your fingers and toes so badly that they become deformed. Distal interphalangeal predominant – This type of psoriatic arthritis is found in about 5% of patients and is characterized by inflammation and stiffness in the joints nearest to the ends of the fingers and toes. Nail changes are often marked. Causes of Psoriatic Arthritis The main contributing factors to the development of psoriatic arthritis are genetics, immunological factors, and the environment. Genetics – As in psoriasis of the skin, many patients with psoriatic arthritis may have a familial tendency toward the condition. However, a twin study found that arthritis was as common in dizygotic (fraternal) twins as in monozygotic (identical) twins so unknown environmental factors may also be important. First-degree relatives of patients with psoriatic arthritis have a 50-fold increased risk of developing psoriatic arthritis compared with the general population. It is unclear whether this is due to a genetic basis of psoriasis alone, or whether there is a special genetic predisposition to arthritis as well. Immune factors – There is evidence to support the theory that psoriatic arthritis occurs as a result of abnormal interaction between the immune system and the joints. People with psoriatic arthritis seem to have an overactive immune system as is evidenced by raised inflammatory markers, in particular, tumor necrosis factor (TNF), and increased antibodies and T-lymphocytes (infection-fighting cells). Environment – Presumably some environmental factor tips the balance in favor of the development of psoriatic arthritis in an individual who is genetically predisposed to the condition. As yet no reliable environmental factor has been identified. Symptoms of Psoriatic Arthritis Symptoms of psoriatic arthritis include Joint pain and swelling may come and go. Joints may also be red and warm. Tenderness in the heel and bottom of the foot. Pain and stiffness in the neck and lower back. Joint stiffness, especially in the morning. Painful, sausage-like swelling of the fingers and/or toes. Thickness and reddening of the skin with flaky, silver-white patches called scales. Pitting of the nails or separation from the nail bed. Tiredness. Pink eye or other eye infections.[rx] In the 60’s and ’70s five clinical forms of PSA were distinguished by Moll and Wright The classic course of the disease with involvement of the distal interphalangeal joints (5% of cases). The destructive form of arthritis (arthritis mutilans) (5% of cases) The destructive form of psoriatic arthritis (arthritis mutilans). Numerous destructive changes in metacarpophalangeal and interphalangeal joints. The destructive form of psoriatic arthritis (arthritis mutilations). Numerous destructive changes in joints of both hands. Ankylosis of the right wrist. Typical for PsA changes called “pencil-in-cup” involving metacarpophalangeal joints. Symmetric polyarthritis was indistinguishable from rheumatoid arthritis with a negative rheumatoid factor (approximately 15% of cases). An asymmetric form involving a few interphalangeal joints (also distal) and metacarpophalangeal joints. It is the most common form of arthritis in psoriasis (approximately 70% of all cases). A form resembling ankylosing spondylitis (5% of cases). A group of diseases with similar clinical manifestations called seronegative spondyloarthropathies (SpA) has also been defined [RX]. The group includes: Ankylosing spondylitis (AS). Psoriatic Arthritis (PsA). Spondylitis with associated bowel disease (or enteropathic spondylitis). Reactive arthritis. Undifferentiated spondyloarthropathies. To support the diagnosis of seronegative spondyloarthropathies, the European Spondyloarthropathy Study Group (ESSG) created some clinical criteria. Basing on these criteria the assessment includes the following features: Inflammatory back pain. Arthritis. Positive family history. Psoriasis. Inflammatory bowel disease. Buttock pain. Enthesitis. Episodes of acute diarrhea. Urethritis. Sacroiliitis. Onset of psoriasis and arthritis are as follows Psoriasis appears to precede the onset of psoriatic arthritis in 60-80% of patients (occasionally by as many as 20 years, but usually by less than 10 years) In as many as 15-20% of patients, arthritis appears before the psoriasis Occasionally, arthritis and psoriasis appear simultaneously Diagnosis of Psoriatic Arthritis Family History Psoriatic arthritis usually shows up between ages 30 and 50, but it may start in childhood. Both men and women get it. Many people have skin disease psoriasis first. Your doctor will look at your body and ask about the symptoms you’ve been having, which might include Joint pain, stiffness, and swelling Fatigue Tenderness, pain, or swelling where tendons and ligaments attach to bones Swollen fingers or toes Patches of red, itchy skin Thick silver or gray scaly areas on your skin Changes or problems with your fingernails or toenails Redness and swelling in your eye Both psoriasis and psoriatic arthritis are related to your genes, so if you have a close family member with these skin or joint problems, you’re more likely to have them, too. Physical Examination In some cases, patients may experience only stiffness and pain, with few objective findings. In most patients, the musculoskeletal symptoms are insidious in onset, but an acute onset has been reported in one-third of all patients. The findings on physical examination are as follows Enthesopathy or enthesitis, reflecting inflammation at tendon or ligament insertions into bone, is observed more often at the attachment of the Achilles tendon and the plantar fascia to the calcaneus with the development of insertional spurs Dactylitis with sausage digits is seen in as many as 35% of patients Skin lesions include scaly, erythematous plaques; guttate lesions; lakes of pus; and erythroderma Psoriasis may occur in hidden sites, such as the scalp (where psoriasis frequently is mistaken for dandruff), perineum, intergluteal cleft, and umbilicus Psoriatic nail changes, which may be a solitary finding in patients with psoriatic arthritis, may include the following Beau lines Leukonychia Onycholysis Oil spots Subungual hyperkeratosis Splinter hemorrhages Spotted lunulae Transverse ridging Cracking of the free edge of the nail Uniform nail pitting Extra-articular features are observed less frequently in patients with psoriatic arthritis than in those with rheumatoid arthritis (RA) but may include the following: Synovitis affecting flexor tendon sheaths, with sparing of the extensor tendon sheath Subcutaneous nodules are rare Ocular involvement may occur in 30% of patients, including conjunctivitis in 20% and acute anterior uveitis in 7%; in patients with uveitis, 43% have sacroiliitis. Laboratory tests ordered and rationale Elevations of the erythrocyte sedimentation rate (ESR) and C-reactive protein level Negative rheumatoid factor in 91-95% of patients In 10-20% of patients with generalized skin disease, the serum uric acid concentration may be increased Low levels of circulating immune complexes have been detected in 56% of patients Serum immunoglobulin A levels are increased in two-thirds of patients Synovial fluid is inflammatory, with cell counts ranging from 5000-15,000/µL and with more than 50% of cells being polymorphonuclear leukocytes; complement levels are either within reference ranges or increased, and glucose levels are within reference ranges IgG foods – Food reactions have been associated with psoriatic arthritis pathogenesis and may contribute to inflammation. Many IgG reactions demonstrate intestinal hyperpermeability, also a factor in inflammatory arthritis. Removing offending foods, if present, will reduce systemic inflammation. DQ genotype (celiac genes) and celiac panel – Celiac disease and psoriatic arthritis have been linked and share common inflammatory etiopathogenic features. Inflammatory markers – Monitoring general inflammatory markers are standard practice for the assessment of treatment efficacy. Multi profile panel – A comprehensive assessment including fatty acids, amino acids, organic acids, oxidative stress markers, and whole blood toxic metals. These tests assist in finding individual etiopathogenic factors that can affect treatment considerations. (Not all findings are discussed below. Panel results not grouped together) Metabolic panel and lipids – General assessment of metabolic imbalances associated with inflammation Thyroid panel – Subclinical hypothyroidism is frequently found in those with complex, chronic diseases. DNA microbial stool profile – Assessment of GI microbial status and GI function. GI imbalances are a common finding in inflammatory conditions. Classification of psoriatic arthritis criteria The Classification Criteria for Psoriatic Arthritis (CASPAR) consist of established inflammatory articular disease with at least 3 points from the following features: Current psoriasis (assigned a score of 2) A history of psoriasis (in the absence of current psoriasis; assigned a score of 1) A family history of psoriasis (in the absence of current psoriasis and history of psoriasis; assigned a score of 1) Dactylitis (assigned a score of 1) Juxta-articular new-bone formation (assigned a score of 1) RF negativity (assigned a score of 1) Nail dystrophy (assigned a score of 1) Radiographic Studies of Psoriatic Arthritis Radiologic features have helped to distinguish psoriatic arthritis from other causes of polyarthritis. In general, the common subtypes of psoriatic arthritis, such as asymmetrical oligoarthritis and symmetrical polyarthritis, tend to result in only mild erosive disease. Early bony erosions occur at the cartilaginous edge, and cartilage is initially preserved, with the maintenance of a normal joint space. The following radiographic abnormalities are suggestive of psoriatic arthritis Pencil-in-cup deformity Arthritis mutilans (ie, “pencil-in-cup” deformities). Joint-space narrowing in the interphalangeal joints, possibly with ankylosis Increased joint space in the interphalangeal joints as a result of the destruction Fluffy periostitis Bilateral, asymmetrical, fusiform soft-tissue swelling Unilateral or symmetrical sacroiliitis Large, nonmarginal, unilateral, asymmetrical syndesmophytes in the cervical, thoracic, and lumbar spine, often sparing some of the segments A lateral radiograph of the cervical spine shows syndesmophytes at the C2-3 and C6-7 levels, with zygapophyseal joint fusion. Magnetic resonance imaging studies Particularly sensitive for detecting sacroiliitis synovitis, enthesitis, and erosions; can also be used with gadolinium to increase sensitivity May show inflammation in the small joints of the hands, involving the collateral ligaments and soft tissues around the joint capsule, a finding not seen in persons with RA. CASPAR Criteria The CASPAR criteria should also help to identify PsA early. While the criteria were established in patients who had a long-standing disease, they work just as well in patients with early disease[rx]– [rx]. However, the CASPAR criteria are based on the stem of inflammatory musculoskeletal disease. Only rheumatologists can accurately make that diagnosis. To address this issue, the Group for Research and Assessment of Psoriasis and PsA (GRAPPA) is developing criteria to identify inflammatory arthritis that can be used by non-experts [rx]. Since it is not feasible for all patients with psoriasis to be reviewed by a rheumatologist, several groups have developed screening tools that can be administered to patients Ultrasound The use of ultrasound may be helpful in identifying patients with PsA early, particularly among patients with psoriasis. Gisondi et al. performed an ultrasound study of entheses in 30 patients with psoriasis and 30 controls [rx]. They found that the entheses were thicker and the overall ultrasound score was higher in patients with psoriasis than in controls. They repeated the ultrasound assessment among the psoriasis patients 2 years later, and three of the 30 had developed PsA [rx]. However, a study that compared ultrasound in patients with PsA, patients with PsC, and healthy controls found that obesity is a confounder in distinguishing between the groups [rx]. Biomarkers Since psoriasis usually precedes the development of PsA, and dermatologists have difficulty identifying inflammatory arthritis, it would be helpful if clinicians had a biomarker that would identify those individuals likely to develop the disease. In the past few years, we have seen several biomarkers tested for PSA. These include genetic, epigenetic, soluble, and cellular biomarkers [rx], [rx]. Isotope Examination The scintigraphic examination is widely performed in patients with inflammatory joint diseases as a useful method of evaluating bone metabolism. It is based on the evaluation of an intense accumulation of radioisotope in areas of increased metabolism within the inflamed joints. Isotope examination is a very sensitive method providing an assessment of joints in whole-body imaging in a single examination. This method, however, is limited due to its low specificity. Early lesions period (0–6 months). Isotope examination – Ultrasound examination of joints found to be abnormal on isotope examination; – Hand X-ray (initial radiographs). MRI – In the case of equivocal ultrasound; – Lesions involving axial skeleton (CT alternatively). A later period (over 6 months). Monitoring of treatment: – Ultrasound of abnormal joints; – Scintigraphy/ultrasound/MRI (alternatively) in case of symptoms suggesting the involvement of other joints. Follow-up hand X-ray after 2 years. Advanced lesions Bilateral hand X-ray examination (if involved) every 2 years. Ultrasound for monitoring activity of the inflammatory process. Magnetic resonance imaging in case of axial skeleton involvement. Ultrasonography To examine large joints such as the knee joint or shoulder joint 5–7,5 Mhz ultrasound transducers can be used. Smaller carpal joints require the use of transducers with frequencies above 10 MHz. [rx]. The grayscale ultrasound scanning used for rheumatological diagnosing provides a possibility to visualize the intraarticular effusion and synovial hypertrophy [rx]. Intraarticular effusion appears as an anechoic area deformable under probe compression, whereas synovial hypertrophy takes a form of intraarticular masses with echogenicity comparable to soft tissues and non-compressible. An ultrasound scan is a sensitive method for detecting the aforementioned lesions and is comparable to magnetic resonance imaging and arthroscopic examination [rx–rx]. Treatment of Psoriatic Arthritis Biological drugs currently licensed for PsA Molecule Mechanism of action Route Dosage Infliximab Chimeric monoclonal antibody against TNF-α IV 5 mg/kg at weeks 0, 2, and 6 and every 6–8 weeks Etanercept Soluble TNF receptor p75-IgG1 fusion protein SC 50 mg/week Adalimumab Fully human anti-TNF-α monoclonal antibody SC 40 mg every 2 weeks Golimumab Fully human IgG1k anti-TNF-α antibody SC 50 mg/month Certolizumab pegol Fab fragment of an anti-TNF-α monoclonal antibody SC 400 mg at 0, 2, and 4 weeks and then 200 mg every 2 weeks Ustekinumab Fully human IgG1 monoclonal antibody against the shared P40 subunit of human IL-12 and IL-23 SC 45 mg at weeks 0 and 4 and then every 12 weeks (90 mg if weight >100 kg) Secukinumab Monoclonal antibody against IL-17A SC 150 (or 300) mg at weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter or directly 150 mg/month Abbreviations: PsA, psoriatic arthritis; TNF, tumor necrosis factor; IV, intravenous; SC, subcutaneous; IL, interleukin. Currently approved biological drugs for PsA: efficacy data from registrative trials Molecule PASI 75 (at week 24) ACR 20 (at week 24) ACR 50 (at week 24) ACR 70 (at week 24) Infliximabrx] (5 mg/kg at weeks 0, 2, 6, 14, and 22) 60% (1%) 54% (16%) 41% (4) 27% (2%) Etanercept[rx] (25 mg twice weekly) 23% (3%) 59%* (15%*) – – Adalimumab[rx] (40 mg every 2 weeks) 59% (1%) 57% (15%) 39% (6%) 23% (1%) Golimumab[rx] (50 mg every 4 weeks) 56% (1%) 52% (12%) – – Certolizumab pegol[rx] (400 mg at weeks 0 and 2 and then 200 mg every 4 weeks) 62% (15%) 64% (24%) 44% (13%) 28% (4%) Ustekinumab[rx] (45 mg at weeks 0 and 4 and then every 12 weeks) 57% (11%) 42%