Psoriatic Arthritis PDF

06.09.2021 https://emedicine.medscape.com/article/2196539-print emedicine.medscape.com Psoriatic Arthritis Updated: Jul 15, 2020 Author: A...

06.09.2021 https://emedicine.medscape.com/article/2196539-print emedicine.medscape.com Psoriatic Arthritis Updated: Jul 15, 2020 Author: Anwar Al Hammadi, MD, FRCPC; Chief Editor: Herbert S Diamond, MD Overview Practice Essentials Psoriatic arthritis is most commonly a seronegative oligoarthritis found in patients with psoriasis, with less common, but characteristic, differentiating features of distal joint involvement and arthritis mutilans. One in five patients with psoriasis has psoriatic arthritis (see the image below). Swelling and deformity of the metacarpophalangeal and distal interphalangeal joints in a patient with psoriatic arthritis. See Psoriasis: Manifestations, Management Options, and Mimics, a Critical Images slideshow, to help recognize the major psoriasis subtypes and distinguish them from other skin lesions. Go to Psoriatic Arthritis Decision Point for expert commentary on psoriatic arthritis diagnosis and treatment decisions and related guidelines. Signs and symptoms 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 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. 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 https://emedicine.medscape.com/article/2196539-print 1/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print 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 Patterns of arthritic involvement The patterns of psoriatic arthritis involvement are as follows: Asymmetrical oligoarticular arthritis Symmetrical polyarthritis Distal interphalangeal arthropathy Arthritis mutilans Spondylitis with or without sacroiliitis See Presentation for more detail. Diagnosis Classification of psoriatic arthritis 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) Laboratory findings No specific diagnostic tests are available for psoriatic arthritis. The most characteristic laboratory abnormalities in patients with the condition are as follows: 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 Radiographic studies 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 maintenance of a normal joint space. https://emedicine.medscape.com/article/2196539-print 2/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print The following radiographic abnormalities are suggestive of psoriatic arthritis: Pencil-in-cup deformity (erosion of the distal end of the phalanx into a sharpened pencil shape, with the proximal surface of the adjoining phalanx worn into a cup shape; see the image below) 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 destruction Fluffy periostitis Bilateral, asymmetrical, fusiform soft-tissue swelling Unilateral or symmetrical sacroiliitis Large, nonmarginal, unilateral, asymmetrical syndesmophytes (intervertebral bony bridges, seen in the image below) in the cervical, thoracic, and lumbar spine, often sparing some of the segments Lateral radiograph of the cervical spine shows syndesmophytes at the C2-3 and C6-7 levels, with zygapophyseal joint fusion. Courtesy of Bruce M. Rothschild, MD. Magnetic resonance imaging studies Particularly sensitive for detecting sacroiliitic 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 https://emedicine.medscape.com/article/2196539-print 3/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print See Workup for more detail. Management Medical treatment regimens include the use of nonsteroidal anti-inflammatory drugs (NSAIDs), Janus kinase (JAK) inhibitors, and disease-modifying antirheumatic drugs (DMARDs). DMARDs include the following : Methotrexate Sulfasalazine Cyclosporine Leflunomide Biologic agents (eg, TNF, PDE4, or interleukin inhibitors; CD80 binders) In patients with severe skin inflammation, medications such as methotrexate, retinoic-acid derivatives, and psoralen plus ultraviolet (UV) light should be considered. These agents have been shown to work on skin and joint manifestations. Intra- articular injection of entheses or single inflamed joints with corticosteroids may be particularly effective in some patients. Use DMARDs in individuals whose arthritis is persistent. Surgical care Arthroscopic synovectomy has been effective in treating severe, chronic, monoarticular synovitis Joint replacement and forms of reconstructive therapy are occasionally necessary Patients in severe pain or with significant contractures may be referred for possible surgical intervention; however, high rates of recurrence of joint contractures have been noted after surgical release, especially in the hand Hip and knee joint replacements have been successful Arthrodesis and arthroplasty have also been used on joints, such as the proximal interphalangeal joint of the thumb The wrist often spontaneously fuses, and this may relieve the patient's pain without surgical intervention For arthritis mutilans, surgical intervention is usually directed toward salvage of the hand; combinations of arthrodesis, arthroplasty, and bone grafts to lengthen the digits may be used Physical therapy The rehabilitation treatment program for patients with psoriatic arthritis should be individualized and should be started early in the disease process. Such a program should consider the use of the following: Rest: Local and systemic Exercise: Passive, active, stretching, strengthening, and endurance Modalities: Heat, cold Orthotics: Upper and lower extremities, spinal Assistive devices for gait and adaptive devices for self-care tasks: Including possible modifications to homes and automobiles Education about the disease, energy conservation techniques, and joint protection Possible vocational readjustments See Treatment and Medication for more detail. Background Psoriatic arthritis is a chronic inflammatory arthritis that develops in at least 5% of patients with psoriasis. The association between psoriasis and arthritis was first made in the mid-19th century, but psoriatic arthritis was not clinically distinguished from rheumatoid arthritis (RA) until the 1960s. Psoriatic arthritis is a chronic disease of the joints and the entheses, including those of the axial skeleton. It has associated features that most commonly involve the skin, but may also affect the nails. Dactylitis, uveitis, and osteitis can be associated features. (An example of flexion deformity in psoriatic arthritis is shown below.) (See Presentation and Workup.) https://emedicine.medscape.com/article/2196539-print 4/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print Severe fixed flexion deformity of the interphalangeal joint. Because of a lack of specific biologic tests, precisely defining psoriatic arthritis remains difficult. The disorder most commonly exists as a seronegative oligoarthritis found in patients with psoriasis. Distal joint involvement and arthritis mutilans are less common, but characteristic, differentiating features. (The first image below compares sites of involvement for psoriatic arthritis with those for RA. The second and third images show distal joint pathology in psoriatic arthritis.) Comparison between sites of involvements in both hands and feet in psoriatic arthritis and rheumatoid arthritis. https://emedicine.medscape.com/article/2196539-print 5/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print Psoriatic arthritis involving the distal phalangeal joint. Psoriatic arthritis involving the distal phalangeal joint. Because 50% of patients with psoriatic arthritis have evidence of spondyloarthropathy, often human leukocyte antigen (HLA)-B27 associated, psoriatic arthritis has also been classified among the seronegative spondyloarthropathies. (See Pathophysiology and Etiology.)[6, 7, 8, 9, 10] Peripheral joint disease occurs in 95% of patients with psoriatic arthritis, while in the other 5%, axial spine involvement occurs exclusively. (See Presentation and Workup.) Evidence from one study indicated that psoriatic arthritis is more frequent in patients with severe psoriasis than in those with milder cases. While this is true, no evidence indicates that the severity of the psoriasis relates to the pattern of joint involvement. In another study, pustular psoriasis was associated with more severe psoriatic arthritis. (See Prognosis.) Psoriatic arthritis occurring in patients over age 60 years (elderly onset psoriatic arthritis) has a more severe onset and more a destructive outcome than does psoriatic arthritis in younger patients. The course of psoriatic arthritis is usually characterized by flares and remissions. The patterns of psoriatic arthritis involvement are as follows: Asymmetrical oligoarticular arthritis Symmetrical polyarthritis Distal interphalangeal arthropathy Arthritis mutilans Spondylitis with or without sacroiliitis Asymmetrical oligoarticular arthritis This was previously thought to be the most common type of psoriatic arthritis. The digits of the hands and feet are usually affected first, with inflammation of the flexor tendon and synovium occurring simultaneously, leading to the typical "sausage" appearance (dactylitis) of the fingers and toes. A large joint, such as the knee, is also commonly involved. Usually, fewer than 5 joints are affected at any one time. An asymmetrical arthritis pattern is shown below. https://emedicine.medscape.com/article/2196539-print 6/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print Asymmetrical arthritis pattern of psoriatic arthritis (fixed flexion deformity). Symmetrical polyarthritis This rheumatoidlike pattern has been recognized as one of the most common types of psoriatic arthritis. The hands, wrists, ankles, and feet may be involved. It is differentiated from RA by the presence of distal interphalangeal (DIP) joint involvement, relative asymmetry, an absence of subcutaneous nodules, and a negative test result for rheumatoid factor (RF). This condition is also generally milder than RA, with less deformity. Distal interphalangeal arthropathy Although DIP joint involvement is considered to be a classic and unique symptom of psoriatic arthritis, it occurs in only 5- 10% of patients, primarily men. Involvement of the nail with significant inflammation of the paronychia and swelling of the digital tuft may be prominent, occasionally making appreciation of the arthropathy more difficult. Arthritis mutilans This is a rare form of psoriatic arthritis, being found in only 1-5% of patients (although some reports suggest that arthritis mutilans may occur in as many as 16% of patients and may be as severe as RA). In arthritis mutilans, resorption of bone (osteolysis), with dissolution of the joint, is observed as the "pencil-in-cup" radiographic finding and leads to redundant, overlying skin with a telescoping motion of the digit. (The effects of arthritis mutilans appear in the images below.) Arthritis mutilans, a typically psoriatic pattern of arthritis, which is associated with a characteristic "pencil-in-cup" radiographic appearance of digits. https://emedicine.medscape.com/article/2196539-print 7/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print Severe psoriatic arthritis showing involvement of the distal interphalangeal joints, distal flexion deformity, and telescoping of the left third, fourth, and fifth digits due to destruction of joint tissue. Arthritis mutilans (ie, "pencil-in-cup" deformities). This "opera-glass hand" is more common in men than in women and is more frequent in early-onset disease. Spondylitis with or without sacroiliitis This occurs in approximately 5% of patients with psoriatic arthritis and has a male predominance. Clinical evidence of spondylitis and/or sacroiliitis can occur in conjunction with other subgroups of psoriatic arthritis. Spondylitis may occur without radiologic evidence of sacroiliitis, which frequently tends to be asymmetrical, or sacroiliitis may appear radiologically without the classic symptoms of morning stiffness in the lower back. Thus, the correlation between the symptoms and radiologic signs of sacroiliitis can be poor. Vertebral involvement differs from that observed in ankylosing spondylitis. Vertebrae are affected asymmetrically, and the atlantoaxial joint may be involved with erosion of the odontoid and subluxation (with attendant neurologic complications). Therapy may limit subluxation-associated disability. Unusual radiologic features may be present, such as nonmarginal asymmetrical syndesmophytes (characteristic), paravertebral ossification, and, less commonly, vertebral fusion with disk calcification. SAPHO syndrome First described by Chamot et al in 1987, synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is characterized by variable bone changes (hyperostosis, arthritis, aseptic osteomyelitis) of the chest wall, sacroiliac joints, and long bones. Dermatologic manifestations include the following: Palmoplantar pustulosis Hidradenitis suppurativa Pustular psoriasis https://emedicine.medscape.com/article/2196539-print 8/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print Dissecting cellulitis of the scalp Sweet syndrome Sneddon-Wilkinson disease Skin and osseous involvement may occur simultaneously or may be separated by as long as 20 years.[11, 12] Juvenile psoriatic arthritis Juvenile psoriatic arthritis accounts for 8-20% of childhood arthritis and is monoarticular at onset. The median age of onset is 4.5 years in girls and 10 years in boys, and there is a female predominance. The disease is usually mild, although occasionally it may be severe and destructive, with the condition progressing into adulthood. In 50% of children, the arthritis is monoarticular; DIP joint involvement occurs at a similar rate. Tenosynovitis is present in 30% of children, and nail involvement is present in 71%, with pitting being the most common, but least specific, finding. In 47% of children, disordered bone growth with resultant shortening may result from involvement of the unfused epiphyseal growth plate in the inflammatory process. Sacroiliitis occurs in 28% of children and is usually associated with HLA-B27 positivity. Although the presence of HLA-B8 may be a marker of more severe disease, HLA-B17 is usually associated with a mild form of psoriatic arthritis. Children have a higher frequency of simultaneous onset of psoriasis and arthritis than adults do, with arthritis preceding psoriasis in 52% of children. Classification of psoriatic arthritis The simple and highly specific Classification Criteria for Psoriatic Arthritis (CASPAR), developed by a large international study group, has a sensitivity and specificity of 98.7% and 91.4%, respectively. The criteria 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 a 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) Pathophysiology and Etiology The pathogenesis of psoriatic arthritis is still not fully understood. Genetics, environmental factors, and immune-mediated inflammation play a complex roles. Psoriasis and psoriatic arthritis are interrelated disorders, so it is not surprising that they have commonalities in their pathogenesis. However, the fact that some of the new biologics and targeted therapy do not control the joint disease as well as the skin lesions highlights the difference between the two disorders. Slight differences exist in the vascular patterns of joints in psoriatic arthritis, compared with those of rheumatoid arthritis (RA), suggesting the possibility of different etiologic mechanisms in these diseases. Genetics Genetic factors play an important role in susceptibility to psoriasis and psoriatic arthritis ; approximately 40% of patients with either of these conditions have a family history of them in first-degree relatives.[16, 17] The recurrence risk ratio for psoriatic arthritis, an estimate of the heritability of the disease, is estimated at 30-55 in first- degree relatives of patients with this condition, while that for psoriasis is 8-10. Diseases with higher heritability have a higher likelihood of having genetic factors underlying disease susceptibility.[19, 20, 21, 22, 23] The following important genetic susceptibility loci have been found (although the exact mechanism of the association between HLA and psoriatic arthritis is not yet clear)[18, 24, 25, 26, 27, 28, 29, 30] : Early-onset psoriasis: HLA-Cw6, HLA-B57, HLA-DR7, and HLA-B17, with HLA-Cw*0602 variant found to be highly associated Psoriasis: HLA-Cw6 (or psoriasis susceptibility 1 [PSOR1] on chromosome 6) and 6 other psoriasis susceptibility loci (PSOR2, PSOR3, PSOR4, PSOR5, PSOR6, PSOR7), transcription factor RUNX1 Psoriatic arthritis: HLA-B7, HLA-B27, HLA-DR4, HLA-38, and HLA-DR7 https://emedicine.medscape.com/article/2196539-print 9/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print Psoriasis and psoriatic arthritis: HLA-Cw6, HLA-B13, HLA-B17, HLA-B57, and HLA-B39 Predictors of disease progression: HLA-B39; HLA-B27 in the presence of HLA-DR7; HLA-DQ3 in the absence of HLA-DR7 Protective: HLA-B22 Comparing psoriasis with psoriatic arthritis, it has been found that in psoriatic arthritis there is a stronger association with HLA-B alleles than with HLA-C alleles, while psoriasis (particularly early onset psoriasis) is associated with HLA-C.[31, 32] The following associated gene polymorphisms are also thought to be associated with psoriasis and psoriatic arthritis[18, 24, 27, 33] : Tumor necrosis factor (TNF)–alpha promoter Major histocompatibility complex (MHC) class I chain–related gene A (MICA): Independent of HLA, MICA*016 influences the risk of developing psoriasis without arthritis, while homozygosity for MICA*00801 increases the risk of developing psoriatic arthritis in patients with psoriasis[35, 36] Caspase-activating recruitment domain (CARD) 15 Interleukin (IL)-12/IL-23p40 and IL-23 receptor: Studies indicate that HLA-C and IL23R are more strongly associated with psoriasis alone, while IL12B is more strongly associated with psoriatic arthritis[19, 20, 21, 37] Additional loci that demonstrate an association with psoriatic arthritis include microsatellite polymorphisms in the TNF promoter. In psoriasis, linkages with loci on 17q, 4q, and 6p have been reported in whole-genome scans, with the strongest evidence for linkage on 6p. Certain immunoglobulin genes may be associated with psoriatic arthritis. Serum levels of immunoglobulin A (IgA) and IgG are higher in psoriatic arthritis patients, whereas IgM levels may be normal or diminished. Identifying susceptibility genes is likely to aid understanding of disease etiopathogenesis and identify potential therapeutic targets. Although loci identified to date explain only a fraction of the heritability estimates, a model of important pathways in psoriasis pathogenesis is emerging that combines the following[19, 20, 21, 22, 23, 38] : Skin barrier function ( LCE3B, LCE3C) The Th17 pathway ( IL12B, IL23A, IL23R, TRAF3IP2, TYK2) Innate immunity involving RANKL and interferon signaling ( TNFAIP3, TNIP1, NFKBIA, REL, TYK2, IFIH1, IL23RA) Beta-defensin Th2 ( IL4, IL13) Adaptive immunity involving CD8 T cells ( ERAP1) A gene-gene interaction between ERAP1 and HLA-C suggesting that ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk allele further implicates immune dysregulation in psoriasis pathogenesis. Immunologic factors Involvement of immunological mechanisms is suggested by the inflammatory process in psoriatic skin lesions and in the synovial fluid, which can be very similar to the inflammation seen in the synovial fluid of RA. There is an increased level of the proinflammatory cytokines including TNF-alpha, IL-1, IL-6, and IL-8 in the synovium and the synovial fluid of psoriatic arthritis patients. Up-regulation of serum IL-10, IL-13, TNF-alpha, and epidermal growth factor also occurs. These changes are similar to those seen in RA patients. Compared with RA patients, however, psoriatic arthritis patients produced less IL-4 and IL-5 in their synovium, had marked vascularity in the synovial lining, and lacked intracellular citrullinated proteins and MHC-Cpg 39 peptides, suggesting that the two diseases have different underlying mechanisms. The cytokine profile for psoriatic arthritis reflects a complex interplay between T cells and monocyte macrophages. Type 1 helper T-cell cytokines (eg, TNF-alpha, IL-1 beta, IL-10) are more prevalent in psoriatic arthritis than in RA, suggesting that these 2 disorders may have different underlying mechanisms. T cells play a major role in the development of inflammation in both psoriasis and psoriatic arthritis. The T cells in the skin are predominantly CD4 positive and CD8 negative, whereas in the synovial fluid they are CD8 positive. Cytokines produced by activated T cells induce the proliferation and activation of fibroblasts in the skin and synovial fluid. Activated T cells may be the cause of arthritis, or it may result from other unknown factors. Studies suggest that psoriatic arthritis is driven by T helper 17 (Th17) cell activation coupled with TNF-promoted inflammation. This is supported by the disease clinical responds to IL-23/IL-17 inhibitors such ustekinumab, secukinumab, ixekizumab, and brodalumab (12) https://emedicine.medscape.com/article/2196539-print 10/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print TNF-alpha and nuclear factor kappa B ligand (RANKL) upregulation and its effect on osteoclasts are important mechanisms in the pathogenesis of erosive psoriatic arthritis. The mechanism driving peripheral arthritis such as ankylosing, periostitis and enthesophytes is less understood, it is thought that prostaglandin E signalling pathways and bone morphogenetic protein BMP pathways are involved. (13) Finally, mechanically stressed enthesis and local trauma may have a role to play in driving inflammation in psoriatic arthritis. Autoantibodies against nuclear antigens, cytokeratins, epidermal keratins, and heat-shock proteins have been reported in persons with psoriatic arthritis, indicating that the disease has a humoral immune component. Dendritic cells have been found in the synovial fluid of patients with psoriatic arthritis and are reactive in the mixed leukocyte reaction; the inference is that the dendritic cells present an unknown antigen to CD4+ cells within the joints and skin of patients with psoriatic arthritis, leading to T-cell activation. Psoriatic plaques in skin have increased levels of leukotriene B4. Injections of leukotriene B4 cause intraepidermal microabscesses, suggesting a role for this compound in the development of psoriasis. Environmental factors The theory of environmental factors playing a role in the etiology of psoriatic arthritis involves a process of superantigens reacting with autoantigens. Several environmental factors have been implicated in the pathogenesis of both psoriasis and psoriatic arthritis. These mainly include bacterial and viral infections and trauma. The temporal relationship between certain viral and bacterial infections and the development or exacerbation of psoriasis and psoriatic arthritis suggests a possible pathogenetic role for viruses and bacteria, which is theorized to involve the interaction of superantigens with autoantigens. Pustular psoriasis is a well-described sequela of streptococcal infections. However, the response to streptococcal antigens by cells from patients with psoriatic arthritis is not different from that of cells from patients with RA, making the role of Streptococcus species in psoriatic arthritis doubtful. Psoriasis and psoriatic arthritis have been reported to be associated with HIV infection and to be prevalent in some HIV- endemic areas. Although the prevalence of psoriasis in patients infected with HIV is similar to that in the general population, patients with HIV infection usually have more extensive erythrodermic psoriasis, and patients with psoriasis may present with exacerbation of their skin disease after being infected with HIV. The Koebner phenomenon (development of new plaques at sites of trauma) is well described with psoriasis, and many patients identified trauma prior to developing joint pain in psoriatic arthritis. Heavy lifting and increased body weight may also confer an increased risk of psoriatic arthritis. There is an inverse association between smoking and psoriatic arthritis, except in HLA-C*06–positive individuals. Epidemiology Occurrence in the United States According to the National Psoriasis Foundation, psoriatic arthritis affects about 1 million people in the United States, or about 30% of all persons with psoriasis. However, prevalence rates vary widely among studies. In one population-based study, less than 10% of patients with psoriasis developed clinically recognized psoriatic arthritis during a 30-year period. A random telephone survey of 27,220 US residents found a 0.25% prevalence rate for psoriatic arthritis in the general population and an 11% prevalence rate in patients with psoriasis. However, the exact frequency of the disorder in patients with psoriasis remains uncertain, with the estimated rate ranging from 5-30%. Moreover, since the late 20th century, the incidence of psoriatic arthritis appears to have been rising in both men and women. Reasons for the increase are unknown; it may be related to a true change in incidence or to a greater overall awareness of the diagnosis by physicians. International occurrence A systematic review and meta-analysis of 28 studies estimated that the global average prevalence of psoriatic arthritis is 133 per 100,000 population (95% confidence index [CI], 107–164 per 100,000), and the incidence is 83 per 100,000 persons per year (95% CI, 41–167 per 100,000). A systematic review and meta-analysis of 266 studies concluded that worldwide, approximately one in four persons with psoriasis has psoriatic arthritis. However, the prevalence of psoriatic arthritis internationally ranges widely, depending on the population studied. A 2013 German study found the rate of psoriatic arthritis in patients with psoriasis to be 30.2%. In a prospective cohort study from Canada that involved psoriasis patients without arthritis at study entry, 51 of 464 patients developed psoriatic arthritis over the course of 8 years of followup. The annual incidence rate was 2.7 cases of psoriatic arthritis per 100 psoriasis patients. Baseline variables associated with the development of psoriatic arthritis in multivariate analysis included the following: https://emedicine.medscape.com/article/2196539-print 11/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print Severe psoriasis (relative risk [RR] 5.4, p=0.006) Low level of education (college/university vs. high school incomplete, RR 4.5, p=0.005; high school education vs. high school incomplete, RR 3.3, p=0.049) Use of retinoid medications (RR 3.4, p=0.02) There is a high prevalence of previously undiagnosed active psoriatic arthritis among patients with psoriasis who are seen by dermatologists. In a 2009 prospective German study, of 1511 patients with plaque-type psoriasis, 20.6% were found to have psoriatic arthritis, with 85% of the cases having been previously undiagnosed. The number of diagnosed cases of psoriasis and psoriatic arthritis has risen dramatically in sub-Saharan Africa in association with the area’s escalating epidemic of HIV infection. Although HIV is not known to affect the incidence of psoriasis, it may significantly exacerbate otherwise limited disease. The evolution of mild psoriasis to erythroderma in the setting of a flare-up of psoriatic arthritis may be a sign of HIV infection. Race- and age-related related demographics Race predilection in psoriatic arthritis has not been well studied. However, whites are known to be affected more commonly than are persons of other racial groups. A multiinstitutional study found that although psoriatic arthritis was less frequent in blacks than in whites, blacks had more severe skin involvement. Psoriatic arthritis characteristically develops in persons aged 35-55 years, but it can occur at almost any age. In the juvenile form, the age of onset is 9-11 years. Sex-related demographics The male-to-female ratio for psoriatic arthritis is 1:1, with the exception of some subsets of patients. Females are more commonly affected with symmetrical polyarthritis resembling RA and with the juvenile form. In contrast, the spondylitic form of psoriatic arthritis, which affects the axial spine, has a male-to-female ratio of 3:1. In a cross-sectional analysis of a large population of patients with psoriatic arthritis, male patients were found to be more likely to exhibit axial involvement and radiographic joint damage, and female patients were more likely to experience impaired quality of life and severe limitations in function. Prognosis Although psoriatic arthritis was originally thought to be relatively mild, as many as 40% of patients may develop erosive and deforming arthritis. A 1998 study from Switzerland found that about 7% of patients with psoriatic arthritis required musculoskeletal surgery; with the first operation at an average of 13.9 years (range 1-46) after onset of joint disease. Although a cohort study from the United Kingdom showed no increase in mortality among 453 patients with psoriatic arthritis compared with the general population, a Canadian study reported a significantly greater risk of hypertension, obesity, hyperlipidemia, type 2 diabetes mellitus, and cardiovascular events in patients with psoriatic arthritis than in those with psoriasis without arthritis. Psoriatic arthritis was also associated with infections not treated with antibiotics (presumably viral), neurologic conditions, gastrointestinal disorders, and liver disease. Labitigan et al reported that the prevalence of obesity, type 2 diabetes, and hypertriglyceridemia was higher in psoriatic arthritis than in RA. Using data from the Consortium of Rheumatology Researchers of North America (CORRONA) registry, the investigators found type 2 diabetes rates in psoriatic arthritis and RA to be 15% and 11%, respectively, and hypertriglyceridemia rates to be 38% and 28%, respectively. A pooled analysis of 2 large interventional lipid-lowering trials indicated that intensive statin treatment is effective in inflammatory joint disease, including rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. Furthermore, patients with and without inflammatory joint disease in the study had a 20% reduced risk of cardiovascular disease. A Norwegian study of 108 pregnancies in 103 women with psoriatic arthritis found that disease activity decreased in pregnancy and increased within 6 months postpartum. Women who used tumor necrosis factor inhibitors during in pregnancy had significantly lower postpartum disease activity than women who did not use those drugs. Patient Education Education is an important component of the psoriatic arthritis treatment plan, because patients must be able to manage their symptoms and be comfortable with self-treatment strategies. Physical therapists can provide education and an exercise https://emedicine.medscape.com/article/2196539-print 12/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print program developed individually for each patient. The wrong kind of exercise or overexertion can be harmful to patients with psoriatic arthritis. Instructing patients with psoriatic arthritis in methods of joint protection is a necessary part of therapy. Patients need to pace themselves and take adequate rest breaks from activity. Other examples of joint protection include the following: Wearing splints on the affected joints Using proper body mechanics and lifting techniques Incorporating assistive devices or adaptive equipment into activities of daily living For patient education information, see the Psoriatic Arthritis Health Center Presentation History Psoriasis appears to precede the onset of psoriatic arthritis in 60-80% of patients (occasionally by as many as 20 y, but usually by less than 10 y). However, in as many as 15-20% of patients, arthritis appears before the psoriasis, in which case a family history may reveal a hereditary pattern of psoriasis. Occasionally, arthritis and psoriasis appear simultaneously. In some cases, patients may experience only stiffness and pain, with few objective findings. In a patient who presents with musculoskeletal symptoms without a history of psoriasis, the diagnosis can be suspected based on a family history of psoriasis and the pattern of arthritis. In most patients, the musculoskeletal symptoms are insidious in onset, but an acute onset has been reported in one third of all patients. Factors that increase the risk of a patients with psoriasis developing arthritis in their lifetime include the presence of nail lesions, as well as more extensive skin involvement. One third of patients may develop inflammatory ocular symptoms reminiscent of reactive arthritis (previously termed Reiter syndrome). Eder et al reported that psoriatic arthritis has a preclinical phase that presages diagnosis of the disease.[58, 59] During this phase, patients have nonspecific musculoskeletal symptoms, including joint pain, fatigue, and stiffness. In their prospective cohort study of 410 patients with psoriasis, 57 of whom developed psoriatic arthritis, the following symptoms predicted the development of psoriatic arthritis: Arthralgia in women (hazard ratio [HR] 2.59, P = 0.02) Heel pain (HR 4.18, P = 0.02) High fatigue score (HR 2.36, P = 0.007) High stiffness score (HR 2.03, P = 0.045) Increase from baseline in fatigue score (HR 1.27, P = 0.001), pain score (HR 1.34, P < 0.001), and stiffness score (HR 1.21, P = 0.03) Worsening in physical function score (HR 0.96, P = 0.04) Physical Examination Psoriatic arthritis may be present with or without obvious skin lesions, with minimal skin involvement (eg, scalp, umbilicus, intergluteal cleft), or with only nail malformations. Less joint tenderness possibly occurs with psoriatic arthritis than with rheumatoid arthritis (RA). Recognition of the patterns of joint involvement seen in psoriatic arthritis, as follows, is essential to the diagnosis: Asymmetrical oligoarticular arthritis Symmetrical polyarthritis Distal interphalangeal arthropathy Arthritis mutilans (seen in the image below) Spondylitis with or without sacroiliitis https://emedicine.medscape.com/article/2196539-print 13/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print Patient with psoriatic arthritis involving the joints and skin displays features of arthritis mutilans with distal interphalangeal joint destruction causing a deformity and compromise to function. As in other spondyloarthropathies, the condition termed enthesopathy or enthesitis, reflecting inflammation at tendon or ligament insertions into bone, may be seen in psoriatic arthritis. Enthesopathy 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 (seen in the image below) occurs in as many as 35% of patients. Diagnosis is also suggested by asymmetrical joint involvement, dactylitis, the absence of RF, and distal interphalangeal (DIP) joint involvement in the absence of osteoarthritis. When localized to the foot or toe, the symptoms of psoriatic arthritis may be mistaken for gout. Psoriatic arthritis showing nail changes, distal interphalangeal joint swelling, and sausage digits. Skin involvement The following skin lesions may be seen in the context of psoriatic arthritis: Scaly, erythematous plaques Guttate lesions Lakes of pus Erythroderma In one study, as previously mentioned, arthritis was noted more frequently in patients with severe skin disease. https://emedicine.medscape.com/article/2196539-print 14/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print In patients presenting with an undefined seronegative polyarthritis, looking for psoriasis in hidden sites, such as the scalp (where psoriasis frequently is mistaken for dandruff), perineum, intergluteal cleft, and umbilicus is extremely important. Nail involvement Nails are involved in 80% of patients with psoriatic arthritis but in only 20% of patients with uncomplicated psoriasis, with nail involvement frequently seen at the onset when skin and joint disease begin simultaneously. The following changes in the nails support the diagnosis of psoriatic arthritis : 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: A direct correlation exists between the number of pits and their diagnostic significance (see the image below) Left, typical appearance of psoriasis, with silvery scaling on a sharply marginated and reddened area of skin overlying the shin. Right, thimblelike pitting of the nail plate in a 56-year-old woman who had suffered from psoriasis for the previous 23 years. Nail pitting, transverse depressions, and subungual hyperkeratosis often occur in association with psoriatic disease of the distal interphalangeal joint. Courtesy of Ali Nawaz Khan, MBBS. Severe, deforming arthritis of the hands and feet is frequently associated with extensive nail involvement. Involvement of DIP joints correlates moderately well with psoriasis in adjacent nails, although this is not an invariable association. In fact, psoriatic nail changes may be a solitary finding in patients with psoriatic arthritis. Fungal infection of the nails is the main consideration in the differential diagnosis in a patient with a seronegative polyarthritis. Extra-articular features Extra-articular features are observed less frequently in patients with psoriatic arthritis than in those with RA. In patients with psoriatic arthritis, synovitis has a predilection for the flexor tendon sheath, with sparing of the extensor tendon sheath; both tendon sheaths are commonly involved in persons with RA. Subcutaneous nodules are rare in patients with psoriatic arthritis. If nodules are present in a patient who has psoriasis and arthritis, particularly if the RF titer is positive, they suggest the coincidental occurrence of psoriasis and RA. Ocular involvement may occur in 30% of patients with psoriatic arthritis, including conjunctivitis in 20% of patients and acute anterior uveitis in 7% of them. In patients with uveitis, 43% have sacroiliitis and 40% are HLA-B27–positive. Scleritis and keratoconjunctivitis sicca are rare. Possible ocular findings also include iritis. Inflammation of the aortic valve root, which may lead to insufficiency, has been described in 6 patients with psoriatic arthritis and is similar to that observed more frequently in persons with ankylosing spondylitis or reactive arthritis. Occasionally, https://emedicine.medscape.com/article/2196539-print 15/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print patients with psoriatic arthritis may develop secondary amyloidosis. DDx Diagnostic Considerations Psoriasiform skin lesions may be observed in association with reactive arthritis, inflammatory bowel disease, and the syndrome of inappropriate secretion of diuretic hormone. The differential diagnosis also includes rheumatoid arthritis of the hands and spine. Enteropathic arthritis (arthritis of inflammatory bowel disease) should also be considered, and spotted bone disease has been reported in a patient with psoriatic arthritis. Lupus erythematosus can produce a rash similar to a psoriatic rash. Usually, however, lupus-associated arthritis is not as deforming as psoriatic arthritis. Secondary syphilis can also cause a rash similar to a psoriatic rash. However, although an arthropathy can be associated with syphilis, it occurs years after the skin lesions have cleared in an untreated patient. Ankylosing spondylitis can produce back pain similar to that associated with psoriatic arthritis but without the associated peripheral arthropathy or skin lesions. Differential Diagnoses Gout and Pseudogout Osteoarthritis Reactive Arthritis Rheumatoid Arthritis (RA) Septic Arthritis Workup Workup Approach Considerations No specific diagnostic tests are available for psoriatic arthritis. Diagnosis of the disease is instead based on clinical and radiologic criteria in a patient with psoriasis. Radiologic features can, for example, help to distinguish psoriatic arthritis from other causes of polyarthritis, such as rheumatoid arthritis (RA). The most characteristic laboratory abnormalities in patients with psoriatic arthritis are elevations of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level. The results from these laboratory tests help to track the activity of the disease by measuring inflammation. Laboratory Studies Erythrocyte sedimentation rate An elevated ESR is found in approximately 40% of patients with psoriatic arthritis. An ESR of greater than 15 mm/h, along with medication use before the first clinical visit, evidence of radiologic damage, and absence of nail lesions, has been associated with increased mortality in patients with psoriatic arthritis. Rheumatoid factor Patients with psoriatic arthritis are typically seronegative for rheumatoid factor (RF), although RF is detected in 5-9% of patients. RF testing is usually associated with a high false-positive rate; thus, RF-positive and RF-negative patients should https://emedicine.medscape.com/article/2196539-print 16/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print receive the same treatment. Antinuclear antibodies Antinuclear antibody titers in persons with psoriatic arthritis do not differ from those of age- and sex-matched controls. In 10- 20% of patients with generalized skin disease, the serum uric acid concentration may be increased and, on occasion, may predispose patients to acute gouty arthritis. Low levels of circulating immune complexes have been detected in 56% of patients with psoriatic arthritis but do not appear to parallel disease activity. Immunoglobulin Serum IgA levels are increased in two thirds of patients with psoriatic arthritis and in one third of patients with psoriasis. Synovial fluid Synovial fluid is inflammatory in psoriatic arthritis, with white blood cell (WBC) counts ranging from 5000-15,000/µL and with polymorphonuclear leukocytes comprising more than 50% of cells. Within the synovium, the infiltrate consists predominantly of T lymphocytes. Glucose levels are within reference ranges, and synovial fluid complement levels are either within reference ranges or increased. Psoriatic versus rheumatoid arthritis The table below compares laboratory values in psoriatic arthritis with those in RA. Table. Comparison of Expected Laboratory Values in Psoriatic Arthritis and Rheumatoid Arthritis (Open Table in a new window) Laboratory Studies Psoriatic Arthritis Rheumatoid Arthritis Erythrocyte sedimentation Elevated (< 100) Elevated (< 100) rate Positive (85% of Rheumatoid factor Negative patients) Positive (30% of Antinuclear antibody Negative patients) C-reactive protein Elevated Elevated WBC count 5000-15,000/µL, >50% polymorphonuclear Synovium WBC count 2000/µL leukocytes Histologic findings The histopathology of psoriatic synovitis is similar to that observed in other inflammatory arthritides, with a notable lack of intrasynovial immunoglobulin and RF production and a greater propensity for fibrous ankylosis, osseous resorption, and heterotopic bone formation. Imaging Studies https://emedicine.medscape.com/article/2196539-print 17/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print Radiologic features may help distinguish psoriatic arthritis from other causes of polyarthritis. For full discussion, see Psoriatic Arthritis Imaging. 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 initially is preserved, with maintenance of a normal joint space. Juxta-articular osteopenia, which is a hallmark of RA, is minimal in persons with psoriatic arthritis. Asymmetrical erosive changes in the small joints of the hands and feet are typical of psoriatic arthritis and have a predilection (in decreasing order) for the distal interphalangeal (DIP), proximal interphalangeal, metatarsophalangeal, and metacarpophalangeal joints. (See the images below.) Swelling and deformity of the metacarpophalangeal and distal interphalangeal joints in a patient with psoriatic arthritis. Psoriatic arthritis involving the distal phalangeal joint. https://emedicine.medscape.com/article/2196539-print 18/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print Psoriatic arthritis involving the distal phalangeal joint. Psoriatic arthritis involving the distal phalangeal joint. Erosive disease frequently occurs in patients with either DIP involvement or progressive deforming arthritis and may lead to subluxation and, less commonly, to bony ankylosis of the joint. Erosion of the tuft of the distal phalanx, and even of the metacarpals or metatarsals, can progress to complete dissolution of the bone. Although this form of acro-osteolysis is not diagnostic, it is highly suggestive of psoriatic arthritis. The pencil-in-cup deformity observed in the hands and feet of patients with severe joint disease usually affects the DIP joints but also may involve the proximal interphalangeal joints. Radiography Radiographic evaluations, along with clinical assessment for joint inflammation or damage, are a traditional method for monitoring patients with rheumatic conditions. Radiography shows a combination of erosion (unlike in ankylosing spondylosis) and bone growth (unlike in RA) in affected joints. The following radiographic abnormalities are suggestive of psoriatic arthritis: Pencil-in-cup deformity (seen in the image below) https://emedicine.medscape.com/article/2196539-print 19/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print 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 destruction Fluffy periostitis Bilateral, asymmetrical, fusiform soft-tissue swelling Unilateral or symmetrical sacroiliitis Large, nonmarginal, unilateral, asymmetrical syndesmophytes (intervertebral bony bridges, seen in the image below) in the cervical, thoracic, and lumbar spine, often sparing some of the segments Lateral radiograph of the cervical spine shows syndesmophytes at the C2-3 and C6-7 levels, with zygapophyseal joint fusion. Courtesy of Bruce M. Rothschild, MD. A study by Tillett et al of four radiographic scoring methods for psoriatic arthritis reached the following conclusions : Modified Sharp score (MSS) and modified Sharp/van der Heijde score (SHS) - The most reliable and sensitive to change, but take longer to perform Modified Steinbrocker score - The most feasible but lacks the sensitivity of the SHS Ratingen score - Smallest detectable change (SDC) close to that of the SHS and MSS, but this score is quicker to perform https://emedicine.medscape.com/article/2196539-print 20/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print Salaffi et al have reported preliminary validation of a novel radiographic scoring system for psoriatic arthritis, the Simplified Psoriatic Arthritis Radiographic Score (SPARS). SPARS correlated strongly with the SHS and Ratingen scores, and proved quicker to calculate (4.5 min, versus 14.4 min for SHS and 10.1 min for Ratingen). CT scanning and MRI Computed tomography (CT) scanning and MRI may be useful for detecting early signs of joint synovitis. MRI is particularly sensitive for detecting sacroiliitic synovitis, enthesitis, and erosions; it can also be used with gadolinium to increase sensitivity. MRI may show inflammation in the small joints of the hands, involving the collateral ligaments and soft tissues around the joint capsule, which is not seen in RA. Ultrasonography Ultrasonography has an emerging role in the diagnosis and management of psoriatic arthritis. Its uses include the following : Predicting progression to psoriatic arthritis in patients with psoriasis by detecting subclinical signs of synovitis and enthesitis Diagnosing psoriatic arthritis Providing accurate and objective monitoring of disease activity Predicting clinical and structural outcome Treatment Approach Considerations The treatment of psoriatic arthritis is directed at controlling the inflammatory process. Although no clear correlation exists between joint inflammation and skin involvement in every patient, the skin and joint aspects of the disease often must be treated simultaneously. The finding that 40% of patients may develop erosive and deforming arthritis has led to recommendations of early treatment with disease-modifying antirheumatic drugs (DMARDs) in patients with active disease (see Guidelines). In addition to older DMARDs, several biologic agents and targeted synthetic agents have become available for use in psoriatic arthritis. Nonpharmacologic treatment such as physical therapy should be considered early in the disease process, with the regimen individualized to the individual patient's need. Different approaches are appropriate, depending on the disease phase. Currently, no prospective studies address surgical intervention in patients with psoriatic arthritis. Patients in severe pain or with significant contractures may be referred for consideration of surgical intervention (eg, synovectomy, joint replacement). Treatment should be aimed at symptom relief and functional improvemnet. Guidelines and recommendations are designed to help physicians work with patients to select the optimum therapy. The following are important considerations that may additionally influence therapy choice: Presence of comorbidities such as infections, inflammatory bowel disease (IBD), diabetes mellitus, and uveitis Previous therapies and reasons for failure Peripheral or axial joint involvement Severity of joint involvement and the patient’s functional status Other active domains of the disease (skin and/or nails) The severity of the psoriatic arthritis and psoriasis is usually assessed on a case-by-case basis, as there is no widely approved definition. In the case of cutaneous psoriasis, particularly in clinical trials, a Psoriasis Area and Severity Index (PASI) score of ≥12 and body surface area (BSA) score ≥10 is widely considered severe. The 2007 National Psoriasis Foundation (NSF) expert consensus statement defined psoriatic arthritis and psoriasis as moderate to severe if one or more items in the lists below were positive. Criteria for psoriatic arthritis: Erosive disease Elevated markers of inflammation attributed to psoriatic arthritis (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]) Long-term damage that interferes with function (eg, joint deformity) Highly active disease that causes a major impairment in quality of life Active psoriatic arthritis at many sites, including dactylitis and enthesitis https://emedicine.medscape.com/article/2196539-print 21/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print Function-limiting psoriatic arthritis at a few sites Rapidly progressive disease Criteria for psoriasis: PASI of 12 or more BSA of 5-10% or more Significant involvement in specific areas (face, hands, feet, nails, scalp, intertriginous areas) where the burden of the disease causes significant disability Impairment of physical of mental function The following indices have been developed for measuring disease activity and response to treatment in psoriatic arthritis : Psoriatic Arthritis Disease Activity Score (PASDAS) Arithmetic Mean of the Desirability Function (AMDF) Composite Psoriatic Disease Activity Index (CPDAI) Disease Activity Index for Psoriatic Arthritis (DAPSA) A study comparing those indices concluded that PASDAS and AMDF were better able to distinguish treatment effect, having larger effect sizes at 24 weeks, while PASDAS, AMDF, and modified CPDAI better reflected domains such as skin, enthesitis, and dactylitis.112 Although the PASDAS can differentiate low, moderate, and high disease activity, its use in routine clinical care has been called into questioned due to its complexity. However, Mulder et al reported successful implementation of PASDAS measurements and skin assessment in routine clinical care for the 1300 psoriatic arthritis patients at their outpatient clinic. Pharmacotherapy Medical treatment regimens include the following: Medication for symptomatic relief, such as nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and glucocorticoid joint injections Oral small molecules (OSMs), such as DMARDs, including methotrexate, sulfasalazine, cyclosporine, leflunomide, and apremilast Biologic therapy Intra-articular injection of entheses or single inflamed joints with corticosteroids may be particularly effective in some patients. Use DMARDs in individuals whose arthritis is persistent. If the skin disease is well controlled with topical medication, the joint disease can be treated with a variety of second-line or cytotoxic drugs. Intramuscular injection of gold was used in the past but has been supplanted by newer DMARDs. In patients with severe skin inflammation, medications such as methotrexate, retinoic acid derivatives, and psoralen plus ultraviolet (UV) light should be considered. These agents have been shown to work on both skin and joint manifestations. Methotrexate A randomized, 6-month study by Scarpa et al showed that the early use of methotrexate in patients with early psoriatic arthritis markedly improved tender and swollen joints and/or entheses. However, no significant difference was found after 3 months of treatment with NSAIDs or methotrexate. These results suggested that other therapeutic approaches capable of modifying the early course of the disease should be used. Patients receiving long-term methotrexate therapy with high cumulative doses can be monitored using serial liver function tests (LFTs). Liver biopsy should be considered if LFT values are persistently elevated. Pro-collagen 3 N-terminal peptide (PIIINP) is an alternative test, although Lindsay et al reported that PIIINP frequently showed elevated values despite normal liver biopsy results. Intolerance to methotrexate was observed in 14.3% of patients with psoriatic arthritis in a cross-sectional study (n=291), as measured with the Methotrexate Intolerance Severity Score (MISS). GI symptoms, including nausea, abdominal pain, and vomiting, occurred during methotrexate treatment in 123 patients (42.3%); behavioral symptoms, including restlessness and irritability, were also common. Methotrexate intolerance was more common with parenteral (20.6%) than oral (6.2%) administration.[73, 74] Biologic therapy Biologic agents include the following: Tumor necrosis factor (TNF) inhibitors - Etanercept, infliximab, adalimumab, golimumab, certolizumab pegol Interleukin (IL)-12/23 inhibitors - Ustekinumab, guselkumab https://emedicine.medscape.com/article/2196539-print 22/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print IL-17 inhibitors - Secukinumab, ixekizumab, brodalumab [75, 76] Janus kinase (JAK) inhibitors - Tofacitinib Phosphodiesterase-4 (PDE4) inhibitor - Apremilast Certolizumab pegol The TNF inhibitor certolizumab pegol (Cimzia) is approved by the U.S. Food and Drug Administration (FDA) for the treatment of active psoriatic arthritis in adults. Approval was based on an ongoing, randomized, double-blind, placebo- controlled trial in 409 patients with active and progressive adult-onset psoriatic arthritis (RAPID-PsA) in which certolizumab- treated patients were significantly more likely to meet American College of Rheumatology 20%, 50%, and 70% response criteria (ACR20, ACR50, ACR70) by week 12 than placebo-treated patients. Certolizumab reduced radiographic progression and improved skin manifestations. Further analysis of the RAPID-PsA showed that improvement occurred with certolizumab pegol used as monotherapy or given with concomitant DMARDs. Golimumab Like certolizumab, golimumab (Simponi Aria) is a fully human anti–TNF-alpha monoclonal antibody. Golimumab received FDA approval for psoriatic arthritis in October 2017. It was initially approved in 2013 for the treatment of moderately to severely active rheumatoid arthritis. Approval for psoriatic arthritis was based on data from the GO-VIBRANT trial. In this phase 3, multicenter, randomized, double-blind, placebo-controlled trial, patients were randomized to either IV or golimumab 2 mg/kg at weeks 0, 4, 12, and 20 with crossover to golimumab at week 24. At week 14, 75.1% in the golimumab group achieved ACR20 vs. 21.8% in the placebo group. Greater proportions of golimumab-treated patients had ACR50 (43.6% vs 6.3%), ACR70 (24.5% vs 2.1%), and PASI75 (59.2% vs 13.6%) at week 14. The golimumab group had greater mean changes at week 14 in Health Assessment Questionnaire-Disability Index (HAQ-DI) compared with placebo (-0.60 vs -0.12;). At week 24, the mean change in van der Heijde-Sharp (vdH-S) score was -0.4 in the golimumab group and 2.0 in the placebo group. Ustekinumab The FDA and the European Union have approved ustekinumab, an IL-12/23 inhibitor, for the treatment of active psoriatic arthritis in adults who have not responded adequately to previous treatment with nonbiologic DMARDs. The drug was previously approved in the US and Europe for treatment of moderate to severe psoriatic plaques in adults. Approval was based on 2 randomized, double-blind, placebo-controlled trials in 927 patients with active psoriatic arthritis who had at least 5 tender and 5 swollen joints and CRP levels of 0.3 mg/dL or higher despite previous conventional therapy. At week 24, 42% of patients receiving ustekinumab 45 mg and 50% of those receiving 90 mg achieved at least 20% improvement; this response was sustained at 52 weeks. Treatment with ustekinumab also improved dactylitis, enthesitis, and skin lesions.[80, 81] Guselkumab Guselkumab (Tremfya) is the first selective interleukin-23 inhibitor approved to treat active psoriatic arthritis in adults. Approval was based on 2 randomized, double-blind. placebo-controlled trials, DISCOVER-1 and DISCOVER-2, which evaluated the efficacy and safety of guselkumab in adults with active psoriatic arthritis. In both trials, the primary endpoint of American College of Rheumatology 20% improvement (ACR20) at week 24 was reached. In Discover-1, 59% (every 4 weeks) and 52% (every 8 weeks) of the guselkumab-treated arms achieved ACR20 at week 24. In Discover-2, 64% (every 4 weeks and every 8 weeks) of the guselkumab-treated arms achieved ACR20 at week 24. Similar responses were seen in both trials regardless of concomitant or previous treatment with classical DMARDs, gender, and body weight. Secukinumab Secukinumab (Cosentyx) is a human IgG1 monoclonal antibody that selectively binds to and neutralizes IL-17A, which is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Secukinumab was approved by the FDA for adults with active psoriatic arthritis in January 2016. Approval of secukinumab was based on the FUTURE 1 and 2 phase 3 trials. In the FUTURE 1 trial (n=606), the ACR20 response rates at week 24 were significantly higher in the group receiving secukinumab at doses of 150 mg (50.0%) and 75 mg (50.5%) than in those receiving placebo (17.3%) (P< 0.001 for both comparisons with placebo). In FUTURE 2, a significantly higher proportion of patients achieved an ACR20 at week 24 with secukinumab doses of 300 mg (54%; P< 0.0001) and 150 mg (51%; P< 0.0001) compared with placebo (15%). Abatacept Abatacept (Orencia) was approved by the FDA for adults with active psoriatic arthritis in June 2017. Approval was based on a randomized, placebo-controlled phase 3 clinical trial in which abatacept significantly increased ACR20 response compared with placebo at week 24 (39.4% vs 22.3%; P < 0.001). The study was continued with open-label abatacept and efficacy was maintained or improved up to week 52. Ixekizumab https://emedicine.medscape.com/article/2196539-print 23/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print Ixekizumab (Taltz) was approved for active psoriatic arthritis in December 2017. Ixekizumab is a humanized monoclonal IgG4 antibody that targets IL-17A, resulting in neutralization of IL-17A’s proinflammatory effects. Approval of ixekizumab was based on 2 randomized, double-blind, placebo-controlled phase 3 studies (SPIRIT-P1 and SPIRIT-P2), which included more than 670 adults. Results from both studies demonstrated that patients treated with ixekizumab achieved significant improvement in joint symptoms, as measured by ACR20, compared with placebo. SPIRIT-P1 evaluated the safety and efficacy of ixekizumab compared with placebo in patients who had never been treated with a biologic DMARD. SPIRIT-P2 evaluated safety and efficacy compared with placebo in patients in whom treatment with 1 or 2 TNF inhibitors had failed. At 24 weeks, patients who received ixekizumab had an ACR20 response superior to placebo (58% vs 30%, respectively, in SPIRIT-P1; 53% vs 20% in SPIRIT-P2).[84, 85] Tofacitinib In December 2017, tofacitinib was approved by the FDA as the first-in-class JAK inhibitor for active psoriatic arthritis in patients who experience inadequate response or intolerance to methotrexate or other DMARDS. Approval was based on data from the phase III Oral Psoriatic Arthritis Trial (OPAL) clinical development program, OPAL Broaden and OPAL Beyond, and available data from the ongoing long-term extension trial, OPAL Balance. In the OPAL Broaden study, 50% of patients who received tofacitinib 5 mg PO BID in combination with a nonbiologic DMARD achieved an ACR20 response at 3 months, compared with 33% of those treated with placebo. In the OPAL Beyond study, 50% of patients achieved an ACR20 response with tofacitinib 5 mg PO BID at 3 months, when compared with 24% taking placebo. In both studies, significant improvements in ACR20 response was also seen with tofacitinib 5 mg PO BID when compared with placebo at week 2, which was a secondary endpoint and the first post-baseline assessment (OPAL Broaden: 22% vs. 6%; OPAL Beyond: 27% vs. 13%). Apremilast Apremilast (Otezla) is approved by the FDA for treatment of active psoriatic arthritis. It is a PDE4 inhibitor that is specific for cyclic adenosine monophosphate (cAMP), resulting in increased intracellular cAMP levels. In studies involving nearly 1500 patients with psoriatic arthritis, improvement was observed in 32-41% of patients at week 6, a statistically significant difference compared with placebo (P < 0.05). Patients received apremilast 30 mg orally twice daily plus concomitant therapy with at least 1 DMARD, methotrexate, leflunomide, oral corticosteroids, or NSAIDs.[88, 89, 90, 91] Other agents In a study by the Psoriatic Arthritis Study Group, patients with psoriasis and psoriatic arthritis who were receiving stable doses of methotrexate were found to benefit from the addition of 1 or more courses of intramuscular alefacept, a T-cell inhibitor via a human lymphocyte function–associated antigen 3 (LFA-3) Fc fusion protein that blocks the interaction between CD2 on T cells and LFA-3 on antigen-presenting cells. Further benefit in psoriatic arthritis was apparent after a second course of alefacept, and no additional toxicity was observed. Sulfasalazine and cyclosporine may control the acute inflammation in persons with psoriatic arthritis, but they have not been found helpful in arresting the progression of clinical and radiologic damage. Thus, earlier treatment or use of more effective drugs is necessary, to prevent the long-term damage that psoriatic arthritis may cause. Cyclosporine appears to be an effective agent for the treatment of psoriasis and psoriatic arthritis. The major concern with this drug is its toxicity, especially its nephrotoxicity, and hypertension. Combination therapy (eg, methotrexate/sulfasalazine, methotrexate/cyclosporine) may be more efficacious in some patients. Other agents that have been tried in psoriatic arthritis but whose efficacy remains unproven include the following: Vitamin D3 Bromocriptine Peptide T Fish oils The Medical Board of the National Psoriasis Foundation weakly recommends vitamin D supplementation in patients with psoriatic arthritis, as well as dietary weight reduction with a hypocaloric diet in overweight and obese patients. The Board recommends that dietary interventions should always be used in conjunction with standard medical therapies. Antimalarials, particularly hydroxychloroquine, are usually avoided in patients with psoriasis for fear of precipitating exfoliative dermatitis or exacerbating psoriasis. However, in 2 studies these reactions did not occur in patients who were treated with hydroxychloroquine; therefore, this drug is occasionally used to treat psoriatic arthritis. Systemic corticosteroids are usually avoided because of possible rebound of the skin disease upon withdrawal. https://emedicine.medscape.com/article/2196539-print 24/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print Nonpharmacologic therapy The 2018 American College of Rheumatology/National Psoriasis Foundation (ACR/NPF) guidelines recommend that all patients with active psoriatic arthritis consider the following forms of nonpharmacologic therapy: Exercise Physical therapy Massage therapy Occupational therapy Acupuncture The ACR/NPF guidelines recommend the use of one form or a combination of those therapies, if tolerated. For patients with active joint disease, low-impact exercise such as tai chi, yoga, and swimming is more suitable than high-impact sports such as running. Smoking cessation is an important consideration. Clinicians should offer their psoriatic arthritis patients referrals or tools to stop smoking, as multiple randomized controlled trials validate the benefit of smoking cessation in other conditions and in the general population.[98, 99] Weight loss in individuals with a high body mass index can potentially provide benefit by reducing mechanical stress on joints, improving mobility, and potentially increasing pharmacologic response. Physical therapy The rehabilitation treatment program for patients with psoriatic arthritis should be individualized and should be started early in the disease process. Such a program should consider the use of the following: Rest: Local and systemic Exercise: Passive, active, stretching, strengthening, and endurance Heat and cold: These modalities can temporarily relieve pain and reduce joint swelling; such treatments include soaking in a warm tub or placing a warm compress or cold pack on the painful joint. Orthotics: Upper and lower extremities, spinal Assistive devices for gait and adaptive devices for self-care tasks: Including possible modifications to homes and automobiles Education about the disease, energy conservation techniques, and joint protection Possible vocational readjustments With regard to the first item above, prolonged rest should be avoided to prevent the deleterious effects of immobility. In a very few cases, psoriatic arthritis may cause extreme fatigue. Acute phase Encourage rest as indicated. Splints may be used for rest and pain relief, especially for the hands, wrists, knees, or ankles. Cold modalities should be used to decrease inflammation and assist with pain relief. Joints should not be moved beyond the limit of pain; passive movements should be limited at this time. Education should be completed during this phase, with topics including the following: The disease itself (see Overview/Patient Education) The importance of rest An exercise program Joint protection Energy conservation Weight loss (if appropriate) Subacute and long-term phase Isometric exercises are begun, with progression to active movement. Gradual range-of-motion (ROM) exercises include passive and active exercises; areas with subluxation should not be forced passively. Heating modalities, including moist heat packs, paraffin wax, diathermy, and ultrasound, can be used to decrease pain; heat therapy should be administered just prior to the performance of ROM exercises. Institute gait activities, with the patient bearing weight as tolerated, with or without an assistive device. Gentle stretching should be gradually introduced. If pain persists beyond 2 hours after therapies, then the intensity should be decreased. If a joint is swollen, then no resistive exercises should be performed through full ROM. https://emedicine.medscape.com/article/2196539-print 25/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print For patients with axial spine involvement, spine extension exercises help with flexibility and strength. ROM exercises should be performed, but not in patients with increased pain. If the patient has sausage toes, extra-depth shoes with a high toe box should be considered to protect the foot. In patients with painful toes, such shoes should have a rocker-bottom modification to alleviate forces during the toe-off phase in the gait cycle. Arch supports may be beneficial if plantar fascitis is a problem. Synovectomy and Arthroplasty Arthroscopic synovectomy has been effective in treating severe, chronic, monoarticular synovitis. Because of an enhanced tendency for patients to develop fibrosis in association with this therapy, anti-inflammatory and physical therapy measures aimed at improving ROM are important adjuncts to this intervention. Joint replacement and forms of reconstructive therapy are occasionally necessary. Hip and knee joint replacements have been successful, for the most part, in patients with psoriatic arthritis. Arthrodesis and arthroplasty have also been used on joints, such as the proximal interphalangeal joint of the thumb. The wrist often spontaneously fuses, and this may relieve the patient's pain without surgical intervention. Because of the diffuse soft-tissue involvement that is associated with psoriatic arthritis, high rates of recurrence of joint contractures have been noted after surgical release, especially in the hand. For arthritis mutilans, surgical intervention is usually directed toward salvage of the hand. Combinations of arthrodesis, arthroplasty, and bone grafts to lengthen the digits may be used. The goal is to maintain the pinch mechanism of the thumb and the first 2 fingers. Consultations If the patient's physician feels uncomfortable with prescribing medications for psoriatic arthritis, referral to a rheumatologist with more experience with these agents may be advisable. A physiatrist may concentrate on functional restoration of the patient. Patients with juvenile psoriatic arthritis should be examined by an ophthalmologist annually to check for the several forms of eye inflammation usually associated with various forms of juvenile arthritis. Given the complexity of pharmacologic therapy, patients with psoriatic arthritis should be cared for by a multidiscplinary team, especially if more than one domain of the disease is active. In addition, those with joint deformities may require consultation with an orthopedic surgeon, as joint replacement, arthrodesis, or contracture release may be needed. Deterrence and Prevention A number of medications can exacerbate psoriasis; therefore, avoidance of these agents may help to prevent or minimize flare-ups. Lithium and withdrawal from systemic corticosteroids are well known to cause disease flare-ups. Other drugs that have been implicated include beta-blockers, antimalarials (although, as previously mentioned, evidence suggests that hydroxychloroquine does not usually exacerbate skin lesions), and NSAIDs. If skin lesions worsen with an NSAID, switch to a different family of NSAID. Prevention includes rest and exercise. Joint protection, including splints, braces, and other supports, may be helpful. No definitive prevention exists, because this is a chronic disease that can wax and wane. Complications Many patients with psoriatic arthritis have comorbidities, such as the following: Cardiovascular disease Metabolic syndrome Inflammatory bowel disease Osteoporosis Malignancy https://emedicine.medscape.com/article/2196539-print 26/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print Ophthalmic disease Liver disease Kocijan et al reported that psoriatic arthritis is associated with significantly decreased trabecular volumetric bone mineral density (BMD) and deterioration of trabecular bone microstructure. Those effects on bone correlated with the duration of skin disease. A study by Simon et al found that despite longer disease duration, patients with psoriatic arthritis treated with biologic DMARDs had higher bone mass and better bone strength than those treated with methotrexate or no DMARDs. A longitudinal cohort study in 1061 Canadian patients with psoriatic arthritis identified liver abnormalities or disease in 32%. In most cases, the liver abnormalities or disease were not present when the patient was first evaluated in clinic, but instead developed after an average of 8.3 years of follow-up and at a mean age of 50.5 years. Drug-induced hepatitis (14%) and fatty liver (13%) were the most common conditions. On multivariable analysis, the following factors were independently associated with liver abnormalities: High body mass index (odds ratio [OR], 1.07) Daily alcohol intake (OR, 4.46) Damaged joint count (OR, 1.04) Elevated C-reactive protein level (OR, 2.00) Treatment with methotrexate or leflunomide (OR, 4.39) Treatment with tumor necrosis factor inhibitors (OR, 10.56) These authors recommend monitoring of liver function in psoriatic arthritis who are at high risk for liver abnormalities. Guidelines Guidelines Summary Guidelines and recommendations on psoriatic arthritis have been published by the following organizations: American College of Rheumatology/National Psoriasis Foundation (ACR/NPF) - updated 2018 European League Against Rheumatism (EULAR) - updated 2015 American Academy of Dermatology (AAD) - updated 2010 British Society of Rheumatology (BSR) - published 2013 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) - updated 2015 American College of Rheumatology/National Psoriasis Foundation recommendations The ACR/NPF guidelines have evidence-based recommendations, based on systematic literature review along with expert opinion, for both pharmacologic and nonpharmacologic treatment of active psoriatic arthritis. GRADE (Grading for Recommendation Assessment, Development and Evaluation) methodology were used for assessment. It is worth mentioning that 6% of the recommendations are strong and 96% are conditional. This highlights the importance of evaluating each case individually and engaging in a discussion with patients to assess their needs and choose optimal therapy. Pharmacologic therapy Treatment recommendations for patients with active psoriatic arthritis who are treatment-naïve are as follows: Tumor necrosis factor (TNF) inhibitors are preferred over oral small molecules (OSM), interleukin-17 (IL-17) inhibitors, or IL-12/23 inhibitors OSM are recommended over IL-17 inhibitors or IL-12/23 inhibitors Methotrexate (MTX) is recommended over nonsteroidal anti-inflammatory drugs (NSAIDs) IL-17 inhibitors are recommended over IL-12/23 inhibitors Treatment recommendations for patients with active psoriatic arthritis despite the use of OSM are as follows: Switch to a TNF inhibitor biologic over another OSM, IL-17 or IL-12/23 inhibitors, abatacept, or tofacitinib Switch to an IL-17 inhibitor biologic over another OSM, IL-12/23 inhibitor, abatacept, or tofacitinib Switch to an IL-12/23 inhibitor biologic over another OSM, abatacept, or tofacitinib Treatment recommendations for patients with active psoriatic arthritis despite TNF inhibitor monotherapy are as follows: Switch to a different TNF inhibitor or add methotrexate over IL-17 or IL-12/23 inhibitors, abatacept, or tofacitinib Switch to an IL-17 inhibitor biologic over IL-12/23 inhibitor, abatacept, or tofacitinib Switch to an IL-12/23 inhibitor biologic over another OSM, abatacept, or tofacitinib https://emedicine.medscape.com/article/2196539-print 27/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print Treatment recommendations for patients with active psoriatic arthritis despite TNF inhibitor plus MTX combination therapy are as follows: Switch to a different TNF inhibitor + methotrexate over TNF inhibitor monotherapy Switch to IL1-7 inhibitor biologic monotherapy over IL17 inhibitor + MTX Switch to IL-12/23 inhibitor inhibitor biologic monotherapy over IL-12/23 inhibitor + MTX Treatment recommendations for patients with active psoriatic arthritis despite IL-17 inhibitor biologic are as follows: Switch to a TNF inhibitor biologic over IL-12/23 inhibitor biologic, a different IL-17 inhibitor, or adding MTX Switch to an IL-12/23 inhibitotr biologic over a different IL-17 inhibitor or adding MTX Treatment recommendations for patients with active psoriatic arthritis despite IL-17 inhibitor biologic are as follows: Switch to a TNF inhibitor biologic over IL-17 inhibitor biologic or adding MTX Switch to an IL-17 inhibitor biologic over adding MTX Other considerations are as follows: If the patient prefers oral medication, consider an OSM or tofacitinib If the patient has inflammatory bowel disease, consider an IL-12/23 inhibitor or tofacitinib If the patient prefers less frequent dosing, consider an IL-12/23 inhibitor If the patient has recurrent or serious infections, avoid TNF inhibitors and consider abatacept If the patient has recurrent Candida infections, consider tofacitinib If the patient has diabetes, start an OSM other than MTX, or IL-12/23i over a TNF inhibitor Uveitis responds well to MTX Consider OSM if the psoriatic arthritis is not severe and psoriasis is absent Nonpharmacologic therapy Recommendations include the following: Using physical therapy, exercise, massage therapy, acupuncture is recommended over not using it. Smoking cessation is advised. Weight loss for patients with high body mass index (BMI) is recommended. EULAR recommendations Based on evidence from systematic literature reviews and expert opinion, EULAR developed the 2012 guidelines, with a 2015 update. The guidelines are centered on five overarching principles, 10 specific recommendations, and a treatment algorithm. Specific treatment recommendations are outlined for peripheral arthritis, axial disease, dactylitis, and enthesitis, along with a consideration of comorbidities in the treatment approach. The 10 recommendations are as follows : 1. Treatment should be aimed at reaching the target of remission or, alternatively, LDA or Mlow or minimal disease activity, by regular monitoring and appropriate adjustment of therapy 2. NSAIDs may be used to relieve musculoskeletal signs. 3. In patients with peripheral arthritis, particularly those with many swollen joints, structural damage, high ESR/CRP, and/or clinically relevant extra-articular manifestations, conventional synthetic DMARDs should be considered, with MTX preferred in those with relevant skin involvement. 4. Local injections of glucocorticoids should be considered as adjunctive therapy; systemic glucocorticoids may be used with caution at the lowest effective dose. 5. In patients with peripheral arthritis and an inadequate response to at least one conventional synthetic DMARD, therapy with a biologic DMARD, usually a TNF inhibitor, should be commenced. 6. In patients with peripheral arthritis and an inadequate response to ≥1 conventional synthetic DMARD in whom TNF inhibitors are not appropriate, biologic DMARDs targeting IL-2/23 or IL-17 pathways may be considered. 7. In patients with peripheral arthritis and an inadequate response to at least one conventional synthetic DMARD, in whom biologic DMARDs are not appropriate, a targeted synthetic DMARD such as a PDE4-inhibitor may be considered. 8. In patients with active enthesitis and/or dactylitis and insufficient response to NSAIDs or local glucocorticoid injections, therapy with a biologic DMARD should be considered, which according to current practice is a TNF inhibitor. 9. In patients with predominantly axial disease that is active and has insufficient response to NSAIDs, therapy with a biologic DMARD should be considered, which according to current practice is a TNF inhibitor. 10. In patients who fail to respond adequately to a biologic DMARD, switching to another bDMARD should be considered, including switching between TNF inhibitors. EULAR has also published recommendations on the following, which are all relevant for patients with psoriatic arthritis: Vaccination in adult patients with autoimmune inflammatory rheumatic disease (2019) Cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders (2016) https://emedicine.medscape.com/article/2196539-print 28/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print Use of imaging and management of spondyloarthritis in clinical practice (2015) American Academy of Dermatology recommendations General recommendations on psoriatic arthritis from the AAD are as follows : Upon diagnosis of psoriatic arthritis, patients should be treated and/or referred to a rheumatologist. MTX or TNF blockade or the combination of these therapies is considered first-line treatment for patients with moderate to severely active psoriatic arthritis. Not all patients with psoriatic arthritis require treatment with MTX or TNF blockade. Patients with mild psoriatic arthritis can be successfully treated with NSAIDs or intraarticular injections of corticosteroids. The choice of which TNF agent to utilize is an individual one, with the degree and severity of cutaneous involvement an important consideration. Common safety concerns need to be considered when using TNF inhibitors to treat patients who have psoriatic arthritis. General recommendations on the use of TNF inhibitors in psoriatic arthrits are as follows: Anti-TNF agents are contraindicated in patients with active, serious infection.s Tuberculosis testing (PPD) should be performed on all patients who will be treated with TNF inhibitors, given the risk of tuberculosis reactivation. Do not use with live vaccines; biologically inactive or recombinant vaccines may be considered, although the immune response to these vaccines could be compromised. Because there is an association between anti-TNF therapy and demyelinating diseases (ie, multiple sclerosis [MS]), TNF inhibitors should not be used in patients with MS or other demyelinating diseases. First-degree relatives of patients with MS have an increased risk of developing MS, with a sibling relative risk of 18 to 36, which strongly suggests that TNF inhibitors should not be used in first-degree relatives of patients with MS. Caution should be used when considering TNF inhibitor use in patients with chronic heart failure (CHF); patients with New York Heart Association (NYHA) class III or IV CHF should avoid all use of TNF inhibitors, and patients with NYHA class I or II CHF should undergo echocardiogram testing, and if their ejection fraction is < 50%, then TNF inhibitor treatment should potentially be avoided. In the appropriate clinical setting, patients should be screened for hepatitis B virus (HBV) infection. British Society of Rheumatology recommendations The BSR issued guidelines for the treatment of adult psoriatic arthritis with biologic agents (particularly anti-TNF therapy). [105, 110] The BSR recommends considering anti-TNF treatment in patients with any of the following : Active peripheral arthritis refractory to at least 2 conventional DMARDs Peripheral disease refractory to 1 DMARD plus the presence of adverse prognostic factors Severe persistent oligoarthritis that is affecting well-being and refractory to at least 2 DMARDs and intra-articular therapy Axial disease The BSR recommendations on response assessment include the following : Use the psoriatic arthritis response criteria as the clinical response criteria for peripheral disease. Use the psoriasis area severity index (PASI) score for significant skin psoriasis.< Safety recommendations include the following : Do not start or continue anti-TNF therapy in patients with serious active infection; use caution in those at high risk of infection. Screen all patients for infection with mycobacteria, human immunodeficiency virus (HIV), HBV, and hepatitis C virus(HCV) before starting anti-TNF therapy. Consider prophylactic vaccination for tuberculosis and HBV in high-risk patients before initiating anti-TNF therapy. In patients with HIV, HBV, or HCV, initiate anti-TNF therapy only in those with well-controlled disease and appropriate monitoring; appropriate antiviral therapy for patients with HBV is also important. Avoid anti-TNF treatment in patients with a current or previous history of malignancy, unless there is a high likelihood of cure or the malignancy was diagnosed and treated more than 10 years ago. Regularly screen for skin cancers in patients who are receiving anti-TNF therapy and who have a history of current or previous malignancy. Discontinue anti-TNF therapy prior to pregnancy; restart anti-TNF treatment following the end of lactation, or delivery if the mother is not breastfeeding. https://emedicine.medscape.com/article/2196539-print 29/44 06.09.2021 https://emedicine.medscape.com/article/2196539-print Consider an alternative anti-TNF agent in patients whose condition is refractory to a first anti-TNF agent; assess the