Published on February 19, 2014
Tutorial presentation Psoriatic arthropathy Moderator:- Dr. Deepak K. Mathur
INTRODUCTION TO PSORIATIC ARTHRITIS (PSA) Chronic progressive, inflammatory disorder of the joints and skin1 Characterized by osteolysis and bony proliferation1 Clinical manifestations include dactylitis, enthesitis, osteoperiostitis, large joint oligoarthritis, arthritis mutilans, sacroiliitis, spondylitis, and distal interphalangeal arthritis1 PsA is one of a group of disorders known as the spondyloarthropathies2 Males and females are equally affected3 PsA can range from mild nondestructive disease to a severely rapid and destructive arthropathy3 Usually Rheumatoid Factor negative3 Radiographic damage can be noted in up to 47% of patients at a median interval of two years despite clinical improvement with standard DMARD therapy4 1Taylor WJ. Curr Opin Rheumatol. 2002;14:98–103. 1Taylor P. Curr OpinWJ. Curr Opin Rheumatol. 2002;14:98–103. Rheumatol. 2004;16:366–370. 2Mease P. Curr Opin Rheumatol. 2004;16:366–370. 3Brockbank J, et al. Exp Opin Invest Drugs. 2000;9:1511–1522. 43Brockbank J,Rheumatology. 2003;42:1460–1468. Kane D, et al. et al. Exp Opin Invest Drugs. 2000;9:1511–1522. 4Kane D, et al. Rheumatology. 2003;42:1460–1468. 2Mease
SPONDYLOARTHRITIS, PSORIASIS AND PSA Spondyloarthritis (SpA) The prevalence of SpA is comparable to that of RA (0.5–1.9%)1,2 Psoriasis (Pso) Psoriasis affects 2% of population Juvenile SpA 3 7% to 42% of patients with Pso will develop arthritis Undifferentiated SpA (uSpA) PsA Ankylosing spondylitis (AS) Arthritis Psoriatic Arthritis Reactive associated with arthritis IBD A chronic and inflammatory arthritis in association with skin psoriasis4 Usually rheumatoid factor (RF) negative and ACPA negative5 Distinct from RA Psoriatic Arthritis is classified as one of the subtypes of spondyloarthropathies Characterized by synovitis, enthesitis, dactylitis, spondylitis, skin and nail psoriasis4 1Rudwaleit RA: Rheumatoid arthritis M et al. Ann Rheum Dis 2004;63:535-543; 2Braun J et al. Scand J Rheumatol 2005;34:178-90; 3 Fitzgerald ―Psoriatic Arthritis‖ in Kelley’s Textbook of Rheumatology, 2009; 4Mease et al. Ann Rheum Dis 2011;70(Suppl 1):i77–i84. doi:10.1136/ard.2010.140582; 5Pasquetti et al. Rheumatology 2009;48:315–325
PSORIATIC ARTHRITIS ACR Slide Collection on the Rheumatic Diseases; 3rd edition. 1994. Data on file, Centocor, Inc.
EPIDEMIOLOGY OF PSA • Recent review undertaken to 20061,2 − Incidence Europe+North America: 3 to 23.1 cases/105 Japan 0.1 case/105 − Prevalence • Europe+North America 20 and 420 cases/105 Japan 1 case/105 Population-based study/Minnesota (CASPAR criteria)2,3 − Incidence 7.2 cases/105 (men 9.1, female 5.4) − Prevalence 158 cases/105 The prevalence of PsA is assumed to be larger than expected, since enthesitis associated with PsA can develop without symptoms or signs that are recognizable by patients themselves or the physicians4 1 Alamos et al. J Rheumatol 2008;35:1354-8; F et al. J Rheumatol 2009;36:361-7; 3Editorial by Chaudran. J Rheumatol 2009;36:213-5; 4Takata et al. J Dermatol Sci. 2011 Nov;64(2):144-7 2Wilson
ETIOLOGY Genetic Factors Immunologic Mechanisms Environmental Trauma – Koebner phenomenon: psoriatic lesions arising at site of trauma (24-52%); development of PsA after trauma to joint. Bacterial infections - association between guttate psoriasis and streptococcal pharyngitis; up to 30% of PsA synovial tissue-derived T cells proliferate following exposure to group A strep
GENETIC FACTORS Has been known to occur in families Up to 40% psoriasis or PsA have a family history in first degree relative The disease is 50 times more likely to occur in first degree relative than controls Tends to be concordant among monozygotic twins more commonly than dizygotic
GENETICS AND HLA ANTIGENS Concordance rate monozygotic twins of 35-70%, 1220% for dizygotic twins. HLA-B27 in the presence of HLA-DR7, HLA-DQ3 in the absence of HLA-DR7, and HLA-B39 are predictors for disease progression, HLA-B22 is protective. HLAB27 less than AS or Reiter’s; some psoriasis and SpA are HLA B27 (-) PsA and HLA B27 who do not have SpA Some patients with HLA DR4: PsA with polyarthritis
ROLE OF TNF Released predominantly by cells of the monocyte/macrophage lineage Accumulation of T-cells, infiltration of synovium: TNF-mediated production of factors that attract T-cells – monocyte chemoattractant protein-1 and macrophage inflammatory protein 3 alpha Induces lymphocyte and neutrophil migration into synovium
TNF IN PSA High levels of TNF-α in PsA synovium Marked upregulation of TNF-α in PsA synovial membrane Inflammation of synovium, enthesis and bone TNF-α transgenic mice – bone destruction Promotes release of matrix-degrading metalloproteinases Enhances secretion of pro-inflammatory cytokines (IL-1, IL-6, IL-8) Potentiates osteoclastic bone resorption
DIFFERENTIAL DIAGNOSIS Rheumatoid Arthritis Symmetric PIP, MCP, not distal Ulnar deviation, swan neck deformities Rheumatoid nodules Ankylosing Spondylitis Strong HLA B27 association Male predominance Axial skeletal involvement – sacroilitis Bamboo spine Schober test demonstrating limited flexion Uptodate.com
DIFFERENTIAL DIAGNOSIS Reactive Arthritis Bowel Inflammatory Disease Associated LE arthritis weeks after an 1-4 Crohn’s infection LE distribution Infectious agents: Shigella Salmonella Yersinia Campylobacter Chlamydia Triad: urethritis, conjunctivitis, arthritis Keratoderma Blennorhagicum AAFP
How to diagnose PsA? CLASSIFICATION CRITERIA OF PSA
CLASSICAL DESCRIPTION OF PSA USING THE DIAGNOSTIC CRITERIA OF MOLL AND WRIGHT Including 5 clinical patterns: Asymmetric mono-/oligoarthritis (~30% [range 12-70%])1-4 Symmetric polyarthritis (~45% [range 15-65%])1-4 Distal interphalangeal (DIP) joint involvement (~5%)1 Axial (spondylitis and Sacroiliitis) (HLA-B27) (~5%)1,3 Arthritis Mutilans (<5%)1,3 • However patterns may change over time and are therefore not useful for classification 5 HLA: Human leucocytes antigen References see notes
ASYMMETRICAL OLIGOARTICULAR ARTHRITIS MC type (70%) Asymmetrical similar to low grade gout. Sausage like swelling of one or more digit (dactylitis). A large joint, such as the knee, is also commonly involved. Usually, <5 joints are affected at any one time. Enthesitis Flexor sheath synovitis
HALLMARK CLINICAL FEATURES IN PSA P so ria tic A rth ritis D a ctylitis E n th e sitis Ritchlin C. J Rheumatol. 2006;33:1435–1438. Helliwell PS. J Rheumatol. 2006;33:1439–1441.
DACTYLITIS • Diffuse swelling of a digit may be acute, with painful inflammatory changes, or chronic wherein the digit remains swollen despite the disappearance of acute inflammation1 • Also referred to as ―sausage digit‖1 • Recognized as one of the cardinal features of PsA, occurring in up to 40% of patients1,2 • Feet most commonly affected1 • Dactylitis involved digits show more radiographic damage1 ACR Slide Collection on the Rheumatic Diseases; 3rd edition. 1994. 1Brockbank J, et al. Ann Rheum Dis. 2005;64:188–190. 2Veale D, et al. Br J Rheumatol. 1994;33:133–38.
DEFINITION OF ENTHESITIS Entheses are the regions at which a tendon, ligament, or joint capsule attaches to bone1 Inflammation at the entheses is called enthesitis and is a hallmark feature of PsA1,2 Pathogenesis of enthesitis has yet to be fully elucidated2 Isolated peripheral enthesitis may be the only rheumatologic sign of PsA in a subset of patients3 1McGonagle D. Ann Rheum Dis. 2005;64(Suppl II):ii58–ii60. 2Anandarajah AP, et al. Curr Opin Rheumatol. 2004;16:338–343. 3Salvarani C. J Rheumatol. 1997;24:1106–1140.
SYMMETRICAL POLYARTHRITIS - - - Rheumatoid like pattern. 15% Hands, wrists, ankles, and feet may be involved. D/D from RA by DIP joint involvement, Morning stiffness Fusiform deformity Wind swept deformity Relative asymmetry, Subcutaneous nodules absent. RF negative. Milder, with less deformity.
DISTAL INTERPHALANGEAL ARTHROPATHY Classical form Less common 16% Involvement of the nail with significant inflammation of the paronychia and swelling of the digital tuft may be prominent, 30 pits with inflammatory arthritis of DIP joints considered diagnostic.
Psoriatic arthritis involving the distal phalangeal joint.
ARTHRITIS MUTILANS Rare form 1-5% Some reports suggest up to 16% of patients. 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. This "opera-glass hand" is M>F and is more frequent in early-onset disease.
ARTHRITIS MUTILANS, A TYPICALLY PSORIATIC PATTERN OF ARTHRITIS, WHICH IS ASSOCIATED WITH A CHARACTERISTIC "PENCIL-IN-CUP" RADIOGRAPHIC APPEARANCE OF DIGITS. Arthritis mutilans (ie, "pencil-in-cup" deformities).
SPONDYLITIS WITH OR WITHOUT SACROILIITIS - - Affect 5% of patients and has a male predominance. Can occur in conjunction with other subgroups of PA. Spondylitis may occurWithout radiologic evidence of sacroiliitis, which frequently tends to be asymmetrical, May appear radiologically without the classic symptoms of morning stiffness in the lower back. Thus, the correlation between symptoms and radiologic signs of sacroiliitis can be poor. Vertebral involvement differs from that observed in AS.
- - 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 feature nonmarginal asymmetrical syndesmophytes (characteristic), paravertebral ossification, and, less commonly, vertebral fusion with disk calcification. Lateral radiograph of the cervical spine shows syndesmophytes at the C2-3 and C6-7 levels, with zygapophyseal joint fusio
PATTERNS MAY CHANGE OVER TIME AND ARE THEREFORE NOT USEFUL FOR CLASSIFICATION Clinical subgroups at baseline and follow-up: Monoarthritis Monoarthritis Oligoarthritis Oligoarthritis DIP DIP Polyarthritis Polyarthritis Spondyloarthritis Spondyloarthritis Mutilans Mutilans No clinical evidence of joint disease McHugh et al. Rheum 2003;42:778-783
CASPAR CRITERIA FOR THE CLASSIFICATION OF PSA Inflammatory articular disease (joint, spine, or entheseal) With 3 points from following categories: − Psoriasis: current (2), history (1), family history (1) − Nail dystrophy (1) − Negative rheumatoid factor (1) − Dactylitis: current (1), history (1) recorded by a rheumatologist − Radiographs: (hand/foot) evidence of juxta-articular new bone formation Specificity 98.7%, Sensitivity 91.4% Taylor et al. Arthritis & Rheum 2006;54: 2665-73
SIGNS AND SYMPTOMS Morning stiffness lasting >30 min in 50% of patients1 Ridging, pitting of nails, onycholysis – up 90% of patients vs nail changes in only 40% of psoriasis cases2,3 Patients may present with less joint tenderness than is usually seen in RA1 Dactylitis may be noted in >40% of patients2,4 Eye inflammation (conjunctivitis, iritis, or uveitis) — 7–33% of cases; uveitis shows a greater tendency to be bilateral and chronic when compared to AS2 Distal extremity swelling with pitting edema has been reported in 20% of patients as the first isolated manifestation of PsA5 1Gladman DD. In: Up To Date. Available at: www.uptodate.com. Accessed December 3, 2004. 2Taurog JD. In: Harrison's Online McGrawHill. Available at: http://www3.accessmedicine.com/popup.aspx?aID=94996&print=yes. Accessed January 2,2005. 3Gladman DD. Rheum Dis Clin N Amer. 1998;24:829–844. 4Veale D, et al. Br J Rheumatol. 1994;33:133–38. 5Cantini F, et al. Clin Exp Rheumatol. 2001;19:291–296.
MAIN FEATURES OF PSA *Low levels of RF and ACPA can be found in 5-16% of patients; **To a lesser degree than in RA ***Spinal disease occurs in 40-70% of PsA patients Helliwell PS & Taylor WJ. Ann Rheum Dis 2005;64(2:ii)3-8 Fitzgerald ―Psoriatic Arthritis‖ in Kelley’s Textbook of Rheumatology, 2009
MAIN FEATURES AND THEIR FREQUENCY Back involvement (50%)1 Skin Involvement In nearly 70% of patients, cutaneous lesions precede the onset of joint pain, in 20% arthropathy starts before skin manifestations, and in 10% both are concurrent. 6 DIP involvement (39%)2 Nail psoriasis (80%)4, 5 Dactyilitis (48%)3 Enthesopathy (38%)2 DIP: Distal interphalangeal 1Gladman D et al. Arth & Rheum 2007;56:840; 2 Kane. D et al. Rheum 2003;42:1460-1468 3 Gladman D et al. Ann Rheum Dis 2005;64:188–190; 4Lawry M. Dermatol Ther 2007;20:60-67 5Jiaravuthisan MM et al. JAAD 2007;57:1-27; 6Yamamoto Eur J Dermatol 2011;21:660-6
COMORBIDITIES IN PSA PATIENTS Ocular inflammation1 (Iritis/Uveitis/ Episcleritis) IBD2 Pso patients6-8 • Psychosocial burden • Reactive depression • Higher suicidal ideation • Alcoholism Metabolic Syndrome3-5 • Hyperlipidemia • Hypertension • Insulin resistent • Diabetes • Obesity Higher risk of Cardiovascular disease (CVD) Nail pitting, transverse depressions, and subungual hyperkeratosis 1Qieiro et al. Semin Arth Rheum 2002;31:264; 2Scarpa et al. J Rheum 2000;27:1241; 3Mallbris et al. Curr Rheum Rep 2006;8:355; et al. J Am Acad Derm 2006;55:829; 5Tam et al. 2008;47:718; 6Kimball et al. Am J Clin Dermatol 2005;6:383-392; 7Naldi et al. Br J Dermatol 1992;127:212-217; 8Mrowietz U et al. Arch Dermatol Res 2006;298(7):309-319 4Neimann
Staging of psoriatic arthritis
Outcomes measurements TREATMENT OF PSA
Dosing schedule, monitoring and side effects of disease modifying drugs
Pharmaceutical treatments for psoriatic arthritis: corticosteroid Generic Name Manufacturer U.S. Trade Name(s)* How Supplied Usual Adult Dose Methyl-prednisolone Multiple ® Medrol , Depo® Medrol , Solu® Medrol Acetate - Injectable IM—20, 40, and 80 mg/ml Sodium succinate Injectable: IM—40, 125, and 500 mg, 1 and 2 g vials Oral: Tabs—2, 4, 8, 16, and 32 mg •Acetate:IM—10 to 80 mg every 1 to 2 weeks •Intra-articular, intralesional —4 to 80 mg every 1 to 5 weeks •Sodium succinate:IM—10 to 80 mg daily •IV—10 to 40 mg every 4 to 6 hours; up to 30 mg/kg every 4 to 6 hours •Oral:2 to 60 mg in 1 to 4 divided doses to start, followed by gradual reduction Prednisone Multiple ® Deltasone , ® Sterapred , ® LiquiPred Oral Solution—1 and 5 mg/ml Tabs—1, 2.5, 5, 10, 20, and 50 mg Use lowest effective dose (5–60 mg/day) Prednisolone Multiple ® Orapred , Oral Solution/Syrup— 5, 15, and 20 mg/5 ml Use lowest effective dose (5 to 7.5 ®
Efficacy of drugs in psoriatic arthritis
Indications for biologic agents in psoriatic arthritis
Mechanism of action, dosing schedule and major risks with the biologic therapies
Generic Name Manufacturer U.S. Trade Name(s)* Injectable Supply Usual Adult Dose Abatacept Bristol Myers Squibb ® Orencia 250 mg vial IV—Dosed according to body weight (<60 kg=500 mg; 60–100 kg=750 mg; >100 kg=1,000 mg); dose repeated at 2 weeks and 4 weeks after initial dose, and every 4 weeks thereafter SQ—may give weight-based IV loading dose, then 125 mg SQ once weekly Adalimuma b Abbott ® Humira 40 mg/0.8 ml, 20 mg/0.4 ml prefilled syringe SQ—40 mg every other week alone or in combination with other DMARDs Anakinra Amgen ® Kineret 100 mg/0.67 ml syringe SQ—100 mg/day; dose should be decreased to 100 mg every other day in renal insufficiency Certolizuma a bPegol UCB ® Cimzia 200 mg powder for reconstitution, 200 mg/ml solution SQ—initial dose of 400 mg (as 2 SQ injections of 200 mg), repeat dose 2 and 4 weeks after initial dose; Maintenance dose is 200 mg every other week (may consider maintenance dose of 400 every 4 weeks) Etanercept Amgen Pfizer Immunex ® Enbrel 50 mg/ml in 25 mg or 50 mg single use prefilled syringe SQ—50 mg once weekly with or without MTX
Golimuma b Centocor Ortho Biotech ® Simponi 50 mg/0.5 ml syringe Infliximab Centocor Ortho Biotech ® Remicade 100 mg in a IV—5 mg/kg at 0, 2 and 6 weeks 20 ml vial followed by maintenance every 8 weeks thereafter; may be given with or without MTX Rituximab Biogen Idec / Genentech ® Rituxan 100 mg/10 ml and 500 mg/50 ml vial Tocilizuma b Genentech / Roche ® Actemra , RoActemra 80 mg/4 ml, IV—4 mg/kg every 4 weeks; increase 200 mg/10 to 8 mg/kg every 4 weeks based on ml, 400 clinical response mg/20 ml vial ® SQ—50 mg once per month, alone or in combination with MTX IV—1,000 mg IV infusion separated by 2 weeks (one course) every 24 weeks or based on clinical evaluation, but not sooner than every 16 weeks
OTHER AGENTS Several other agents have been tried, including vitaminD3, bromocriptine, peptide T, and fish oils, but their efficacy remains to be proven. Antimalarials, particularly hydroxychloroquine (Plaquenil), are usually avoided in patients with psoriasis for fear of precipitating exfoliative dermatitis or exacerbating psoriasis. However, 2 studies showed that these reactions did not occur in patients who were treated with hydroxychloroquine; therefore, this drug is occasionally used to treat PA. Systemic corticosteroids are usually avoided because of possible rebound of the skin disease upon withdrawal.
SURGICAL CARE IN PSORIATIC ARTHRITIS 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 thumb PIP joint. 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.
CONSULTATIONS AND MONITORING IN PSORIATIC ARTHRITIS If the patient's physiatrist feels uncomfortable with prescribing medications for PA, referral to a rheumatologist with more experience with these agents may be advisable. The physiatrist may then concentrate on functional restoration of the patient. Referral to a surgeon should be considered for appropriate patients. Children with juvenile PA should be examined by an ophthalmologist annually to check for the several forms of eye inflammation usually associated with various forms of juvenile arthritis. In addition, consultation with an orthopedic surgeon is warranted for individuals who may benefit from joint replacement, arthrodesis, or contracture release.
DIETARY CONSIDERATIONS For people who have morning stiffness, the optimal time for taking an NSAID may be after the evening meal and again upon awakening. Taking NSAIDs with food can reduce stomach discomfort. Any NSAID can damage the mucous layer and cause ulcers and GI bleeding when taken for long periods. Cyclooxygenase (COX)–2 selective inhibitors are associated with a lower prevalence of gastric ulcer formation.
PHYSICAL THERAPY IN PSORIATIC ARTHRITIS The rehabilitation treatment program 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
DETERRENCE AND PREVENTION 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 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.
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