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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 therapy41Taylor WJ. Curr Opin Rheumatol. 2002;14:98–103.
2Mease P. Curr Opin Rheumatol. 2004;16:366–370.3Brockbank J, et al. Exp Opin Invest Drugs. 2000;9:1511–1522.
4Kane D, et al. Rheumatology. 2003;42:1460–1468.
1Taylor WJ. Curr Opin Rheumatol. 2002;14:98–103.2Mease P. Curr Opin Rheumatol. 2004;16:366–370.3Brockbank J, et al. Exp Opin Invest Drugs. 2000;9:1511–1522.4Kane D, et al. Rheumatology. 2003;42:1460–1468.
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 7% to 42% of patients with Pso will develop arthritis3
Psoriatic Arthritis 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 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
Juvenile SpA
Reactivearthritis
Arthritis associated with
IBD
PsA
UndifferentiatedSpA (uSpA)
Ankylosingspondylitis (AS)
RA: Rheumatoid arthritis
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;
2Wilson 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
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%, 12-20% 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 LE arthritis 1-4 weeks after an
infection Infectious agents:
Shigella Salmonella Yersinia Campylobacter Chlamydia
Triad: urethritis, conjunctivitis, arthritis
Keratoderma Blennorhagicum
Inflammatory Bowel Disease Associated Crohn’s LE distribution
AAFP
CLASSIFICATION CRITERIA OF PSA
How to diagnose 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
References see notes
• However patterns may change over time and are therefore not useful for
classification 5
HLA: Human leucocytes antigen
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
D a c ty lit is E n th e s it is
P so ria tic A rth rit is
Ritchlin C. J Rheumatol. 2006;33:1435–1438.Helliwell PS. J Rheumatol. 2006;33:1439–1441.
DACTYLITIS
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.
• 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
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 occur- Without 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 fusion.
PATTERNS MAY CHANGE OVER TIME AND ARE THEREFORE NOT USEFUL FOR CLASSIFICATION
McHugh et al. Rheum 2003;42:778-783
Clinical subgroups at baseline and follow-up:
Monoarthritis Monoarthritis
Oligoarthritis Oligoarthritis
DIP DIP
Polyarthritis Polyarthritis
Spondyloarthritis Spondyloarthritis
Mutilans Mutilans
No clinical evidence ofjoint disease
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
Helliwell PS & Taylor WJ. Ann Rheum Dis 2005;64(2:ii)3-8Fitzgerald “Psoriatic Arthritis” in Kelley’s Textbook of Rheumatology, 2009
*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
MAIN FEATURES AND THEIR FREQUENCY
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;20:60-675Jiaravuthisan MM et al. JAAD 2007;57:1-27; 6Yamamoto Eur J Dermatol 2011;21:660-6
Enthesopathy (38%)2
Dactyilitis (48%)3
DIP involvement (39%)2
Back involvement (50%)1
Nail psoriasis (80%)4, 5
Skin
Invo
lvemen
t
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: Distal interphalangeal
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)
Ocular inflammation1
(Iritis/Uveitis/ Episcleritis)
IBD2
COMORBIDITIES IN PSA PATIENTS
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; 4Neimann 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
Nail pitting, transverse depressions, and subungual hyperkeratosis
Staging of psoriatic arthritis
TREATMENT OF PSA
Outcomes measurements
Dosing schedule, monitoring and side effects of disease modifying drugs
Generic Name Manufacturer U.S. Trade Name(s)* How Supplied Usual Adult Dose
Methyl-prednisolone
MultipleMedrol®, Depo-Medrol®, Solu-Medrol®
Acetate - InjectableIM—20, 40, and 80 mg/mlSodium succinate - Injectable:IM—40, 125, and 500 mg, 1 and 2 g vialsOral: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 MultipleDeltasone®, Sterapred®, LiquiPred®
Oral Solution—1 and 5 mg/mlTabs—1, 2.5, 5, 10, 20, and 50 mg
Use lowest effective dose (5–60 mg/day)
Prednisolone MultipleOrapred®, Pediapred®, Prelone®, Delta-Cortef®, Econopred®
Oral Solution/Syrup—5, 15, and 20 mg/5 mlOral Tabs—5 and 15 mg
Use lowest effective dose (5 to 7.5 mg/day)
Pharmaceutical treatments for psoriatic arthritis: corticosteroids.
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 NameManufacturer
U.S. Trade Name(s)*
Injectable Supply Usual Adult Dose
Abatacept Bristol MyersSquibbOrencia®
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 thereafterSQ—may give weight-based IV loading dose, then 125 mg SQ once weekly
Adalimumab
AbbottHumira®
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 AmgenKineret®
100 mg/0.67 ml syringe
SQ—100 mg/day; dose should be decreased to 100 mg every other day in renal insufficiency
CertolizumabPegola
UCBCimzia®
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
AmgenPfizerImmunexEnbrel®
50 mg/ml in 25 mg or 50 mg single use prefilled syringe
SQ—50 mg once weekly with or without MTX
Golimumab
Centocor OrthoBiotechSimponi®
50 mg/0.5 ml syringe
SQ—50 mg once per month, alone or in combination with MTX
Infliximab
Centocor OrthoBiotechRemicade®
100 mg in a 20 ml vial
IV—5 mg/kg at 0, 2 and 6 weeks followed by maintenance every 8 weeks thereafter; may be given with or without MTX
Rituximab
Biogen Idec / GenentechRituxan®
100 mg/10 ml and 500 mg/50 ml vial
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
Tocilizumab
Genentech / RocheActemra®
, RoActemra®
80 mg/4 ml, 200 mg/10 ml, 400 mg/20 ml vial
IV—4 mg/kg every 4 weeks; increase to 8 mg/kg every 4 weeks based on clinical response
OTHER AGENTS
Several other agents have been tried, including vitamin-D3, 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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