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 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

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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.

Thanks