Psoriatic Arthritis - Boca Raton Regional Hospitalweb.brrh.com/msl/IM2019/IM Saturday/Saturday - 2 -...

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Psoriatic Arthritis

Benjamin Wang, M.D., FRCPC Division of Rheumatology

Mayo Clinic Jacksonville, FL

Boca Raton Regional Hospital Internal Medicine Conference 2019


Disclosures

Nothing to disclose


Outline

• Clinical features

• Pathophysiology

• Treatment


• Inflammatory arthritis

• Many variants and clinical forms

• Seronegative

• Destructive, disabling

• Occurs in up to 30% of persons with psoriasis

• Arthritis precede skin disease

• Increased cardiovascular mortality

© Merck Manual


Arthritis

• Symmetric polyarthritis

• Asymmetric oligoarthritis

• DIP-included arthritis

• Spondylitis

• Arthritis mutilans

Papazoglou A et al. “Psoriasis” in Brent LH, SG Arthritis (2016)

Torpy JM et al. JAMA. 2011;306(8):896


Symmetric Polyarthritis • May be mistaken for rheumatoid arthritis

• “Seronegative RA” may actually be psoriatic arthritis

• More joint erythema than RA

• Less periarticular osteopenia on x-ray than rheumatoid arthritis

Papazoglou A et al. “Psoriasis” in Brent LH, SG Arthritis (2016)


Asymmetric Oligoarthritis • Monoarthritis of a large joint (knee, hip, elbow, ankle) – often associated with spondylitis

• Oligoarthritis, often asymmetric, of large joints

• Small joint oligoarthritis

• May evolve into a symmetric polyarthritis

Michet CJ et al. Ann Rheum Dis 2005;64:1068–1070. Emad Y et al. J Rheum 2005;39(10):1979-1986


Spondylitis

• Back pain Inflammatory characteristics

• prolonged AM stiffness

• better with use

• responsive to anti-inflammatories and corticosteroids

• May be asymptomatic

• May accompany peripheral arthritis

• Always worth doing: SI joint x-rays

Baraliakos X et al. Clin Exp Rheumatol 2015; 33 (Suppl. 93):S31-S35.

© eMedicine 2005


DIP-included Polyarthritis

• May be mistaken for OA (Heberden nodes) and vice-versa

• Look for nail dystrophy, pitting and onycholysis

• Look for periungual erythema Martel W et al. AJR 1980;134:125-135

Sandre MK. Sem Arthritis Rheum 2014; 44:162-169


Arthritis Mutilans

• Aggressive, destructive form (1%)

• May affect all joint areas

• “Telescoping digits” and “flail joints”

• Advanced osteolysis Alejandra-Lopez R et al. Int. J. Clin. Rheumatol. (2018) 13(6), 384-387

Butendieck Jr RR and Abril A. J Rheum 2013; 40:1921-1922


Enthesitis

• Enthesis: a bone-tendon or bone-ligament interface

• Specialized histology

• Inflammatory potential

• History of heel pain or Achilles insertional pain

• Inflammation leads to new bone formation—osteophytes, syndesmophytes


Tendonitis and Dactylitis

McGonagle D et al. Nature Rev Rheumatology 2019; 15:113-121

Kaeley GS et al. Sem Arthritis Rheum 2018;48:35–43.

© American Academy of Dermatology


Combinations of the Above

• Polyarthritis with spondylitis

• Oligoarthritis with spondylitis

• DIP-only with spondylitis (uncommon)

• Spondylitis

• Enthesitis and/or tendonitis and/or dactylitis may accompany any of the above

• Other: uveitis, IBD and enteropathic arthritis


How is Psoriatic Arthritis Classified?

• No autoantibody production yet inflammatory

• Involvement of innate immune system more than adaptive immunity

• A member of a broad family of ‘seronegative’ conditions

• Ankylosing spondylitis • Reactive arthritis • Psoriasis • Uveitis • Inflammatory bowel

disease

Generali E et al. Autoimmunity Reviews 17 (2018) 935–941


HLA-B27 and Psoriatic Arthritis

• Prevalence of HLA-B27 varies according to the clinical presentation:

• Psoriasis: 5% (increases risk of developing PsA)

• Psoriatic arthritis (peripheral): 20%

• Psoriatic arthritis (axial): 70%

• HLA-C06 is a biomarker of skin disease, with no influence on the development of joint disease


Genetic Contributions


Gene-Environment Interactions

• Trauma and the Koebner phenomenon: local trauma found in 25% on patients prior to disease onset

• Streptococcal antibodies: triggers shift in CD8/CD4 balance

• Microbiota: significant reductions in Akkermansia, Ruminococcus, and Pseudobutyrivibrio species; increased soluble IgA and decreased RANKL concentrations.

• Smoking

Veale DJ and Fearon U. Lancet 2018; 391: 2273–84


Pathophysiology

• Macroscopic vascular pattern

• The presence of immature vessels suggests that many of the vessels remain in a plastic state and, thus, primed for endothelial cell activation and sprouting

• Relative hypoxia induces upregulation of key metabolic pathways

• Increased expression of vascular growth factors permits ingress of inflammatory cells



• A variety of cell types are active to mediate tissue inflammation and destruction

• A combination of innate and adaptive immunity

Pathophysiology



Drug Therapy

• Symptom relief

• NSAIDs

• Corticosteroids

• Disease-modifying antirheumatic drugs (DMARDs)

• Methotrexate

• Sulfasalazine

• Hydroxychloroquine

• Leflunomide

• Azathioprine

• Mycophenolate


Biologic DMARDs for Psoriatic Arthritis

• Directed at cytokines

• TNF inhibitors: etanercept (Enbrel®), infliximab (Remicade ®), adalimumab (Humira®), golimumab (Simponi®), certolizumab (Cimzia®)

• IL-12/23 antagonist: uskekinumab (Stelara®)

• IL-17 antagonists: secukinumab (Cosentyx®), ixekizumab (Taltz®)

• Directed at cells:

• T cell-directed therapy: abatacept (Orencia®)

• Small molecules:

• Phosphodiesterase-4 antagonist: apremalast (Otezla®)

• Tofacitinib (Xeljanz®)


Coates LC et al. Semi Arthritis Rheum 2016; 46:291–304


Infliximab – IMPACT2 Trial (2005)

Antoni C et al. Ann Rheum Dis 2005;64:1150–1157.


Etanercept and Certolizumab pegol

Mease PJ et al. Arthritis Rheum 2004 Jul;50:2264e72. Mease PJ et al. Ann Rheum Dis 2014; 73(1):48e55.


Secukinumab (Cosentyx®)

• FUTURE2 Trial

• 76 center multinational RCT

• 397 patients randomized in 1:1:1:1 ratio

• SCK 300 mg/mo

• SCK 150 mg/mo

• SCK 75 mg/mo

• Placebo

• SCK 300 mg and 150 mg doses similar

• In TNF nonresponders, SCK 300 mg was superior

McInnes IB et al. Lancet 2015;386(9999):1137e46.


Apremilast (Otezla®) Tofacitinib (Xeljanz®)

Gladman D et al. N Engl J Med 2017 19;377(16):1525e36. Kavanaugh A et al. Ann Rheum Dis 2014;73:1020–6.


Summary

• An inflammatory, erosive form of arthritis accompanied by psoriasis

• Occurs in 30% of people with psoriasis

• Varied clinical manifestations

• Cellular and cytokine-mediated pathophysiology

• Growing selection of directed biologic therapy encompassing various mechanisms of action


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