Psoriasis. Learning Objectives

Transcription

1 Learning Objectives Upon completion of this educational activity, participants should be able to: Summarize the epidemiology and pathophysiology of psoriasis and PsA. Describe the diagnosis, classification, and assessment associated with psoriasis and PsA. Incorporate patient preferences and shared decision making into tailored treatment plans for patients with psoriasis and PsA. Evaluate the efficacy and safety of recently available therapies for the management of psoriasis and PsA. Psoriasis 1

2 Psoriasis Chronic, immune-mediated skin Most common autoimmune Correlation between skin and systemic inflammation High comorbidity burden Affects almost 8 million Americans Rachakonda TD, et al. J Am Acad Dermatol. 2014;70(3): ; Eder L, et al. Arthritis Rheumatol. 2016;68(4): ; Helmick CG, et al. Am J Prev Med. 2014;47(1):37-45; Nestle FO, et al. N Engl J Med. 2009;361(5): Psoriasis Pediatric incidence: 40.8/100,000 population Adult incidence: 78.9/100,000 population # of Patients with Psoriasis Psoriasis in Adults (n=2564) >80 Age in Years Men Women Tollefson MM, et al. J Am Acad Dermatol. 2010;62(6): ; Icen M, et al. J Am Acad Dermatol. 2009;60(3): ; Rachakonda TD, et al. J Am Acad Dermatol. 2014;70(3): ; Helmick CG, et al. Am J Prev Med. 2014;47(1): Psoriasis Patients (%) Impact of Psoriasis on QoL 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Emotional and Physical Impact of Psoriasis No Yes ~80% to 90% of psoriasis patients experience significant impairment of QoL and work productivity Adapted by Lilian McVey from Armstrong AW, et al. PLoS One. 2012;7(12):e Used with permission. 2

3 Pathogenesis Ainsworth C. Nature. 2012;492(7429):S52-S54. Used with permission. Erythrodermic Psoriasis Types Scalp Plaque Nail psoriasis Genital/Inverse Plaque Photos courtesy of Margaret Bobonich, DNP, FNP-C, DCNP, FAANP. Used with permission. Psoriasis Assessment: Types Plaque psoriasis Well-defined erythematous plaques Elbows, knees, scalp, lower trunk Scalp psoriasis Presentation ranges from slight scaling to thick, crusted plaques that cover the scalp Nail psoriasis Nail pitting and crumbling, separation of nail plate from bed with white discoloration, nail thickening Inverse psoriasis Shiny, erythematous plaques with minimal scaling Groin and/or other intertriginous areas (eg, under breasts, in abdominal skin folds) Young M, et al. J Am Assoc Nurse Pract. 2017;29(3):

4 Psoriasis Assessment: Types (cont d) Pustular psoriasis Eruption of sterile pustules Generalized and extensive or localized to existing plaques Palmoplantar pustular psoriasis Yellow-brown sterile pustules on hands and feet May include scaling and severe pruritis Erythrodermic psoriasis Generalized exfoliative dermatitis, often with hair loss and nail dystrophy Affects large body surface area (BSA); 80% Guttate psoriasis Small, scattered, pink, oval-shaped papules w/silvery scaling Affects trunk and extremities Young M, et al. J Am Assoc Nurse Pract. 2017;29(3): Psoriasis Assessment Comprehensive exam Medication history Assess for comorbidity Psoriatic arthritis (PsA) and other arthropathies Diabetes Hyperlipidemia Obesity Cardiovascular Malignancy Depression Differential diagnoses Eczema Contact dermatitis Seborrheic dermatitis Drug eruption Tinea infections Pityriasis rosea Lichen planus Candidal intertrigo Onychomycosis Psoriasis can be difficult to diagnose When in doubt, REFER! Young M, et al. J Am Assoc Nurse Pract. 2017;29(3): Clinical Pearls for Diagnosis Distribution Eczema common on flexors Psoriasis common on extensors Auspitz sign Well-defined vs eczema with diffuse border Consider treatment secondary infection Inverse psoriasis vs candidiasis vs intertrigo Skin biopsy if unsure (punch biopsy) 4

5 Psoriasis Assessment: Severity Scoring tools: PASI: Psoriasis Area and Severity Index BSA: Body Surface Area DLQI: Dermatology Life Quality Index Remember: Severity amount of area affected Consider Area(s) of involvement Palms, genitals, soles, scalp, nails Interference with QoL US Perspectives: MAPP Survey Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey N=1,005 patients, 101 dermatologists, and 100 rheumatologists Key findings Both psoriasis and PsA remain undertreated in patients with moderate-to-severe Gaps in care include screening, assessing, diagnosing and treating psoriasis patients with symptoms of PsA Lebwohl MG, et al. Am J Clin Dermatol. 2016;17(1): US Perspectives: MAPP Survey Key findings (cont d) Widespread dissatisfaction with current treatment options Lack of efficacy Long-term safety unknown Administration challenges Cost Difference in perceptions of severity, treatment impact in patients vs clinicians Lebwohl MG, et al. Am J Clin Dermatol. 2016;17(1):

6 Perceptions of Disease Severity: MAPP Survey Perceptions of severity differ between patients and clinicians Respondents (%) Most important factors contributing to severity in psoriasis, as reported by patients and clinicians Patients (n=735) Dermatologists (n=101) Adapted by Lilian McVey from Lebwohl MG, et al. Am J Clin Dermatol. 2016;17(1): Used with permission. Psoriatic Arthritis PsA in Psoriasis Patients Up to 30% of individuals with psoriasis will develop PsA (higher than previously thought) Risk factors Severe psoriasis Psoriatic nail pitting Uveitis Eder L, et al. Arthritis Rheumatol. 2016;68(4): Karreman MC, et al. Arthritis Rheumatol. 2016;68(4): Photos courtesy of Margaret Bobonich, DNP, FNP-C, DCNP, FAANP. Used with permission. 6

7 PsA Inflammatory arthritis Skin typically precedes joint Variable course Flares and remission Severe is associated with: Progressive joint damage Increased mortality Increase in cardiovascular risk 20% 80% Eder L, et al. Arthritis Rheumatol. 2016;68(4): Gladman DD. Clin Exp Rheumatol. 2008;26(5 Suppl 51):S62-S65. Arumugam R, McHugh NJ. J Rheumatol Suppl. 2012;89: Photo courtesy of Margaret Bobonich, DNP, FNP-C, DCNP, FAANP. Used with permission. Diagnosis of PsA High prevalence of undiagnosed PsA (~10%-15%) Patients with PsA report a mean interval of 12.4 years between onset of skin symptoms and onset of joint symptoms Arthritis symptoms precede skin involvement in 13% to 17% of patients 15% of patients have undiagnosed or unrecognized psoriasis Joint symptoms represent DESTRUCTIVE, IRREVERSIBLE DISEASE. Early diagnosis is critical for preventing progression. 1. Villani A, et al. J Am Acad Dermatol. 2015;73(2): Karreman MC, et al. Arthritis Rheumatol. 2016;68(4): Gottlieb A, et al. J Am Acad Dermatol. 2008;58(5): Diagnosis of PsA Common signs and symptoms Musculoskeletal (32.1%) Joint symptoms (88.2%) Tendon symptoms (50.4%) Dactylitis Low back pain (73.9%) Peripheral arthritis Psoriatic nail dystrophy (15.5%) Enthesitis (4.6%-7.0%) Uveitis Plaque psoriasis Karreman MC, et al. Arthritis Rheumatol. 2016;68(4):

8 Diagnosis of PsA 2 primary patterns Peripheral joint (~95% of PsA patients) Axial involvement only (~5% of PsA patients) Diagnosis is typically made in a patient with psoriasis and inflammatory arthritis in a PsA-type pattern Patients with psoriasis may have other types of arthritis including RA, OA, gout, reactive arthritis, and arthritis of IBD Gottlieb A, et al. J Am Acad Dermatol. 2008;58(5): Diagnosis Is Made Clinically History Skin Joints involved Enthesitis, dactylitis, eye, inflammatory back pain (age <40, worse at night with AM stiffness, better with activity) Family history Physical exam Laboratory testing CBC BUN, creatinine, uric acid, and UA ESR and CRP (elevated in 40% of patients) RF (2%-10%), anti-ccp (8%- 16%) and ANA (low titer 50%) HLAB27 (50%) Arthrocentesis To rule out septic arthritis, gout and CPPD Imaging Plain film, ultrasound, MRI Co-existence of erosive changes and new bone formation, which may occur in same joint or within same digit Diagnosis can be challenging: REFER Menter A, et al. J Am Acad Dermatol. 2011;65(1): ; Alenius GM, et al. Ann Rheum Dis. 2006;65(3): ; Johnson SR, et al. Ann Rheum Dis. 2005;64(5): ; Eder L, et al. Ann Rheum Dis. 2012;71(1): ClASsification Criteria for Psoriatic ARthritis (CASPAR) Valuable in clinical trials, can be used for diagnosis Limited to peripheral arthritis, axial, and enthesitis Specificity of 98.7% and sensitivity of 91.4% Advantages over Moll and Wright Criteria* High specificity and sensitivity Includes family history of psoriasis Includes inflammatory articular Includes RF status *To meet the Moll and Wright 1973 classification criteria for psoriatic arthritis, a patient with psoriasis and inflammatory arthritis who is seronegative for RA must present with 1 of 5 clinical subtypes: polyarticular, symmetric arthritis; pligoarticular (less than 5 joints), asymmetric arthritis; distal interphalangeal joint predominant; spondylitis predominant; or arthritis mutilans. Taylor W, et al. Arthritis Rheum. 2006;54(8): ; Congi L, Roussou E. Clin Exp Rheumatol. 2010;28(3): ; Gottlieb A, et al. J Am Acad Dermatol. 2008;58(5):

9 PsA is diagnosed when 3 points below are assigned in the presence of inflammatory articular (joint, spine, or entheseal) Category Description Points Current or personal history of psoriasis Family history of psoriasis Psoriatic nail dystrophy on current physical exam Negative for RF Current dactylitis or history of dactylitis documented by a rheumatologist Radiographic evidence of juxtaarticular new bone formation CASPAR Psoriatic skin or scalp confirmed by dermatologist or rheumatologist; history of psoriasis from patient, family physician, dermatologist, rheumatologist, or other qualified practitioner Patient-reported history of psoriasis in first- or second-degree relative Includes onycholysis, pitting, and hyperkeratosis 1 Enzyme-linked immunosorbent assay or nephelometry preferred (no latex) using local laboratory reference range Swelling of entire digit 1 Ill-defined ossification near joint margins excluding osteophyte formation on plain X-rays of hand or foot Taylor W, et al. Arthritis Rheum. 2006;54(8): Treatment of Psoriasis and PsA Treatment of Psoriasis Type of treatment Recommended for Comments Topical Therapy (emollients, corticosteroids, vitamin D analogues, calcipotriene, tazarotene, calcineurin inhibitors, anthralin) Mild (standard) Limited by poor adherence rates Ultraviolet (UV) Light (UVB radiation, narrow-band UVB, photochemotherapy [PUVA]) Methotrexate Moderate-to-severe Moderate-to-severe Associated with accelerated photodamage and increased risk of malignancy; will not treat PsA Most widely used systemic treatment; inexpensive; pregnancy category X Cyclosporine Psoriasis flares Used as a bridging agent during induction of other maintenance agents or for flares Acitretin Biologic Agents (infliximab, etanercept, adalimumab, ustekinumab, secukinumab, tofacitinib, apremilast) Menter A, et al. J Am Acad Dermatol. 2011;65: Moderate-to-severe Moderate-to-severe Low toxicity and no immunosuppression; can be used in patients with infection, malignancy, or HIV; need to monitor LFTs and triglycerides; contraindicated if considering pregnancy May be used as first-line systemic agent depending on comorbidities and other considerations; highly efficacious; expensive 9

10 Treatment Considerations Age Pregnancy/lactation (current or future) Patient/family medical history Malignancies Multiple sclerosis or CHF Inflammatory bowel Depression or suicide Chronic infections Other autoimmune s (ie, lupus) Exposure to fungus or TB History of HCV, HBV, HIV or high risk behavior Social alcohol consumption Psoriasis Treatment Algorithm Yes Psoriasis + PsA No Anti-TNF +/- MTX* Extent of Mild (limited) -Topicals -Targeted phototherapy Moderate/Severe (extensive) -UVB/PUVA -Systemic -Biologic Effective Not Effective *Patients with nondeforming PsA without any radiographic changes, loss of range of motion, or interference with tasks of daily living should not automatically be treated with tumor necrosis factor (TNF ) inhibitors. It would be reasonable to treat these patients with a nonsteroidal anti-inflammatory agent or to consult a rheumatologist for therapeutic options. Patients with limited skin should not automatically be treated with systemic treatment if they do not improve, because treatment with systemic therapy may carry more risk than the itself. Adapted by Lilian McVey from Menter A, et al. J Am Acad Dermatol. 2008;58(5): Used with permission. Treatment of Mild-to-Moderate Psoriasis Topical therapy Corticosteroids, vitamin D derivatives, tazarotene, anthralin, tacrolimus, pimecrolimus, newer tar formulations Must be prescribed appropriately and used consistently for weeks to months for clinical improvement Potential AEs Cutaneous atrophy Telangiectasias Hypothalamic-pituitary axis suppression Stein Gold LF. Semin Cutan Med Surg. 2016;35(2 Suppl 2):S36-S44. Koyama G, et al. Int J Pharm Compd. 2015;19(5):

11 Treatment of Mild-to-Moderate Psoriasis Topical therapy (cont d) Primary limitation is medication adherence Strategies to optimize adherence: Consider dosage/schedule, choice of vehicle Fixed-combination gels, foams Address patient preference about treatment Address concerns about treatment-related toxicities Manage patient expectations Assess patient response and know when to refer! Up to 80% of psoriasis patients receive no treatment or only topical therapy Stein Gold LF. Semin Cutan Med Surg. 2016;35(2 Suppl 2):S36-S44. Lebwohl MG, et al. Am J Clin Dermatol. 2016;17(1): Treatment of Moderate-to-Severe Psoriasis Refer to dermatology Primary care: Emphasize need for long-term follow-up and adherence to prescribed therapy Encourage lifestyle changes Smoking cessation Decreased alcohol consumption Healthy diet and increased physical activity Monitor for AEs Consider early screening/intervention for CVD and metabolic Aldredge LM, et al. J Dermatol Nurses Assoc. 2016;8(1): Menter A, et al. J Am Acad Dermatol. 2008;58(5): Treatment Phototherapy Methotrexate Cyclosporin Acitretin Biologics Potential AEs Squamous cell carcinoma, photoaging Hepatotoxicity, bone marrow suppression, pneumonitis Impaired renal function, hypertension, lymphoma, cutaneous malignancies Mucocutaneous side effects, dyslipidemia Tuberculosis, and latent infections, hepatitis, CNS complications, cytopenia, multiple sclerosis, CHF Treatment of PsA Treatment is guided by severity and symptoms Treat to target (T2T) approach Comorbidities may limit options (diabetes, metabolic syndrome, fatty liver, CAD) Screening CV risk factors (BP, lipids, smoking) Weight loss counseling Ultrasound of liver with elevated LFTs Hepatitis screening Tuberculosis screening quantiferon gold TB is standard (or PPD skin test) Vaccinations 11

12 Treatment of PsA Will not affect plaque psoriasis Can also treat plaque psoriasis Biologic DMARDs anti-tnf, PDE4 inhibitors, anti-il-12/23, anti-il-17a Nonbiologic DMARDs methotrexate, sulfasalazine, leflunomide, cyclosporin, Intra-articular injections NSAIDs Adapted by Lilian McVey from Gossec L, et al. Clin Exp Rheumatol. 2015;5 (Suppl 93):S73-S77. Used with permission. Biologic Agents for Psoriasis/PsA Drug Target FDA-Approved for Psoriasis FDA-Approved for PsA Etanercept TNF-receptor X X Infliximab TNF-alpha X X Adalimumab TNF-alpha X X Ustekinumab Anti-IL-12/-23 X X Brodalumab IL-17 receptor X Ixekizumab IL-17A X Secukinumab IL-17A X X Apremilast Phosphodiesterase X X 4 (PDE4) Tofacitinib Janus Kinase (JAK- X STAT pathway) Golimumab TNF-alpha X Certolizumab TNF-alpha X Alwan W, Nestle FO. Clin Exp Rheumatol. 2015;33(5 Suppl 93):S2-S6. Biologic Agents in PsA Benefits Induce a durable long-term response 56% improvement in tender joint counts 70% improvement in swollen joint counts 64% improvement in CRP level 36% improvement in overall activity score (DAS) Improve Health Assessment Questionnaire (HAQ) scores Long-term safety confirmed Drawbacks Potential AEs Injection site reactions Serious infections Possible association with increase of some malignancies Lack of sustained response to TNF inhibitors in some PsA patients Intravenous dosing of some medications Cost Coates LC, et al. Ann Rheum Dis. 2008;67(5): Cawson MR, et al. BMC Musculoskelet Disord. 2014;15:26. Bissonnette R, et al. J Cutan Med Surg. 2009;13(Suppl 2):S67-S76. 12

13 Treatment of PsA Mild arthritis NSAIDs Moderately severe arthritis or resistant to NSAID Methotrexate Leflunomide Apremilast Severe peripheral arthritis/adverse prognosis TNF inhibitor Etanercept Infliximab Adalimumab Golimumab Certolizumab pegol Other biologic DMARDs Secukinumab Ustekinumab Axial NSAIDs Biologic DMARD Enthesitis NSAIDs Biologic DMARD Dactylitis NSAIDs DMARD. Stay Tuned American College of Rheumatology and the National Psoriasis Foundation Guideline for the Management of Psoriatic Arthritis Anticipated completion 2018 Monitoring National Psoriasis Foundation (NPF) treatment targets for plaque psoriasis Acceptable: Either BSA 3% or BSA improvement 75% from baseline at 3 months after treatment initiation Target: BSA 1% at 3 months after treatment initiation Monitor at least every 3 to 6 months during maintenance therapy Reassess if skin symptoms or arthritis not under control Armstrong AW, et al. J Am Acad Dermatol. 2017;76(2):

14 Comorbidities Established in Psoriasis and PsA Cardiovascular (CVD) Metabolic syndrome Obesity Dyslipidemia Diabetes Mood disorders Inflammatory bowel Malignancy Uveitis Alcohol and addictive behaviors Abuaara K, et al. Br J Dermatol. 2010;163(3): ; Armstrong AW, et al. J Hypertens. 2013;31: ; discussion ; Azfar RS, et al. Arch Dermatol. 2012;148(9): ; Gelfand JM, et al. JAMA. 2006;296(14): ; Gelfand JM, et al. J Invest Dermatol. 2006;126(10): ; Kurd SK, et al. Arch Derm. 2010;146: ; Langan SM, et al. J Invest Derm. 2012;132(3 Pt 1): ; Li W, et al. Am J Epidemiol. 2012;175(5): ; Ma C, et al. Br J Dermatol. 2013;168(3): ; Mehta NN, et al. Eur Heart J. 2010;31(8): ; Najarian DJ, et al. J Am Acad Dermatol. 2003;48(6): ; Yeung H, et al. JAMA Derm. 2013;149(10): Emerging Comorbidities COPD Adverse infectious outcomes Nonalcoholic steatohepatitis Renal Sleep apnea Psoriatic Peptic ulcer Callis Duffin K, et al. J Am Acad Dermatol. 2009;60(4): ; Wakkee M, et al. J Am Acad Dermatol. 2011;65(6): ; Van der Voort ET, et al. J Am Acad Dermatol. 2014;70: ; Yeung H, et al. JAMA Derm. 2013;149(10): ; Yang YW, et al. Br J Derm. 2011;165(5): Risk of Cardiometabolic Disease in Patients with More Severe Psoriasis Clinical significance: Increased risk of MI, stroke, CV death, and diabetes 5 years shorter life expectancy 10-year risk of major CV event attributable to psoriasis = 6% Risk of CV in patients with severe psoriasis similar to risk conferred by diabetes Patients treated for severe psoriasis are 30 times more likely to experience MACE (attributable to psoriasis) than to develop a melanoma MI = myocardial infarction, MACE = major adverse cardiac events, RR = relative risk. 1. Abuaara K, et al. Br. J. Dermatol. 2010;163(3): ; 2. Gelfand JM, et al. JAMA. 2006;296(14): Gelfand JM, et al. J Invest Derm. 2009;129(10): ; 4. Mehta NN, et al. Eur Heart J. 2010;31(8): Mehta NN, et al. Am J Med. 2011;124(8):775.e Azfar R, et al. Arch Derm. 2012;148(9):

15 Cardiovascular Comorbidity in PsA Rates of CVD and MACE are higher in patients with PsA compared to those without PsA PsA patients IR/1000 PYs Non-PsA patients IR/1000 PYs Rates of incident CVD All Rates of MACE IR = incidence rate, PY = person-years. Li L, et al. J Clin Rheumatol. 2015;21(8): Case Study 28-year-old female nurse being followed in rheumatology clinic for fibromyalgia diagnosed 5 years prior presents c/o worsening back and hand pain over the last several months. History Inflammatory back pain Somewhat responsive to NSAIDs, h/o gastric ulcer No h/o psoriatic Physical exam Scalp psoriasis Dactylitis right second finger Laboratory ANA 1:40 Neg RF, anti-ccp ESR 35, CRP 7 HLAB27 positive Case Study Diagnosed with psoriasis and PsA after review of labs and films Treatment considerations Negative hepatitis and TB screening History of gastric ulcer Considering pregnancy in the next year Options Methotrexate Unable to tolerate: GI distress and hair loss TNF inhibitor Etanercept At 3-month follow-up, dactylitis absent, scalp psoriasis clear, AM stiffness 30 minutes, back pain improved though not gone 15

16 Case Study Two years later, stopped etanercept with pregnancy confirmation Back pain worse during pregnancy At 2 months postpartum Scalp psoriasis worse, patches on elbows and hands Joint pain and stiffness in hands and knees Difficulty with ADLs Resumed etanercept with reduction in symptoms Primary Care Pearls Take a good history from the patient Complete a thorough skin examination Assess for joint signs and symptoms Monitor patients for comorbidities sooner than the general population Monitor for side effects and treatment complications Primary Care Pearls Assess for adherence to therapy Ensure all age-appropriate screening Assess for QoL and ADLs Assess for psychosocial Patients on biologics or immunosuppressants Do not give live vaccines Notify specialist (dermatology or rheumatology) if patient develops Serious signs or symptoms of infection Change in medical condition 16

17 Updates in Psoriasis and Psoriatic Arthritis Management: Best Practices for Effective Care References Abuaara K, Azfar RS, Shin DB, Neimann AL, Troxel AB, Gelfand JM. Cause-specific mortality in patients with severe psoriasis: a population-based cohort study in the U.K. Br J Dermatol. 2010;163(3): Ainsworth C. Immunology: A many layered thing. Nature. 2012;492(7429):S52-S54. Aldredge LM, Young MS. Providing guidance for patients with moderate-to-severe psoriasis who are candidates for biologic therapy: role of the nurse practitioner and physician assistant. J Dermatol Nurses Assoc. 2016;8(1): Alenius GM, Berglin E, Rantapää Dehlqvist S. Antibodies against cyclic citrullinated peptide (CCP) in psoriatic patients with or without joint inflammation. Ann Rheum Dis. 2006;65(3): Alwan W, Nestle FO. Pathogenesis and treatment of psoriasis: exploiting pathophysiological pathways for precision medicine. Clin Exp Rheumatol. 2015;33(5 Suppl 93):S2-S6. Armstrong AW, Diegel MP, Bagel J, et al. From the Medical Board of the National Psoriasis Foundation: Treatment targets for plaque psoriasis. J Am Acad Dermatol. 2017;76(2): Armstrong AW, Harskamp CT, Armstrong EJ. The association between psoriasis and hypertension: a systematic review and meta-analysis of observational studies. J Hypertens. 2013;31(3): ; discussion Armstrong AW, Schupp C, Wu J, Bebo B. Quality of life and work productivity impairment among psoriasis patients: findings from the National Psoriasis Foundation survey data PLoS One. 2012;7(12):e Arumugam R, McHugh NJ. Mortality and causes of death in psoriatic arthritis. J Rheumatol Suppl. 2012;89: Azfar RS, Seminara NM, Shin DB, Troxel AB, Margolis DJ, Gelfand JM. Increased risk of diabetes mellitus and likelihood of receiving diabetes mellitus treatment in patients with psoriasis. Arch Dermatol. 2012;148(9): Bissonnette R, Ho V, Langley RG. Safety of conventional systemic agents and biologic agents in the treatment of psoriasis. J Cutan Med Surg. 2009;13(Suppl 2):S67-S76. Callis Duffin K, Wong B, Horn EJ, Krueger GG. Psoriatic arthritis is a strong predictor of sleep interference in patients with psoriasis. J Am Acad Dermatol. 2009;60(4): Cawson MR, Mitchell SA, Knight C, et al. Systematic review, network meta-analysis and economic evaluation of biological therapy for the management of active psoriatic arthritis. BMC Musculoskelet Disord. 2014;15:26. Coates LC, Cawkwell LS, Ng NW, et al. Sustained response to long-term biologics and switching in psoriatic arthritis: results from real life experience. Ann Rheum Dis. 2008;67(5): Congi L, Roussou E. Clinical application of the CASPAR criteria for psoriatic arthritis compared to other existing criteria. Clin Exp Rheumatol. 2010;28(3): Eder L, Chandran V, Pellet F, et al. Human leucocyte antigen risk alleles for psoriatic arthritis among patients with psoriasis. Ann Rheum Dis. 2012;71(1): Eder L, Haddad A, Rosen CF, et al. The incidence and risk factors for psoriatic arthritis in patients with psoriasis: a prospective cohort study. Arthritis Rheumatol. 2016;68(4):

18 Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006;296(14): Gelfand JM, Shin DB, Neimann AL, Wang X, Margolis DJ, Troxel AB. The risk of lymphoma in patients with psoriasis. J Invest Dermatol. 2006;126(10): Gelfand, JM, Dommasch ED, Shin DB, et al. The risk of stroke in patients with psoriasis. J Invest Derm. 2009;129(10): Gladman DD. Mortality in psoriatic arthritis. Clin Exp Rheumatol. 2008;26(5 Suppl 51):S62-S65. Gossec L, Smolen JS. Treatment of psoriatic arthritis: management recommendations. Clin Exp Rheumatol. 2015;5 (Suppl 93):S73-S77. Gottlieb A, Korman NJ, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics. J Am Acad Dermatol. 2008;58(5): Helmick CG, Lee-Han H, Hirsch SC, Baird TS, Bartlett CL. Prevalence of psoriasis among adults in the U.S.: and National Health and Nutrition Examination Surveys. Am J Prev Med. 2014;47(1): Icen M, Crowson CS, McEvoy MT, Dann FJ, Gabriel SE, Maradit Kremers H. Trends in incidence of adult-onset psoriasis over three decades: a population-based study. J Am Acad Dermatol. 2009;60(3): Johnson SR, Schentag CT, Gladman DD. Autoantibodies in biological agent naive patients with psoriatic arthritis. Ann Rheum Dis. 2005;64(5): Karreman MC, Weel AE, van der Ven M, et al. Prevalence of psoriatic arthritis in primary care patients with psoriasis. Arthritis Rheumatol. 2016;68(4): Koyama G, Liu J, Scaffidi A, Khazraee M, Epstein B. Novel approaches to topical psoriasis therapy. Int J Pharm Compd. 2015;19(5): Kurd SK, Troxel AB, Crits-Christoph P, Gelfand JM. The risk of depression, anxiety, and suicidality in patients with psoriasis: a population-based cohort study. Arch Derm. 2010;146(8): Langan SM, Seminara NM, Shin DB, et al. Prevalence of metabolic syndrome in patients with psoriasis: a populationbased study in the United Kingdom. J Invest Derm. 2012;132(3 Pt 1): Lebwohl MG, Kavanaugh A, Armstrong AW, Van Voorhees AS. US perspectives in the management of psoriasis and psoriatic arthritis: patient and physician results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey. Am J Clin Dermatol. 2016;17(1): Li L, Hagberg KW, Peng M, Shah K, Paris M, Jick S. Rates of cardiovascular and major adverse cardiovascular events in patients with psoriatic arthritis compared to patients without psoriatic arthritis. J Clin Rheumatol. 2015;21(8): Li W, Han J, Choi HK, Qureshi AA. Smoking and risk of incident psoriasis among women and men in the United States: a combined analysis. Am J Epidemiol. 2012;175(5): Ma C, Harskamp CT, Armstrong EJ, Armstrong AW. The association between psoriasis and dyslipidaemia: a systematic review. Br J Dermatol. 2013;168(3): Mehta NN, Azfar RS, Shin DB, Neimann AL, Troxel AB, Gelfand JM. Patients with severe psoriasis are at increased risk of cardiovascular mortality: cohort study using the General Practice Research Database. Eur Heart J. 2010;31(8):

19 Mehta NN, Yu Y, Pinnelas R, et al. Attributable risk estimate of severe psoriasis on major cardiovascular events. Am J Med. 2011;124(8):775.e1-6. Menter A, Gottlieb A, Feldman S, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. J Am Acad Dermatol. 2008;58(5): Menter A, Korman NJ, Elmets CA. Guidelines of care for the management of psoriasis and psoriatic arthritis. J Am Acad Dermatol. 2011;65(1): Najarian DJ, Gottlieb AB. Connections between psoriasis and Crohn s. J Am Acad Dermatol. 2003;48(6): Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med. 2009;361(5): Rachakonda TD, Schupp CS, Armstrong AW. Psoriasis prevalence among adults in the United States. J Am Acad Dermatol. 2014;70(3): Stein Gold LF. Topical Therapies for Psoriasis: Improving Management Strategies and Patient Adherence. Semin Cutan Med Surg. 2016;35(2 Suppl 2):S36-S44. Taylor W, Gladman D, Helliwell P, et al. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum. 2006;54(8): Tollefson MM, Crowson CS, McEvoy MT, Maradit Kremers H. Incidence of psoriasis in children: a population-based study. J Am Acad Dermatol. 2010;62(6): Van der Voort ET, Koehler EM, Dowlatshahi EA, et al. Psoriasis is independently associated with nonalcoholic fatty liver in patients 55 years old or older: Results from a population-based study. J Am Acad Dermatol. 2014;70(30): Villani A, Rouzaud M, Sevrain M, et al. Prevalence of undiagnosed psoriatic arthritis among psoriasis patients: Systematic review and meta-analysis. J Am Acad Dermatol. 2015;73(2): Wakkee M, de Vries E, van den Haak P, Nijsten T. Increased risk of infectious requiring hospitalization among patients with psoriasis: a population-based cohort. J Am Acad Dermatol. 2011;65(6): Yang YW, Keller JJ, Lin HC. Medical comorbidity associated with psoriasis in adults: a population-based study. Br J Derm. 2011;165(5): Yeung H, Takeshita J, Mehta NN, et al. Psoriasis severity and the prevalence of major medical comorbidity: a populationbased study. JAMA Derm. 2013;149(10): Young M, et al. Article in press. Young M, Aldredge L, Parker P. Psoriasis for the primary care practitioner. J Am Assoc Nurse Pract. 2017;29(3):

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