Psoriasis and Management in Primary Care

Psoriasis and its management in primary care

1. 1 Psoriasis DR CHIA KOK KING PEGAWAI PERUBATAN & KESIHATAN GRED U44 KLINIK KESIHATAN KUAH, LANGKAWI

2. Psoriasis Chronic skin disorder Psora = itch Also termed psoriasis vulgaris T-cell mediated inflammatory disease Accelerated epidermal turnover with hyperproliferation 2 O to activation of immune system Altered maturation of epidermal keratinocytes Inflammation Vascular changes

3. 4 DERMIS STRATUM BASALE STRATUM SPINOSUM STRATUM GRANULOSUM STRATUM CORNEUM Proliferation Immaturity Neutrophil accumulation Disorganized N O R M A L P S O R I A S I S

4. Prevalence Psoriasis occurs in 2% of the world’s population Highest in Caucasians (Scandinavian/European descent) In Africans, African Americans and Asians between 0.4% and 0.7% Equal frequency in males and females May occur at any age from infancy to the 10 th decade of life First signs of psoriasis Females mean age of 27 years Males mean age of 29 years

5. Prevalence Two Peaks of Occurrence One at 20-30 years One at 50-60 years Psoriasis in children Low – between 0.5 and 1.1% in children 16 years old and younger Mean age of onset - between 8 and 12.5 years

6. Prevalence Two-thirds of patients have mild disease One-third have moderate to severe disease Early onset (prior to age 15) Associated with more severe disease More likely to have a positive family history Life-long disease Remitting and relapsing unpredictably Spontaneous remissions of up to 5 years have been reported in approximately 5% of patients

7. Psoriasis, an inherited disease If you have psoriasis, what is the risk to: Your unrelated neighbor? About 2% Your sibling? 15-20% Your identical twin? 65-70% Your child? 25%

8. Psoriasis: Associated Factors Genetic Factors: - 30% of people with psoriasis have had psoriasis in family - Autosomal dominant inheritance Nongenetic Factors: - Mechanical, ultraviolet, chemical injury - Infections: Strep, viral, HIV - Prescription drugs, stress, endocrine, hormonal, obesity, alcohol, smoking

9. Why might psoriasis be a systemic inflammatory disease? Immune abnormalities are profound Psoriasis severity is associated with greater levels of systemic inflammation (e.g. CRP, Th-1 cytokines) Inflammation may be a common pathway to a variety of diseases including atherosclerosis, obesity, and insulin resistance Krueger JG, Bowcock , A. Ann Rheum Dis 2005;64:30-36.

10. Psoriasis as a Systemic Disease Koebner Phenomenon Elevated ESR Increased uric acid levels → gout Mild anemia Elevated α 2 -macroglobulin Elevated IgA levels Increased quantities of Immune Complexes Psoriatic arthropathy Aggravation of psoriasis by systemic factors Medication Focal infections Stress Life-threatening forms of psoriasis

11. ESR / CRP in psoriasis Although psoriatic arthritis sometimes causes an increased erythrocyte sedimentation rate (ESR), mild anemia , and elevated blood uric acid levels, these symptoms are also associated with other rheumatic diseases, including gout ESR and CRP can be normal in psoriatic arthritis Increasing PASI was linked to increasing CRP and a trend to higher elastase and lactoferrin . CRP levels were shown to correlate with PASI, total leucocytes, neutrophils , elastase , lactoferrin and α1- antitrypsin. Psoriatic arthritis, CP Rajendran , SG Ledge, Kanaka P Rani , Radha Madhavan JAPI • VOL. 51 • NOVEMBER 2003 Journal of the European Academy of Dermatology & Venereology , 24(7):789-796

12. Natural history of psoriasis Disease severity 85% Mild, 10% Moderate, 5% severe Control of severe disease 50% of patients intensively treated continue to have very active disease (PUVA cohort) 75% of patients with severe disease are not receiving appropriate therapies (NPF survey) Pathways affected and possible outcomes Inflammatory atherosclerosis, thrombosis Angiogenesis endothelial (endothelial progenitor cells)dysfunction Metabolic oxidative stress

13. PSORIASIS

14. Paradigm of the Natural History of Psoriasis and Co-morbidities Risk factors Genes Environment Outcomes Cancer Cardiovascular disease Metabolic disease Arthritis Mortality Mediating Factors Pathophysiology (inflammation, hyper-proliferation, angiogenesis) Treatment Psychosocial impact

15. Psoriasis is associated with cardiovascular risk factors Smoking Obesity Dyslipidemia Hypertension Diabetes Neiman AN, Porter S, and Gelfand JM . Expert Review of Derm . 2006;1:63-75

16. Psoriasis: a risk factor for CAD and MI? Psoriasis CAD MI Smoking HTN DM Obesity Lipids

17. Psoriasis is independently associated with carotid atherosclerotic disease and impaired endothelial function Balci DD et al , Increased carotid artery intima -media thickness and impaired endothelial function in psoriasis JEADV ISSN 1468-3083 In patients with Psoriatic arthritis, psoriasis severity is an independent predictor of cardiovascular disease Gladman , DD et al . Cardiovascular morbidity in psoriatic arthritis. Ann Rheum Dis 2008.094839

18. Clinical Presentation Sharply demarcated ERYTHEMATOUS plaque with silvery white scales typically on extensor surfaces Symmetric Pruritic / Painful Pitting Nails Inflammatory arthropathy in 10-20% of patients, which in severe cases may be the dominant cause of morbidity Histopathology Thickening of the epidermis Tortuous and dilated blood vessels Inflammatory infiltrate primarily of lymphocytes

19. Plaque psoriasis AKA psoriasis vulgaris is the most common form of psoriasis. It affects 80 to 90% of people with psoriasis. Typically appears as raised areas of inflamed skin covered with silvery white scaly skin (plaques)

20. Plaques may be as large as 20 cm Symmetrical disease Sites of predilection Elbows Knees Presacrum Scalp Hands and Feet

21. Psoriatic Plaque

22. Symptoms of Plaque Psoriasis Pruritus Pain Excessive heat loss Patient Complaints Unsightliness of the lesions Low self-esteem Feelings of being socially outcast Excessive scale

23. May be widespread – up to 90% BSA Genitalia involved in up to 30% of patients Most patients have nail changes Nail pitting “Oil Spots” Involvement of the entire nail bed Onychodystrophy Loss of nail plate

24. Plaque Psoriasis

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26. 30 Guttate Psoriasis

27. Guttate Psoriasis Characterized by numerous 0.5 to 1.5 cm small oval (tear drop shaped) papules and plaques Appear over large areas of the body, such as the trunk, limbs, and scalp . Early age of onset Most common form in children Streptococcal throat infection often a trigger and rashes develop 1-2 weeks following infection Spontaneous remissions in children Often chronic in adults

28. 32 Guttate Psoriasis

29. AKA inverse psoriasis appears as smooth inflamed patches of skin. Occurs in skin folds, particularly around the genitals (between the thigh and groin), the armpits, under an overweight stomach ( pannus ), and under the breasts ( inframammary fold). It is aggravated by friction and sweat, and is vulnerable to fungal infections. Flexural psoriasis

30. appears as raised bumps that are filled with non-infectious pus (pustules). skin under and surrounding pustules is red and tender. can be localised , commonly to the hands and feet , or generalised with widespread patches occurring randomly on any part of the body. May cause long lasting disability include palmoplantar chronic pustular psoriasis ( palmoplantar pustulosis ), acrodermatitis continua of Hallopeau ( acropustulosis ) Pustular psoriasis

31. Changes in the appearance of finger and toe nails including discolouring under the nail plate, pitting of the nails, lines going across the nails, thickening of the skin under the nail, and the loosening ( onycholysis ) and crumbling of the nail. Nail psoriasis

32. Psoriatic arthritis involves joint and connective tissue inflammation. Psoriatic arthritis can affect any joint but is most common in the joints of the fingers and toes. This can result in a sausage-shaped swelling of the fingers and toes known as dactylitis . Psoriatic arthritis can also affect the hips, knees and spine ( spondylitis ). About 10-15% of people who have psoriasis also have psoriatic arthritis. Psoriatic arthritis

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34. Generalized Pustular Psoriasis Erythrodermic Psoriasis May be complicated by high-output cardiac failure, temperature dysregulation , and septicaemia , particularly in elderly patients . Life–Threatening Forms of Psoriasis

35. Generalized Pustular Psoriasis Unusual manifestation of psoriasis Can have a gradual or an acute onset Characterized by waves of pustules on erythematous skin often after short episodes of fever of 39˚ to 40˚C Weight loss Muscle Weakness Hypocalcemia Leukocytosis Elevated ESR

36. Cause is obscure Triggering Factors Infection Pregnancy Lithium Hypocalcemia secondary to hypoalbuminemia Irritant contact dermatitis Withdrawal of glucocorticosteroids , primarily systemic

37. Generalized Pustular Psoriasis

38. Erythrodermic Psoriasis Classic lesion is lost Entire skin surface becomes markedly erythematous with desquamative scaling. It may be accompanied by severe itching, swelling and pain. Often only clues to underlying psoriasis are the nail changes and usually facial sparing

39. Triggering Factors Systemic Infection Withdrawal of high potency topical or oral steroids Withdrawal of Methotrexate Phototoxicity Irritant contact dermatitis Often the result of an exacerbation of unstable plaque psoriasis, particularly following the abrupt withdrawal of systemic treatment. This form of psoriasis can be fatal, as the extreme inflammation and exfoliation disrupt the body's ability to regulate temperature and for the skin to perform barrier functions.

40. Erythrodermic Psoriasis

41. Nail Changes In 78% of psoriatic patients Fingernails>Toenails Four changes Onycholysis (= separation from nail bed) Pitting* Subungual debris accumulation Color alterations *Pitting rules out a fungal infection

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43. Psoriatic Arthritis In 10-20% of psoriasis patients Often seen in patients with nail and scalp psoriasis Peripheral interphalangeal joints No elevated serum levels of rheumatoid factors (as seen in rheumatoid arthritis, yet has all other features)

44. Diagnosis: Based on the appearance of the skin. There are no special blood tests or diagnostic procedures. A skin biopsy (or scraping) may be needed to rule out other disorders and to confirm the diagnosis. When the plaques are scraped, one can see pinpoint bleeding from the skin below ( Auspitz's sign) 27/03/2011 University of Jordan/Faculty of Pharmacy

45. Severity of Disease Three Cardinal Signs of Psoriatic Lesions Plaque elevation Erythema Scale Body Surface Area

46. The Psoriasis Area Severity Index (PASI) : - The most widely used measurement tool for psoriasis. - Combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease). http://www.pasitraining.com/pasi_score/ http://pasi.corti.li/ Severity: - Mild - Moderate - Severe

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48. Management

49. Discuss with Patient Explanation/no cure Treatment options (including none) Patient’s expectation When to Refer? Diagnostic difficulty Education Failed Topical >30% skin surface Increasing steroids Pustular / erythrodermic Systemic therapy

50. The Majority of Moderate-Severe Psoriasis Patients Are Under-Treated 50 % of patients with moderate or worse disease are currently untreated 46% have topical therapy only Reason dermatologists do not use more aggressive therapies Safety concerns Time consuming Cost 1 Leonardi , 2003; 2 Market Measures/ Cozint LLP, June 2003. Other therapies 54% Topicals only 46%

51. Targeting dual disease processes Ryan S. Br J Nurs 2010;19:822-5 Two key disease processes underlie psoriasis 1 Cell proliferation AIM: Prevent the infiltration of inflammatory cells into the epidermis AIM: Reduced cell turnover time and reduce scale Inflammation

52. Three step management Adapted from Primary Care Dermatology Society (PCDS) 2010. Available from www.pcds.org.uk (Last accessed 24 January 2012)

53. Treatment options - Topical Treatment type Mode of action Treats inflammation Treats cell proliferation Emollients 1 Reduce dryness, scaling and cracking  ? Topical corticosteroids 2 Dampen down inflammation   Tar preparations 1 Remove loose scales may act as an anti-inflammatory   Dithranol 2 Suppresses production of skin cells   Vitamin D analogues 2 Reduce excessive skin cell production   Vitamin D + steroid combination 3 Reduce excessive skin cell production + dampen down inflammation   Tazarotene 2 Slows production of skin cells   British National Formulary (BNF) BNF 62 Section 13.5.2; September 2011: 62. Available from www.bnf.org (Last accessed 19 January 2012) Menter A et al . J Am Acad Dermatol 2009:60;643-659 Dovobet® Gel Summary of Product Characteristics. Available from www.medicines.org.uk (Last accessed 9 January 2012)

54. Treatment options - Phototherapy Bandwidth Characteristics Narrowband UVB (311nm) Patients receive TL01 narrowband UVB 1 UVB slows keratinocyte proliferation and differentiation 2 3x weekly for 6-8 weeks (max. once weekly) Equivalent to a two week holiday in the Mediterranean PUVA (Psoralen + UVA) Penetrates skin more deeply than UVB 3 Used for those with a long history of PsO unresponsive to NBUVB 3 – or considered first line for palmoplantar PsO Maximum 150 exposures in a lifetime Twice weekly for 5-10 weeks . Gambichler T et al . J Am Acad Dermatol 2005:52;660-670 Menter A et al . J Am Acad Dermatol 2010:62;114-135 Lapolla, W et al . J Am Acad Dermatol 2011:64:936-949

55. Treatment options - Systemic Treatment Action Systemics Methotrexate 1 5-25mg weekly (PO or SC) Folate antagonist with immunosuppressive, cytostatic and anti-inflammatory effects Acitretin 1 (10-75mg OD) Retinoid – reduces keratinocyte production/turnover. Anti-inflammatory effects. Can combine with TLO1 Ciclosporin 1 (3-5mg/kg/day) Calcineurin inhibitor – prevents T-cell activation from translation into the release of inflammatory cytokines Others Fumaric acid esters, Mycophenolate mofetil, Calcitriol Biologics TNF-α blockers 2 Etanercept, Adalimumab, Infliximab Block activity of TNF alpha – the master regulator (central cytokine) involved in psoriasis 2 Anti IL-12/23p40 Ustekinumab Neutralises all Th1(IL-12) and Th17(IL-23) cell-mediated responses Menter A et al . J Am Acad Dermatol 2009;61:451-485 Menter A et al . J Am Acad Dermatol 2008;58:826-850

56. Medications with the least potential for adverse reactions are preferentially employed. As a first step, medicated ointments or creams are applied to the skin. If topical treatment fails to achieve the desired goal then the next step would be to expose the skin to ultraviolet (UV) radiation. This type of treatment is called phototherapy. The third step involves the use of medications which are taken internally by pill or injection : systemic treatment. Over time, psoriasis can become resistant to a specific therapy. Treatments may be periodically changed to prevent resistance developing ( tachyphylaxis ) and to reduce the chance of adverse reactions occurring: treatment rotation.

57. Psoriasis: Treatment Lubrication Removal of scales Slow down lesion proliferation Pruritus management Prevent complications Lessen patient stress Season and climate

58. Topical agents available in klinik kesihatan Aqueous cream Hydrocortisone cream 1% Betamethasone cream 0.025% Betamethasone cream 0.1% Clobetasol propionate cream 0.05%

59. Emollients and Moisturizers Moisturizes, lubricates and soothes dry and flaky skin *Recommended* May be the only treatment for mild psoriasis ? Minimises Koebner phenomenon Produces occlusive film to limit water evaporation from skin/by osmotic effect increased hydration allows stratum corneum to swell scaling decreases, skin is more pliable, less itch, less scaling Adverse Effect : contact dermatitis, folliculitis (rare) When in control of psoriasis, regular use of emollients should continue to be encouraged The only option available in our KK  AQUEOUS CREAM

60. Corticosteroids Reduce inflammation, itching and scaling Anti-inflammatory effect Decrease in vascular permeability, decreasing dermal edema and leukocyte penetration into skin Antiproliferative effect Immunosuppressive effect 69

61. Topical corticosteroids Not indicated for widespread psoriasis – careful supervision Can enhance effects by occlusion ONLY in suitable patients Reduce inflammation, itching and scaling Anti-inflammatory effect Decrease in vascular permeability, decreasing dermal edema and leukocyte penetration into skin Antiproliferative effect Immunosuppressive effect Use for specific targeted flares, e.g. scalp ( Dovobet ® gel, Etrivex ® Shampoo) Consider combination products, e.g. Diprosalic ® ointment for thick scale Maybe hazardous for a number of reasons including: Rebound relapses Development of tolerance Risk of generalised pustular psoriasis Development of local/systemic toxicity due to impaired barrier function

62. Ointments: helps hydrate; good for dry, hyperkeratotic , scaly lesions Cream: for use on all areas, useful for infected lesions Solutions: for scalp psoriasis, often contain alcohols which can be painful with open lesions 71

63. Hydrocortisone

64. Betamethasone

65. Clobetasol

66. Adverse Effects: (esp. with occlusion) Systemic absorption Dermal atrophy Telangiectasis Ecchymoses Peri-orbital acne Poor wound healing Pyogenic infections

67. I hope no question Thank you for bearing this with me