Psoriasis

1. Psoriasis Aneta Szczerkowska - Dobosz

2. Psoriasis – epidemiology Kanada 4,7% USA 1,4-4,6% Indianie Płd Am. 0% Australia 2,6% Aborygeni 0% Szwecja 2,3% Rosja 2,0% Chiny 0,05-0,8% Japonia 0,29% Hiszpania 3,7% Low incidence : West Africans, Japanese, very low : incidence or absence in North and South American Indians males = females

3. Psoriasis – epidemiology Peak incidence - 22.5 years of age Late onset ( type II) ≈ age 55 Early onset ( type I) predicts a more severe and long- lasting disea se , positive family history

4. Psoriasis - history 460-377 p.n.e – Hipokrates first description 129-99 p.n.e – Galen : term „ psora ” = pruritus 1841 - Ferdinand von Hebra : separated psoriasis from lepra

5. Psoriasis – genetic background 1963 r. Gunnar Lomhold 1972 r. – HLA: susceptibility markers 1970 - 1990 – twin studies

6. Genetics of psoriasis PSORS Lokalizacja PSORS1 6q21.3 PSORS2 17q25 PSORS3 4q34 PSORS4 1q21 PSORS5 3q21 PSORS6 19p13.2 PSORS7 1p35-p34 PSORS8 16q PSORS9 4q31 2000: susceptibility loci

7. Genetics of psoriasis Nair RP . Am J Hum Gen 2006 , 78 , 827.

8. Genetics of psoriasis( GWAS, Genome wide association scans ) candidate genes James T. Elder . Genes Immun , 2009, 10, 201.

9. Polygenic trait one parent has psoriasis - 8% of offspring develop psoriasis both parents have psoriasis - 41% of children develop psoriasis Psoriasis - complex disease

10. Physical trauma ( Koebner phenomenon) isomorphic sign - the psoriatic papules occur in the site of the mechanical trauma within a couple of days Infections acute streptococcal infection - guttate psoriasis Stress as high as 40% in adults and higher in children Drugs systemic glucocorticoids , oral lithium, antimalarial drugs, interferon, beta blockers ( flares existing psoriasis or psoriasiform drug eruption ) Alcohol ingestion , smoking, obesity PSORIASIS - environmental f actors

11. Nestle F. N Engl J Med , 2009, 361, 496. Immunopathogenesis of psoriasis – history 1980’:immunological background 1990-2000’: psoriasis - Th1 /Th17 mediated disease 1961r . van Scott epidermal hiperproliferation

12. Immunopathogenesis of psoriasis Nestle F. N Engl J Med , 2009, 361, 496 . Innate , adaptive immunity Keratynocytes Macrophages Dendytic cells Lymphocytes T

13. Psoriasis - immunopathogenesis angiogenesis epidermal neutrophiles and lymphocytes infiltrations keratynocytes , endothelium cells activation Th 1 Th 17 Treg INF- γ TNF- α IL-17 IL-22 TNF – α ↓ IL-10 TGF- β

14. Clinical phenotypes A. Localised forms B. Generalised forms Psoriasis of folds Plaque Seborhoic psoriasis Guttata Psoriasis capitis Generalised plaque Psoriasis palmo-plantaris ( non-pustular ) Erytrodermia Psoriasis plaque ( limbs ) Psoriasis plaque ( trunk ) Psoriasis – phenotype classification International Psoriasis Council 2007

15. Psoriasis – sides of lesions

16. Auspitz sign - the appearance of bleeding spots when psoriasis scales are scraped off T he candle grease sign (the removal of the scale reveals the skin with a glossy grease-like appearance

17. Psoriasis – Koebner sign

18. Psoriasis -c hronic s table t yp e

19. Sharply marginated , dull-red plaques with loosely adherent, lamellar, silvery-white scales Plaques coalesce to form polycyclic, geographic lesions and may partially regress, resulting in annular, serpiginous , and arciform patterns Lamellar scaling can easily be removed, or, when the lesion is extremely chronic, it adheres tightly to the underlying inflammatory and infiltrated skin, resulting in hyperkeratosis Psoriasis -c hronic s table t ype

20. Finger nails and toenails frequently involved ( arthritis ) pitting subungual hyperkeratosis , onycholysis yellowish-brown spots under the nail plate—the oil spot ( pathognomonic ) Psoriasis – nails

21. O ne of the most common forms of the disease-occurring in 50-80% of patients, it is often the first clinical manifestation of the dermatosis . They are usually located at the border between the glabrous skin and the hairy scalp, forming the so called "psoriatic crown". Plaques, sharply marginated , with thick adherent scales Scattered discrete or diffuse involvement of entire scalp , Scalp psoriasis may be part of generalized psoriasis or coexist with isolated plaques, or the scalp may be only site involved. Psoriasis – scalp

22. Uncommonly involved when involved, usually associated with a refractory type of psoriasis Psoriasis -face

23. not scaly but macerated, bright red and fissured t he sharp demarcation - distinction from intertrigo , candidiasis , contact dermatitis, tinea , this form is seen rarely in clinical practice. It occurs in 3 to 6.8% of all patients with psoriasis, and if it is the only clinical presentation it may cause difficulties in getting the correct diagnosis. Scales are not found in the psoriasis of the skin folds, but maceration and secondary infections are seen. Chronic Psoriasis of the Perianal and Genital Regions and of the Body Folds – Inverse Psoriasis

24. Acute Guttate Type Salmon-pink papules ( guttate : Latin gutta , "drop"), 2.0 mm to 1.0 cm with or without scales Scattered discrete lesions generally concentrated on the trunk, less on the face and scalp, usually sparing palms and sole s Guttate lesions may resolve spontaneously within a few weeks but usually become recurrent and may evolve into chronic, stable psoriasis

25. Acute g uttate t ype

26. Napkin psoriasis

27. Psoriasis palmo-plantaris Palms and Soles m ay be the only areas involved m assive silvery white or yellowish hyperkeratosis and scaling not easily removed t here may be cracking and painful fissures and bleeding

28. Pustulosis palmo-plantaris (PPP)

29. Pustulosis palmo-plantaris (PPP) Pustules in stages of evolution, 2–5 mm, deep-seated, yellow, develop into dusky-red macules and crusts; present in areas of erythema and scaling or normal skin Limited to palms and soles, may be only a localized patch on the sole or hand, or involve both hands and feet

30. Pustulosis palmo – plantaris Psorasis ? Distinct entity ?

31. PPP PPP - Genetic studies Asumalahti i inni.: J Invest Dermatol 2003, 120. Mossner R i inni.: J Invest Dermatol 2005, 124, 282-284.

32. PPP Clinical observations : Females : 90% Age onset : V-VI decade of life Nicotine – trigger factor 95%

33. Generalized Acute Pustular Psoriasis (Von Zumbusch ) Fever , generalized weakness , severe malaise Rare The constellation of fiery-red erythema followed by formation of pustules occurs over a period of less than 1 day Patient frightened , " toxic .„ Nikolsky phenomenon - positive Pustules are sterile The eruption generalized

34. Psoriatic erytroderma psoriasis is one of the most common causes of erythrodermia in adults, it can arise anew or complicate chronic plaque psoriasis (often if the treatment is not appropriate). Inflammation with dandruff-like scaling involving the whole skin surface, accompanied by elevated leukocyte count, elevated ESR, and lymphadenopathy

35. Psoriatic arthritis seronegative spondyloarthropathies , which include ankylosing spondylitis , enteropathic arthritis, and reactive arthritis Incidence is 5–8%. Rare before age 20 May be present (in 10% of individuals) without any visible psoriasis; if so, search for a family history !

36. Psoriatic arthritis Types " Distal"— seronegative , without subcutaneous nodules, involving, asymmetrically, a few distal interphalangeal joints of the hands and feet: an asymmetric oligoarthritis . Enthesitis —inflammation of ligament insertion into bone. Multilating psoriatic arthritis with bone erosion and ultimately leading to osteolysis or ankylosis . " Axial" —especially involving the sacroiliac, hip, and cervical areas with ankylosing spondylitis .

37. Psoriatic arthritis Skin s ymptoms and s igns Swelling, redness, tenderness of involved joints or site of enthesitis (e.g., insertion of Achilles tendon in calcaneus ) Dactylitis —sausage fingers , May or may not be associated with psoriasis elsewhere. Often psoriatic involvement of fingertips and periungual skin. Massive nail involvement by psoriasis is frequent Arthritis may lead to arthritis mutilans : destruction of interphalangeal joints results in telescope fingers with mutilation of hand and considerable functional impairment

38. PSORISIS as chronic inflammatory systemic disease

39. CISD Common ganetic background II. Pathogenesis / efficacy of pathogenesis based treatment III. CVD risk

40. I. CISD – common genetic background Gen Chromosom Skojarzone choroby IL-12B 5q Łuszczyca, Ch . Crohna IL-23R 1p Łuszczyca, Ch . Crohna , ZZSK, łzs CDKAL1 6p Łuszczyca, Ch . Crohna , cukrzyca typu 1 PTPN22 18p Łuszczyca, RZS, SLE, cukrzyca typu 2 Region genów rodziny IL-4 IL-13 5q Łuszczyca, Ch . Crohna

41. II. CISD - common pathogenesis Th1/Th17 mediated immunological responce Role of TNF- α Role of DC Endothelium dysfunction Oxidative stres Inflammatory markers in circulation

42. Psoriasis / atheromatosis – common pathogenesis Spach F. Br J Dermatol 2008, 159, 10 . łuszczyca miażdżyca

43. Environmental factors associated with psoriasis Nicotine Alkohol Low physical activity

44. Psoriasis comorbidities increasing risk of CVD Metabolic syndrom Associated with systemic inflammatory disease Obestity Diabetes Hiperlipidemia Hypertension

45. Psoriasis and obesity Hamminga EA i inni. Med. Hypoth 2006, 67, 76. Johnson A i inni. Br J Dermatol 2008, 159, 342. Obesity 2x increases psoriasis risk BMI correlates with psoriasis severity

46. Psoriasis and diabetes Psoriatics have diabetes more often Role of TNF- α in insuline resistence Significant correlation of resistine in blood with psoriasis severity Cohen A. J Am Acad Dermatol, 2007, 56, 629.

47. Psoriasis and atherogenic dyslipidemia Rocha-Pereira i inni. Clin Chim Acta 2001, 303, 33. ↑ LDL, VLDL, TG, cholesterol, ↓HDL in psoriatics LDL correlates with psoriasis severity Oxydative stres accelerates atherogenesis Side effect of antipsoriatics drugs on lipide profile

48. Psoriasis and hipertension Hypertension more often in psoriatics Side effect of antipsoriatics drugs Cohen A. J Am Acad Dermatol , 2006, 55, 829.

49. Psychosocial impact of psoriasis Stygmatisation J Am Acad Dermatol. 1999 Sep;41(3 Pt 1):401-7.

50. Depression : 60 % Suicidal tendency : 7,2 % Psychosocial impact of psoriasis Esposito M. Dermatology , 2006, 212,123. Gupta M. Br J Dermatol 1998, 139, 846.

51. thickening of the epidermis ( acanthosis ) and thinning of epidermis over elongated dermal papillae Increased mitosis of keratinocytes , fibroblasts , and endothelial cells Parakeratotic hyperkeratosis ( nuclei retained in the stratum corneum ) Inflammatory cells in the dermis ( lymphocytes and monocytes ) and in the epidermis ( lymphocytes and polymorphonuclear cells ), forming microabscesses of Munro in the stratum corneum . Psoriasis - laboratory examinations dermatopathology

52. Psoriasis - laboratory examinations Serology Increased antistreptolysin titer in acute guttate psoriasis with antecedent streptococcal infection . Sudden onset of psoriasis may be associated with HIV infection Culture Throat culture for group A - hemolytic streptococcus infection .

53. Psoriasis treatment – factors selection of treatment Age: childhood, adolescence, young adulthood, middle age, >60 years Type of psoriasis: guttate , plaque, palmar and palmopustular , generalized pustular psoriasis, erythrodermic psoriasis Site and extent of involvement: localized to palms and soles, scalp, anogenital area, scattered plaques but <5% involvement; generalized and >30% involvement Previous treatment: ionizing radiation, systemic glucocorticoids , photochemotherapy (PUVA), cyclosporine (CS), methotrexate (MTX) Associated medical disorders (e.g., HIV disease , CVD ).

54. Psoriasis – local treatment emolients and keratolytics a nthralin vitamine D analogues topical steroids topical retinoids

55. Emmolients and keratolytics preparations containing salicylic acid (5-10%) urea craems

56. Anthralin ( dithranol ) usual concenrations 0.1-2% efficacy - good in a short term side efects : irritation hypersensitivity , staining of nails and hair contraindication : acute or actively inflamed psoriasis

57. Calcipotriene ( vitamine D derivative ) benefit in mild to moderate psoriasis combination of calcipotrene with topical steroids provides better clearance and maintenance may cause skin irritation should not be used by patients with hypercalcemia or vitamine D toxicity

58. Topical steroids short period of up to 4 weeks for flexural or facial psoriasis long-term use must be avoided - side effects : - atrophy - striae - teleangiectasia - skin fragility - dyspigmentation - systemic side effects !

59. Topical retinoids Tazarotene indicated for mild to moderate psoriasis risk : skin irritation - desquamation , pruritus , burning , stinging , dryness , discoloration

60. Psoriasis - treatment

61. oral ingestion of 8-methoxypsoralen (8-MOP) (0.6 mg 8-MOP per kilogram body weight) or, 5-MOP (1.2 mg/kg body weight) and exposure to doses of UVA that are adjusted to the sensitivity of the patient. three times a week . m ost patients clear after 19 to 25 treatments, and the amount of UVA needed ranges from 100 to 245 J/cm 2 . Long-term side effects : PUVA keratoses and squamous cell carcinomas Oral PUVA Photochemotherapy

62. Oral r etinoids in psoriasis Acitretin usual range 25-50mg/day very effective in inducing desquamation but only moderately effective in suppressing psoriatic plaques (an exception is pustular psoriasis They are highly effective when combined according to established protocols with 311-nm UVB or PUVA (called Re-PUVA) Contraception is mandatory during treatment and for 2 years after it is completed Combinations of oral retinoids and PUVA improve the efficacy of each and permit a reduction of the dose and duration of each if refractory to treatment

63. Psoriasis – retinoids - s ide effects teratogenic - women of childbearing age should use contraception during and for two years after therapy!!! ro -dermatitis: eyes, ears, nose and throat: cheilitis , dry eyes and nose, conjunctivitis abnormal liver function tests , hipertriglyceridemia , hiperglycemia muscosceletal : arthralgia , myalgia central nervous system: dizziness , fatigue , headache

64. Psoriasis - retinoids - patient information therapeutic effect after 2-4 week avoid pregnancy for one month before and 2 years after treatment avoid tetracycline don’t donate blood one year ( teratogenic effect ) avoid excessive sunlight !

65. Cyclosporine in psoriasis CS treatment is highly effective at a dose of 3–5 mg/kg per day . As the patient responds, the dose is tapered to the lowest effective maintenance dose. Monitoring blood pressure and serum creatinine is mandatory because of the known nephrotoxicity of the drug. CS should be employed only in patients without risk factors . !

66. Psoriasis – antibacterial interventions antistreptococcal interventions - antibiotics and tosillectomy - guttate psoriasis

67. Methotrexate Therapy Schedule of Methotrexate : the single-dose MTX once weekly (12.5-25 mg/ week ) 80% improvement but total clearing only in some , and higher doses increase the risk of toxicity . Higher doses may be needed in overweight patients CBC, Liver Function Contraindications : anemia, thrombocytopenia or leukopenia nursing mothers, pregnancy (avoid conception for 6 month after stopping men and women) gastric or duodenal ulcer

68. Lancet. 2002 Apr 6;359(9313):1173-7.

69. alkohol intake abnormal liver parameters liver disease in anamnesis positive familial anamnesis into genetic liver diseases diabetes obesity significant exposure into chemical substances no folic acid suplemmentation hiperlipidemia Risk factors of liver damage in patients treated with mtx

70. Liver damage after Mtx in psoriatics Fibrosis cirrhosis Histological features of NAHS ( non-alkoholic hepatic steatosis )

71. Liver toxicity in patient treated with mtx – cumulative dose Patients with risk factors 1,5 g Mtx Patients with no risk factors 3,5-4 g Mtx

72. Biologicals in psoriasis – antilymphocyte

73. Anty – TNF infliksimab adalimumab etanercept Anty – IL-12 IL-23 ustekinumab Biologicals in psoriasis – antycytokines

74. Specifity Short and long term efficacy ↓ organ toxicity ↓risk of drug interactions Cardioprotective action Biologics in psoriasis

75. Risk of infection Risk of neoplasms ? moAb antibodies Long-term efficacy ? Costs Biologics in psoriasis

76. Psoriasis - p revention no effective preventive measures to be taken against the development of psoriasis flare-ups may be potentially reduced by modification of risk factors – infections, stress, drugs, smoking, alkohol interaction alert! beta-blockers for hypertensives may cause the flare of psoriasis

77. Psoriasis prognosis debilitating disease due to psychosocial impact genaralized pustular psoriasis and erythrodermic psoriasis may be life-threatening if untreated course of disease is chronic and may be refractory to treatment 5-8% of patients with psoriasis may develop psoriatic arthropathy

78. Th1 i Th17 in psoriasis pathogenesis Psoriasis as a systemic disease decreasing QL

79. Severe psoriasis as a risk factor of CVD Pathogenesis based therapy

80. Lichen planus acute or chronic inflammatory dermatosis involving skin and/or mucous membranes

81. Lichen planus – epidemiology Worldwide occurrence; incidence < 1%, all races Age of Onset : 30–60 years Sex Females > males Hypertrophic LP more common in blacks

82. LP-onset Acute (days) or insidious (over weeks). Lesions last months to years, asymptomatic or pruritic ; sometimes severe pruritus . Mucous membrane lesions are painful, especially when ulcerated

83. LP-etiology Idiopathic in most cases but cell-mediated immunity plays a major role. Majority of lymphocytes in the infiltrate are CD8+ and CD45Ro+ (memory) cells. Drugs, metals (gold, mercury), or infection [hepatitis C virus (HCV)] result in alteration in cell-mediated immunity. There could be HLA-associated genetic susceptibility that would explain a predisposition in certain persons. Lichenoid lesions of chronic graft-versus-host disease (GVHD) of skin are indistinguishable from those of LP

84. Lichen planus - d istribution : predilection for flexural aspects of arms and legs, can become generalized

85. LP – clinical manifestation Papules, flat-topped, 1 to 10 mm, sharply defined, shiny. Violaceous , with white lines (Wickham striae ), seen best with hand lens after application of mineral oil. Polygonal or oval. Grouped, annular, or disseminated scattered discrete lesions when generalized. In dark-skinned individuals, postinflammatory hyperpigmentation is common. May present on lips and in a linear arrangement after trauma ( Koebner or isomorphic phenomenon ) .

86. LP - variants Hypertrophic Atrophic Follicular Individual keratotic-follicular papules and plaques that lead to cicatricial alopecia. Spinous follicular lesions , typical skin and mucous membrane LP, and cicatricial alopecia of the scalp are called Graham Little syndrome Vesicular Vesicular or bullous lesions may develop within LP patches or independent of them within normal-appearing skin. Pigmentosus Hyperpigmented , dark-brown macules in sun-exposed areas and flexural folds . In Latin Americans and other dark-skinned populations . Significant similarity with ashy dermatosis Actinicus Papular LP lesions arise in sun-exposed sites , especially the dorsa of hands and arms Ulcerative LP may lead to therapy-resistant ulcers , particularly on the soles

87. LP - Mucous Membranes Oral 40–60% of individuals with LP Reticular LP Reticulate ( netlike ) pattern of lacy white hyperkeratosis on buccal mucosa lips , tongue , gingiva ; the most common pattern of oral LP Erosive or Ulcerative LP Superficial erosion with / without overlying fibrin clot ; occurs on tongue and buccal mucosa ); shiny red painful erosion of gingiva ( desquamative gingivitis ) or lips Carcinoma may very rarely develop in mouth lesions . Genitalia Papular , annular , or erosive lesions arise on penis ( especially glans), scrotum , labia majora, labia minora , vagina .

88. LP- nails Destruction of nail fold and nail bed with longitudinal splintering

89. LP-treatment Cyclosporine Oral prednisone is effective for individuals with symptomatic pruritus , painful erosions, dysphagia , or cosmetic disfigurement. A short, tapered course is preferred Systemic Retinoids ( Acitretin ) 1 mg/kg per day is helpful as adjunctive measure in severe (oral, hypertrophic) cases, but usually additional topical treatment is required. PUVA Photochemotherapy In individuals with generalized LP or cases resistant to topical therapy.