1. Psoriasis Prof. (Dr.) Iffat Hassan Head of the Department, Dept. of Dermatology, sexually Transmitted Diseases & Leprosy Govt. Medical College Srinagar (University of Kashmir), Jammu and Kashmir, India Digital Lecture Series : Chapter 12

2. CONTENTS  Introduction  Epidemiology  Etiology  Pathogenesis  History  Morphology  Morphological types  Distributional variation  Psoriasis in children  Psoriasis in HIV  Psoriatic arthritis  Histopathology of psoriasis  Co-morbidities in psoriasis  Differential diagnoses  Management of psoriasis  MCQs  Photo Quiz

3. Introduction  Psoriasis is a complex, chronic, multifactorial, inflammatory disease that involves hyperproliferation of the keratinocytes in the epidermis, with an increase in the epidermal cell turnover rate  Environmental, genetic, and immunologic factors appear to play a role  Characterised by red, scaly, sharply demarcated indurated papules and plaques of various sizes

4. Epidemiology  2-3% of world’s population  Males = Females  Two types Early onset (type I) : More severe and long- lasting disease Positive family history Late onset (type II) : Milder form Family history usually absent

5. Etiology  Environmental, genetic, and immunologic factors appear to play a role Systemic Chronic Inflammation Immune Factors Environmental Factors Heredity PSORS1 HLA-Cw6

6. Pathogenesis Two hypothesis  Keratinocyte hyperproliferation may be due to immunological responses. Cytokines released by lymphocytes and langerhan cells may further stimulate the inflammatory cells to cause an increased rate of epidermal cell turnover  Epithelial cells themselves produce cytokines which promote proliferation of epithelial cells and attract lymphocytes

7. Trigger Factors  Trauma : Mechanical, chemical, radiation  Infections : Streptococcus, staphylococcus, HIV  Stress  Alcohol and smoking  Metabolic factors : hypocalcemia  Sunlight : usually beneficial but in some may cause exacerbation

8. Trigger Factors : Drugs COMMON  Beta blockers  Lithium  Antimalarials  NSAIDS  ACE Inhibitors  Antibiotics  Interferons  Terbinafine  Benzodiazepines LESS COMMON  Digoxin  Clonidine  Amiodarone  Quinidine  Gold  TNF alpha inhibitors  Imiquimod  Fluoxetine  Cimetidine

9.  Prominent itchy, red areas with increased skin scaling and peeling  New lesions appearing at sites of injury/trauma to the skin (Koebner phenomenon)  Actual clearance of lesions following trauma to the skin (Reverse Koebner phenomenon)  Exacerbation in winter, improvement in summer  Significant joint pain, stiffness, deformity in 10-20%  Family history of similar skin condition History

10. Morphology  Lesions : Erythematous, scaly papules and plaques. Characteristic lesions include well-demarcated, erythematous plaques with adherent silvery white scales.  Cardinal features : ERYTHEMA, INDURATION & SCALING. The commonest type is Psoriasis vulgaris.  Sites : Mostly extensors sites are involved. Elbows, knees, scalp, lumbosacral areas, intergluteal clefts. Palms / soles involved commonly.

11. Auspitz Sign  On scraping a lesion of psoriasis with a blunt glass slide, silvery scales are observed followed by a glistening transparent membrane. On removal of this membrane [Bulkeley’s membrane] multiple small bleeding points are observed.  This sign is absent in pustular psoriasis and inverse psoriasis While eliciting the Auspitz sign,the characteristic coherence of scales seen as if one scratches a wax candle (candle grease sign) Grattage Test

12. Woronoff‘S Ring  A blanched halo of approximately uniform width surrounding psoriatic lesions usually following phototherapy or coal tar therapy  Local inability to synthesize PGE2 in response to an ultraviolet light stimulus, resulting from the presence of an inhibitor of prostaglandin synthesis.

13. Auspitz Sign Woronoff’s Ring

14. Morphological Types  Chronic plaque psoriasis : Most common form. Typically appears as erythematous plaques covered with silvery white scales  Guttate psoriasis : Characterized by numerous small oval (teardrop- shaped) spots. Associated with streptococcal throat infection. Common in children, good prognosis.  Pustular psoriasis : Crops of pustules on erythematous base Localised Generalised

15. Morphological Types  Erythrodermic psoriasis : Generalised erythema and scaling (involving > 90% of BSA) May be accompanied by fever, chills, hypothermia, and dehydration secondary to the large BSA involvement.  Follicular psoriasis: Scaly, follicular papules over trunk and extremities  Linear psoriasis : Linear distribution of psoriatic lesions along Blaschko's lines  Annular psoriasis : Clearing in the centre of the plaque  Rupioid (limpet like or cone shaped lesions), elephantine and ostraceous psoriasis (lesions resembling oyster shells)

16. Chronic Plaque Psoriasis

17. Guttate Psoriasis

18. Erythrodermic Psoriasis

19. Pustular Psoriasis

20. Distributional Variation  Scalp psoriasis  Palmoplantar psoriasis  Nail psoriasis : Nails involved in 25-50% patients. Pitting, onycholysis, subungual hyperkeratosis, splinter hemorrhages, the oil-drop sign.  Mucosal psoriasis  Inverse psoriasis : Spares the typical extensor surfaces Affects intertriginous (i.e, axillae, inguinal folds, inframammary creases) areas with minimal scaling.

21. Scalp Psoriasis

22. Palmo-plantar Psoriasis

23. Nail Psoriasis

24. Inverse Psoriasis

25. Psoriasis in Children  Common in girls  More pruritic  Lesions are relatively thinner, softer, and less scaly  More frequently precipitated by infections  Facial involvement more common than in adults  Certain clinical variants like erythroderma, arthropathy and pustular psoriasis are rare.

26. Psoriasis In HIV  Acute onset  More severe  Refractory to conventional treatment  Poor prognosis

27. Psoriatic Arthritis  Seen in 5-10% of psoriatic patients  Types : Classic -Distal interphalangeal arthropathy (15%) Asymmetrical oligoarticular arthritis (70%) Symmetrical polyarthritis -Rheumatoid type(5%) Psoriatic spondylitis with or without sacroiliatis (5%) Arthritis mutilans (5%)

28. Histopathology  Parakeratosis  Microabscesses of Munro in the horny layer  Absence of granular layer  Regular elongation of rete ridges (camel-foot shaped)  Suprapapillary thinning  Spongiform pustules of Kogoj  Dilated and tortuous capillaries in dermal papillae  Superficial perivascular inflammatory infiltrate

29. Comorbidities in Psoriasis  Cardiovascular disease / stroke  Metabolic syndrome  Diabetes  Psoriatic arthritis  Mood disorders ( anxiety, depression, suicide)  Crohn’s disease

30. Differential Diagnosis  Seborrheic dermatitis  Nummular eczema  Tinea corporis  Lichen planus  Secondary syphilis  Pityriasis rosea  Drug eruption  Candidiasis/ Diaper dermatitis  Tinea unguium  Mycosis fungoides

31. Management of Psoriasis  Psoriasis is a chronic disease that can have a significant effect on quality of life.  Management involves addressing both psychosocial and physical aspects of the disease. Psychosocial Aspects :  Laying out reasonable aims of treatment  Patient education  Counselling and/or treatment with psychoactive medications

32. General Measures  Avoidance of trauma or irritating agents  Weight reduction in obese patients  Reduce intake of alcoholic beverages  Reduce emotional stress  Sunlight and sea bathing improve psoriasis except in photosensitive

33. Topical Therapy  Emollients Minimize the symptoms of itching and tenderness Help prevent irritation and thus the potential for – Subsequent Koebnerization  Tar Antiproliferative effect 2% or 3% crude coal tar –Alternative is 4 to 10% LCD –(liquor carbonis detergens, a tar distillate)

34. Topical Therapy  Anthralin May restore normal epidermal –proliferation and keratinization Stains clothes, irritant  Salicylic acid Keratolytic agent Adjuvant to other topicals

35. Topical Therapy  Topical corticosteroids Mainstay of topical treatment especially for plaque psoriasis Antiinflammatory, antiproliferative, and immunosuppressive actions Can be used as monotherapy 1-2 times daily or combined with other topical agents  Topical vitamin D analogues Inhibition of keratinocyte proliferation and enhancement of keratinocyte differentiation Calcipotriene, Calcitriol, Tacalcitol, Maxacalcitol, Becocalcidiol

36. Topical Therapy  Topical retinoids Tazarotene (0.05% / 0.1%) Act by normalizing abnormal keratinocyte differentiation, diminishing hyperproliferation, and by decreasing expression of inflammatory markers  Calcineurin inhibitors Tacrolimus/ Pimecrolimus Act by blocking the synthesis of numerous inflammatory cytokines Facial & intertriginous psoriasis

37. UVB Phototherapy Indication  Generalized psoriasis unresponsive to topicals.  Narrow band UVB is not only more effective than broad band UVB but also leads to rapid clearance of lesions. Dosage :  Initial dosing according to skin type (130-400 mJ/cm 2 ) or MED (50% of MED)[ MED = Minimal erythema dose]  Subsequent dosage increase by 15-65 mJ/cm2 or ≤10% of initial MED  Treatment 3-5 times/week

38. UVB Phototherapy Duration of Treatment  Response observed at 8-10 treatments  Single course is 15-20 treatments  Maintenance therapy may prolong remission

39. Combination of UVB with systemic therapies  Methotrexate with UVB therapy has shown potential value because of the synergistic effects of these two therapies.  Retinoids with UVB have been extensively studied and accelerate the response to phototherapy, reducing the cumulative dosage of UVB and the dose of acitretin required to achieve psoriasis clearance.

40. Targeted Phototherapy Excimer lasers/ lamps and targeted UVB therapy selectively target affected lesions of psoriasis while leaving unaffected skin untreated. Highly effective, can be used for resistant localised lesions such as scalp and palmoplantar psoriasis

41. PUVA Photochemotherapy  Systemic psoralen plus ultraviolet A is indicated for adults with generalized psoriasis who are resistant to topical therapy.  Contraindicated in patients with known lupus erythematosus, porphyria, or xeroderma pigmentosum. Dosage :  8-Methoxypsoralen, 0.4-0.6 mg/kg.  Taken 1-2 hours before exposure to UVA.  Other available forms of psoralen include 5-methoxypsoralen and trimethylpsoralen.  UV protective eye wear should be worn when outdoors for 12 hours post-ingestion.  Treatment 2-3 times/week.

42. PUVA Photochemotherapy Duration of treatment :  Initial improvement frequently seen within 1 month of therapy  Single course is 20-25 treatments  May be repeated as indicated Topical PUVA Therapy  Topical PUVA is indicated for adults with psoriasis of palms and soles.  Bath PUVA is indicated for adults and children with generalized psoriasis.

43. Combination of PUVA with other therapies  Combination of topical calcipotriol with PUVA leads to a decrease in duration of PUVA therapy along with an improved clinical response  Combination of oral retinoids with PUVA is more effective compared with monotherapy with either acitretin or PUVA alone  Because patients who have previously received PUVA treatment have an increased risk for developing SCC when subsequently treated with cyclosporine, this combination should be avoided.  PUVA with MTX - safety questioned.

44. Systemic Therapy General Principles A BSA of 10% has been traditionally used as a prerequisite to start a systemic therapy. However a subset of patients with limited disease having debilitating symptoms with significant negative affect on quality of life of patient makes a systemic approach to treatment appropriate.

45. Methotrexate Indication : Severe, recalcitrant, disabling psoriasis that is not adequately responsive to other forms of therapy. Dosing : Weekly single oral dose Total dose should not ordinarily exceed 30 mg/wk A test dose of 2.5-5 mg is recommended Folate supplementation

46. Cyclosporine Indication : Adult, non immunocompromised patients with severe, recalcitrant psoriasis. Efficacy observed in erythrodermic psoriasis, generalized pustular psoriasis, and palmoplantar psoriasis. Dosing : 2.5-5.0 mg/kg/d in two divided doses/day

47. Acitretin Indication : Adults with severe plaque type psoriasis (FDA approved). Rapid and impressive responses seen in patients with pustular psoriasis Because of a lack of significant immunosuppression, acitretin is generally considered effective and the treatment of choice in HIV- positive patients with severe psoriasis. Dosing : 10-50 mg/day given as a single dose. Efficacy rates when used in combination with phototherapy are higher

48. Second Line Systemic Agents Azathioprine : Due to absence of data from controlled trials, it is best to conclude that there is no good evidence that azathioprine is an effective treatment for psoriasis. Fumaric acid esters : Several well designed randomized studies of fumarates demonstrate mean PASI improvement rates of between 50% and 80% after 12 to 16 weeks of treatment. Hydroxyurea : May be a valuable reserve drug for patients needing systemic treatment and who are resistant to methotrexate or develop side effects. Leflunomide : May be used in patients of psoriasis with arthritis.

49. Second Line Systemic Agents Mycophenolate Mofetil : Therapy of severe psoriasis probably in combination with cyclosporin as a cyclosporin sparing agent. Systemic Steroids :  Not to be used in the routine care of psoriasis.  Role in the management of persistent, otherwise uncontrollable erythroderma that is causing metabolic complications.  Generalized pustular psoriasis of the Von Zumbusch type if other drugs are contraindicated or ineffective.  Steroids may occasionally be needed, and in high dosage to control hyperacute polyarthritis.

50. Others  6 - Thioguanine  Tacrolimus & Pimecrolimus  Cytokines  Protein kinase C inhibitor  Zidovudine  Somatostatin  Liarazole  Gluten free diet  Photodynamic therapy Apremilast : A phosphodiesterase 4 inhibitor, is a new oral agent for the treatment of moderate to severe plaque psoriasis

51. Biologic Agents Biologicals use should be restricted to :  Patients with severe disease defined by a PASI score of 10 or more (or BSA of 10% or greater where PASI is not applicable) and DLQI of greater than 10.  Patients who have failed to respond to, or who have a contraindication to, or who are intolerant to other systemic therapies such as cyclosporin and methotrexate.

52. Biologic Agents Biological agents licensed for treatment of psoriasis vulgaris  Etanercept, a fully human soluble p75 TNF-α receptor fusion protein  Infliximab, a chimeric human-immune antibody to TNF-α  Adalimumab, a fully human recombinant antibody to TNF-α  Ustekinumab, a fully human recombinant antibody to the p40 component of IL-12/IL-23  Alefacept, a fusion protein of lymphocyte function associated antigen-3 and IgG that inhibits T-cell activation  Secukinumab, an anti-IL-17A monoclonal antibody

53. Biologic Agents Infliximab is administered by IV infusion while the others are administered by SC injection. Biological agent of choice  For stable disease, particularly if not too severe (e.g. PASI >10 but <20) etanercept or adalimumab  For patients requiring rapid disease control adalimumab or infliximab  For patients with unstable or generalized pustular psoriasis severe nail disease infliximab Ustekinumab should be reserved for use as a second-line biological agent.

54. Future Therapies  Therapies targeting Th17 pathway Briakinumab Ixekizumab Brodalumab  Anti TNF therapy : Certolizumab pegol  Janus kinase inhibitor : Tofacitinib  Other molecules : Ponesimod Exenatide / Liraglutide

55. MCQ’s Q.1) The appearance of punctate bleeding spots when psoriasis scales are scraped off is known as A.Nikolsky’s sign B.Crowe’s sign C.Auspitz sign D.Darier’s sign Q.2) Psoriasis is exacerbated by A.Lithium B.B-Blockers C.Antimalarials D.All of the above

56. MCQ’s Q.3) Psoriasis A.Most commonly affects intertriginous areas B.Plaques usually have diffuse edges C.Does not occur before the age of 10 D.May follow streptococcal infections E.In the area under the breasts is characterised by many dry, silvery scales.

57. MCQ’s Q.4) Patient presents with erythematous scaly lesions on extensor aspect of elbows and knee. The clinical diagnosis is obtained by? A.Auspitz sign B.KOH smear C.Tzanck smear D.Skin biopsy Q.5) The characteristic clinical features of psoriasis include A.Sparing of the skin over the head, face and neck B.Guttate psoriasis usually affects the elderly C.Nail changes with pitting and onycholysis D.Red non-scaly skin areas in the natal cleft and submammary folds

58. Q. Identify the morphological type of psoriasis. Photo Quiz

59. Q. identify the nail changes Photo Quiz

60. Q. Identify the morphological type of psoriasis Photo Quiz

61. Thank You!