Management of psoriasis

management of psoriasis according to ROOK's dermatology

1. Management of psoriasis By Dr maria saeed

2. Management

3. Topical treatment Emollients Topical corticosteroids Vitamin D analogue Salicylic acid (de scaling) dithranol Refined coal tar Tazarotene Calcinuerin inhibitors

4. 1.Topical steroid It is an anti-inflammatory  preparation used to  control  eczema/dermatitis   and many other skin conditions( e.g psoriasis etc). available in creams, ointments, solutions and other vehicles. Newer formulations of corticosteroids, particularly foams can be used for scalp, truncal or limb psoriasis. Intralesional corticosteroid : localized lesions of psoriasis by needle injection in small resistant plaques. In the treatment of psoriasis of the fingernails, the nail fold can be injected.

5. emollients Helps to lift scale and reduce fissuring Use as a soap substitute Salicylic acid Keratolytic agent that reduces scaling to allow other topical treatments to penetrate Used as combination therapy

6. List of topical steroids according to potency POTENCY TYPE Mild Hydrocortisone Moderate Clobetasone Potent Betamethasone Fluticasone Mometasone triamicinolone Very potent Clobetasol propionate Mild to moderate : face and neck, flexures and genitalia and in pustular psoriasis. Potent and very potent : scalp psoriasis and in extensor surfaces.

7. Mechanism of action In  psoriasis, corticosteroids suppress the immune system, particularly proinflammatory cytokines and chemokines thereby inhibiting T cell activation.

8. Effects of topical steroid Anti-inflammatory Immunosuppressive Anti-proliferative Vasoconstrictive . The amount that reaches the target cell Absorption through the skin (0.25%–3%) formulation Potency of topical steroids

9. Formulations of topical steroid Creams and lotions are general purpose and are the most popular formulations. 2 .Ointment for dry, non-hairy skin Oil based 3 . Gel or solution Useful in hair-bearing skin Has an astringent (drying) effect Water based

10. Combination products Topical steroid is sometimes combined with another active ingredient, including antibacterial,  antifungal agent  or  calcipotriol . The combination of a potent topical corticosteroid with calcipotriol provides the most effective strategy for topical treatment of limited plaque psoriasis over a short period of time.

11. Very potent steroid (clobetasol) with different formulations

12. Potent steroid ( Betamethasone ) with different formulations

13. Calcipotriol + betamethasone Combination of steroids with different medications

14. Side effects of steroids Side effects are uncommon or rare Skin thinning (atrophy) Stretch marks ( striae ) in armpits or groin Easy bruising ( senile/solar  purpura ) and tearing of the skin Enlarged blood vessels ( telangiectasia ) Localized increased hair thickness and length ( hypertrichosis )

15. Striae induced by potent topical corticosteroids in psoriasis

16. 2.Vitamin D analogues

17. Mechanism of action  Inhibit keratinocyte proliferation and induce keratinocyte differentiation. Calcipotriol reduces the number of new skin cells and making the new cells mature more quickly.  Antiproliferative mechanism of vitamin D in keratinocytes involves the induction of the growth inhibitory factor transforming growth factor-β and of cyclin-dependent kinase inhibitors, with subsequent growth arrest in the G1 phase of the cell cycle. Vitamin D also has an  immunomodulatory  effect, suppressing activation and differentiation of Th17/Th1 cells and inducing a Th2 response.

18. Combination therapy Combination therapy of calcipotriol and betamethasone dipropionate is commonly used and its highly effective   combination treatment flattens psoriasis plaques, removing scale, and reducing discomfort. Promotes greater anti-inflammatory and anti-proliferative effects than either component alone.

19. Calcipotriol (50 μg /g) ointment has also been shown to be effective and safe in children when administered in amounts up to 45 g/week/m2. It is prudent to restrict the amount of calcipotriol (50 μg /g) ointment to less than100 g or 50 g/m 2 per week. Calcitriol 3 μg /g ointment is better tolerated than calcipotriol ointment for treatment of the face and flexures. Tacalcitol 4 μg /g ointment applied once daily is effective for the treatment of plaque psoriasis but is probably less effective than calcipotriol 50 μ g/g ointment. Calcipotriol and Tacalcitol uses

20. Calcipotriol ointment enhances the efficacy of PUVA and UVB phototherapy. It is recommended that calcipotriol is not applied immediately prior to phototherapy exposure. Tacalcitol ointment when combined with PUVA is UVA sparing and calcitriol is UVB sparing in combination. Calcipotriol and Phototherapy

21. Side effects Application site irritation Application site  pruritus Folliculitis Hypopigmentation Hypercalcaemia Urticaria Exacerbation of  psoriasis .

22. 3. Dithranol Dithranol is a synthetic derivative of chrysarobin , which was originally extracted from the bark of the araroba tree. It could penetrate the epidermis in 100 min led to the concept of short‐contact dithranol . It has a similar efficacy to topical vitamin D analogues. Three times weekly short‐contact dithranol may be as effective as five times weekly.

23. Mechanism of action Antiproliferative and pro‐apoptotic effects on keratinocytes. Reduces neutrophil and lymphocyte migration. Side effects Dithranol produces brown staining of the skin which resolves about 2 weeks after therapy is completed. Generally not useful for facial or flexural psoriasis due to significant irritation.

24. Coal tar Coal tar is the byproduct of coal distillation. Goeckerman regimen : combination of coal tar with suberythemogenic doses of UVB. Topical tar therapy decreases the serum levels of inflammatory cytokines. Goeckerman regimen apply 5hr per day for moderate to severe psoriasis. Mean remission time (i.e. maintenance of PASI‐75 ) was 22 months . Use of topical tar therapies in an in‐patient setting and day care setting. Coal tar may cause folliculitis and contact allergy. PASI score is a tool used to measure the severity and extent of  psoriasis .

25. Topical retinoids Tazarotene is a synthetic retinoid, whose main metabolite, tazarotenic acid, binds to RARs β and γ. Tazarotene applied daily for 3 months. main drawback of tazarotene is local irritation at the site of application. Tazarotene is probably best reserved for thick recalcitrant plaques of psoriasis .

26. Topical calcineurin inhibitors Topical calcineurin inhibitors tacrolimus and pimecrolimus are effective for psoriasis affecting the face, neck, flexures and genitalia. May be effective under occlusion for psoriatic plaques at other sites. Do not produce skin atrophy making them more suitable for long‐term us.

27. Phototherapy

28. Introduction Phototherapy is the use of non- ionising portions of the electromagnetic spectrum for its therapeutic effect. In dermatology, the term phototherapy is usually applied to the use of ultraviolet (UV) radiation in the treatment of skin diseases. Broadband UVB (BB-UVB, 290-320nm). Narrowband UVB (NB-UVB, wavelength 311-313nm). Photochemotherapy : PUVA (Psoralen with UVA, wavelength 320-400nm). Excimer laser : for  localised  psoriasis, not yet available in many countries.

29. Small uva unit for hand/foot PUVA treatment

30. Full body UVA cabinet

31. Phototherapy Indications Psoriasis (80% patients) Atopic dermatitis Other forms of dermatitis Pruritus Vitiligo Contraindications Childhood Pregnancy and breastfeeding (PUVA ). Immobility or inability to stand unassisted for 10 min. Very fair skin (skin type 1 and 2, especially PUVA) Immunosuppressive  medication Past skin cancer, especially  melanoma Lupus erythematous Xero derma pigmentosum

32. UVB phototherapy Psoriasis is the most common skin disease treated with UVB. NB-UVB phototherapy clears about 75% of patients, where clearance is defined as 90% or greater reduction in extent of psoriasis compared to baseline. The number of treatments required ranges from 10 to 40, delivered two to five times weekly ( most often three times weekly ). The initial dose and incremental increases in dose each week depend on skin type and response to treatment. For most patients the whole body is treated except the face and genitals.

33. Extensive psoriasis prior to NB-UVB Psoriasis has cleared after 22 months of treatment

34. The mechanism of action of UVB is the suppression of cell-mediated immunity Localized or generalized erythema is a common complication of treatment. It begins 2 to 6 hours after exposure, peaks at 12-18 hours after exposure and generally persists for 48 hours . Imp note :eyes and genitals should be covered under phototherapic treatment

35. Complications of UVB phototherapy Acute complications Acute sunburn effect: tender erythema &/or pruritus. Photokeratitis: ocular grittiness, pain, photophobia, tearing and blepharospasm. Photosensitivity. Worsening skin disease. Long term complications Photo-ageing: wrinkling, freckling, xerosis, telangiectasia, elastosis and atrophy. Skincancer :  actinic keratoses, squamous cell carcinoma, basal cell carcinoma and melanoma.

36. Photoxic erythema and blistering due to NB-UVB

37. PUVA is the acronym used for the combination of psoralens and long‐wave ultraviolet radiation (UVA 320–400 nm). PUVA is used for more severe long-lasting and resistant disease Delivered two to four times weekly Most patients are treated with 8-methoxypsoralen ( methoxsalen ) orally 2 hours prior to exposure to UVA.  PUVA

38. Psoralen interacts with UVA in the epidermis to form DNA photo-adducts. The resulting photoproduct: Slows down  keratinocyte  proliferation Suppresses the cutaneous immune reaction Affects melanocytes, fibroblasts and endothelial cells PUVA results in inflammation  ( phototoxicity )and  melanogenesis  (tanning) in normal skin. Phototoxic inflammation reaches a peak 48-96 hours after exposure and lasts days to weeks. As photosensitivity persists for some hours after taking methoxsalen , patients should wear covering clothing, apply broad-spectrum sunscreen and wear wrap-around UVA-blocking sunglasses at least until nightfall of the treatment day.

39. PUVA for psriasis Elbows after 20 weeks of treatment

40. Complications of PUVA Acute complications S imilar to those described for UVB A norexia, nausea, headache and dizziness. Phototoxicity can result in tender erythema &/or deep pruritus for several weeks or longer. Long-term complications Photo-ageing: wrinkling, freckling, xerosis, telangiectasia, elastosis, white macules, skin atrophy, cataracts. Skin cancer: actinic keratoses , ( SCC )>> ( BCC) and melanoma. Genital skin cancer risk is alarming, always shield genitalia.

41. PUVA freckles

42. Systemic therapy for psoriasis

43. Methotrexate  a synthetic analogue of folic acid  used in the treatment of psoriasis and psoriatic arthritis . effective because of its immunosuppressive effects . has antimetabolite activity .

44. Mechanism of action Methotrexate has the following actions: Competitive inhibitor of the enzyme  dihydrofolate reductase Inhibits DNA synthesis and cell division Inhibits replication and function of T and B cells Suppresses the secretion of cytokines such as interleukin 1, interferon-g, and  tumour  necrosis factor. Suppresses epidermal cell division in psoriasis

45. Dose adjustment Methotrexate is administered either as a single weekly dose usually orally, or as an intermittent oral schedule of three divided doses up to about 25mg over a 36-hour period once a week . Folic acid 1-5mg daily may help reduce adverse effects such as nausea and  macrocytic  anemia. Methotrexate can take up to 6 months to achieve maximum efficacy improvement can be see from about 2 months Safety should be monitored by regular blood count, renal and liver function tests.

46. Side effects Gastrointestinal complaints Malaise, headaches Mouth ulceration Pulmonary fibrosis Bone marrow suppression and macrocytic   anaemia Liver damage including fibrosis and cirrhosis

47. Ciclosporin Ciclosporin is an effective immunosuppressive agent used to prevent allograft rejection. It is very effective in the treatment of all forms of psoriasis. Ciclosporin is a calcinerin inhibitor, which inhibits T cell activation and so reduces the production of cytokines especially IL-2 and interferon-g. Administered dose of 2.5 to 5mg/kg/day . Renal function and blood pressure must be carefully monitored

48. Side effects Nephrotoxicity Hypertension (may be treated using calcium channel blockers) Gastrointestinal symptoms Headache, myalgias , arthralgias , paresthesias and fatigue Hypertrichosis  and gingival hypertrophy Induction of skin cancer, especially  squamous  cell carcinoma Risk of lymphoma Numerous drug interactions .

49. Acitretin Acitretin is an oral retinoid (vitamin A derivative) used to treat psoriasis and other disorders of  keratinisation . It appears to thin down thick psoriatic plaques and reduce inflammation . Acitretin is especially useful for pustular psoriasis, erythrodermic psoriasis and  palmoplantar   keratoderma . usual dose is 10-50mg daily It can be combined with other topical or systemic therapy and is especially useful with phototherapy Monitoring requires pregnancy testing in females, complete blood count, lipids and liver function tests.

50. Side effects Teratogenic Mucocutaneous  adverse effects: dry fragile lips, skin, nose and eyes, peeling palms and soles, hair loss, thinned fragile nails, delayed wound healing Arthralgias , myalgias , raised intracranial pressure (oral  retinoids  must not be taken with tetracycline or tetracycline derivatives), decreased night vision Hepatotoxicity  (rare) and  hypertriglyceridaemia  (more common)

51. Other immunosuppressive agents Although less effective that methotrexate and ciclosporin , the following immunosuppressive medications are sometimes used to treat psoriasis: Hydroxyurea Azathioprine 6-Thioguanine Mycophenolic mofetil Tacrolimus Other drugs : Apremilast , Fumaric acid esters, Tofacitinib , Ponesimod

52. Biological therapy

53. Biological therapy TNF‐ α inhibitors IL‐12/IL‐23 p40 inhibitors IL‐17 inhibitors

54. TNF‐ α inhibitors Alefacept : binds to CD2 on activated memory T cells , once weekly with IM or IV  Efalizumab : ( anti-CD11a) is a humanized monoclonal antibody. Infliximab : anti- TNFa   chimeric  IgG1 monoclonal antibody very effective in controlling psoriasis,delivered IV three times over six weeks and then every 8 weeks Etanercept : a fusion protein, which acts as a competitive inhibitor of TNF-a.

55. IL‐12/IL‐23 p40 inhibitors Ustekinumab IL‐17 inhibitors Brodalumab ixekizumab secukinumab

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