1. treatment of psoriasis (Evidence -based Dermatology) H.Mozayyeni
هوالشافی
treatment of psoriasis
(Evidence -based Dermatology)
H.Mozayyeni

2. Background Definition
Psoriasis is an inflammatory disease of the skin characterised by an accelerated rate of epidermal turnover, with hyperproliferation and defective maturation of epidermal keratinocytes.
manifests itself as well-demarcated, often symmetrically distributed, thickened, red, scaly plaques.
They are found most typically on the extensor surfaces of the knees and elbows, in the sacral area and on the scalp.

3. Cont’d
Psoriasis Variants: Plaque type Inverse type Guttate type Pustular type Generalized Localized Erythrodermic

4. Cont’d
Prevalence:
Psoriasis first manifests itself most commonly in the second and third decades of life.
Its prevalence varies from 0·3% to more than 2%
Etiology
there is a strong genetic component.
Stress, heavy alcohol consumption, smoking, infection and local trauma (Koebner phenomenon) are all thought to influence the severity of psoriasis

5. Treatment of Psoriasis (Emollients and occlusive dressings)
Emollients may help to soften psoriatic scale by increasing its water content, either by forming an occlusive layer on the skin surface or by an osmotic effect. There is little published evidence documenting the efficacy of emollient therapy alone in the management of psoriasis ,although Some evidence suggests that emollients may have a steroid-sparing effect in psoriasis managed with topical corticosteroids. Occlusive dressings have also been used for treating psoriatic plaques, often to enhance penetration of active drugs such as topical corticosteroids.

6. Cont’d
Hydrocolloid gel dressings may be useful on their own for selected recalcitrant psoriatic plaques and may enhance the response to topical corticosteroids and calcipotriol. In one open-label study show , the combination of a once daily application of a water-in-oil cream or lotion with once-daily betamethasone dipropionate cream was found to be more effective than once daily and of equal efficacy to twice-daily betamethasone dipropionate cream.

7. Cont’d
In another within patient study (n = 43) the application of an oil-in-water emollient cream before UVB exposure significantly enhanced the rate of psoriasis improvement with UVB phototherapy.

8. Hydrocolloid dressings
In a small study , 47% of treated plaques resolved after weekly applications of an adhesive hydrocolloid occlusive dressing for 10 weeks.
The dressing was found to be more effective than twice-daily applications of a potent corticosteroid cream for 10 weeks (12% resolution rate) although less effective than erythemogenic UVB phototherapy.
In a small study , chronic plaques were treated by day 12 , with either calcipotriol ointment or a superpotent corticosteroid ointment under hydrocolloid occlusion; dressings were changed every 4 days.

9. Drawback
Local irritation and allergic contact dermatitis may result from use of emollients or occlusive dressings.

10. Summary
Patients with mild psoriasis may choose to use emollients alone because of their convenience and lack of adverse effects. Hydrocolloid gel dressings may be useful on their own for selected recalcitrant psoriatic plaques and may enhance the response to topical corticosteroids and calcipotriol.

11. Keratolytics
Salicylic acid is the most commonly used keratolytic agent and is often advocated for removing psoriatic scale. It is considered beneficial not only because it reduces scaling and skin shedding but also because it thereby removes barrier to the penetration of more active compounds into the skin. Concentrations between 2% and 10% in an ointment base are usually dispensed. Salicylic acid is often used in combination with coal tar or corticosteroids.

12. Cont’d
There is little information from RCTs on the efficacy of salicylic acid monotherapy as descaling agent. Addition of salicylic acid to a topical corticosteroid preparation enhances efficacy in psoriasis.

13. Drawbacks
Topical salicylic acid may be absorbed through the skin and could thus cause systemic toxicity (salicylism), but this seems to be rare in practice. It may irritate and inflame the skin. in one RCT, the addition of salicylic acid to an emollient applied before UVB phototherapy decreased the rate of clearance of psoriasis.

14. Vitamin D analogues
One systematic review of calcipotriol found that it was at least as effective as potent topical corticosteroids, calcitriol, short contact anthralin (dithranol) therapy and coal tar.
Much less evidence is available for other vitamin D analogues, including tacalcitol and maxacalcitol.
The authors concluded that calcipotriol is an effective treatment for mild-tomoderate chronic plaque psoriasis

15. Cont’d
Although calcipotriol causes more skin irritation than topical corticosteroids, this has to be balanced against the potential long-term effects of corticosteroids. The combination of calcipotriol cream applied in the morning with a moderately potent to potent topical corticosteroid at night has been shown to be at least as effective as twice-daily calcipotriol cream but to cause significantly less irritation.

16. Cont’d
A compound ointment containing calcipotriol, and betamethasone dipropionate, has been evaluated in a RCT. The mean percentage decrease in psoriasis severity score at 4 weeks was 74⋅4% in the combination group, 55⋅3% in the calcipotriol group and 61⋅3% in the betamethasone group . These differences were highly significant. At the end of 8 weeks, however, the severity scores did not differ.

17. Drawbacks
Skin Irritation (the face and flexures being most susceptible) Hypercalcemia ( Dose related)

18. Summary
Calcipotriol has been extensively studied and shown to be of value in suppressing mild to- moderate psoriasis. Psoriasis may improve more rapidly when calcipotriol is initially combined with a potent corticosteroid for 4 weeks .

19. Phototherapy and photochemotherapy
1) photochemotherapy (PUVA) using a combination of either oral or topical psoralen with UVA was effective in clearing psoriasis.The incidence of side-effects was much lower with 5- than with 8- methoxypsoralen .
2) UVA alone did not clear psoriasis
3) BBUVB ( nm) was effective in clearing psoriasis
4)NBUVB (311nm) offered the possibility of clearance with fewer episodes of erythema and may require a lower cumulative dose of UVB to achieve this.

20. Cont’d
5) PUVA or UVB in combination with systemic retinoids appeared to be more effective than either therapy alone.
6) it was not possible to reach a conclusion on the effects of combining topical tar or anthralin with phototherapy.
7) PUVA is of similar efficacy to daily anthralin dressings in clearing psoriasis.
8) combinations of either UVB or PUVA either with vitamin D3 analogues or with topical corticosteroids all appeared to be superior to each agent used alone.

21. Cont’d
9)NBUVB phototherapy used three times weekly is of similar efficacy to twice-weekly PUVA. 10) There is little evidence to support the use of balneophototherapy in which phototherapy is combined with bathing in various mineral or salt waters. 11) Heliotherapy using natural sunlight(+/- 8 MP ) is effective at clearing psoriasis , but is associated with an increased risk of skin cancer. 12) bath PUVA was of similar efficacy to oral PUVA.

22. Cont’d
In a larger parallel-group RCT in which 54 patients with >10% coverage with psoriasis were randomised to standard regimens of PUVA (twice weekly) or NBUVB (three times weekly), no difference in response was found. And relapse rates were similar. The authors thought that NBUVB probably had a less adverse effect than PUVA, and so recommended that NBUVB should be preferred.

23. PUVA versus retinoids
In one RCT (n = 40) good or excellent responses were seen in 80% of people treated with PUVA and moderate response were seen in 55% of those given etretinate .

24. PUVA or UVB versus other systemic therapies
No RCTs comparing phototherapy with other systemic therapies such as ciclosporin or methotrexate were identified.

25. PUVA or UVB versus topical therapies
PUVA or UVB (phototherapy) is more effective than topical therapies

26. Cont’d
The main risks of PUVA therapy are photoaging and skin cancer, notably SCC(14- fold), It is therefore advisable to limit the number of treatments to 200 or the cumulative UVA dose to 1500 J/cm2. bath PUVA is possibly safer than oral PUVA The risks of developing BCC do not appear to be substantially increased except in patients exposed to very high cumulative doses of UVA Therapeutic BBUVB irradiation does not appear to be associated with development of skin cancer.

27. Ciclosporin
A dose of 1·25 mg/kg/day was ineffective whereas 5 mg/kg/day appeared to be more effective than 2·5 mg/kg/day. Higherdoses appeared to give little extra benefit(are limited by side-effects, particularly on renal function). Ciclosporin appears to be more effective than etretinate. It appears to achieve more rapid improvement of psoriasis than methotrexate but produces similar benefit by 16 weeks. Two RCTs found no difference in efficacy at 12 weeksEvidence based Dermatology between Neoral and its precursor Sandimmun.

28. Drawback increase in serum creatinine levels Hypertension
decrease in GFR
Comment
Although ciclosporin is highly effective at inducing remission of psoriasis when used at the upper end of the recommended dose range, maintenance of remission requires continued therapy, with a significant risk of eventual hypertension and/or impairment of renal function.

29. Systemic retinoids
It concluded that relatively high doses (approximately 1 mg/kg/day) are needed for monotherapy to show superiority over placebo and that the responses achieved are less than those achieved with low-dose ciclosporin. Combinations of retinoids with PUVA, UVB, topical corticosteroids and topical calcipotriol have been shown to be more efficacious than the individual components of each combination.

30. Cont’d
The use of retinoids is limited by their liability to cause birth defects in women of child-bearing potential and by the high incidence of symptomatic mucocutaneous sideeffects. Nevertheless they retain an important place in the management of severe psoriasis. Etretinate and acitretin were of equal efficacy in inducing remission of psoriasis.

31. Cont’d
. Three RCTs showed a benefit of the combination retinoid and UVB over UVB alone

32. Cont’d
Two RCTs concluded that etretinate was less effective than ciclosporin at inducing remission of psoriasis within 10–12 weeks. A small open RCT has claimed benefit from the addition of eicosapentaenoic acid ( fish oil ) to low-dose etretinate in the treatment of stable,chronic plaque psoriasis.

33. Drawback Mucocutaneous side-effects (reversible, dose-dependent )
Hyperlipidaemia (fish oil supplementation resulted in a 27% reduction in triglyceride levels)
cumulative hepatotoxicity
teratogenic

34. Comment
Apart from the risk of teratogenicity, the potential for serious harm from retinoid therapy appears to be less than from other interventions used in severe psoriasis such as methotrexate, PUVA or ciclosporin.
Retinoid therapy is not suitable for every patient with severe psoriasis. It should normally be used in combination with either phototherapy or topical therapy

35. Methotrexate It was the first potent systemic antipsoriatic agent .
Benefit for arthritis.
No significant difference in response at 16 weeks was found in psoriatic patients to receive either methotrexate or ciclosporin, appeared to act more rapidly although the latter

36. Drawbacks Nausea( most common )
Acute myelosuppression (most important potential side-effect)
Folate deficiency
Exacerebation of CKD
homocysteine levels are elevated (associated with atherothrombotic vascular disease)
Drug interaction ( TMP_SMX, NSAID , ASPIRIN ,…)
Cytopenia
Hepatic fibrosis

37. Cont’d
The original method of administering methotrexate in small daily doses was shown to be much more hepatotoxic than the same overall amount given as a single weekly dose.
An alternative regimen in which the weekly dose is divided into three parts taken at 12-hourly intervals is still widely used
patients who cannot restrict alcohol consumption are not suited to methotrexate therapy
No correlation between cumulative methotrexate dose or duration of therapy and the risk of liver fibrosis or cirrhosis was found.

38. Cont’d The Psoriasis Task Force of the American Academy of Dermatology
recommends that liver biopsy should be
performed on psoriasis patients after treatment
has been established and there after with each
cumulative dose of 1⋅5 g methotrexate
In practice about every 18 months to 2 years for the
average patient

39. Hydroxyurea
Hydroxyurea is a systemic therapy for severe psoriasis which is mainly used as a substitute for more commonly used systemic drugs such as ciclosporin or methotrexate when these are contraindicated
Hydroxyurea has not been directly compared with other systemic therapies
The authors commented that it took 6 weeks for maximal improvement to be achieved( 1 g Daily )
Side effects include Bone-marrow suppression and teratogenicity

40. Fumarates
It is an effective systemic treatment for psoriasis( Northern Europe) Formal comparisons with topical or with other systemic therapies have not been performed. Versus placebo In the two RCTs comparing the standard compound fumaric acid ester therapy with placebo , 56% of people treated for up to 16 weeks achieved at least a 70% reduction in PASI score whereas only 8% receiving placebo showed similar improvement

41. Drawback
Flushing
GI disturbance
Eosinophilia
Mild lymphocytopenia

42. Azathioprine
Nowadays azathioprine is rarely used in psoriasis suggests that it is not as effective asother systemic therapies such as methotrexate, ciclosporin and PUVA.
It may cause catastrophic myelosuppression
Nausea and vomiting are common. A drug-induced hepatitis may occur.

43. Sulfasalazine
It is a moderately effective treatment for severe psoriasis although probably less so than acitretin, ciclosporin, PUVA and methotrexate.
The most common side-effects are headache, nausea and vomiting

44. How effective are treatments for guttate psoriasis?
Antibiotic therapy
Although it is well known that guttate psoriasis may be precipitated by streptococcal infection, and antibiotics have frequently been advocated for patients with recurrent guttate psoriasis, the authors of the reviews concluded that there was no firm evidence to support the use of antibiotics either in the management of established guttate psoriasis or in preventing the development of guttate psoriasis

45. Cont’d
Tonsillectomy
Although tonsillectomy has been advocated for patients with recurrent streptococcal sore throat associated with either recurrent guttate psoriasis or recalcitrant chronic plaque psoriasis, there is no firm evidence to date that such ntervention is beneficial

46. How effective are treatments for chronic palmoplantar pustular psoriasis?
Topical corticosteroids with and without occlusion
Moderately potent corticosteroids under hydrocolloid occlusion may induce rapid clearance of chronic palmoplantar pustular psoriasis; such therapy is more effective than superpotent corticosteroids without occlusion.

47. Systemic retinoid monotherapy
39% patients who received etretinate (modal dose 1 mg/kg/day) as compared with 17% who received placebo achieved a good or excellent response.
Acitretin versus etretinate
One RCT found no difference in efficacy of the two retinoids as judged by reduction in pustule counts.

48. Photochemotherapy alone
there is little to support the use of topical PUVA but that oral systemic PUVA cleared chronic palmoplantar pustular psoriasis in a minority of people.

49. RePUVA
Studies demonstrated that the combination is more effective than either PUVA or retinoids alone and suggest that this modality is the most effective treatment available for achieving remission of palmoplantar pustular psoriasis.

50. Tetracycline antibiotics
Ciclosporin
64% people receiving ciclosporin improved, compared with 20% receiving placebo.
Tetracycline antibiotics
There is good RCT evidence that tetracyclines may induce limited improvement in chronic palmoplantar pustular psoriasis

51. Other therapies
One of two RCTs comparing colchicine with placebo claimed benefit from the former but at the expense of troublesome side- effects.
In one RCT of Grenz ray therapy, 13 of 17 sides receiving Grenz ray showed greater improvement than the contralateral side.
There is no good evidence from RCTs to support the use of tar or anthralin.
There are no RCTs of methotrexate therapy for chronic palmoplantar pustular psoriasis.

52. How effective are treatments for acrodermatitis continua of Hallopeau?
The greatest number of published case reports in which successful response to treatment is claimed is for ciclosporin, although acitretin, methotrexate and dapsone have been reported in individual case reports to produce resolution

53. Chronic plaque psoriasis
• calcipotriol • ciclosporin • systemic retinoids (acitretin and etretinate), especially in combination with phototherapy • phototherapy including broadband ultraviolet B (UVB), narrowband UVB and psoralen photochemotherapy (PUVA) • combinations of topical vitamin D3 analogues and topical corticosteroids with either UVB or PUVA • heliotherapy (natural sunlight) • fumaric acid esters

54. Cont’d
• methotrexate, although effectiveness of this widely accepted drug has been examined specifically in chronic plaque psoriasis in only one RCT. • There is evidence of lack of efficacy of UVA sunbed (with low UVB emission) and balneotherapy (spa water). • There is a lack of firm RCT evidence of effectiveness of other therapies for chronic plaque psoriasis, including tacalcitol, azathioprine, hydroxyurea and sulfasalazine (although one small RCT has shown moderate efficacy from sulfasalazine).