National Skin Centre, Singapore



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National Skin Centre, Singapore


Guidelines on Management of Psoriasis

Prepared by Dr Wong Su-Ni and Dr Lawrence Khoo

Dated: 26th November 2003

___________________________________________________________



Introduction
Psoriasis is usually diagnosed clinically, based on typical appearance on typical sites.

The following clinical subtypes are seen and their management will be outlined separately:




  1. Chronic plaque psoriasis (most common)

  2. Guttate psoriasis

  3. Erythrodermic psoriasis

  4. Pustular psoriasis – localized or generalized

  5. Palmoplantar psoriasis

  6. Scalp psoriasis

  7. Inverse psoriasis

  8. Nail psoriasis

  9. Psoriatic arthritis

  10. Acrodermatitis continua of Hallapeau

Within each subgroup, management should be tailored according to patient age, sex, occupation, intelligence, personality and access to resources, as well as disease severity, duration and response to previous treatments.


Potential precipitating factors should be elicited and addressed accordingly. These include:

  • drugs e.g. beta-blockers, anti-malarials, withdrawal of oral or potent topical corticosteroids

  • stress

  • environmental factors e.g. heat

  • trauma (Köbner phenomenon) - physical, chemical, electrical, surgical, infective and inflammatory

  • infection e.g. streptococcal throat infection

  • HIV infection

  • Metabolic e.g. hypocalcaemia (in pustular psoriasis)

GENERAL TREATMENT PRINCIPLES


AIMS:

  1. Induction therapy to achieve clearance or substantial improvement

  2. Maintenance therapy after initial improvement

  3. Minimise significant side effects

METHODS:


  1. Monotherapy

  2. Combination therapy – for greater efficacy & to enable lower doses of more toxic agent to be used (e.g re-NBUVB, re-PUVA, MTX-NBUVB, PUVA + UVB, MTX + cyclosporin)




  1. Rotational therapy – rotate to other therapies after a specified period, to minimize long-term toxicity of and reduce resistance to any given therapy




  1. Sequential therapy – use of stronger agent initially to achieve faster clearance, followed by weaker but less toxic agent in maintenance phase.



CHRONIC PLAQUE PSORIASIS (PSORIASIS VULGARIS)





  1. First line: topicals




  • Coal tar (LPC 5%, 10%, 15%)

  • Add salicylic acid 2 % or 5% for thick plaques

Add to LPC or topical steroids

Inactivates calcipotriol



  • Topical corticosteroids for face, hairline, flexures

e.g. ¼ str Betamethasone valerate cr

  • Dithranol 1-2% ung for thick plaques

1/2hour short contact anthralin therapy (SCAT)


  • Adjunctive therapy:

  • Moisturizers e.g. 10% urea cream, white soft paraffin: liquid paraffin, aqueous cream

  • Coal tar bath or soap, or emulsifying ung as soap



  1. Second line:


(1). Topical


  • Calcipotriol cream or ointment sequential therapy:

Eg: Induction therapy with calcipotriol OM, potent topical corticosteroid ON

 calcipotriol bd weekdays, potent topical corticosteroid bd weekends

 calcipotriol bd




  • Calcitriol cream for face, hairline, flexures

Add om if suboptimal response to topical steroids alone
(2). Phototherapy

  • extensive plaque psoriasis with BSA >10-15%

  • not responding to topicals or intolerable side effects to topicals

  • Refer to Photo Clinic for commencement of phototherapy




  • NBUVB

  • PUVA – bath or oral

  • Combination of topicals and phototherapy:

  • Coal tar + phototherapy

  • Topical steroids + phototherapy

  • SCAT (short contact anthralin therapy) + phototherapy

  • Excimer laser

For patients with recalcitrant localized plaques which have failed topical therapy.




  • Other combination of topicals and phototherapy may be considered if the above treatments fail:

  • Calcipotriol +phototherapy

  • Tazarotene + phototherapy




  • Add MTX or acitretin if suboptimal improvement:

  • re-NBUVB

  • MTX-NBUVB

  • re-PUVA



  1. Third line: systemic therapy

  • Methotrexate

  • Acitretin

  • Hydroxyurea

  • Azathioprine

  • Sulphasalazine

  • combinations




  1. Fourth line: Newer non-standard drugs

- Severe, recalcitrant psoriasis not responding to above therapies or adverse reactions precluding use of above therapies

    • cyclosporin

    • mycophenolate mofetil

    • biologic agents

e.g. infliximab IV infusion efalizumab subcutaneously


GUTTATE PSORIASIS
Initial evaluation
Assess for streptococcal throat infection as precipitating cause

May consider ASOT, throat swab and use of anti-streptococcal antibiotic e.g. penicillin V or erythromycin


First line: Topical treatment

Second line: Phototherapy

Thrid line: Systemic therapy

ERYTHRODERMIC PSORIASIS
Initial evaluation
These patients should be hospitalized.

Please refer to erythroderma guidelines for supportive care, monitoring for and management of complications


Specific therapy
First line: Methotrexate or Acitretin

Second line: add NBUVB or PUVA

Third line: cyclosporin
PUSTULAR PSORIASIS
If generalized, patient should be hospitalised for monitoring of blood pressure, temperature, serum calcium, FBC, U/E/Cr and swabs for pyogenic culture. Consider use of anti-staphylococcal antibiotics e.g. cloxacillin.
Specific therapy
First line: MTX or Acitretin

Second line: Cyclosporin
PALMOPLANTAR PSORIASIS
First line: topical therapy


  • Coal tar (LPC 10%, 15%)

  • Add salicylic acid 2 % or 5% for thick plaques

  • Mid-potency to potent topical corticosteroids

e.g. 0.1% Betamethasone valerate cr or ung

Clobetasol 0.05% cr or ung



Betamethasone dipropionate 0.05% cr

Second line: Soak PUVA, oral PUVA

Third line: Systemic therapy e.g. MTX, Acitretin

SCALP PSORIASIS
Patients with severe scalp involvement or suboptimal response to topical therapy may be referred to Day Care Unit at Photo Clinic for demonstration and education on scalp treatment
First line: Coal Tar shampoo (sufficient as monotherapy in mild cases)

Second line:


Third line: Calcipotriol scalp lotion, clobetasol scalp lotion (sequential therapy possible)

Fourth line: systemic therapy e.g. MTX

INVERSE PSORIASIS
First line: Topical corticosteroids

e.g.¼ str betamethasone valerate cr, ¼ str fluocinolone cr


Second line: Vit D derivatives

e.g Calcipotriol cream may be used in flexural areas



NAIL PSORIASIS
Initial evaluation
Onycholysis is due to involvement of the nailbed, while ridging, pitting, and thickened nails are due to involvement of the nail matrix. Topical treatment should be targeted at the relevant sites.
Onychomycosis may occur in psoriasis and should be excluded with fungal scrape and/or fungal culture
Specific therapy
Nail psoriasis is difficult to treat, often refractory to topical therapies. Benefit versus risks of more potent systemic treatment should be carefully discussed with patients who have only nail involvement and are insistent on treatment, so that an informed decision can be made.
First line: topical therapy

e.g. 0.1% betamethasone valerate ung or lotion, calcipotriol ung



Second line: intralesional kenacort 10mg/ml injection to nail matrix

Third line: systemic therapy e.g. MTX, Acitretin

PSORIATIC ARTHRITIS
Initial evaluation
Consider X-rays of the affected joints to assess for erosive arthritis. DMARDs should be instituted if present.
Specific therapy
First line: NSAIDS

e.g. Indomethacin 25-50mg tds

with famotidine 20mg bd as gastric prophylaxis
Second line: DMARDS

e.g. sulphasalazine (joints), MTX (joints and skin),

cyclosporin, azathioprine

Third line: biologic agents

e.g. etanercept SC, infliximab IV infusion



APPENDIX 1: SYSTEMIC THERAPIES

Methotrexate

Particularly beneficial for patients with psoriatic arthritis.

Also indicated for erythrodermic and pustular psoriasis.

Helpful in psoriasis refractory to topical therapies and phototherapy


Contraindications:

  • pregnancy or possibility thereof

  • active infections

  • liver disease

  • alcoholism


Use with caution in:

  • obesity, diabetes (fatty liver, increased risk cirrhosis)

  • renal impairment (renally excreted)


Dosage


  • Range: 2.5 -30mg/week, average 5-15mg/week

  • Starting dose: 2.5 –7.5mg/week

  • Higher starting dose may be used under close monitoring

  • When improved, taper by 2.5mg/month


Given as single dose weekly Weinstein 3x 7 eg.

If severe nausea, add folic acid, split dose over am/pm or 2 consecutive days, or prescribe an anti-emetic



Side-effects





  • Leucopenia, thrombocytopenia, anaemia

  • Hepatotoxicity: transaminitis, liver cirrhosis

  • Mucosal ulcerations, stomatitis

  • Nausea, macrocytic anemia (improves with folic acid 5mg daily)

  • Pulmonary fibrosis (idiosyncratic)

  • Increased risk of malignant lymphomas

  • Radiation recall

  • Teratogenicity – C/I in pregnancy

  • May temporarily affect fertility in males


Monitoring during therapy





  • FBC at baseline and one week later, then every visit on arrival

  • LFT at baseline then every 3 months

  • Se urea/creatinine at baseline then every 3 to 6 months

  • Liver biopsy at cumulative dose of 1.5g, repeat every 1.5g thereafter if LFT and liver Bx normal, every 1g if not.

Acitretin (Neotigason)

One of the safest systemic psoriasis therapies currently available, but more expensive and less likely to achieve complete clearance in severe plaque psoriasis when used as monotherapy.

Effective as monotherapy for pustular and erythrodermic psoriasis.

Can dramatically improve response to phototherapy or photochemotherapy.

May temporarily suppress development of non-melanoma skin cancers.

Dosage


.

  • Range: 10-50mg/day; 10-25mg/day if combined with phototherapy

  • Maximum dose often limited by mucocutaneous side effects.

  • Average dose: 20- 25mg od



Side effects





  • Teratogenicity

  • Mucocutaneous effects e.g. cheilitis, conjunctivitis, dry skin, hair loss, nail abnormalities including periungual pyogenic granulomas

  • Hyperlipidaemia

  • Liver transaminitis

  • Rarely: pseudotumour cerebri, osteoporosis, skeletal hyperostoses, calcification of ligaments



Baseline monitoring





  • Pregnancy test and document last menstrual period

  • FBC, LFT, fasting triglyceride and cholesterol


Monitoring during therapy


  • LFT: monthly for 1st 3 months, thereafter 3 monthly

  • Fasting TG & Cholesterol: monthly for 1st 3 months, then 3 monthly

  • Pregnancy test as indicated


Hydroxyurea

May be used as monotherapy or in conjunction with acitretin


Dosage


  • Range: 1-2g/day, average 1g daily

  • Starting dose: 5oomg bd

  • Dose increments of 500mg/month

  • Hold dose if TW<2.5 x 109/L, plt < 100 x 109/L, or severe anemia



Side-effects





  • Leucopenia and/or thrombocytopenia (bone marrow toxicity) occurs in almost 50% of patients who achieve marked improvement

  • Megaloblastic anaemia (rarely needs treatment)

  • Cutaneous reations in most patients treated e.g. leg ulcers, hyperpigmentation, oral ulcers, dermatomyositis-like skin changes

  • Hepatotoxicity (rare & early)



Monitoring during therapy





  • FBC: weekly for 1st month post-initiation & at every dose increase, then monthly for 3 months, thereafter at each visit

  • LFT, U/Cr : baseline & 3 monthly


Azathioprine

Can be useful in psoriasis, but bone marrow suppression occurs at effective doses in many patients.


Refer to Immunobullous guidelines for details on dosage and monitoring.

Sulfasalazine


Side effects troublesome e.g. headache, GI symptoms, rash.

Dosage


.

  • Initial dose: 500mg bd

  • Dose increment after 3 days, if tolerated, to 1g tds ; increase to 1g qds after 6 weeks

  • Expected therapeutic response by 4-6 weeks



Monitoring during therapy
LFT, FBC, UFEME: monthly for 1st 3 months, thereafter 3 monthly
Cyclosporin

Extremely effective for all forms of psoriasis but very expensive.



Not recommended for use beyond 1 year because of nephrotoxicity – rotate to other therapy.

Sequential therapy with Acitretin in the maintenance phase has been suggested.

Not teratogenic – useful in women of child-bearing potential.
Contraindications
1.Acute infections

2. Active malignancies



Dosage





  • Range: 2-5mg/kg/day

  • High dosage approach: 5mg/kg/day in divided doses and taper.

  • Lower dosage approach: 2.5mg/kg/day in 2 divided doses; dose increments of 1mg/kg/day every 2 –4 weeks

  • Consider failed response if no response by 8 weeks

  • After maximal therapeutic response achieved, taper by 1mg/kg/day every 2 weeks to maintenance dose of 0.5 –1mg/kg/day



Side effects


  • nephrotoxicity

  • hypertension (easily controlled with Ca channel blockers)

  • derangements of liver function

  • hyperlipidaemia

  • hyperkalaemia (avoid potassium-rich foods, KIV hydrochlorthiazide)

  • hyperuricaemia

  • hypomagnesaemia

  • gastrointestinal upset eg. nausea and abdominal pain

  • tremor

  • gingival hyperplasia

  • malignancies e.g. skin cancers and lymphoproliferative disorders in transplant doses & long duration

  • Multiple drug interactions (ref table 1 in Cyclosporin in Atopic Dermatitis Guidelines)



Baseline monitoring





  • FBC, U/E/Cr, LFT, UFEME

  • Mg, Uric Acid, serum lipids

  • Blood pressure



Monitoring during therapy





  • Cr, BP every 2 weeks for 8 weeks, thereafter every visit

  • LFT, serum lipids, UFEME, Mg, Uric acid at 4 weeks

Please print cyclosporin monitoring chart in Cyclosporin in Atopic Dermatitis Guidelines


Mycophenolic mofetil

Can be useful in psoriasis as monotherapy, or as adjunctive therapy in patients with inadequate response to cyclosporine alone or were unable to tolerate higher doses of cyclosporine. May be effective for psoriatic arthiritis.



Very expensive.

Dosage


  • Range: 1-1.5g bd

  • Taper to 0.5g bd when improvement seen

Refer to Immunobullous guidelines for details on adverse effects and monitoring.


REFERENCES:


  1. AAD consensus statement on psoriasis therapies. J Am Acad Dermatol 2003;49:897-9

  2. Treatment of psoriasis. Part 1. Topical therapy and phototherapy. J Am Acad Dermatol 2001; 45:487-98

  3. Treatment of psoriasis. Part 2. Systemic therapies. J Am Acad Dermatol 2001; 45:649-61.

  4. Current systemic therapies for psoriasis: where are we now? J Am Acad Dermatol 2003; 49:S66-77.





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