Psoriasis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]

## Overview[edit | edit source]

The mainstay of therapy for psoriasis consists of the application of topical agents directly onto the lesions. Topical agents include corticosteroids, vitamin D analogues, tar, anthralin, tazarotene, calcineurin inhibitors, and aloe vera extracts. Systemic therapy may also be used, including immunosupressants to counteract the progression of the disease.

## Medical Therapy[edit | edit source]

Therapies are administered according to disease severity as assessed by the Psoriasis Area and Severity Index (PASI, ranging from 0 to 72), which takes into account appearance and extension of the lesions. Interventions in medical therapy for psoriasis include:

* Topical therapy
* Phototherapy
* Systemic therapy (immunosuppressive agents and biological therapy)

### Topical therapy[edit | edit source]

* Medicated creams and ointments applied directly to psoriatic lesions can help decrease inflammation, remove built-up scale, reduce skin turnover, and clear affected skin of plaques.[1]
* Approved drugs that can be used as topical therapy for acute management of psoriasis include:[2][3][4][5][6]
* Corticosteroids
* Vitamin D analogues (calcipotriol)
* Tar
* Dithranol (anthralin)
* Tazarotene (a retinoid)
* Calcineurin inhibitors (tacrolimus and primecrolimus are used specially for flexural or facial psoriasis)
* Aloe vera extract 0.5% hydrophilic cream
* Anti-IL-8 monoclonal antibody cream
* Betamethasone 17-valerate 21-acetate plus tretinoin plus salicylic acid
* Fish oil plus occlussion
* Combination of nicotinamide and calcipotriene

* Combined treatment with vitamin D/corticosteroid on either the body or the scalp generates significantly better outcomes than vitamin D alone.[7]

* The disadvantages of topical agents are that they can often irritate normal skin, can be time consuming and awkward to apply, cannot be used for long periods, can stain clothing, and can have a strong odor. As a result, it is sometimes difficult for people to maintain the regular application of these medications.
* Abrupt withdrawal from the use of some topical agents, particularly corticosteroids, can cause an aggressive recurrence of the condition.
* Some topical agents are commonly used in conjunction with other therapies, especially phototherapy.

### Phototherapy[edit | edit source]

* It has long been recognized that daily, short, non-burning exposure to sunlight can help clear or improve psoriasis.[8]
* Niels Finsen was the first physician to investigate the therapeutic effects of sunlight scientifically and to use sunlight in clinical practice. This became known as phototherapy.

* The narrow band part of the UVB spectrum (311 to 312 nm) is most helpful for the management of psoriasis. Exposure to UVB several times per week over several weeks can facilitate remission from psoriasis.

* Ultraviolet light treatment is frequently combined with topical (coal tar, calcipotriol) or systemic treatment (retinoids).
* The Ingram regime involves UVB and the application of anthralin paste.
* The Goeckerman regime combines coal tar ointment with UVB.

### Systemic therapy[edit | edit source]

The following drugs may be used in the treatment of psoriasis:[9][10][11][12][13]

Type of agent  | Mechanism of action  | Name  | Molecular target  | Formulation  | Administration route

|
|
|
|
|

Biologic  | Anti-metabolite | Methotrexate | DHFR | NA  | Oral or IV
Anti-T cell  | Cyclosporine | Cyclophilin | NA  | Oral or IV
Alefacept | CD2 | Human LFA-3/IgG1 fusion protein  | IM or IV
Efalizumab | CD11a | Humanized IgG1 monoclonal antibody  | SC
Abatacept | CTLA-4 | Human CTLA4–Ig-IgG1 fusion protein  | SC or IV
Anticytokine  | Etanercept | TNF | Human TNF-R (p75)-lgG1 fusion protein  | SC
Infliximab | TNF | Mouse-human IgG1 chimeric monoclonal antibody | IV
Adalimumab | TNF | Human IgG1 monoclonal antibody | SC
Ustekinumab | IL-2, IL-23  | Human IgG1 monoclonal antibody | SC
Briakinumab (discontinued in USA in 2011)  | IL-12, IL-23  | Human IgG1 monoclonal antibody | SC
Guselkumab  | IL-23p19  | Human IgG1 monoclonal antibody | SC
Brodalumab  | IL-17R  | Human IgG2 monoclonal antibody | SC
Ixekizumab  | IL-17 | Humanized IgG4 monoclonal antibody | SC
Secukinumab | IL-17 | Human IgG1 monoclonal antibody | SC or IV
Fezakinumab  | IL-22 | Human IgG1 monoclonal antibody | SC or IV
Small molecule  | PDE4 inhibitor  | Apremilast | PDE4  | NA  | Oral
JAK inhibitor  | Tofacitinib | JAK1 and JAK3  | NA  | Oral
Baricitinib  | JAK1 and JAK2  | NA  | Oral
PKC inhibitor  | AEB071  | PKC | NA  | Oral
A3AR agonist  | CF101  | A3AR  | NA  | Oral

Abbreviations:

DHFR: Dihydrofolate reductase

SC: Sub-cutaneous

IV: Intra-venous

IM: Intra-muscular

NA: Not Applicable

PDE4: Phosphodiesterase 4

JAK: Janus Kinase

PKC: Protein Kinase C

LFA: Lymphocyte function associated antigen

TNF: Tumor necrosis factor

### Treatment of psoriasis according to severity[edit | edit source]

The American Academy of Dermatology has published guidelines for the treatment of psoriasis. The guidelines are as follows:[14]

* 1 Mild-moderate psoriasis
* 1.1 Adults
* Preferred regimen (1): Topical betamethasone plus calcipotriene q 12 hours for 1 week
* Preferred regimen (2): Topical clobetasol propionate plus tazarotene q 12 hours for 2-4 weeks
* Alternative regimen (1): Topical clobetasol propionate plus calcipotriene ointment q 12 hours for 2-4 weeks
* Alternative regimen (2):Topical clobetasol propionate plus calcitriol ointment topical 3 mcg per g q 12 hours for 2-4 weeks
* Alternative regimen (3): Topical clobetasol propionate plus tar q 12 hours for 2-4 weeks
* Alternative regimen (4): Localized phototherapy 500-900 mJ per cm2 2-3 times per week for 10 weeks
* Alternative regimen (5): Topical pimecrolimus 0.1% cream q 12 hours for 8 weeks
* Alternative regimen (6): Topical tacrolimus 0.1% ointment q 12 hours for 8 weeks
* 1.2 Pediatrics
* Preferred regimen (1): Topical clobetasol propionate emulsion formulation foam 0.05% q 24 hours for 2 weeks
* Preferred regimen (2): Topical hydrocortisone ointment 1%q 24 hours for 3 weeks
* Preferred regimen (3): Topical calcipotriene 50 μg/g q 24 hours for 8 weeks
* Alternative regimen (1): Topical tacrolimus 0.1% q 48 hours for 6 months
* Alternative regimen (2): Topical pimecrolimus 1% q 48 hours for 11 weeks
* Alternative regimen (3): Topical dithranol cream 0.1%-2% q 24 hours for 2 months
* Alternative regimen (4): Topical UVB phototherapy 50 mJ initial dose 2-3 sessions per week; increments of 10% at each session for 12 weeks
* 2 Severe psoriasis
* 2.1 Adults
* Preferred regimen (1): Topical UVB phototherapy plus systemic PO methotrexate for 2-4 weeks
* Alternative regimen (1): Topical UVB phototherapy plus systemic PO cyclosporine for 2-4 weeks
* Alternative regimen (2): Topical UVB phototherapy plus systemic PO tazarotene for 2-4 weeks
* Alternative regimen (3): Topical UVB phototherapy plus PUVA therapy (PO 8-methoxypsoralen 0.4-0.6 mg per kg given 1.5 hours before exposure to UVA) for 2-4 weeks
* Alternative regimen (4): Topical UVB phototherapy plus IM alefacept 15 mg per week for 12 weeks
* Alternative regimen (5): Topical UVB phototherapy plus SC efalizumab 0.7 mg per kg first dose followed by 1.0 mg per kg per week for 3 months
* Alternative regimen (6): Topical UVB phototherapy plus SC adalimumab 80 mg the first week, 40 mg the second wk, followed by 40 mg every other week
* Alternative regimen (7): Topical UVB phototherapy plus SC etanercept 50 mg twice per week for 3 months
* Alternative regimen (8): Topical UVB phototherapy plus IV infliximab 5 mg per kg dose infusion schedule at week 0, 2, and 6 and then every 6-8 weeks for 3 months
* 2.2 Pediatrics
* Preferred regimen (1): Systemic PO methotrexate 0.2 and 0.4 mg per kg per week for 2 to 16 months
* Preferred regimen (2):  Topical dithranol 0.016%-0.0625% q 24 hours for 3 months

### Treatment of psoriasis according to disease sub-type[edit | edit source]

Treatment of various sub-types of psoriasis includes the following:[15][16]

* 1 Localized pustular psoriasis
* 1.1 Adults
* Preferred regimen (1): Topical clobetasol propionate plus topical bath psoralen plus UVA phototherapy (PUVA) for 3 weeks
* Alternative regimen (2): Topical clobetasol propionate plus PO acitretin 25-40 mg q 24 hours for 3 weeks
* 1.2 Pediatrics
* Preferred regimen (1) Topical clobetasol propionate plus topical tazarotene q 12 hours for 2-4 weeks
* 2 Nail psoriasis
* 2.1 Adults
* Preferred regimen (1): Topical clobetasol propionate q 24 hours for 2-4 weeks
* Preferred regimen (2): Topical calcipotriene ointment q 12 hours for 2-4 weeks
* 3 Erythrodermic psoriasis
* 3.1 Adults
* Preferred regimen (1): IV infliximab 5 mg per kg at week 0, week 2, week 6 and methotrexate 15 mg per week
* Preferred regimen (2): IV cyclosporine 3.5-4 mg per kg per day and etretinate 0.5-0.6 mg per kg per day for 1 week
* Preferred regimen (3): SC etanercept 50 mg twice per week for 3 months
* Preferred regimen (4): SC adalimumab 80 mg the first week, 40 mg the second wk, followed by 40 mg every other week
* Preferred regimen (5): SC ustekinumab 45 mg at 0 and 4 weeks, and then every 12 weeks thereafter
* Alternative regimen (1): IV infliximab 5 mg per kg at week 0, week 2, week 6 followed by 5 mg/kg every 8 weeks thereafter and acitretin 0.3-0.6 mg per kg
* 3.2 Pediatrics
* Preferred regimen (1): Topical clobetasol propionate plus topical tazarotene q 12 hours for 2-4 weeks
* Alternative regimen (1): Topical UVB 2-3 sessions per week for 12 weeks

### Treatment of psoriasis in specific populations[edit | edit source]

Specific populations may require modified regimens for the treatment of psoriasis. The following are the considerations:[17][18][19][20]

*     * 1.1 Pregnancy (methotrexate, tazarotene and acitretin are contraindicated)
* Preferred regimen (1): Topical betamethasone plus petroleum jelly q 24 hours till remission
* Alternative regimen (1): Topical UVB 2-3 sessions per week for 12 weeks
* Alternative regimen (2): IV infliximab 5 mg per kg at week 0 , week 2, week 6 followed by 5 mg/kg every 8 weeks thereafter (discontinue at 30 weeks of gestation; avoid live vaccine administration to infants born to treated women is suggested until the age of seven months)
* 1.2 Chronic hepatitis B (methotrexate, acitretin and cyclosporine are contraindicated)
* Preferred regimen (1): Topical UVB phototherapy 2-3 sessions per week plus topical tar for 12 weeks
* 1.3 Chronic hepatitis C (methotrexate, acitretin and cyclosporine are contraindicated; PUVA is relatively contraindicated in chronic liver disease)
* Preferred regimen (1): Topical UVB phototherapy 2-3 sessions per week plus topical tar for 12 weeks
* Alternative regimen (1): Topical UVB phototherapy plus PUVA therapy (PO 8-methoxypsoralen 0.4-0.6 mg per kg given 1.5 hours before exposure to UVA) for 2-4 weeks

Note: All treatments of psoriasis may include mid-potency topical corticosteroids (if not using topical steroids already), emollients, wet dressings, and oatmeal baths

### Treatment of psoriatic arthritis[edit | edit source]

The following drugs may be used in the treatment of psoriatic arthritis:[21]

Drug  | Mechanism  | Comments

|
|

NSAIDs |

* Inhibits cyclooxygenase

* First line agent for symptomatic treatment

Corticosteroids |

* Inhibits inflammatory cytokines

Sulfasalazine |

* Unknown mechanism

* One-third of patients have gastrointestinal distress, dizziness, or hepatotoxicity

Methotrexate |

* Inhibits dihydrofolate reductase and lymphocyte proliferation

* Hepatotoxicity common

Cyclosporine |

* Inhibitor of T lymphocytes

* More often used for cutaneous psoriasis

Leflunomide |

* Inhibits pyrimidine synthesis via dihydrofolate dehydrogenase inhibition

* Effective for symptoms of arthritis, cutaneous psoriasis, and for prevention of disability

Etanercept |

* TNF-alpha receptor analogue that inhibits TNF-alpha action

* Administered as subcutaneous injection

Infliximab |

* Chimeric monoclonal antibody that attaches to membrane-bound and soluble TNF-alpha

* Administered as intravenous infusion

Adalimumab |

* Human anti TNF-alpha

* Administered as subcutaneous injection

Alefacept |

* Human LFA-3/IgG fusion protein, which attaches to CD2 receptor on T cells

* Combination with methotrexate for effective than monotherapy

Efalizumab |

* Humanized monoclonal antibody directed against CD11a, which disrupts T cell costimulatory LFA-1/ICAM-1 interaction

* Associated with progressive multifocal leukoencephalopathy (PML)

Abatacept |

* Recombinant human fusion protein; binds CD80/86 and inhibits CD28 receptor on T cells

* May be used for psoriatic arthritis, but not commonly employed as a therapy

## References[edit | edit source]

1. ↑ Smith CH, Barker JN (2006). "Psoriasis and its management". BMJ. 333 (7564): 380–4. doi:10.1136/bmj.333.7564.380. PMC 1550454. PMID 16916825.
2. ↑ Ashcroft DM, Po AL, Williams HC, Griffiths CE (2000). "Systematic review of comparative efficacy and tolerability of calcipotriol in treating chronic plaque psoriasis". BMJ. 320 (7240): 963–7. PMC 27334. PMID 10753146.
3. ↑ Syed TA, Ahmad SA, Holt AH, Ahmad SA, Ahmad SH, Afzal M (1996). "Management of psoriasis with Aloe vera extract in a hydrophilic cream: a placebo-controlled, double-blind study". Trop. Med. Int. Health. 1 (4): 505–9. PMID 8765459.
4. ↑ Naldi L, Rzany B (2009). "Psoriasis (chronic plaque)". BMJ Clin Evid. 2009. PMC 2907770. PMID 19445765.
5. ↑ Escobar SO, Achenbach R, Iannantuono R, Torem V (1992). "Topical fish oil in psoriasis--a controlled and blind study". Clin. Exp. Dermatol. 17 (3): 159–62. PMID 1451289.
6. ↑ Levine D, Even-Chen Z, Lipets I, Pritulo OA, Svyatenko TV, Andrashko Y, Lebwohl M, Gottlieb A (2010). "Pilot, multicenter, double-blind, randomized placebo-controlled bilateral comparative study of a combination of calcipotriene and nicotinamide for the treatment of psoriasis". J. Am. Acad. Dermatol. 63 (5): 775–81. doi:10.1016/j.jaad.2009.10.016. PMID 20599292.
7. ↑ "Topical treatments for chronic plaque psoriasis - Mason - 2013 - The Cochrane Library - Wiley Online Library".
8. ↑ Naldi L, Rzany B (2009). "Psoriasis (chronic plaque)". BMJ Clin Evid. 2009. PMC 2907770. PMID 19445765.
9. ↑ Rosmarin DM, Lebwohl M, Elewski BE, Gottlieb AB (2010). "Cyclosporine and psoriasis: 2008 National Psoriasis Foundation Consensus Conference". J. Am. Acad. Dermatol. 62 (5): 838–53. doi:10.1016/j.jaad.2009.05.017. PMID 19932926.
10. ↑ Schmitt J, Rosumeck S, Thomaschewski G, Sporbeck B, Haufe E, Nast A (2014). "Efficacy and safety of systemic treatments for moderate-to-severe psoriasis: meta-analysis of randomized controlled trials". Br. J. Dermatol. 170 (2): 274–303. doi:10.1111/bjd.12663. PMID 24131260.
11. ↑ Nowicki B, Holthöfer H, Saraneva T, Rhen M, Väisänen-Rhen V, Korhonen TK (1986). "Location of adhesion sites for P-fimbriated and for 075X-positive Escherichia coli in the human kidney". Microb. Pathog. 1 (2): 169–80. PMID 2907770.
12. ↑ Hsu S, Papp KA, Lebwohl MG, Bagel J, Blauvelt A, Duffin KC, Crowley J, Eichenfield LF, Feldman SR, Fiorentino DF, Gelfand JM, Gottlieb AB, Jacobsen C, Kalb RE, Kavanaugh A, Korman NJ, Krueger GG, Michelon MA, Morison W, Ritchlin CT, Stein Gold L, Stone SP, Strober BE, Van Voorhees AS, Weiss SC, Wanat K, Bebo BF (2012). "Consensus guidelines for the management of plaque psoriasis". Arch Dermatol. 148 (1): 95–102. doi:10.1001/archdermatol.2011.1410. PMID 22250239.
13. ↑ Menter A, Gottlieb A, Feldman SR, Van Voorhees AS, Leonardi CL, Gordon KB, Lebwohl M, Koo JY, Elmets CA, Korman NJ, Beutner KR, Bhushan R (2008). "Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics". J. Am. Acad. Dermatol. 58 (5): 826–50. doi:10.1016/j.jaad.2008.02.039. PMID 18423260.
14. ↑ "Psoriasis: Recommendations for broadband and narrowband UVB therapy | American Academy of Dermatology".
15. ↑ Rosenbach M, Hsu S, Korman NJ, Lebwohl MG, Young M, Bebo BF, Van Voorhees AS (2010). "Treatment of erythrodermic psoriasis: from the medical board of the National Psoriasis Foundation". J. Am. Acad. Dermatol. 62 (4): 655–62. doi:10.1016/j.jaad.2009.05.048. PMID 19665821.
16. ↑ de Jager ME, de Jong EM, van de Kerkhof PC, Seyger MM (2010). "Efficacy and safety of treatments for childhood psoriasis: a systematic literature review". J. Am. Acad. Dermatol. 62 (6): 1013–30. doi:10.1016/j.jaad.2009.06.048. PMID 19900732.
17. ↑ Frankel AJ, Van Voorhees AS, Hsu S, Korman NJ, Lebwohl MG, Bebo BF, Gottlieb AB (2009). "Treatment of psoriasis in patients with hepatitis C: from the Medical Board of the National Psoriasis Foundation". J. Am. Acad. Dermatol. 61 (6): 1044–55. doi:10.1016/j.jaad.2009.03.044. PMID 19811848.
18. ↑ Murase JE, Heller MM, Butler DC (2014). "Safety of dermatologic medications in pregnancy and lactation: Part I. Pregnancy". J. Am. Acad. Dermatol. 70 (3): 401.e1–14, quiz 415. doi:10.1016/j.jaad.2013.09.010. PMID 24528911.
19. ↑ Heller MM, Wu JJ, Murase JE (2011). "Fatal case of disseminated BCG infection after vaccination of an infant with in utero exposure to infliximab". J. Am. Acad. Dermatol. 65 (4): 870. doi:10.1016/j.jaad.2011.04.030. PMID 21920245.
20. ↑ Weatherhead S, Robson SC, Reynolds NJ (2007). "Management of psoriasis in pregnancy". BMJ. 334 (7605): 1218–20. doi:10.1136/bmj.39202.518484.80. PMC 1889937. PMID 17556479.
21. ↑ Day MS, Nam D, Goodman S, Su EP, Figgie M (2012). "Psoriatic arthritis". J Am Acad Orthop Surg. 20 (1): 28–37. doi:10.5435/JAAOS-20-01-028. PMID 22207516.

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