Psoriasis systemic therapy

Compare and contrast the treatment modalities for psoriasis, including topical and systemic therapies and phototherapy. 

Pustular psoriasis may be localized or generalized and may be an acute emergency requiring systemic therapy. Generalized pustular psoriasis is characterized by disseminated deep-red erythematous areas and pustules, which may merge to become "lakes of pus."... 

Erythrodermic psoriasis is a generalized, life-threatening condition that presents with erythema, desquamation, and edema, and may require life support measures as well as systemic therapy. 

Management of patients with psoriasis generally involves both nonpharmacologic and pharmacologic therapies. Pharmacologic alternatives for plaque psoriasis include topical treatments, phototherapy, photochemotherapy, and systemic therapies alone (orally or by injection). The choice of treatment is usually dictated by the severity of disease.15-17 In some cases, a combination of treatment options may be preferred. Topical therapies can be used in patients with limited or mild... 

Systemic therapies are seldom used for mild to moderate psoriasis, and are generally reserved for patients with moderate to severe psoriasis.17 29 Oral agents include sulfasalazine, acitretin, methotrexate, cyclosporine, mycophenolate mofetil, azathioprine, tacrolimus, and hydroxyurea. Parenteral agents include the biologic response modifiers alefacept, efalizumab, etanercept, infliximab, and many others, currently at various stages of research or approval for psoriasis. 

Sulfasalazine has variable efficacy and is of limited potency. However, its side-effect profile is better than other systemic therapies and it is sometimes tried as an initial systemic agent for moderate to severe psoriasis. Usual doses are 2 to 4 g/day in divided doses.10... 

Kormeili T, Lowe NJ, Yamauchi PS. Psoriasis immunopathogenesis and evolving immunomodulators and systemic therapies United States experiences. Br J Dermatol 2004 151 3-15. 

Adalimumab (Humira) is a human immunoglobulin Gj monoclonal TNF-a antibody. The binding of adalimumab results in inactivation of the proinflammatory cytokine TNF-a. It is indicated for psoriatic arthritis and treatment of adults with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy. The recommended dose for psoriatic arthritis is 40 mg subcutaneously every other week. The recommended dose for adults with plaque psoriasis is an initial dose of 80 mg, followed by 40 mg every other week starting 1 week after the initial dose. The most common adverse reactions are infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, and rash. 

Psoriasis Neoral and Gengraf are indicated for the treatment of adult, nonimmunocompromised patients with severe (ie, extensive and/or disabling), recalcitrant, plaque psoriasis who have failed to respond to at least 1 systemic therapy (eg, PUVA, retinoids, methotrexate) or in patients for whom other systemic therapies are contraindicated or cannot be tolerated. While rebound rarely occurs, most patients will experience relapse with Neoral or Gengraf as with other therapies upon cessation of treatment. 

Plaque psoriasis For the treatment of patients with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. P.1192... 

Corticosteroids have a range of activity. They have potent antiinflammatory and immunosuppressive activity. Many synthetic drugs are available as corticosteroids. In appropriate doses, these are used as replacement therapy in adrenal insufficiency. The topical application of corticosteroids is safer when compared with systemic use. Corticosteroids should be used in smaller doses for the shortest duration of time. A high dose may be used for life-threatening syndromes or diseases. A tapering pattern of withdrawal should be followed to avoid complications of sudden withdrawal. Systemic therapy is indicated in a variety of conditions. These are administered by intraarticular injections with aseptic conditions for rheumatoid arthritis and osteoarthritis. In skin diseases, such as eczema, contact dermatitis, and psoriasis, corticosteroids are used topically. In some cases, steroids are combined with antimicrobial substances such as neomycin. 

Changes in barrier function due to skin disease generally result either from alteration of the lipid/protein composition of the stratum comeum or from abnormal epidermal differentiation (e.g. in psoriasis). As far as transdermal bioavailability is concerned, however, patches intended for systemic therapy are labelled for application only at normal skin sites, free from dermatologic pathology. 

Hoefnagel JJ, Thio HB, Willemze R, Bouwes Bavinck JN. Long-term safety aspects of systemic therapy with fumaric acid esters in severe psoriasis. Br J Dermatol 2003 149(2) 363-9. 

Candidates for PUVA therapy usually have moderate to severe, incapacitating psoriasis unresponsive to conventional topical and systemic therapies. A recent comparison of PUVA and NB-UVB involved 100 patients, 51 treated with NB-UVB and 49 receiving PUVA, with the results clearly favoring PUVA. Of these patients, 84% cleared with 16 PUVA treatments, whereas 63% cleared with 25 treatments of NB-UVB. °... 

Lebwohl M, Ali S. Treatment of psoriasis. Part 2. Systemic therapies. J Am Acad Dermatol 2001 45 649-661. 

Yamauchi PS, Rizk D, Kormeih T, et al. Current systemic therapies for psoriasis where are we now J Am Acad Dermatol 2003 49(2 Suppl) S66-77. 

Sobell JM, Hallas SJ. Systemic therapies for psoriasis understanding current and newly emerging therapies. Semin Cutan Med Surg 2003 22 187-195. 

In rheumatoid arthritis, cyclosporine is used in severe cases that have not responded to methotrexate. Cyclosporine can be combined with methotrexate, but the levels of both drugs must be monitored closely. In psoriasis, cyclosporine is indicated for treatment of adult immunocompetent patients with severe and disabling disease for whom other systemic therapies have failed. Because of its mechanism of action, cyclosporine also has been used successfully in inflammatory bowel disease see Chapter 38). 

Schaefer H, Schalla W, Lamaud E. Pharmacological and pharmacokinetic aspects in local and systemic therapy of psoriasis. In Kroger H, Stiittgen G, editors. Current research problems in psoriasis. Berlin Gross 1984. p. 104-10. 

Many patents have been issued on the use of pyrogaUol derivatives as pharmaceuticals. PyrogaUol has been used extemaUy in the form of an ointment or a solution in the treatment of skin diseases, eg, psoriasis, ringworm, and lupus erythematosus. GaUamine triethiodide (16) is an important muscle relaxant in surgery it also is used in convulsive-shock therapy. Trimethoprim (2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine) is an antimicrobial and is a component of Bactrin and Septra. Trimetazidine (l(2,3,4-trimethoxybenzyl)piperazine (Vastarel, Yosimilon) is used as a coronary vasodilator. l,2,3,4-Tetrahydro-6-methoxy-l-(3,4,5-trimethoxyphenyl)-9JT-pyrido[3,4- ]indole hydrochloride is useful as a tranquilizer (52) (see Hypnotics, sedatives, ANTICONVULSANTS, AND ANXIOLYTICS). Substituted indanones made from pyrogaUol trimethyl ether depress the central nervous system (CNS) (53). Tyrosine-and glycine(2,3,4-trihydroxybenzyl)hydrazides are characterized by antidepressant and anti-Parkinson activity (54). 

The topical and oral use of retinoids for treatment of hyperkeratotic disorders such as psoriasis and Darier s disease has long been established. Systemic retinoid therapy is often combined with topical diugs such as corticosteroids, dithranol, tar, and also UVA/UVB phototherapies where synergistic effects have been reported. 

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