Treatment of psoriasis

There is no cure for psoriasis but there are many therapies and treatment depends on the extent and severity of the disease. 

As with eczema, emollients can have beneficial effects on dry, cracked skin and may also reduce hyperproliferation in mild psoriasis. 

They are also useful as adjuncts to other more specific treatments. 

Calcipotriol is a vitamin D analogue. Its use in psoriasis came about relatively recently following the observation that an oral vitamin D derivative used for osteoporosis coincidentally seemed to improve psoriasis. 

The mode of action of calcipotriol in psoriasis is apparently unconnected to the role of vitamin D in calcium metabolism. 

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For the topical treatment of some chronic inflammatory skin diseases (like atopic dermatitis) immunosuppressive macrolides (like TRL and pimecrolimus) that permeate the inflamed epidermis are of benefit for patients. Severe side effects comparable to those after systemic application of TRL in transplanted patients (see above) have not been observed so far. For the treatment of psoriasis vulgaris these drugs are less effective. The CD2 antagonist alefacept may be a suitable alternative to allergic reactions. 

Topical antipsoriatics are drugs used in the treatment of psoriasis (a chronic skin disease manifested by bright red patches covered with silvery scales or plaques). These drug help remove tiie plaques associated with this disorder. Examples of antipsoriatics include antiiralin (Anthra-Derm) and calcipotriene (Dovonex). 

Lebwohl M, Ali S. Treatment of psoriasis. Part 1. Topical therapy and phototherapy. J Am Acad Dermatol 2001 45 487-498. 

The forms of phototherapy in common use include (i) the phototherapy of jaundice (neonatal hyperbilirubinemia) in the newborn, and especially in the prematurely born 5 (ii) the treatment of psoriasis using light in the UV-A range (320 100 nm) and an administered photosensitizer, such as 8-methoxypsoralen 6 (iii) the treatment of the wet form of age-related macular degeneration with a photosensitizer such as a benzoporphyrin derivative (VISUDYNE ), and a laser light source 7 and (iv) the treatment of certain cancers with a photosensitizer such as a porphyrin derivative, and red light.8... 

Tin protoporphyrin, when administered in conjunction with UVA irradiation, has been reported to be of possible benefit in the treatment of psoriasis.404... 

Psoralen, or derivatives of 9-methoxy-7H-furo[3,2-g]chromen-7-one tricyclic ring structures, are used as photoreactive groups in crosslinkers, biotinylation compounds, and nucleic acid probes. Psoralens have been used for many years as photochemotherapy agents for treatment of psoriasis and vitiligo (Smith and Barker, 2006). Psoralens react when exposed to UV light... 

Calcitriol and tacalcitol are other vitamin D derivatives that have been studied for treatment of psoriasis. 

Hydroxyurea inhibits cell synthesis in the S phase of the DNA cycle. It is used selectively in the treatment of psoriasis, especially in those with liver disease who would be at risk of adverse effects with other agents. However, it is less effective than methotrexate. The typical dose is 1 g/day, with a gradual increase to 2 g/day as needed and as tolerated. Adverse effects include bone marrow toxicity with leukopenia or thrombocytopenia, cutaneous reactions, leg ulcers, and megaloblastic anemia. 

Examples of antibodies in the market include trastuzumab (anti-HER2 monoclonal antibody), rituximab, natalizumab (x4-integiin antibody), abciximab, infiximab (targets TNF-a in Crohn s disease and rheumatoid arthritis), alemtuzumab, adalimumab (TNF-a antibody for the treatment of rheumatoid arthritis) and efalizumab (anti-CDlla monoclonal antibody for the treatment of psoriasis)Rituximab is a mouse/human chimeric anti-CD20 monoclonal antibody used for the treatment of various l)unphoid malignancies. As CE)20 antigen is found on the surface of... 

Infliximab is a monoclonal antibody against TNF-a (see Chapter 26, Section III.d.1). It has been approved for the treatment of psoriasis, Crohn s disease, ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis and ulcerative colitis. Similar immunosuppressants are etanercept, and adali-mumab. 

Calcipotriol is a vitamin D3 derivative which is used as a topical agent in the treatment of psoriasis. Although not completely elucidated its mechanism of action seems to be based on inhibition of the proliferation and stimulation of the differentiation of epidermal keratinocytes. Adverse effects include irritation of the skin but also urticarial reactions. Calcipotriol has 100 fold less vitamin D activity as its active vitamin D3 metabolite calcitriol. However, calcipotriol in overdose can cause symptoms of hypercalcemia. 

In the United States, tazarotene has been approved for topical treatment of psoriasis (involving up to 20% body surface area) and mild to moderate facial acne. Application site burning, stinging, and desquamation are common side effects, especially with acne. Tazarotene is contraindicated in women who are pregnant. 

Anthralin (Anthra-Derm) is a potent reducing agent whose mechanism of action is unknown. It is approved for the treatment of psoriasis and also may be helpful in alopecia areata. The major toxicides are discoloration of skin, hair, and nails and irritant dermatitis. 

The past twenty years have witnessed considerable progress in the synthesis and use of other retinoid-like molecules related to vitamin A. The aromatic retinoid etretin (8.54) and its ester etretinate (8.55) had some effectiveness in the treatment of psoriasis, a disorder of skin. 13-cA-Retinoic acid (isotretinoin) produces sebaceous gland atrophy and could prove useful in the treatment of severe acne vulgaris. Although these compounds have toxic side effects and are not in regular use, they have opened up new therapeutic possibilities. Retinoic acid (tretinoin, 8.56) has been employed in the treatment of acne. 

It is a metabolite of the aromatic retinoid, etretinate used in the treatment of psoriasis. 

Recognition of the photosensitizing effect of the naturally occurring furanocoumarin psoralin (desmethoxy (3-6)) led to trials of its utility for the treatment of skin diseases such as psoriasis. The partial effectiveness of this compound led to the preparation of synthetic analogues. The two commercially available drugs, methoxsalen (3-8) and trioxsalen (4-6), are used in a procedure that goes by the acronym PUVA (psoralen and UVA irradiation) for the treatment of psoriasis and other skin diseases. 

A French patent claims l,2,4-oxadiazetidin-4-one is effective in the treatment of psoriasis (76FRP2341309). The reaction of nitrosobenzenes and arylmethyleneimines was reported to give 1,3-diaryl-1,2,4-oxadiazetidines with only C,H,N analysis to support their formation. They also supposedly decompose to diarylcarbodiimides with loss of water, which mechanistically is hard to envision (24JCS87). 

The main folate antagonist is methotrexate, an analogue of folic acid. Methotrexate competitively inhibits dihydrofolate reductase, the enzyme responsible for the synthesis of purine and pyramidine from folic acid. Trimetrexate, a methotrexate analogue, is useful in treating methotrexate-resistant tumours. It is also used to treat Pneumocystis carinii infections. Methotrexate is usually given orally, but may also be given intravenously or intrathecally. In addition to its use in cancer therapy, it is used in the treatment of psoriasis. Methotrexate can cause an obstructive nephropathy due to its precipitation in the renal calyx. 

Acitretin (Soriatane), a metabolite of the aromatic retinoid etretinate, is quite effective in the treatment of psoriasis, especially pustular forms. It is given orally at a dosage of 25-50 mg/d. Adverse effects attributable to acitretin therapy are similar to those seen with isotretinoin and resemble hypervitaminosis A. Elevations in cholesterol and triglycerides may be noted with acitretin, and hepatotoxicity with liver enzyme elevations has been reported. Acitretin is more teratogenic than isotretinoin in the animal species studied to date, which is of special concern in view of the drug s prolonged elimination time (more than 3 months) after chronic administration. In cases where etretinate is formed by concomitant administration of acitretin and ethanol, etretinate may be found in plasma and subcutaneous fat for many years. 

Treatment of psoriasis should be limited to once-daily application not to exceed 20% of total body surface area. Adverse local effects include a burning or stinging sensation (sensory irritation) and peeling, erythema, and localized edema of the skin (irritant dermatitis). Potentiation of photosensitizing medication may occur, and patients should be cautioned to minimize sunlight exposure and to use sunscreens and protective clothing. 

Tar preparations are used mainly in the treatment of psoriasis, dermatitis, and lichen simplex chronicus. The phenolic constituents endow these compounds with antipruritic properties, making them particularly valuable in the treatment of chronic lichenified dermatitis. Acute dermatitis with vesiculation and oozing may be irritated by even weak tar preparations, which should be avoided. However, in the subacute and chronic stages of dermatitis and psoriasis, these preparations are quite useful and offer an alternative to the use of topical corticosteroids. 

Some naturally occurring furocoumarins such as psoralen (494) and especially methoxalen (495) have been used for many years in medicine for the treatment of psoriasis and other dermal diseases (80JHC985). The commercial source is plant materials, mainly the seeds of Amni mafus L. 

Kawahara C, Okada Y, Tanikawa T, Fukusima A, H, Tanaka Y. Severe hypercalcemia and hypernatremia associated with calcipotriol for treatment of psoriasis. J Bone Miner Metab 2004 22 159-62. 

In addition to the antineoplastic activity, camptothecin was found to be an effective inhibitor of adenovirus replication [268, 269] and herpes virus replication [252, 270]. 10-Methoxycamptothecin is about 8-times more potent than camptothecin as an inhibitor of herpes virus [252]. A combination of camptothecin and dimethyl sulphoxide is very effective for the topical treatment of psoriasis [271]. Since, in the goldfish brain, camptothecin blocks RNA synthesis in eucaryotic cells by blocking the incorporation of uridine into RNA, this alkaloid can block the memory of conditioned avoidance and produces no measurable effect on retention of the learned response [272]. 

Two vitamin D derivatives, calcipotriol and tacalcitol (Figure 5.107) are widely used in the topical treatment of psoriasis, to inhibit the cell proliferation characteristic of this condition. 

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