Psoriasis treatment: phototherapy, local and systemic treatment

Treatments for psoriasis vary and include emollients, salicylic acid, tar preparations, anthralin, glucocorticoids, calcipotriol, tazarotene, methotrexate, retinoids, immunosuppressants, immunotherapeutic agents, and phototherapy.

Phototherapy

Phototherapy is commonly used to treat patients with extensive psoriasis. The mechanism of action is unknown, although UVB rays inhibit DNA synthesis. Phototherapy with psoralen and ultraviolet A radiation, oral use of methoxypsoralen, photosensitizers accompanied by exposure to long waves of UVA (330-360 nm). Phototherapy has an antiproliferative effect and helps to normalize the differentiation of keratinocytes. The initial dosage of phototherapy is small, but can be increased later. Overdose of drugs or UVA can cause severe burns. Although this form of treatment is easier than the use of topical agents, long-term remission is possible, but repeated treatment can cause skin cancer. Less UV rays are required with oral retinoids. Narrow spectrum UVB is an effective treatment and does not require psoralen. Excimer laser therapy is a type of phototherapy using an extremely narrow spectrum of long waves.

Systemic (general) photochemotherapy (PUVA therapy). In the absence of contraindications to PTC, the sensitivity of the patient's skin to ultraviolet radiation is necessarily determined. For this, a biodose or MED (minimum erythemal dose) is used, that is, the minimum duration of irradiation at which clearly defined reddening of the skin occurs. Biodose is expressed in minutes or in the amount of energy per unit area: mJ/cm2 ⁽ UV-B), or J/cm2 ^. PUVA therapy is most effective in the vulgar form of psoriasis. Skin clearing from psoriatic rashes by 75-90% is noted after 15-20 PUVA therapy procedures.

Selective phototherapy (SPT). SPT uses medium-wave ultraviolet rays (UV-B) at a wavelength of 315-320 nm. Therapy begins with a UV-B dose of 0.05-0.1 J/cm2 ^using the method of 4 6-times irradiation per week with a gradual increase in the UV-B dose by 0.1 J/cm2 ^for each subsequent procedure. The course of treatment usually includes 25-30 procedures.

Aromatic retinoids (AR). Neotigazon is used at a rate of 0.5 mg per 1 kg of the patient's weight. If necessary, the dosage of the drug can be increased to 1 mg per 1 kg of the patient's weight per day. The course of treatment lasts 6-8 weeks. Neotigazon has a good therapeutic effect in the treatment of psoriatic arthritis, psoriasis of the palms and soles, and psoriatic lesions of the nail plates.

Re-PUVA therapy. This method of therapy is based on the combined use of PUVA therapy and AR. In this case, the dose of UFO and AR is significantly reduced (almost to half the dose). Re-PUVA therapy has a pronounced therapeutic effect in the treatment of psoriatic erythroderma (after the removal of acute symptoms), persistent and severe vulgar psoriasis, psoriatic arthritis.

Topical medications for psoriasis

The choice of external psoriasis therapy agents is extensive and depends on the stage and clinical form of the disease. The use of local preparations reduces inflammation, peeling and skin infiltration. Such preparations include ointments and creams containing salicylic acid (2%), sulfur (2-10%), urea (10%), digranol (0.25-3%), as well as glucocorticoid creams, ointments (diprosalik, belosalik, dermovate, lokazalen, etc.) and lotions (for lesions of the scalp) depending on the stage and clinical course of the disease. Local immunomodulators (elidel, protopic) and calcipatriol, application of cytostatics are also effective.

Emollients include creams, ointments, petroleum jelly, paraffin, and vegetable oils. They reduce scaling and are most effective when used twice daily or immediately after bathing. The lesions may become redder once the scaling subsides. Emollients are safe and should be used for mild to moderate cases.

Salicylic acid is a keratolytic that softens scales, makes them easier to remove, and increases the absorption of other products, especially helpful when treating the scalp, as flaking of the skin can be quite severe.

Subtypes of psoriasis

Subtype	Description	Treatment and prognosis
Guttate psoriasis	The sudden appearance of numerous plaques on the body of children and young people with a diameter of 0.5 to 1.5 cm following streptococcal pharyngitis	Treatment: Antibiotics for streptococcal infection Prognosis: Good with continued treatment
Psoriatic erythroderma	Gradual or sudden development of widespread erythema with or without plaque formation. Most often due to inappropriate use of topical or systemic glucocorticoids or phototherapy	Treatment: potent systemic drugs (eg, methotrexate, cyclosporine) or intensive local therapy. Tar, anthralin, and phototherapy may cause exacerbation. Prognosis: good if causative factors are eliminated.
Generalized pustular psoriasis	Sudden onset of widespread erythema with pustule formation	Treatment: use of systemic retinoids Prognosis: possible fatal outcome due to cardiac arrest
Pustular psoriasis of the palms and soles	Gradual onset of deep pustules on the palms and soles that can be painful and disabling. Typical rash may not be present.	Treatment: use of systemic retinoids
Psoriasis of large folds	Psoriasis of the groin, gluteal areas, armpits, substernal, retroauricular areas and penis with unremoved foreskin. Cracks may form in the center or along the edges of lesions	Treatment: topical application of minimally active glucocorticoids. Tar or anthralin may cause irritation.
Nail psoriasis	Pitting, graining, spotting, discoloration and/or thickening of the nail plate with or without separation (onycholysis). May resemble a fungal infection. Occurs in 30-50% of patients with other forms of psoriasis	Treatment: responds well to systemic therapy. Possible intralesional glucocorticoid administration Prognosis: usually poorly treatable
Acrodermatitis Gallopeau	Lesions of the distal parts of the limbs, sometimes only one finger, with subsequent formation of scales	Treatment: use of systemic retinoids, calcipotriol

Ointments, solutions and shampoos containing coal tar have an anti-inflammatory effect and reduce the hyperproliferation of keratinocytes. Tar preparations are usually applied at night and washed off in the morning, and can also be used in combination with topical glucocorticoids or with exposure to natural or artificial ultraviolet B light (280-320 nm) with a gradual increase in exposure (Gekkerman regimen).

Anthralin is a topical substance with antiproliferative and anti-inflammatory action, the mechanism of which is unknown. The effective dose is 0.1% cream or ointment with the content of the substance increasing to 1%. Anthralin can cause irritation and staining of the skin, so caution should be exercised when applied to intertriginous areas. Irritation and staining can be avoided if anthralin is removed 20-30 minutes after application. Much less discomfort occurs when using liposomal anthralin.

Glucocorticoids are usually used topically but may be given intralesionally. Systemic glucocorticoids may accelerate the progression of pustular psoriasis and should not be used in any form of psoriasis. Topical glucocorticoids are used twice daily, sometimes with anthralin or coal tar, at bedtime. Glucocorticoids are most effective when applied at night with occlusive dressings. Creams are applied during the day without dressings. The choice of glucocorticoid potency is determined by the extent of the lesion. As the lesion improves, glucocorticoids should be used less frequently or at lower potency levels to minimize the formation of striae and telangiectasias. Ideally, after about 3 weeks, glucocorticoids should be replaced by emollients for 1 to 2 weeks. This will limit the dosage of glucocorticoids and prevent tachyphylaxis. Topical glucocorticoids are expensive because larger amounts of drug (approximately 1 ounce, or 30 grams) are required to treat the entire body. Use of glucocorticoids over a long period of time on large body surfaces may aggravate the condition. For small, infiltrated, localized, or widespread lesions, potent glucocorticoids are effective with occlusive dressings applied at night and changed in the morning. Relapse occurs sooner after discontinuation of topical glucocorticoids than with other agents.

Calcipotriol is a vitamin D analogue that helps normalize proliferation and keratinocyte keratinization. It can be used in combination with topical glucocorticoids (for example, calcipotriol can be used on weekdays, and glucocorticoids on weekends).

Tazarotene is a topical retinoid that is less effective than glucocorticoids but is useful as an adjunct.

Systemic treatment of psoriasis

Oral methotrexate is the most effective treatment for severe forms of psoriasis, especially psoriatic arthritis or psoriatic erythroderma or pustular psoriasis that do not respond to topical medications or phototherapy with psoralen and ultraviolet A light.

Methotrexate suppresses the proliferation of epidermal cells. Blood count, renal function, and liver function should be constantly monitored. The dosage regimen varies, so only a doctor specializing in this area can prescribe methotrexate. Methotrexate is widely used in the treatment of particularly severe cases of refractory psoriasis (arthropathic, pustular, erythroderma) and other lymphoproliferative processes. It is usually prescribed daily in 2 doses orally at 2.5 mg or 5 mg once a day intramuscularly for 5 days, followed by a 3-day break. According to another scheme, methotrexate is taken in doses of up to 25 mg orally or 25-30 mg intramuscularly, or intravenously once a week. To achieve clinical remission of psoriasis, 4 or 5 such cycles are usually carried out. Clinical experience shows that methotrexate (EBEWE), along with a high therapeutic effect, has fewer side effects. To avoid side effects, it is advisable to combine it with calcium folinate.

The use of systemic retinoids (acitretin, isotretinoin) can be effective in the persistent course of psoriasis vulgaris, pustular psoriasis (for which isotretinoin is preferable) and palmoplantar psoriasis. Due to the teratogenic effect and long-term presence of acitretin in the body, it should not be taken by pregnant women, and pregnancy should be avoided for at least 2 years after stopping treatment. There are also restrictions on pregnancy when using isotretinoin, but it does not remain in the body for more than 1 month. Long-term treatment can cause widespread idiopathic skeletal hyperostosis.

Cyclosporine is an immunosuppressant that can be used to treat severe forms of psoriasis. The course of treatment is carried out for several months (sometimes up to 1 year), alternating it with other types of therapy. The effect on the kidneys and long-term effect on the immune system prevents long-term use. Cyclosporine A (Sandimmune-Neoral) is prescribed orally at a dose of 3-4 mg / kg / day. Cyclosporine is indicated for patients with severe forms of psoriasis when conventional therapy is ineffective or there are contraindications to other methods of treatment.

Other immunosuppressants, such as uric acid, 6-thioguanine, and mycophenolate mofetil, are not entirely safe and are used only for stubborn psoriasis.

Immunotherapeutic agents include tumor necrosis factor (TNF)-alpha inhibitors (etanercept and infliximab), alefacept, and efalizumab. TNF-alpha inhibitors have been shown to resolve psoriasis, but their safety is still being studied. Alefacept is a recombinant human protein mixture consisting of CD2 bound to leukocyte functional-associated antigen (LFA) type 3 and the Fc portion of human IgG _v. Alefacept suppresses memory T-cell numbers without compromising T-cell numbers and is effective in preventing plaque formation. Efalizumab is a monoclonal antibody that competitively binds CD 11a, a subset of LFA-1, thereby blocking T-cell activity.

Glucocorticoids are prescribed for pustular, arthropathic psoriasis and psoriatic erythroderma when other methods of systemic therapy are contraindicated for the patient, have proven less effective or have had no effect. It is advisable to use triamcinolone or dexamethasone rather than prednisolone. The hormone dose is determined individually depending on the severity and clinical course of psoriasis. Usually, small (25-30 mg/day) or medium (40-50 mg/day) doses are prescribed.

In recent years, fundamentally new groups of drugs have been developed and introduced into clinical practice, called "biological" agents, which selectively affect certain links in the pathogenesis of the disease and, to a minimal extent, the normal function of the immune system. The drugs infliximab and etanercept block tumor necrosis factor alpha (TNF-a), reduce its activity, and as a result, the inflammatory process in the lesion decreases. These drugs are approved for the treatment of psoriasis and psoriatic arthritis. Other "biological" agents - ezfalizumab and alefacept - are T-cell antagonists and, accordingly, block these cells. They are indicated for the treatment of psoriasis only.

Choice of therapy for psoriasis

The choice of specific drugs and combinations requires close collaboration with the patient, keeping in mind the potential for adverse reactions. There is no single ideal combination, but simple treatments should be followed. Monotherapy is preferred, but combination therapy is also the norm. Rotational therapy consists of replacing one treatment with another after 1-2 years to reduce the adverse effects of chronic use and to control disease resistance. Sequential treatment consists of initially using potent agents (eg, cyclosporine) to achieve rapid results, followed by safer agents.

Mild psoriasis can be treated with emollients, keratolytics, coal tar, topical glucocorticoids, calcipotriol and/or anthralin alone or in combination. Sun exposure may be used, but may exacerbate the condition.

Phototherapy or oral medications should be used to treat moderate plaque psoriasis. Immunosuppressants are used for rapid, short-term control of the disease and in severe cases. Immunotherapy is used for moderate to severe cases that have not responded to other treatments.

Scalp plaques are difficult to treat and are resistant to systemic therapy because the hair interferes with drug application and protects the skin from UV rays. A solution of 10% salicylic acid in mineral oil can be rubbed into the scalp before bed by hand or with a toothbrush, then covered with a shower cap to increase penetration and avoid contamination, and washed off in the morning. More cosmetically acceptable glucocorticoid solutions can be applied during the day. Treatment of psoriasis should be continued until response is achieved. If plaques persist, intralesional injections of triamcinolone acetonide in saline 2.5 or 5 mg/ml can be used, depending on the size and severity of the lesion. Injections may result in local atrophy, which is usually reversible.