koeb generisk chloramphenicol mechanism
The thick keratin of the nail blocks absorption of topical agents.
For onycholysis, a topical corticosteroid in a solution vehicle may be used under the nail. Systemic therapy may be required to improve severe disease.
The thin skin of the genitalia is highly sensitive to the adverse effects (atrophy) of topical corticosteroids.
A low-potency topical corticosteroid ointment is recommended. Topical calcipotriene, which is not associated with a risk of atrophy, may be used.
The thick stratum corneum of palms and soles is a barrier to penetration of topical agents.
A highest-potency topical corticosteroid is recommended. Methotrexate (Rheumatrex) or acitretin (Soriatane; a systemic retinoic acid analog) may be needed.
Topical corticosteroids are the most commonly prescribed treatment for psoriasis.5 They are available in ointment, cream, lotion and solution forms. Corticosteroids have well-recognized anti-inflammatory and antiproliferative effects, which are thought to be their primary mechanism of action in psoriasis.6 Topical steroids are classified as low-, medium-, high- and super-high potency agents (Table 2). In general, treatment is initiated with a medium-strength agent, and high-potency agents are reserved for the treatment of thick chronic plaques that are refractory to weaker steroids. Low-potency agents are used on the face, on areas where the skin tends to be thinner, and on the groin and axillary areas, where natural occlusion increases the potency of a low-potency agent to the equivalent of a higher potency agent. Use of high-potency agents in these areas increases the risk of side effects and therefore should be avoided.
Potential side effects from corticosteroids include cutaneous atrophy, telangiectasia and striae, acne eruption, glaucoma, hypothalamus-pituitary-adrenal axis suppression and, in children, growth retardation. The true incidence of corticosteroid-induced hypothalamus-pituitary-adrenal suppression is unknown, but it is of concern with prolonged use.7 Often, evidence of hypothalamus-pituitary-adrenal axis suppression is found on the laboratory results, even when clinical symptoms are absent. Careful long-term follow-up of patients receiving topical corticosteroid therapy is highly recommended to detect potential complications.
Although corticosteroids are rapidly effective in the treatment of psoriasis, they are associated with a rapid flare-up of disease after discontinuation, and they have many potential side effects. Consequently, topical corticosteroids are frequently used in conjunction with another agent to maintain control. Topical calcipotriene is often used in combination with topical corticosteroids to speed clearing of the lesions and maintain control after the initial phase of treatment is completed.
Calcipotriene is a vitamin D3 analog available in cream, ointment and solution formulations. It inhibits epidermal cell proliferation and enhances normal keratinization. This agent has a slow onset of action, and patients should be aware that the effects of calcipotriene may not be noticeable for up to six to eight weeks after the initiation of therapy.
Although calcipotriene monotherapy has been shown to be moderately effective in reducing the thickness, scaliness and erythema of psoriatic lesions,8 maximal benefits are achieved when calcipotriene is used in combination with potent topical corticosteroids. A simplified approach for combination therapy is to begin therapy with a “quick-fix” phase, followed by a “transitional phase” and then a “maintenance phase.”9 For example, treatment could be initiated with twice-daily applications of a topical corticosteroid and calcipotriene until the lesions are flat; the maximum duration of this phase is four weeks.
When the lesions have become flat, therapy can then be changed to twice daily use of calcipotriene only, with corticosteroid “pulse” therapy twice daily on weekends only. This second phase helps prevent rebound from abrupt withdrawal of corticosteroids. When the lesions have remained flat and the intensity of their color has declined from bright red to pink, the maintenance phase begins, with use of calcipotriene alone and discontinuation of the weekend use of topical corticosteroids.
After appropriate control of the disease is maintained, topical therapy can be discontinued until a flare-up occurs. Use of emollients should be recommended, to reduce the scaly appearance of the lesions and to potentially reduce the amount of corticosteroid needed.
The only cutaneous side effect of calcipotriene is local irritation, which occurs in approximately 15 percent of patients.10 Calcipotriene is not recommended for use on the face or with occlusion. Hypercalcemia is a potential side effect of this agent when the dosage exceeds 100 g per week. This effect does not usually occur with weekly use of 100 g or less.11, 12 Most reports of hypercalcemia have been in patients who received prolonged therapy with 200 g or more per week. For localized psoriasis, the recommended dosages do not require monitoring of serum or urinary calcium levels. However, calcipotriene should be used with caution in patients with compromised renal function or a history of renal calculi.
Coal tar is a black viscous fluid that was first described by Goeckerman in 1925, when it was combined with ultraviolet light for the treatment of psoriasis. It is thought to suppress epidermal DNA synthesis.13
Coal tar is available as an ointment, cream, lotion, shampoo, bath oil and soap. Coal tar is most effective when it is used in combination with other agents, especially ultraviolet B light. Like calcipotriene, coal tar is effective when it is combined with topical corticosteroids. Coal tar shampoo can be used in combination with a corticosteroid scalp solution for the treatment of psoriasis on the scalp.
Because coal tar is messy and malodorous and can stain clothing, nighttime application is recommended. Patients should be advised to use old bed linens and and to wear old pajamas when they are using coal tar. Tar products can cause folliculitis, but they otherwise are generally not associated with side effects.
If good control of psoriasis is not achieved with topical corticosteroids, alone or in combination with calcipotriene or coal tar, consideration should be given to the addition of anthralin or tazarotene therapy. Anthralin, also known as dithranol, is an antipsoriatic topical preparation derived from wood tar.4 It has been available since 1916, but it is a second-line agent because of its irritating and staining properties.
Anthralin is available in 0.1 percent to 1 percent ointments, creams and solutions. It is generally used on notably thick, large plaques of psoriasis, and therapy is initiated at low concentrations for short periods. The concentration and duration of contact with each treatment is gradually increased, up to a maximum of 30 minutes per application.4 Anthralin can be combined with ultraviolet phototherapy; this is known as the traditional Ingram regimen.
Patients should be warned that anthralin has a tendency to stain any surface, including the skin, clothing and bathtub. Its use should be limited to well-demarcated plaques, and it should be applied with a cotton-tipped applicator or a gloved hand. Patients should be warned that normal skin surrounding the psoriatic lesion may become irritated if it comes in contact with anthralin.
Topical tazarotene is the first topical receptor-selective retinoid approved for the treatment of psoriasis. It is available only in gel form and exerts its effects through gamma and beta retinoic acid receptors. Tazarotene helps to normalize the proliferation and differentiation of keratinocytes, as well as to decrease cutaneous inflammation.14, 15 Once-daily application of tazarotene gel, 0.05 percent or 0.1 percent concentration, has been shown to be as effective as twice-daily application of 0.05 percent fluocinonide cream.16
As monotherapy, tazarotene has been shown to significantly reduce plaque elevation in mild to moderate psoriasis.17 However, because of its modest efficacy, slow onset of action and high potential for causing irritation, tazarotene should usually be used in combination with corticosteroids. The primary side effect of topical tazarotene is minor skin irritation and increased photosensitivity. Tazarotene is classified as a pregnancy category X drug and its use should be avoided in women of childbearing age.
Sun exposure in addition to topical therapy may be beneficial when multiple areas are affected with psoriasis. Patients should be encouraged to obtain natural sunlight exposure or tanning-bed light exposure for a few minutes a day, and then to slowly increase the duration of exposure as tolerated. Unaffected areas should be covered with a sunscreen, especially the face. Ultraviolet light exposure can be used judiciously to prevent flare-ups during the maintenance phase of therapy.
Psoriatic plaques that fail to respond to topical therapy may be improved by administration of intralesional corticosteroid injections. Triamcinolone (Kenalog) is often used for this purpose. The agent is injected directly into the dermis of a small, persistent plaque. The concentration is generally 3 to 10 mg per mL, depending on the size, thickness and area of the lesion. The dose of triamcinolone is released gradually over three to four weeks; additional injections may be needed every four to six weeks to improve the response. Disadvantages of intralesional injections include pain during the injection and potential side effects of local atrophy and systemic absorption.
The patient with refractory lesions may benefit from more advanced forms of treatment, such as phototherapy (ultraviolet B alone or psoralens plus ultraviolet A), outpatient treatment at a clinic specializing in psoriasis and systemic therapy with oral retinoids, methotrexate (Rheumatrex) or cyclosporine (Sandimmune). Combination therapy has also been shown to be effective, especially phototherapy in combination with topical anthralin, coal tar or calcipotriene (Table 4).
Psoriasis er en kronisk inflammatorisk hudsygdom, karakteriseret ved et aktiveret immunsystem og hyperproliferation af keratinocytterne i epidermis. Sygdommen ses hos 2-3% af befolkningen. Den mest almindelige præsentation er nummulate plaques, som typisk er lokaliseret til knæ, albuer og skalp. De første udbrud af sygdommen kan være i form af et papuløst eksantem (guttat psoriasis). Ved invers psoriasis afficeres hudfolder.
Diagnosen psoriasis stilles sædvanligvis på de kliniske forandringer, dog kan der være behov for histologisk verificering ved atypisk præsentation.
Lokalbehandling vil ofte være tilstrækkelig ved mild til moderat psoriasis, mens fototerapi og systemisk behandling anvendes ved sværere former, herunder psoriasisartritis.
- Calcipotriol i kombination med gruppe III-kortikosteroidet betamethason har effekt på linje med meget stærkt virkende kortikosteroider (gruppe IV), og kan ved daglig anvendelse i 4 uger inducere hurtig remission. Efter 4 uger aftrappes behandlingen gradvis. Ved relaps kan gentagen behandling med calcipotriol i kombination med betamethasondipropionat initieres efter behov.
- Kortikosteroider kan være virksomme ved mild til moderat nummulat-plaquepsoriasis. Generelt anvendes stærkere virkende kortikosteroider til hårbund, krop og ekstremiteter, og svagerevirkende kortikosteroider til ansigt, hudfolder og ano-genitalregionen. Stærkt virkende kortikosteroider bør ikke anvendes ved svær udbredt psoriasis på grund af risiko for præcipitering af pustuløs- eller erytrodermisk psoriasis.
I starten bør salver foretrækkes frem for cremer, idet salvegrundlaget er med til at opløse psoriasisskæl. Ved meget hyperkeratotiske forandringer kan det være en fordel dagligt at fjerne det tykke stearinagtige skællag med madolie eller salicylsalve 5% eller 10% før påsmøring af det aktive stof, dog er det ikke nødvendigt at fjerne skæl før anvendelse af calcipotriol-betamethason gel til psoriasis, herunder skalp psoriasis.
- Tjæresalve eller -bade, ofte givet under indlæggelse, kan være et alternativ til kortikosteroid- og calcipotriolbehandling. Se endvidere Tjæreholdige midler mod psoriasis.
Systemisk behandling og fototerapi
Ved udbredt psoriasis eller svær psoriasis på hænder og fødder, eller svær ano-genital psoriasis, vil man ofte vælge at behandle med:
- enten fototerapi UVB eller UVB-TL01 (smalspektret UVB)
- eller systemisk behandling med fotokemoterapi (PUVA), methotrexat, acitretin, dimethylfumarat, ciclosporin, apremilast eller et biologisk middel.
Systemisk behandling kan med fordel kombineres med lokalbehandling med calcipotriol, idet der opnås additiv effekt.
Ved i øvrigt behandlingsrefraktær moderat til svær psoriasis eller ved intolerans/kontraindikationer mod anden systemisk behandling kan et biologisk middel eller apremilast anvendes. Det er alment accepteret at man før anvendelse af et af de biologiske midler eller apremilast har forsøgt behandling med mindst en anden systemisk behandling, herunder methotrexat.