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60 Part I Disorders Presenting in the Skin and Mucous Membranes Figure 3-15. Psoriatic arthritis Dactylitis of index finger. Note sausage-like thickening over interphalangeal joints. There is psoriasis of the nail. by betamethasone valerate, 1% lotion; if refractory, clobetasol propionate, 0.05% scalp application. In thick, adherent plaques (Fig. 3-8): scales have to be removed by 10% salicylic acid in mineral oil, covered with a plastic cap and left on overnight before embarking on topical therapy. If this is unsuccessful, consider systemic treatment (see below). Palms and Soles (Fig. 3-7). Occlusive dressings with class I topical glucocorticoids. If ineffective, PUVA either systemically or as PUVA soaks (immersion in 8-methoxypsoralen solution and subsequent UVA exposure). Retinoids (acitretin > isotretinoin), orally, removes the thick hyperkeratosis of the palms and soles; however, combination with topical glucocorticoids or PUVA (re-PUVA) is much more efficacious. Systemic treatments should be considered. Palmoplantar Pustulosis (Fig. 3-12). PUVA soaks and glucocorticosteroids are effective. Systemic treatment for recalcitrant cases. Inverse Psoriasis (Fig. 3-10) Topical glucocorticoids (caution: these are atrophy-prone regions; steroids should be applied for only limited periods of time); switch to topical vitamin D derivatives or tazarotene or topical tacrolimus or pimecrolimus. If resistant or recurrent, consider systemic therapy. Nails (Fig. 3-11). Topical treatments of the fingernails are unsatisfactory. Systemic MTX and CS therapy effective but takes time and thus prone to side effects. Generalized Psoriasis Acute, Guttate Psoriasis (Fig. 3-2). Treat streptococcal infection with antibiotics. Narrowband UVB irradiation most effective. Generalized Plaque-Type Psoriasis (Fig. 3-4). PUVA or systemic treatments that are given as either mono—or combined—or rotational therapy. Combination therapy denotes the combination of two or more modalities, while rotational therapy denotes switching the patient after clearing and a subsequent relapse to another different treatment. Narrowband UVB Phototherapy (311 nm). Effective only in thin plaques; effectiveness is increased by combination with topical glucocorticoids, vitamin D analogues, tazarotene, or topical tacrolimus/pimecrolimus. Oral PUVA. Treatment consists of oral ingestion of 8-methoxypsoralen (8-MOP) (0.6 mg 8-MOP per kilogram body weight) or, in some European countries, 5-MOP (1.2 mg/kg body weight) and exposure to doses of UVA that are adjusted to the sensitivity of the patient. Most patients clear after 19–25 treatments, and the amount of UVA needed ranges from 100 to 245 J/cm 2 . Long-term Side effects. PUVA keratoses and squamous cell carcinomas in some patients who receive an excessive number of treatments. Oral Retinoids. Acitretin and isotretinoin are effective in inducing desquamation but only moderately effective in clearing psoriatic plaques. Highly effective when combined with 311-nm UVB or PUVA (called re-PUVA). The latter is in fact the most effective therapy to date for generalized plaque psoriasis. Methotrexate Therapy. Oral MTX is one of the most effective treatments but response is slow and long-term treatment is required. Hepatic toxicity may occur after cumulative doses in normal persons (≥1.5 g). the triple-Dose (Weinstein) Regimen. Preferred by most over the single-dose MTX once weekly, 5 mg is given every 12 h for a total
Section 3 Psoriasis and Psoriasiform Dermatoses 61 of three doses, i.e., 15 mg/week. Achieves an 80% improvement but total clearing only in some, and higher doses increase the risk of toxicity. Patients respond, the dose of MTX can be reduced by 2.5 mg periodically. Determine liver enzymes, complete blood count, and serum creatinine periodically. Be aware of the various drug interactions with MTX. Cyclosporine 1 . CS treatment is highly effective at a dose of 3–5 mg/kg per day. If the patient responds, the dose is tapered to the lowest effective maintenance dose. Monitoring blood pressure and serum creatinine is mandatory because of the known nephrotoxicity of the drug. Watch out for drug interactions. Monoclonal Antibodies and Fusion Proteins 2 (so-called biologicals). Some of these proteins, specifically targeted to pathogenically relevant receptors on T cells or to cytokines, have been approved and more are being developed. They should be employed only by specifically trained dermatologists who are familiar with the dosage schedules, drug interactions, and short- or long-term side effects. Alefacept is a human lymphocyte functionassociated antigen (LFA)-3-IgG1 fusion protein that prevents interaction of LFA-3 and CD2. Given intramuscularly once weekly leads to considerable improvement and there may be long periods of remissions, but some patients do not respond. tumor necrosis Factor-Alpha (tnF-α) antagonists that are effective in psoriasis are infliximab, adalimumab, and etanercept. Infliximab is a chimeric monoclonal antibody to TNF-α. Administered intravenously at weeks 0, 2, and 6, it is highly effective in psoriasis and psoriatic arthritis. Adalimumab is a fully human recombinant monoclonal antibody that specifically targets TNF-α. It is administered subcutaneously every other week and is similarly effective as 1 For details and drug interactions, see MJ Mihatsch, K Wolff. Consensus conference on cyclosporin A for psoriasis. Br J Dermatol. 1992;126:621. 2 For details and drug interaction, see S Richardson, J Gelfand. In: Goldsmith L, Gilchrest B, Katz S, Paller A, Leffel D, Wolff K. eds. Fitzpatrick’s Dermatology, in General Medicine. 8th ed. New York, NY: McGraw- Hill; 2013: pp 2814–2826. infliximab. Etanercept is a human recombinant, soluble TNF-α receptor that neutralizes TNFα activity. Administered subcutaneously twice weekly and is less effective than infliximab and adalimumab but is highly effective in psoriatic arthritis. Ustekinumab (Anti-interleukin (iL) 12/interleukin 23 p40) is a human IgG1κ monoclonal antibody that binds to the common p40 subunit of human IL-12 and IL-23, preventing its interaction with its receptor. Given every 4 months subcutaneously, it is highly effective. All these biologicals and others currently developed in clinical trials have side effects, and there are long-term safety concerns. Also, currently they are extremely expensive that limits their use in clinical practice. For doses, warnings, and side effects. 2 Generalized Pustular Psoriasis (see Fig. 3-13) These ill patients with generalized rash should be hospitalized and treated in the same manner as patients with extensive burns, toxic epidermal necrolysis, or exfoliative erythroderma—in a specialized unit. Isolation, fluid replacement, and repeated blood cultures are necessary. Rapid suppression and resolution of lesions is achieved by oral retinoids (acitretin, 50 mg/day). Supportive measures should include fluid intake, IV antibiotics to prevent septicemia, cardiac support, temperature control, topical lubricants, and antiseptic baths. Systemic glucocorticoids to be used only as rescue intervention as rapid tachyphylaxis occurs. Oral PUVA is effective, but logistics of treatment are usually prohibitive in a toxic patient with fever. Acrodermatitis Continua Hallopeau (Figure 3-14B) Oral retinoids as in von Zumbusch pustular psoriasis; MTX, once-a-week schedule, is the second-line choice. Psoriatic Arthritis Should be recognized early in order to prevent bony destruction. MTX, once-a-week schedule as outlined above; infliximab or etanercept are highly effective.
Page 2 and 3: FITZPATRICK’S Color AtlAs And sYn
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Page 6 and 7: This seventh edition of Fitzpatrick
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Page 18 and 19: xviii Contents Section 28 Dengue 65
Page 20 and 21: xx Contents Section 33 Onycholysis
Page 22 and 23: xxii Contents SECTION 35 APPENDICES
Page 24 and 25: Our secretary, Renate Kosma, worked
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