Factors Influencing Selection of Treatment
Age: childhood, adolescence, young adulthood, middle age, >60 years.
Type of psoriasis: guttate, plaque, palmar and palmopustular, generalized pustular psoriasis, erythrodermic psoriasis.
Site and extent of involvement: localized to palms and soles, scalp, anogenital area, scattered plaques but <5% involvement; generalized and >30% involvement.
Previous treatment: ionizing radiation, systemic glucocorticoids, photochemotherapy (PUVA), cyclosporine (CS), and methotrexate (MTX).
Associated medical disorders (e.g., HIV disease).
Management of psoriasis is discussed in the context of types of psoriasis, sites, and extent of involvement. Psoriasis has to be managed by a dermatologist.
Topical fluorinated glucocorticoid covered with plastic wrap. Glucocorticoid-impregnated tape also useful. Beware of glucocosteroid side effects (see Fig. 3-3).
Hydrocolloid dressing, left on for 24–48 h, is effective and prevents scratching.
For small plaques (≤4 cm), triamcinolone acetonide aqueous suspension 3 mg/mL diluted with normal saline injected intradermally into lesions. Beware of hypopigmentation in skin of color.
Topical anthralin also effective but can be irritant.
Vitamin D analogues (calcipotriene, ointment and cream) are good nonsteroidal antipsoriatic topical agents but less effective than corticosteroids; they are not associated with cutaneous atrophy; can be combined with corticosteroids. Topical tacrolimus, 0.1%, similarly effective.
Topical pimecrolimus, 1%, is effective in inverse psoriasis and seborrheic dermatitis-like psoriasis of the face and ear canals.
Tazarotene (a topical retinoid, 0.05 and 0.1% gel) has similar efficacy, best combined with class II topical glucocorticoids.
All these topical treatments can be combined with 311-nm UVB phototherapy or PUVA.
Superficial scaling and lacking thick plaques: Tar or ketoconazole shampoos followed 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).
(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.
(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.
(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.
(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.
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/cm2.
Long-Term Side Effects. PUVA keratoses and squamous cell carcinomas in some patients who receive an excessive number of treatments.
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.
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 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.
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.1 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
(so-called biologicals).2 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 function-associated 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 infliximab. Etanercept is a human recombinant, soluble TNF-α receptor that neutralizes TNF-α 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
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 (see Fig. 3-13). 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.
Should be recognized early in order to prevent bony destruction. MTX, once-a-week schedule as outlined above; infliximab or etanercept are highly effective.
Pityriasis Rubra Pilaris (PRP)
ICD-9: 696.4 ○ ICD-10: L44.4
Rare, chronic, papulosquamous disorder often progressing to erythroderma.
Six types exist.
Follicular hyperkeratotic papules, reddish-orange progressing to generalized erythroderma. Sharply demarcated islands of unaffected (normal) skin.
Waxy, diffuse, orange keratoderma of palms and soles; nails may be affected.
Most effective therapy is MTX, systemic retinoids
Type 1: Classic Adult Generalized, beginning on head and neck.3
Type 2: Atypical Adult Generalized, sparse hair.
Type 3: Classic Juvenile Appears within the first 2 years of life, generalized.
Type 4: Circumscribed Juvenile In prepubertal children, localized.
Type 5: Atypical Juvenile Onset in first few years of life, familial, generalized.
Type 6: HIV-Associated Generalized, associated with acne conglobata, hidradenitis suppurativa, and lichen spinulosus.
Rare. Affects both sexes and occurs in all races.
Etiology and Pathogenesis
Both insidious and rapid onset occur.
All types of PRP. An eruption of follicular hyperkeratotic papules of reddish-orange color usually spreading in a cephalocaudal direction (Fig. 3-16). Confluence to a reddish-orange psoriasiform, scaling dermatitis with sharply demarcated islands of unaffected skin (Fig. 3-37). In dark skin papules are brown (Fig. 3-18).
Pityriasis rubra pilaris (type 1, classic adult) Orange-red follicular papules beginning on the head and neck have coalesced on the chest of a 57-year-old male. There are sharply demarcated islands of unaffected normal skin.
Pityriasis rubra pilaris (type 1, classic adult) Orange-reddish papules have coalesced to near erythroderma, sparing isolated islands of normal skin. Also note involvement of the hands in this 55-year-old woman.
Pityriasis rubra pilaris in black skin Here papules do not have the classical orange color seen in Caucasians but are brown and therefore pose a diagnostic problem. Their shape and distribution and the areas of spared normal skin are diagnostic clues.
Distribution. Types 1, 2, 3, 5, and 6: Generalized, classically beginning on the head and neck, then spreading caudally. Progression to erythroderma (except for types 2 and 4).
Scalp affected, as in psoriasis, often leading to asbestos-like accumulation of scale. Hair not affected except in type 2 where sparse scalp hair is observed.
Palms and Soles Pityriasis Pilaris (Type 1, Classic Adult)
Palm shows diffuse, waxy, yellowish/orange hyperkeratosis (Fig. 3-19).
Pityriasis rubra pilaris on palms There is diffuse, waxy hyperkeratosis with an orange hue.
Common but not diagnostic. Distal yellow-brown discoloration, nail plate thickening, subungual hyperkeratosis, and splinter hemorrhages. See Section 34.
Ichthyosiform lesions on legs in type 2. Scleroderma-like appearance of hands and feet in type 5. Acne conglobata, hidradenitis suppurativa, and lichen spinulosus in type 6.
Diagnosis and Differential Diagnosis
The diagnosis is made on clinical grounds. The differential diagnosis includes psoriasis, follicular ichthyosis, erythrokeratodermia variabilis, and ichthyosiform erythrodermas.
Not diagnostic but suggestive: Hyperkeratosis, acanthosis with broad short rete ridges, alternating orthokeratosis, and parakeratosis. Keratinous plugs of follicular infundibula and perifollicular areas of parakeratosis. Prominent granular layer may distinguish PRP from psoriasis. Superficial perivascular lymphocytic infiltrate.
A socially and psychologically disabling condition. Long duration; type 3 often resolves after 2 years; type 4 may clear. Type 5 has a very chronic course. Type 6 may respond to highly active antiretroviral therapy (HAART).
Topical therapies consist of emollients, keratolytic agents, vitamin D3 (calcipotriol), glucocorticoids, and vitamin A analogues (tazarotene). All are not very effective. Phototherapy (ultraviolet A phototherapy, narrowband ultraviolet B phototherapy, and photochemotherapy) is effective in some cases. Most effective treatment consists of systemic administration of MTX or retinoids (both as in psoriasis). In type 6: HAART. The anti-TNF agents, e.g., infliximab and etanercept are effective.