White : Diseases of the Skin - Psoriasis and Related Disorders

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Gary M. White & Neil H. Cox

Diseases of the Skin

7	Psoriasis and Related Disorders

TREATMENT OF PSORIASIS AND RELATED DISORDERS

Numerous agents may be used with success in the treatment of psoriasis (Figs 7.32–7.41, Tables 7.8–7.10). However, there are important considerations in choice of therapy, which must be tailored to the individual patient. Several of the topical agents are potentially irritant if used on thin skin (face and flexures) or on very inflamed lesions (unstable psoriasis), while all the systemic agents have (at least potentially) severe toxicity and would therefore be inappropriate for milder psoriasis that might respond to safer treatments. Body site(s) affected, clinical pattern, chronicity, response to initial treatment choices, social aspects for the patient, and ability to use treatments effectively may all influence the choice of treatment and the progression from one to another. Some of these issues are summarized in the following sections on topical and systemic therapies.

There are a few fundamental issues that are worth considering.

•	Treatment is likely to work only if it is used—a treatment that is too messy (Fig.7.32), too irritant for the type of psoriasis (Figs 7.33 and 7.34), too time consuming, cosmetically inelegant (Fig.7.35), or inadequately explained may therefore fail. Using an expert nurse to demonstrate treatment is greatly appreciated by many patients.
•	Patients who are admitted to hospital, or who attend a day treatment center, respond faster than those performing treatment at home, although the reasons for this are often unclear.
•	If there is significant scaling, use of a keratolytic agent is important at the start of therapy (Fig.7.36), as other topical agents will otherwise fail to penetrate and will thus be ineffective. This simple measure can often resurrect ‘failed' treatment, and is particularly important for the palms, soles, and scalp.

Figure. 7.32 Crude coal tar is an effective treatment for psoriasis but is usually too messy for home use.

Figure. 7.33 Treatment with anthralin (dithranol): erythema around treated lesions. If symptomatic, this usually resolves by omitting treatment for a day or two, then using a lower concentration, but it may limit treatment in some patients.

Figure. 7.34 Vitamin D analogs are a potentially useful and clean therapeutic agent, but may irritate psoriasis if used on ‘unstable’ inflamed lesions, as in this case.

Figure. 7.35 Treatment with anthralin (dithranol): residual brown staining after treatment. This lasts only a week or so after lesional clearance, but some patients may not wish to use it on exposed sites such as the hands.

Figure. 7.36 Scalp hyperkeratosis. This often requires treatment with a keratolytic agent.

•	Strong topical corticosteroids have significant side effects, especially at thinner skin areas (Fig.7.37); if the need for higher potency is increasing, it may be best to combine treatment with another, more specific, antipsoriatic agent.
•	It is technically difficult for patients to treat widespread small lesions such as those of guttate psoriasis, particularly with messy or irritant treatments; UVB phototherapy is often a better option, a short course over 4–6 weeks generally being adequate.
•	Systemic therapies such as methotrexate or retinoids have potentially significant side effects (Figs 7.38 and 7.39), as does PUVA (Figs 7.40 and 7.41).
•	Unstable psoriasis should not be treated with irritant agents—it is likely to get worse.
•	The pattern or body site of psoriasis may significantly influence the best choice of treatment (Table 7.8).

Figure. 7.37 Topical corticosteroids are useful for psoriasis, but are often best used either as a preliminary treatment to control inflammation, or in conjunction with other more specific therapy. Use in isolation carries the risks of tachyphylaxis and rebound, resulting in increased strengths being required, and increased risk of side effects such as striae, as shown here around the plaques of psoriasis.

Figure. 7.38 Mouth ulceration in a patient taking methotrexate for psoriasis. This is a warning of potential hematologic toxicity.

Figure. 7.39 Systemic retinoids are helpful for hyperkeratotic psoriasis of palmoplantar skin, but treatment involves a balance between excessive keratosis due to the disease and excessive peeling (leaving a rather red, thin, glazed-looking skin) due to the treatment.

Figure. 7.40 Psoriasis before ( a ) and after ( b ) treatment with PUVA photochemotherapy.

Figure. 7.41 Marked lentiginosis may occur in patients treated with PUVA. The lesions are typically angular or stellate in shape, and affect the usually covered skin of the buttock by comparison with the (usually paler) lesions caused by sunlight exposure. In some instances, as shown here, lesions are confined to the distribution of a resolved plaque of psoriasis.

Table 7.8 SOME THERAPEUTIC IMPLICATIONS OF THE DIFFERENT CLINICAL PATTERNS AND SITE-RELATED VARIANTS OF PSORIASIS

Variant

Therapeutic implications

Main pattern

Plaque psoriasis

Guttate psoriasis

Generalized pustular psoriasis

Palmoplantar pustulosis

Acropustulosis of Hallopeau

‘Unstable’ psoriasis

Erythrodermic or exfoliative

Subacute annular (Lapière)

Linear

Most options potentially applicable, depending on extent and degree of inflammation

Self-limiting, but pattern makes it difficult to treat (especially if messy or irritant treatment); often treated with UVB phototherapy

Usually requires hospitalization to monitor systemic effects, usually needs systemic therapy

Chronic; usually treated topically initially, but often poor response

Nail destruction often requires systemic therapy

Avoid potentially irritant topical agents, monitor carefully

Usually requires hospitalization to monitor systemic effects, usually needs systemic therapy

Rare, may respond to simple topicals but often scattered lesions

Usually topicals as for plaque psoriasis, but response is usually incomplete and recurrence is expected

Specific sites

Elbows and/or knees

Hands and feet

Scalp

Flexures and genital

Nails

Face and ears

Topicals as for plaque psoriasis

Usually requires a keratolytic as well as other topical agent(s); thick skin, therefore use an adequate potency if using a corticosteroid; may warrant systemic therapy

Usually requires a keratolytic as well as topical corticosteroid or other topical agent (s); thick skin, therefore use an adequate potency if using a corticosteroid, but beware of overuse at scalp margin and reat ears with milder agents; expert nurses can greatly influence success of scalp treatment

Mild agents, avoid irritant treatments

Difficult; may respond to strong corticosteroids to nail fold; may need intralesional steroid to nail matrix or bed (but painful); may respond to systemic therapy, but usually only used if severity of skin involvement warrants this

Mild agents as for flexures

Specific therapies that may be used are listed in Tables 7.9 and 7.10, and are discussed in more detail in the general therapeutic chapters (Chs 3–5).

Table 7.9 TOPICAL DRUG THERAPY FOR PSORIASIS

Agent	Comments
Emollients and keratolytics	Emollients are important, should be used in most patients, and may be all that is required in some. Keratolytics include salicylic acid, coconut oil. An important part of therapy of psoriasis: failure to remove scaling or hyperkeratosis (especially on the scalp and palmoplantar surfaces) before using other topicals is a common reason for poor treatment response.
Corticosteroids	Antiinflammatory and antiproliferative actions; effective and widely used, but potential disadvantage of tachyphylaxis and of rebound exacerbation of psoriasis if strong agents are suddenly discontinued. This can lead to ever-increasing strengths being applied, with the attendant risks of skin atrophy. Useful as first-line therapy for localized plaques, areas where other treatments may irritate (e.g. flexures) or stain (e.g. scalp), and also in ‘unstable’ psoriasis to allow introduction of more specific agents.
Vitamin D analogs	Antiproliferative, clean to use. Some irritate face or flexures. May worsen unstable psoriasis. In some patients, hyperkeratosis responds well but redness does not, therefore potential to use in conjunction with topical corticosteroid.
Anthralin (dithranol)	A potent antipsoriatic agent, which has disadvantages of staining and skin irritation; only suitable for stable disease. Very effective if used carefully, usually as 30-min ‘wash-off’ regimen in conjunction with other agents. Benefits from demonstration to the patient.
Tars	Antimitotic and antiinflammatory, also help to remove scale. Preparations vary considerably in strength and cosmetic suitability. Mild preparations are useful for areas such as the ears. Used in conjunction with UVB in the Goeckerman regimen.
Vitamin A analogs	Used systemically for psoriasis, more recently topically. Useful for descaling.

Table 7.10 DRUG THERAPY AND PHOTOTHERAPY FOR PSORIASIS

Agent	Comments
Methotrexate	Usually effective for skin or joints, cheap. Nausea may limit treatment. Given once weekly, often with folate supplementation. Myelosuppression(Fig. 7.38) and liver side effects are important.Less popular than it was, due to additional new agents plus need for liver biopsy; newer monitoring methods (PIIINPa) may help.
Acitretin	Especially useful for hyperkeratotic psoriasis, palms and soles. Pregnancy must be avoided for 2 years, so use is limited in younger women. Rarely useful for joints. May cause dry lips, peeling palms and soles (Fig. 7.39), hair loss, arthralgia, hyperlipidemia. Expensive.
Ciclosporin	Useful for skin and joints, but nausea is common. Main adverse reactions are hypertension and renal impairment (risk increases with time) and numerous drug interactions.
Mycophenolate mofetil	Less experience in psoriasis than ciclosporin, but can be useful; the two may be used together. See Chapter 4 for additional details.
Hydroxyurea	Generally safe. Causes myelosuppression, but rarely severe and is reversible. May cause gradually increasing anemia, often paralleled by a gradually decreasing efficacy over some years.
Systemic corticosteroids	Avoid due to risk of pustular psoriasis on withdrawal.
Azathioprine	Infrequently used in psoriasis.
UVB phototherapy	Often used for guttate psoriasis or for widespread, essentially stable, plaque psoriasis, generally for intermittent courses. Narrow-band 311 nm is now usually used in preference to broadband UVB.
PUVA photochemotherapy	Effective (Fig. 7.40), relative lack of short-term side effects. However, has a skin-aging effect, increased risk of squamous cell carcinoma and lesser risk of melanoma. Severe lentiginosis may occur (Fig. 7.41). Concurrent use of retinoids can be helpful.
Anti-tumor necrosis factor	A new treatment for severe psoriasis. Effective but hugely expensive; several potentially important side effects (see Monoclonals Ch. 4) and uncertain long- term side effects.
Lasers	Excimer laser 308 nm has been used but can treat only small areas, and often causes burning or blistering.
Intralesional corticosteroid	Occasionally used for thick, stubborn, localized plaques; also used in severe nail disease, but painful, usually needs ring-block anesthesia.

aAmino terminal peptide of type III procollagen.

Some individuals would recommend a therapeutic approach based on body surface area (BSA) involved. This can be useful as one method of guiding therapy, but it needs considerable flexibility depending on the pattern, sites, degree of inflammation, and other factors discussed in this section. For example, 2% BSA involvement may seem minor if it is a thin plaque on the buttock, but can be career threatening (and totally alter the therapeutic approach) if the 2% BSA happens to be 1% contributed by each palm. Similarly, limited but very inflammatory psoriasis would require a different approach to that for pale, thin, chronic plaques of the same extent. Some possible options for plaque psoriasis based on BSA affected, and some limitations of the BSA approach, are provided in Table 7.11.

Table 7.11 A POSSIBLE APPROACH TO PLAQUE PSORIASIS, AND SOME LIMITATIONS OF THE BODY SURFACE AREA (BSA) APPROACH^a

BSA involved (approximate%)^b	Usual options	Non-responders	Limitations and comments
< 10%	Initial treatment: topical corticosteroid and/or vitamin D analog. May need pretreatmen with an emollient or keratolytic if very scaly, andongoing concurrent use of emollientisgenerally helpful. If starting with a topical corticosteroid to reduce inflammation, try tocombine with otheragentsafter2–3 weeks, suchastars, anthralin,vitamin A analog (usually onetreatment either end oftheday,but someat areavailable incombination formulations, and short-contact formulations, and short-contact anthralin can be added in with other treatments).	Try other topicals in thefirst instance, or combining agents if not already tried. If doinghome treatment, day center attendance with nurse supervision mayimprove response. Combine topicals with phototherapy (usually narrow-band UVB initially) or consider admission (and possible use of messieroptions, (and possibleuseof messieroptions,such as stronger tars, orstronger anthralinpreparations). Possibly use systemic agents if still poor response.	Purely flexural psoriasis is usually in thisBSArange, but requires a different approach (e.g. some vitamin D analogs may be irritant). Guttate psoriasisis often in this BSA range if assessed accurately (often overestimated), but requires a differentapproach with an early move to UVB phototherapy potentially being more useful than trying multiple topicals. The same may apply to widespread, scattered, stable, small-plaque disease. Localized hand or foot plaques will be in this BSA range but typically require use of a keratolytic with other topical options, and may warrant an early move tosystemic therapy. Toxicity of systemic agents should limit their use in patients with BSAinvolvement at this level without careful consideration of, and usually failure of, simpler options.
10–20%	Topicals as above; phototherapy is often used at an earlier stage (the two approaches would generally be used together).	Hospital admission or systemic treatments, as above.	Widespread small plaques amounting to 10–20% BSA are a more valid indication for phototherapy than a small number of larger plaques, as topical therapy is more difficult and time consuming. Hospital admission may avoid the need for systemic therapy if side effects (especially long term) are an issue: rate and severity of relapse may be more important in making this decision than the initial extent of psoriasis.
> 20%	Phototherapy is often suggested as first-line treatment, but there is actually no good reason not to use topicals as first-line therapy, especially on a supervised treatment center or inpatient basis.	UVB phototherapy if not already tried. PUVA or systemic agents if UVB plus topicals has failed.	Patients with BSA involvement over 20% are oftenthose with more inflammatory psoriasis; choice of topicals is important. Phototherapy takes time to work (weeks), so may not be the best option in isolation unless plaques are stable. The > 20% BSA option covers a huge range; an additional group are therefore considered below.
Semiconfluent plaques and suberythrodermic	May need topical corticosteroid to decrease inflammation (with close outpatient supervision or inpatient management, usually the latter); early use of a systemic agent.	Responders to topical therapy may still need to be considered for systemic therapy for ongoing control. If systemic therapy fails, thencombination with topicals or with other systemic agents, or a differentsystemic agent, may be needed.	Phototherapy with UVB or PUVA is generally not appropriate for this group: the psoriasis isusuallyinflammatory, and phototherapy is too slow to work anyhow.

^aThe subject of this table is plaque psoriasis of varying extent; erythrodermic and pustular psoriasis are not considered.
^bAdvice is usually based on < 10%, 10–20%, and > 20% but has been extended for this table.