Psoriasis: an update on topical and systemic therapies

SUMMARY

Psoriasis is an immune-mediated inflammatory disease with a genetic predisposition.

Although manifesting predominantly as a hyperproliferative skin disorder, psoriasis is a systemic disease associated with a range of comorbidities including arthritis, cardiovascular disease and depression.

Educating the patient that psoriasis is chronic and that there are possible comorbidities is paramount.

Patients with a limited number of plaques and no systemic symptoms may be managed with intermittent use of topical therapies. Those with more extensive or debilitating disease may require phototherapy or systemic medicines such as methotrexate or one of the newer targeted therapies.

Newer systemic therapies, including oral medicines and injectable biologics, can only be used following unsuccessful treatment with traditional therapies such as methotrexate and phototherapy.

Biologic therapies for psoriasis offer the possibility of near-complete symptom resolution in people with psoriatic disease.

 

Introduction

Psoriasis is a multisystem immune-mediated inflammatory disease. It manifests predominantly as a hyperproliferative papulosquamous skin disorder, but is associated with a range of comorbidities, such as psoriatic arthritis and cardiovascular disease. The physician-diagnosed prevalence of psoriasis in adults in Australia is estimated at around 2.4%.¹

Psoriasis can have a large impact on quality of life, with 75% of patients reporting alterations in daily activities, difficulties with body image and self-esteem, and feelings of stigma, shame and embarrassment.² Severe psoriasis is debilitating, with significant disease burden. Years lived with disability (YLDs) have been estimated at around 43.³

Psoriasis has a multi-factorial inheritance,⁴ and well-documented environmental triggers (e.g. infections such as Streptococcus, trauma, smoking, alcohol, and medicines such as beta-blockers and lithium).

The onset of psoriasis has 2 peaks: at age 15 to 20 years (more common in females), and over the age of 40 (equal sex distribution).⁵ Young children rarely get psoriasis, so this article focuses on teens and adults.

 

Diagnosis and assessment

Diagnosis of psoriasis is almost always clinical. Biopsy is not recommended in most cases.

Typical psoriatic lesions have been classically described as well-circumscribed, salmon-pink plaques with a loosely adherent scale. The plaques are usually symmetrical and often occur on areas of skin trauma such as elbows and knees (Koebner phenomenon). They are generally not itchy, but pruritus (itch) can be prominent particularly in older patients.

Children may present with thick plaques with dense scale in the scalp (pityriasis amiantacea). Teenage patients often present with widespread, truncal, pink plaques which may be itchy (guttate psoriasis) following streptococcal pharyngitis. Older adults may present with widespread erythema and sometimes minimal scale (erythrodermic psoriasis).

The multiple presentations of psoriasis can make the diagnosis difficult and often other clues are sought including nail changes, such as pitting and separation of the nail from its nail bed (onycholysis), thick skin in weight-bearing areas, stubborn dandruff and family history of psoriasis.

Differential diagnosis

The differential diagnoses for similar well-circumscribed scaly plaques include skin cancer (Bowen disease), eczematous patches, dermatophyte infection, cutaneous lupus erythematosus and mycosis fungoides. The wide differential and variable morphology of psoriasis mean that it is often misdiagnosed.⁶

Severity assessment

There are Australian consensus criteria for the assessment of psoriasis severity and determining suitability for systemic therapy (Box 1).⁷ Some of the criteria are mainly used in the context of access to biologic drugs via the Pharmaceutical Benefits Scheme (PBS) in Australia. For example, dermatologists are required to use the Psoriasis Area of Severity Index (PASI) as part of their assessment of eligibility for, and response to, biologic therapy.

 

Comorbidities and mortality

Psoriasis is a systemic disease and is associated with a range of significant comorbidities. Moderate and severe psoriasis have also been associated with excess mortality.⁸

Specific comorbidities

Specific comorbidities are part of the psoriatic disease; these include arthritis, inflammatory bowel disease and uveitis. Up to 40% of patients with psoriasis may have some form of joint involvement.⁹ There is often significant delay in the diagnosis of joint disease, up to 10 years in non-radiographic axial spondyloarthritis.¹⁰ A delay in diagnosis of more than 6 months increases the risk of irreversible joint changes with poor radiographic and functional outcomes.¹¹ Hence all patients with psoriasis should be screened for possible psoriatic arthritis.¹² Inflammatory bowel disease and uveitis are far less prevalent than arthritis, but occur with greater frequency compared with non-psoriatic patients.^13-15

Nonspecific comorbidities

Severe psoriasis is associated with nonspecific comorbidities such as metabolic syndrome and obesity. Psoriasis is an independent risk factor for atherosclerosis, myocardial infarction and stroke.^16,17

Patients with psoriasis have higher rates of mental illness, substance abuse and self-harm, and higher likelihood of suicidal ideation, attempts and completion.^18-20

 

Management

Because psoriasis is a systemic disease that may affect, for example, joints, bowel and eyes, systemic therapy may be required. Management of the skin disease using topical agents reduces the symptoms (itch, scale) and the impact of skin symptoms on quality of life, but does not treat the systemic disease. Also, topical therapies can be hard to use, messy and have relatively poor compliance.

Patients with a limited number of plaques and no systemic symptoms may be managed with intermittent use of topical therapies. Patients with moderate to severe psoriasis with features such as skin disease affecting more than 10% of body surface, pustular psoriasis, erythroderma, recalcitrant plaques or disease with significant impact on quality of life (e.g. interfering with function) (Box 1) should be referred to a dermatologist for consideration of systemic therapy. Joint symptoms and stiffness should be referred to a rheumatologist.⁷

Systemic corticosteroids (e.g. oral prednisolone) must be avoided as a rapid reduction of dose can precipitate catastrophic pustular psoriasis, a potentially life-threatening medical emergency.

Patient education and behavioural strategies

Educating the patient that psoriasis is chronic and that there are possible comorbidities is paramount. Patients can be reassured that the rash is not contagious, and that steps can be taken to reduce flares such as reducing alcohol intake, stopping smoking and optimising diet.²¹

Topical treatments

Initial management of mild to moderate psoriasis typically involves the use of topical treatments, such as emollients, corticosteroids, calcipotriol, tar and dithranol. There is little evidence to guide the selection of topical treatments, so it can be based on patient and prescriber preference.

Emollients with or without keratolytics

Regular (at least once daily) use of a fragrance-free moisturiser, particularly on thick plaques of elbows, knees and the sacral area, can reduce the scale and discomfort associated with cracking skin. Emollients can be supplemented with keratolytics such as urea (10%) or salicylic acid (up to 6%) with a thick cream base or white soft paraffin. Stronger keratolytics (e.g. urea 25%, salicylic acid greater than 8%) are useful on the thick skin of palms and soles but can be painful on raw or open skin.

Topical corticosteroids

Topical corticosteroids have anti-inflammatory action and reduce the scale and hyperproliferation of the skin. Although topical corticosteroids are effective at reducing the erythema and scale, prolonged use will cause tachyphylaxis (less efficacy) over time, extension of the area of disease and flare after stopping. Hence, they should be used only for a short time (e.g. 2 to 3 weeks) and/or intermittently (e.g. weekends).

Low-potency corticosteroids (e.g. methylprednisolone aceponate or hydrocortisone 1%) can be used on the face and genital areas. More potent topical corticosteroids (e.g. mometasone furoate, betamethasone dipropionate) are needed for thick plaques on the scalp, elbows and knees, and palms and soles.

Calcipotriol

Topical calcipotriol, a vitamin D analogue, is antiproliferative and reduces the size of psoriatic plaques. It can be irritant and should be avoided on the face, flexural areas and groin. Excessive use (more than 100 g per week) can increase the risk of hypercalcaemia.²²

Calcipotriol is only available on the PBS as a combination product with a potent topical corticosteroid; due to the steroid component, this should only be used short term or intermittently.

Tar and dithranol

Tar and dithranol are traditional topical therapies that can be cost-effective but have fallen out of favour because they are messy and odorous.

Liquid coal tar (liquor picis carbonis, LPC) creams with or without keratolytics (salicylic acid or sulfur) can be extemporaneously prepared by pharmacies. Tar shampoos can be bought over the counter. They reduce itch and scale, and can be used in conjunction with weekly topical corticosteroid scalp lotions. Cocois compound (e.g. Coco-Scalp) is a thick ointment of salicylic acid, tar and sulphur in coconut oil and is effective if left for several hours and washed off to reduce thick scalp disease.

Dithranol (1%) ointment can be applied to thick plaques and washed off after 10 to 30 minutes (short-contact dithranol therapy). It can stain skin and light-coloured hair.

Management of moderate to severe psoriasis

Management options for moderate to severe psoriasis include:

• phototherapy (narrowband UVB)
• older oral medicines (methotrexate, acitretin and cyclosporin)
• newer oral medicines (apremilast, deucravacitinib)
• injectable biologic medicines (tumour necrosis factor [TNF] alpha inhibitors, and anti-interleukin [IL]‑17, anti-IL-23, and anti-IL-12 and 23 therapies).²³

There is little evidence to inform the order of treatment selection; however, the newer oral medicines and injectable biologic medicines require prior unsuccessful treatment with older therapies such as methotrexate and/or phototherapy, and consultation with a dermatologist, rheumatologist or general physician to obtain PBS subsidy (Box 2).

It may be reasonable to start treatment with oral methotrexate in primary care if there will be a long delay (e.g. more than 3 months) in accessing a dermatologist or other specialist who can prescribe newer therapies.

Phototherapy

Narrowband UVB (wavelength 311 to 312 nm) is effective at clearing most thin plaques of psoriasis in 80% of patients. The patient stands in a treatment box with shielded eyes or face for up to 15 minutes at a time. Treatment requires 3 days per week therapy over several weeks. Downsides of phototherapy are the time commitment, potential increased risk of skin cancer and premature ageing.^24,25

Methotrexate

Oral methotrexate, generally 10 to 20 mg once weekly with a folic acid supplement, has been shown to improve psoriasis in about 60% of patients. With regular monitoring of blood count, liver function and kidney function, it is relatively safe and effective.

Methotrexate is a folate antagonist and is absolutely contraindicated in pregnancy. It is passed on in breast milk, and it affects spermatogenesis.

Methotrexate has many potential side effects, including gastrointestinal upset, mouth ulceration, and bone marrow suppression. It can be hepatotoxic, particularly in psoriatic patients with metabolic syndrome and associated steatotic liver disease. Permanent liver cirrhosis can occur with prolonged use and high cumulative doses. Clinicians need to be aware that this is not a set-and-forget treatment; it requires ongoing monitoring.

Acitretin

Acitretin is an orally administered retinoid that has some efficacy in palmoplantar psoriasis and erythrodermic psoriasis. At psoriatic effective doses, there are significant side effects including dryness of lips, eyes and skin with peeling palms and soles. There is often diffuse hair loss, especially in older women. It can cause impaired liver function; concomitant alcohol use is discouraged. It usually increases serum lipids. It is teratogenic and should not be used in women of childbearing age. Patients cannot donate blood for up to 3 years after stopping treatment as the drug and teratogenic metabolites can remain long term. State or territory health department authorisation may be required before prescribing acitretin.

Acitretin can be used in conjunction with phototherapy where it can enhance therapy especially in thick plaques.

Cyclosporin

Cyclosporin is a calcineurin inhibitor that is immunosuppressive. It has a limited role because it invariably causes renal impairment and hypertension with prolonged use, and psoriasis flares rapidly on stopping.

Cyclosporin is, however, very effective in rapidly clearing disease and can be used as a rescue treatment in patients with pustular or widespread disease while starting other agents with slower onset of action but better long-term safety. Monitoring of blood pressure and renal function is essential. It can be effective in treating acute psoriatic arthritis.

Apremilast

Apremilast is an oral phosphodiesterase-4 inhibitor with efficacy in both psoriasis and psoriatic arthritis.²⁶ About 30% of patients have a 75% improvement in psoriasis severity after 16 weeks. A small proportion of patients experience diarrhoea, and most describe softening of stools. It is particularly useful in patients with mild to moderate disease with psoriatic arthritis. There are no major contraindications, and patients do not require close haematological and biochemical monitoring.

Deucravacitinib

Deucravacitinib is a new oral tyrosine kinase 2 inhibitor.^27,28 Approximately 60% of patients will have a 75% improvement in severity of psoriasis over 16 weeks with peak efficacy around week 26. There is a good safety profile, but patients should be monitored for raised lipids and triglycerides. There is a small increase in acne and reactivation of herpes simplex infections and mouth ulceration. There are no data regarding use in pregnancy or in children.

Biologic medicines

The advent of injectable biologic therapies for psoriasis has resulted in the possibility of nearly disease-free activity, with very high efficacy in treatment of psoriatic disease. In clinical trials there were also reductions in depression and anxiety scores,²⁹ and large improvements in quality-of-life scores.³⁰ Effective treatment of psoriasis reduces the likelihood of psoriatic arthritis,³¹ and possibly other nonspecific comorbidities including metabolic syndrome.¹⁷

Biologic therapies are very costly and use in Australia is restricted to patients with PASI over 15, or more than 30% disease on face, palms and soles, as well as failure of 2 systemic therapies of at least 6 weeks duration each.

Tumour necrosis factor (TNF) alpha inhibitors

TNF alpha inhibitors (etanercept, adalimumab, infliximab and their biosimilars) are rarely used today as first-line therapies due to the availability of more effective drugs with higher psoriasis clearance rates and longer persistence of effect. However, they are often utilised in inpatient treatment for severe pustular psoriasis due to their rapidity of action. TNF alpha inhibitors are contraindicated in patients with active infections including tuberculosis, and have a higher rate of infection than the other biologic agents. They may worsen congestive cardiac failure. Although effective in clearing skin disease (up to 45% in infliximab), most patients show loss of efficacy over 2 to 3 years.³²

Anti-interleukin (anti-IL) therapies

Anti-IL-17 therapies (bimekizumab, ixekizumab, secukinumab), anti-IL-23 therapies (guselkumab, risankizumab, tildrakizumab) and anti-IL-12 and 23 therapies (ustekinumab) show strong efficacy (up to 88% patients with near-complete skin clearance) and long persistence.³³

Anti-IL-17 therapies have slightly higher rates of infection, particularly oral thrush, but have demonstrated better efficacy on joints, compared with anti-IL-23 therapies. Anti-IL-17 therapies are contraindicated in inflammatory bowel disease as they may catastrophically flare active disease.

Anti-IL-23 and anti-IL-12 and 23 therapies have few side effects (injection-site reaction is most common). They have some efficacy especially in peripheral psoriatic arthritis, and in higher doses are effective in inflammatory bowel disease.

Spesolimab is a new anti-IL-36 biologic therapy that has been approved in Australia for management of flares associated with generalised pustular psoriasis.

 

Conclusion

Psoriasis is a common multisystem inflammatory disease that has profound impact on patients. Although skin disease is the most common presentation, effective management of psoriasis requires identification and management of associated comorbidities. Topical therapies are useful in reducing the skin symptoms. Systemic treatments, including new biologic medicines, treat both skin and systemic disease.

This article was finalised on 22 May 2025

Conflicts of interest: Jonathan Chan has received speaker fees or conference registration fees from Johnson & Johnson (Janssen), Abbvie, Novartis, La Roche Posay, Sanofi and UCB Pharma, and has been on advisory boards for Abbvie, Bristol Myer-Squibb, Janssen and Novartis.

This article is peer reviewed.

 

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