More than skin deep

A clinical overview of the presentation, management and treatment options for plaque psoriasis

Introduction

Psoriasis is a chronic, inflammatory skin condition characterised by erythematous plaques covered with silver scales. Psoriasis is the most prevalent immune-mediated inflammatory disease, with a prevalence ranging from 0.2 to 4.8 per cent. The condition primarily affects the skin, but can also affect the joints and eyes. Approximately 10 per cent of patients experience eye involvement, while at least 15 per cent of patients with plaque psoriasis develop psoriatic arthritis.

There are several subtypes of psoriasis, including guttate, inverse, erythrodermic and pustular psoriasis, but plaque psoriasis is the most common subtype, accounting for approximately 90 per cent of cases. Plaque psoriasis is a chronic disease with no cure. Therefore, it requires long-term management and pharmacists play an important role in this. Pharmacists are important in identifying symptoms, managing medication, educating patients, addressing adverse effects and promoting adherence.^1,2

Overview

Plaque psoriasis has a multifactorial aetiology. It is an immune-mediated condition, but it is influenced by both genetic and environmental factors. T-cells and cytokines such as tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-17 and IL-23 are dysregulated, leading to hyperproliferation of keratinocytes and inflammation. Environmental factors that can increase the risk of psoriasis include trauma, certain medications, infection, metabolic factors, stress, alcohol and smoking.

Medications that can exacerbate psoriasis include calcium channel blockers, beta blockers, penicillin, terbinafine, lithium and captopril. Sunlight is often beneficial for psoriasis patients, but in a small number of cases, psoriasis may be worsened by sunlight. The development of plaques at the site of trauma is known as the Koebner phenomenon. Additionally, excessive scratching can trigger localised plaques.^1,2

Plaque psoriasis generally presents as erythematous plaques with well-defined edges, primarily affecting the scalp, knees, elbows and lower back. The plaques are typically symmetrical and are covered with silver-white scales. Plaque psoriasis tends to be persistent and follows a relapsing-remitting disease course, with periods of exacerbation and remission. It can vary in severity, ranging from mild cases to severe cases involving more than 10 per cent of the body surface area.

Many patients develop psoriatic arthritis, which is a debilitating and inflammatory joint condition associated with psoriasis. Metabolic comorbidities are often observed in association with psoriasis, which contribute to significant morbidity, including type 2 diabetes mellitus, cardiovascular disease, hypertension and metabolic syndrome. Psychological conditions, including depression and anxiety, are also common, leading to reduced quality of life and complicating disease management.^1,2

Diagnosis

The diagnosis of plaque psoriasis is generally clinical and it is made by observing the clinical morphology and site of lesions. A differential diagnosis may be used to rule out conditions such as eczema, seborrheic dermatitis and fungal infections, while a skin biopsy may be ordered to rule out other dermatologic conditions. Laboratory studies including a full blood count, hepatic and renal function tests, rheumatoid factor and uric acid levels may also be useful.

Plaque psoriasis can be classified based on the extent of body surface area involved. Mild psoriasis affects less than 3 per cent of body surface area, moderate psoriasis involves 3-to-10 per cent, and severe psoriasis affects more than 10 per cent. Patients with moderate-to-severe disease should be screened for other conditions such as inflammatory arthritis, hypertension, diabetes and cardiovascular disease.^1,2

Treatment

The management of plaque psoriasis is multifaceted, with different options based on the severity of disease, the presence of comorbidities, patient preference, and the response to previous therapies. There is no specific cure for plaque psoriasis, but there are several effective management options. The main treatment options include phototherapy, topical therapy, systemic therapy and biologics. A combination of different treatment options is often more effective than monotherapy. The objective of treatment is to reduce inflammation, delay skin cell turnover and improve quality of life for the patient.³

Topical treatment

Corticosteroids

Topical corticosteroids are a first-line treatment for plaque psoriasis. They are effective in reducing inflammation and itching, as well as slowing the production of skin cells. The mechanism of action of corticosteroids is vast and consists of anti-inflammatory and immunosuppressive effects.

The potency of corticosteroids can vary, with low-potency corticosteroids useful for sensitive areas. Medium-to-high potency corticosteroids can be used to treat most areas on the body, including the trunk and extremities. These are useful in areas of thick skin, particularly in psoriatic plaques. Hydrocortisone is an example of a low-potency corticosteroid; fluticasone and mometasone are medium-potency and clobetasol are examples of high-potency corticosteroids.

Potential adverse effects of topical corticosteroids are usually localised and include bruising and thinning of the skin. Systemic adverse effects are rare and include adrenal insufficiency, hypertension, mood swings, weight gain, hyperglycaemia, glaucoma and Cushing’s syndrome.^3,4

Vitamin D analogues

Vitamin D analogues are a first-line topical treatment option for plaque psoriasis. They work by inhibiting T lymphocyte activity and modulating keratinocyte proliferation and differentiation. This can reduce inflammation and slow the production of skin cells. Calcipotriol is an example of a commonly used vitamin D analogue. It is effective in the treatment of mild plaque psoriasis. Calcipotriol is generally well tolerated when used correctly, and adverse effects can include local skin irritation, which usually resolves within a week. Hypercalcemia is a possible adverse effect of excessive use. Calcipotriol can be used as monotherapy or in combination with topical corticosteroids. It is licensed for use in Ireland in combination with betamethasone. Combination therapy is more effective than monotherapy and improves compliance in patients with chronic plaque psoriasis.³

Emollients and keratolytic agents

Emollients and keratolytic agents can play an important role in treating plaque psoriasis when used appropriately. Emollients and moisturisers can help improve barrier function and retain hydration of the stratum corneum.

Topical keratolytic agents, such as lactic acid, salicylic acid, urea and coal tar help to loosen and exfoliate excess skin cells. Salicylic acid can be used in combination with a topical corticosteroid to treat plaques with thicker scales and allow better penetration of medication. However, salicylic acid can reduce the efficacy of vitamin D analogues and shouldn’t be used in combination therapy.⁴

Phototherapy

Phototherapy can be an effective treatment option for moderate-to-severe plaque psoriasis or in patients who are unresponsive to topical therapy. Phototherapy is available as psoralen plus UVA (PUVA), broadband UVB and narrowband UVB (NBUVB). While phototherapy is effective for treating plaque psoriasis, it may be more effective in treating guttate psoriasis. Phototherapy has a relatively safe profile and can be used in children and pregnant women. Adverse effects can include the formation of cataracts, gastrointestinal discomfort and carcinogenic effects particularly with PUVA.³

Systemic treatment

Methotrexate

Methotrexate is a folate antagonist and reduces inflammation and the proliferation of skin cells. Methotrexate can be effective against severe plaque psoriasis or if the patient does not respond to topical therapy. It is often used to treat psoriatic arthritis. It reduces activity of the immune system by multiple mechanisms, including repressing T-cell activation, down-regulating B-cells and increasing the sensitivity of activated CD-95 T cells.

Methotrexate is administered once weekly, while folic acid can be co-administered to reduce adverse effects. The most common adverse effects of methotrexate are gastrointestinal and include nausea, vomiting, mucosal ulcers and reduced appetite. There are many potential serious adverse effects, including bone marrow suppression, hepatotoxicity, renal failure, increased risk of infection, malignancy and teratogenicity. Methotrexate can be administered orally, but subcutaneous injection increases bioavailability and reduces gastrointestinal adverse effects.^3,5

Calcineurin inhibitors

Ciclosporin is a calcineurin inhibitor and is used in the treatment of severe psoriasis in patients where other treatment options have failed or are contraindicated. It exerts its mechanism of action by inhibiting the synthesis of interleukins and thereby reducing the activation of T-cells. It is generally administered orally every 12 hours for the treatment of psoriasis. It has the advantages of a quicker onset of action and less myelosuppression and hepatotoxicity than methotrexate. However, potential adverse effects of ciclosporin include nephrotoxicity, hypertension, hyperkalaemia, dyslipidaemia, increased risk of infection and increased risk of lymphoma.^3,6

Retinoids

Acitretin is a synthetic oral retinoid that is effective in treating severe plaque psoriasis. It works by regulating skin cell growth and proliferation. It can be used as monotherapy or as an adjunct to other treatment options to enhance efficacy, lower doses and reduce adverse effects. Acitretin should be administered orally after food once daily. It has significant teratogenic potential and therefore, should be avoided in pregnant women and women of childbearing potential unless all conditions of the pregnancy prevention programme are met. The most common adverse effects of acitretin include photosensitivity, gastrointestinal discomfort, arthralgia and dryness of the skin, lips, nostrils and eyes.⁷

Apremilast 

Apremilast is used to treat moderate-to-severe plaque psoriasis in patients who have failed to respond to or are intolerant of other systemic treatment options. Apremilast works by selective inhibition of the phosphodiesterase 4 (PDE4) enzyme and inhibition of the production of TNF-alpha from rheumatoid synovial cells. It is administered orally as part of a twice daily dosing schedule. Apremilast is contraindicated in pregnancy, and women of childbearing potential should use an effective method of contraception during treatment. Gastrointestinal adverse effects, including nausea and diarrhoea, are the most common adverse effects during the early stages of treatment and can lead to weight loss. In rarer cases, apremilast can also affect mood and cause suicidal ideation.⁸

Biologics

Biologic therapies have been used in recent years for the treatment of moderate-to-severe plaque psoriasis. Biologics are immunomodulators that target specific components of the body’s immune system involved in the pathogenesis of plaque psoriasis. They exert their mechanism of action by targeting pro-inflammatory cytokines.

Adalimumab, etanercept, infliximab and certolizumab work by inactivating TNF-alpha. Secukinumab and ixekizumab work by blocking IL-17, while risankizumab and guselkumab work by inhibiting IL-23. Ustekinumab works by blocking IL -12 and IL-23. Biologics are very effective in treating plaque psoriasis and can improve symptoms within three-to-four months.

The choice of biologic should be made by a specialist in the area and tailored to the needs of each individual patient. The choice of biologic is influenced by the disease state, outcome of previous treatments, comorbidities, dosing frequency, and lifestyle considerations. Biologics are generally administered subcutaneously using syringes or pre-filled pens, or they may be administered as infusions. The dosing schedule is generally weekly, biweekly, monthly or bimonthly. Patients should be screened for tuberculosis and hepatitis before initiating treatment.

There are many potential adverse effects associated with biologic therapy. Some relatively mild adverse effects can include fever, muscle aches, fatigue, loss of appetite, nausea, vomiting, diarrhoea and irritation at the site of injection. Biologics also increase the risk of infection, as they reduce the activity of the immune system. Finally, biologics can also increase the risk of malignancies including Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, leukaemia and non-melanoma skin cancer.^8,9

Janus kinase inhibitors

Janus kinase (JAK) inhibitors are small molecules used in the targeted treatment of moderate-to-severe plaque psoriasis. Tofacitinib and upadacitinib are examples of JAK inhibitors used to treat psoriasis. They work by inhibiting JAK enzymes involved in immune reactions in certain immune-mediated inflammatory diseases. Serious adverse effects associated with the use of JAK inhibitors include infection, malignancy, thrombosis, tuberculosis and cardiovascular events.^10,11

Role of the pharmacist 

Pharmacists are uniquely positioned in the healthcare setting to play an important role in the management of plaque psoriasis. Pharmacists have expertise in medication management, patient counselling, promoting medication adherence and reducing adverse effects. Pharmacists are involved in counselling patients on their medication. This includes advising on how to apply topical treatments, how to use multiple therapies concurrently and injection techniques for parenteral drugs. Furthermore, pharmacists can educate patients on how to reduce adverse effects, as well as monitor for adverse effects associated with treatment. Plaque psoriasis is a chronic condition and medication adherence is important for symptom control, which pharmacists play a crucial role in. Pharmacists can also educate and empower patients with knowledge to manage this condition.

Finally, pharmacists are an important component of the multidisciplinary team that manages this chronic condition and helps improve clinical outcomes and quality of life for patients with plaque psoriasis.