Skin: Psoriasis treatments and dietary changes

Introduction

Psoriasis is a chronic inflammatory dermatosis characterized by erythematous, scaly plaques that frequently involve extensor surfaces, scalp, and intertriginous zones. The disease exhibits a complex interplay between genetic predisposition, immune dysregulation, and environmental triggers. Historically, descriptions of psoriatic lesions date back to ancient Egyptian and Greek manuscripts, yet systematic therapeutic approaches only emerged in the twentieth century with the advent of topical corticosteroids and phototherapy. The escalating prevalence of psoriasis, particularly in industrialised societies, underscores its significance in contemporary pharmacology and clinical dermatology. Understanding both pharmacotherapeutic modalities and adjunctive dietary modifications is therefore essential for future clinicians and pharmacists who will manage this multifactorial condition.

Learning objectives for this chapter are:

• To delineate the pathophysiological mechanisms underlying psoriatic skin inflammation.
• To evaluate the spectrum of pharmacologic agents, including conventional systemic drugs, biologics, and emerging small molecules, and to examine their mechanisms of action.
• To analyse the evidence supporting dietary interventions and identify nutritional factors that may influence disease activity.
• To integrate pharmacologic and nutritional strategies into patient-centred care plans, recognising potential drug–nutrient interactions.
• To apply clinical reasoning to case scenarios involving complex therapeutic decisions in psoriasis management.

Fundamental Principles

Core Concepts and Definitions

Psoriasis is defined as a relapsing, immune-mediated skin disorder characterised by hyperproliferation of keratinocytes and dermal angiogenesis. It is classified clinically into plaque, guttate, inverse, pustular, erythrodermic, and nail variants, each presenting distinct therapeutic challenges. The disease burden is quantified using indices such as the Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA), which provide standardized metrics for evaluating treatment response.

Theoretical Foundations

The immunopathogenesis of psoriasis centres on the innate and adaptive immune system. Dendritic cells release interleukin (IL)-23, which polarises T helper 17 (Th17) cells to produce IL‑17A, IL‑17F, IL‑22, and IL‑21. These cytokines act on keratinocytes, driving proliferation and the release of antimicrobial peptides, which further amplify the inflammatory cascade. The IL‑12/IL‑23 axis and tumour necrosis factor‑α (TNF‑α) are additional critical mediators, forming the therapeutic targets of many biologic agents. The synergy between cytokines and the epidermal barrier leads to the characteristic plaque morphology.

Key Terminology

• Topical agents – medications applied directly to the skin, including corticosteroids, vitamin D analogues, and calcineurin inhibitors.
• Phototherapy – controlled exposure to ultraviolet (UV) radiation, primarily UVA or UVB, to modulate skin immune responses.
• Systemic therapy – oral or parenteral agents that exert effects throughout the body, such as methotrexate, cyclosporine, and biologics.
• Biologic response modifiers – monoclonal or fusion proteins that selectively inhibit cytokines or cellular receptors.
• Small‑molecule inhibitors – oral agents that target intracellular signalling pathways, including Janus kinase (JAK) inhibitors.
• Dietary intervention – modification of macronutrient or micronutrient intake, or use of supplements, aimed at influencing disease activity.

Detailed Explanation

Pharmacologic Therapies

Topical corticosteroids remain the first‑line treatment for mild to moderate plaque psoriasis. Their anti‑inflammatory effect is mediated through genomic and non‑genomic pathways, reducing cytokine transcription and stabilising mast cells. Potency grading (from class I to VII) guides clinical selection, balancing efficacy against the risk of skin atrophy. Adjunctive topical vitamin D analogues, such as calcipotriol, synergise with steroids by inhibiting keratinocyte proliferation and modulating immune responses.

Phototherapy, particularly narrow‑band UVB (311 nm), is effective for extensive disease. The mechanism involves DNA photoadduct formation that induces apoptosis of pathogenic T cells and suppression of cytokine production. UVA‑1 phototherapy penetrates deeper dermal layers, potentially benefitting psoriatic arthropathy. Combined PUVA (psoralen plus UVA) therapy enhances efficacy but increases carcinogenic risk, warranting careful patient selection.

Systemic agents are reserved for moderate to severe disease or when topical options fail. Methotrexate, a folate antagonist, inhibits dihydrofolate reductase, reducing lymphocyte proliferation. Cyclosporine, a calcineurin inhibitor, suppresses IL‑2 transcription, thereby dampening T‑cell activation. Acitretin, an oral retinoid, normalises keratinocyte differentiation and exerts anti‑inflammatory effects via retinoic acid receptors. These agents require routine monitoring for hepatotoxicity, myelosuppression, and nephrotoxicity.

Biologic Therapies

Biologics target specific cytokines implicated in psoriasis pathogenesis. Tumour necrosis factor‑α inhibitors (adalimumab, etanercept, infliximab, golimumab, certolizumab) neutralise TNF‑α, a pivotal pro‑inflammatory mediator. Interleukin‑12/23 inhibitors (ustekinumab) bind the p40 subunit shared by IL‑12 and IL‑23, thereby attenuating Th1 and Th17 pathways. IL‑17 inhibitors (secukinumab, ixekizumab, brodalumab) block IL‑17A or its receptor, directly interrupting keratinocyte activation. IL‑23 inhibitors (guselkumab, tildrakizumab, risankizumab) bind the p19 subunit of IL‑23, offering a more selective approach and potentially superior safety profiles.

These agents are administered via subcutaneous injection or intravenous infusion, depending on the formulation. Pharmacokinetic parameters such as C_max, t_1/2, and clearance dictate dosing intervals. For example, the average clearance of ustekinumab is approximately 0.75 L day⁻¹, resulting in a half‑life of 3–4 weeks. Immune modulation may lead to reactivation of latent infections, necessitating screening for tuberculosis and hepatitis B prior to initiation.

Small‑Molecule Inhibitors

Janus kinase (JAK) inhibitors, including upadacitinib, abrocitinib, and tofacitinib, block intracellular signalling downstream of multiple cytokine receptors, thereby reducing inflammatory responses. These oral agents offer rapid onset of action, with clinical improvement observed within weeks. Dose‑response relationships are characterised by a sigmoidal curve, where efficacy increases with dose until a plateau is reached. Adverse effects such as thrombosis, lipid alterations, and infection risk warrant monitoring of coagulation parameters and lipid panels.

Dietary Interventions

Emerging evidence suggests that dietary composition can modulate systemic inflammation and thus influence psoriasis severity. The Mediterranean diet, rich in monounsaturated fatty acids, omega‑3 polyunsaturated fatty acids, fruits, and vegetables, has been associated with reduced PASI scores in observational studies. The anti‑oxidant burden of such a diet may attenuate oxidative stress, a recognised contributor to psoriatic inflammation.

Specific nutrients appear to exert immunomodulatory effects. Omega‑3 fatty acids (EPA and DHA) compete with arachidonic acid for cyclooxygenase and lipoxygenase enzymes, reducing pro‑inflammatory eicosanoid production. Vitamin D, obtainable from sunlight or diet, modulates T‑cell differentiation and keratinocyte proliferation. Zinc deficiency is linked to impaired wound healing and may exacerbate skin lesions; supplementation has shown modest benefits in controlled trials.

Conversely, high glycaemic load diets may promote insulin resistance, which is associated with increased psoriatic activity. Alcohol consumption, particularly beer, has been implicated in triggering relapses. Weight reduction in obese patients often yields significant clinical improvement, possibly through reduced adipokine secretion (e.g., leptin, resistin) and lower systemic cytokine levels.

Mathematical Relationships and Models

Pharmacodynamic modelling of biologic agents frequently employs the E_max model:
C(t) = C₀ × e⁻ᵏᵗ, where C(t) denotes drug concentration at time t, C₀ initial concentration, and k elimination constant. The area under the concentration–time curve (AUC) is calculated as Dose ÷ Clearance. For JAK inhibitors, the relationship between dose (D) and effect (E) can be expressed as E = E_max × D ÷ (EC₅₀ + D), where EC₅₀ is the concentration achieving 50 % of maximal effect. These models assist in optimizing dosing regimens to achieve therapeutic thresholds while minimising adverse events.

Factors Affecting Treatment Response

Genetic polymorphisms in HLA‑C*06:02, IL‑23R, and TYK2 genes influence disease susceptibility and therapeutic response. Pharmacogenomic screening may predict responsiveness to biologics, particularly IL‑17 or IL‑23 inhibitors. Comorbidities such as psoriatic arthritis, metabolic syndrome, and depression affect treatment selection and adherence. Concomitant medications, including biologic‑related immunosuppressants and anticoagulants, may interact with systemic agents, altering efficacy or safety profiles. Lifestyle factors—sleep quality, stress, smoking, and alcohol use—also modulate disease activity and medication effectiveness.

Clinical Significance

Relevance to Drug Therapy

Understanding the mechanistic basis of each pharmacologic class allows clinicians to tailor therapy based on disease severity, comorbidities, and patient preferences. For example, biologics are preferred for moderate to severe disease with systemic involvement, whereas topical agents suffice for limited plaques. The selection of a specific biologic may be guided by safety considerations, such as infection risk or malignancy surveillance. Small‑molecule JAK inhibitors provide an oral alternative for patients contraindicated for biologics or seeking rapid symptom relief.

Practical Applications

Therapeutic decision‑making often requires balancing efficacy, safety, cost, and patient adherence. Monitoring protocols for systemic agents include liver function tests, complete blood counts, and renal panels, typically performed at baseline and at defined intervals. For biologics, screening for latent infections and monitoring for infusion reactions are essential. Dietary counselling should be incorporated into the treatment plan, focusing on weight management, reduced alcohol intake, and increased consumption of anti‑inflammatory foods.

Clinical Examples

<pIn a patient with severe plaque psoriasis and comorbid psoriatic arthritis, a TNF‑α inhibitor may be chosen for dual efficacy. If concomitant hepatitis B infection is present, an IL‑23 inhibitor may be preferable due to a lower risk of viral reactivation. A patient with a smoking history and cardiovascular disease may benefit from an IL‑17 inhibitor, given the favourable cardiovascular safety profile reported in phase III trials. In individuals with obesity, weight‑loss interventions combined with topical therapy can lead to substantial PASI reductions.

Clinical Applications/Examples

Case Scenario 1: Moderate Plaque Psoriasis in a Middle‑Aged Female

A 45‑year‑old woman presents with erythematous plaques covering 15 % of body surface (BSA). She reports minimal joint pain and no systemic symptoms. Current medications include intermittent topical corticosteroids. Baseline laboratory workup is normal. PASI score is 9.2. Treatment recommendation: initiate narrow‑band UVB phototherapy thrice weekly combined with a medium‑potency topical corticosteroid applied twice daily. Dietary counselling: adopt a Mediterranean‑style diet, reduce processed foods, and limit alcohol consumption. Follow‑up in 12 weeks with reassessment of PASI and BSA.

Case Scenario 2: Severe Psoriasis with Psoriatic Arthritis in an Elderly Male

A 68‑year‑old male exhibits extensive plaques covering 35 % BSA and joint swelling in the knees and ankles. He has a history of hypertension and type 2 diabetes. Baseline labs show elevated C‑reactive protein (CRP). PASI score is 18.5. Treatment recommendation: start an IL‑23 inhibitor (risankizumab) subcutaneously every 12 weeks, given its favourable metabolic profile. Continue metformin and antihypertensives as per guidelines. Initiate a structured weight‑loss program with nutritional support, aiming for a 5 % reduction in body weight over 6 months. Monitor lipid panel and blood glucose at each visit.

Case Scenario 3: Psoriasis in a Patient with Chronic Viral Hepatitis

A 52‑year‑old woman with chronic hepatitis B presents with moderate plaque psoriasis involving 20 % BSA. She is currently on entecavir. PASI score is 12.3. Treatment recommendation: avoid TNF‑α inhibitors due to risk of viral reactivation. Consider an IL‑17 inhibitor (secukinumab) with careful monitoring of liver enzymes. Reassess hepatitis B viral load and liver function tests at baseline and every 3 months during biologic therapy.

Problem‑Solving Approach to Drug‑Nutrient Interactions

1. Identify the pharmacologic agent and its metabolic pathway (e.g., CYP450 isoforms).
2. Determine dietary components that influence the same pathway (e.g., grapefruit juice inhibits CYP3A4).
3. Evaluate the clinical significance of the interaction (e.g., increased drug exposure leading to toxicity).
4. Implement dietary modifications or alternative therapies to mitigate risk.
5. Monitor drug levels or clinical response as appropriate.

Summary/Key Points

• Psoriasis involves a complex immune dysregulation centred on the IL‑23/Th17 axis and TNF‑α signalling.
• Topical corticosteroids and vitamin D analogues remain cornerstone treatments for mild disease; phototherapy offers a non‑pharmacologic alternative.
• Systemic agents (methotrexate, cyclosporine, acitretin) and biologics (TNF‑α, IL‑12/23, IL‑17, IL‑23 inhibitors) provide targeted therapeutic options for moderate to severe disease.
• Small‑molecule JAK inhibitors represent an emerging oral therapy with rapid onset of action.
• Dietary interventions, particularly the Mediterranean diet and omega‑3 supplementation, may reduce systemic inflammation and improve clinical outcomes.
• Weight reduction, alcohol moderation, and smoking cessation are integral components of comprehensive care.
• Pharmacokinetic and pharmacodynamic modelling facilitates dose optimisation and risk assessment.
• Genetic, comorbid, and lifestyle factors influence treatment response and should be incorporated into individualized management plans.
• Regular monitoring of laboratory parameters, infection screening, and patient education are essential to maximise efficacy and safety.

By integrating pharmacologic therapy with evidence‑based dietary strategies, clinicians can enhance disease control, minimise adverse events, and improve quality of life for patients with psoriasis.

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