Skin Conditions: Eczema, Psoriasis, and Acne

1. Introduction

The integumentary system, comprising the skin and its appendages, serves as the primary physical barrier against environmental insults. Disorders of this system, including eczema, psoriasis, and acne, represent a significant proportion of global disease burden, with profound implications for patient quality of life, mental health, and healthcare economics. These conditions, while distinct in their underlying pathophysiology and clinical manifestations, share common ground as chronic, relapsing inflammatory disorders that are frequently managed in both primary and secondary care settings. Their management often requires a nuanced understanding of skin biology, immunology, and pharmacology, bridging fundamental science with clinical therapeutics.

The historical understanding of these dermatoses has evolved from humoral theories to modern molecular biology. Psoriasis, for instance, was historically conflated with leprosy, while the distinction between endogenous eczema and contact dermatitis was a later development. The 20th and 21st centuries have seen a paradigm shift with the elucidation of immune pathways, such as the role of the interleukin-23/T-helper 17 axis in psoriasis and the identification of Cutibacterium acnes in acne pathogenesis, leading to targeted biologic and small-molecule therapies.

From a pharmacological perspective, these conditions are paramount. They exemplify the principles of topical drug delivery, the challenges of percutaneous absorption, and the strategic escalation from topical to systemic therapy. The armamentarium includes agents ranging from simple emollients and antiseptics to sophisticated monoclonal antibodies and retinoids, providing a rich context for studying drug mechanisms, therapeutic indices, and adverse effect profiles. The chronic nature of these diseases also highlights the importance of adherence, patient education, and long-term safety monitoring in pharmacotherapy.

Learning Objectives

• Differentiate the core pathophysiological mechanisms underlying atopic eczema, plaque psoriasis, and acne vulgaris, with emphasis on key immune cells, cytokines, and structural changes.
• Analyze the pharmacological rationale, mechanisms of action, and clinical applications of first-line and advanced therapies for each condition, including topical corticosteroids, calcineurin inhibitors, vitamin D analogs, retinoids, and biologic agents.
• Evaluate the risk-benefit profiles of common systemic treatments, such as methotrexate, cyclosporine, and isotretinoin, including their monitoring requirements and contraindications.
• Formulate a structured approach to treatment selection and escalation based on disease severity, morphology, and patient-specific factors.
• Identify common therapeutic challenges and complications, such as topical steroid withdrawal, antimicrobial resistance in acne, and the management of psoriatic comorbidities.

2. Fundamental Principles

Effective management of inflammatory skin diseases rests upon a foundation of core dermatological and pharmacological principles. A clear grasp of skin anatomy, the inflammatory cascade, and the determinants of topical drug efficacy is essential.

Core Concepts and Definitions

Eczema and Dermatitis are often used interchangeably to describe a pattern of inflammatory skin reaction characterized clinically by erythema, edema, vesiculation, and pruritus, and histologically by spongiosis (intercellular edema). Atopic Dermatitis (AD) is a specific, chronic, relapsing form of eczema with a strong genetic predisposition, associated with personal or familial atopy (asthma, allergic rhinitis).

Psoriasis is a chronic, immune-mediated, papulosquamous disorder defined by well-demarcated, erythematous plaques with adherent silvery scale. Its hallmark histopathological features include epidermal hyperplasia (acanthosis), parakeratosis (retention of nuclei in the stratum corneum), elongated rete ridges, and a neutrophilic infiltrate forming Munro’s microabscesses.

Acne Vulgaris is a chronic inflammatory disorder of the pilosebaceous unit, clinically presenting with a polymorphic mix of comedones (open and closed), papules, pustules, nodules, and cysts. Its pathogenesis is multifactorial, classically described by the interplay of four key factors: follicular hyperkeratinization, increased sebum production, colonization by Cutibacterium acnes, and inflammation.

Theoretical Foundations

The pathophysiology of these conditions is underpinned by dysregulated interactions between the skin barrier, the innate and adaptive immune systems, and, in the case of acne, the cutaneous microbiome. The “outside-inside” and “inside-outside” models in atopic dermatitis illustrate this interplay: barrier dysfunction allows for allergen penetration and immune activation (outside-inside), while a primary immune dysregulation drives inflammation that secondarily damages the barrier (inside-outside). In psoriasis, the paradigm is one of a self-perpetuating inflammatory loop, where activated immune cells (e.g., dendritic cells, T-helper 1 and 17 cells) release cytokines (e.g., TNF-α, IL-17, IL-23) that drive keratinocyte hyperproliferation, which in turn releases more inflammatory mediators. Acne pathogenesis represents a disruption of pilosebaceous unit homeostasis, where androgen-driven sebum production and abnormal follicular keratinization create an anaerobic, lipid-rich environment conducive to C. acnes proliferation and subsequent inflammation.

Key Terminology

• Spongiosis: Intercellular edema within the epidermis, a histologic hallmark of eczema.
• Acanthosis: Thickening of the stratum spinosum layer of the epidermis, seen in psoriasis and chronic eczema.
• Parakeratosis: Retention of nuclei in the stratum corneum, characteristic of psoriasis.
• Comedogenesis: The process of comedone formation, initiated by hyperkeratinization of the follicular infundibulum.
• Percutaneous Absorption: The process by which topically applied drugs penetrate the stratum corneum and reach target sites in the skin or systemic circulation. Governed by factors like drug lipophilicity, vehicle formulation, and skin integrity.
• Vehicle: The base (cream, ointment, gel, lotion, foam) in which a drug is delivered. Influences drug release, skin feel, and patient adherence.

3. Detailed Explanation

An in-depth exploration of each condition reveals distinct yet complex pathogenic networks. Understanding these mechanisms is critical for rational therapeutic intervention.

Pathophysiology of Atopic Eczema

The pathogenesis of atopic eczema is multifactorial, involving a complex interplay of genetic, immunologic, and environmental factors. A primary defect in the epidermal barrier is central, most commonly due to loss-of-function mutations in the filaggrin gene (FLG). Filaggrin is a key protein essential for the formation of the natural moisturizing factor and the cornified cell envelope. Its deficiency leads to increased transepidermal water loss, dry skin (xerosis), and impaired barrier function. This defective barrier facilitates the penetration of allergens, microbes, and irritants.

This breach triggers a biphasic immune response. In the acute phase, there is a predominant T-helper 2 (Th2) cell activation, with elevated cytokines such as interleukin-4 (IL-4), IL-13, and IL-31. IL-4 and IL-13 promote B-cell class switching to IgE production, while IL-31 is a potent pruritogen. In chronic lesions, the immune response shifts to a more Th1- and Th22-dominated profile, with increased IFN-γ, IL-12, and IL-22. IL-22 contributes to epidermal hyperplasia and acanthosis. The itch-scratch cycle is a critical amplifier of disease; scratching further damages the barrier and releases alarmins like thymic stromal lymphopoietin (TSLP) from keratinocytes, which potently activates dendritic cells and perpetuates inflammation.

Pathophysiology of Plaque Psoriasis

Psoriasis is now recognized as a systemic immune-mediated disorder with primary cutaneous manifestations. The inflammatory cascade is initiated when an unknown trigger (e.g., trauma, infection, stress) activates plasmacytoid dendritic cells to produce interferon-α. This leads to the maturation of myeloid dendritic cells, which migrate to draining lymph nodes and present antigen to naïve T cells, polarizing them into effector subsets, primarily Th1, Th17, and Th22 cells.

These activated T cells enter the circulation and home to the dermis. Th17 cells, in particular, are pivotal, producing IL-17A, IL-17F, and IL-22. IL-23, produced by dendritic cells and macrophages, is essential for the maintenance and survival of Th17 cells. The cytokine milieu (TNF-α, IFN-γ, IL-17, IL-22) acts on keratinocytes, stimulating hyperproliferation, altered differentiation, and the production of antimicrobial peptides and chemokines (e.g., CXCL8, CCL20). This results in the characteristic clinical and histological features: shortened epidermal turnover time from ≈28 days to 3–4 days, leading to immature keratinocytes, retained nuclei (parakeratosis), and poor cohesion (scale). The dermal vasculature becomes dilated and tortuous, contributing to the bright erythema.

Pathophysiology of Acne Vulgaris

Acne vulgaris originates in the pilosebaceous unit. The sequence of pathogenic events is often described as follows. First, under the influence of androgens (e.g., dihydrotestosterone), sebaceous glands undergo hypertrophy and produce excess sebum, a lipid-rich medium. Concurrently, abnormal follicular keratinization occurs in the infundibulum, where keratinocytes become hyper-adherent, leading to the formation of a microcomedone—the primary subclinical lesion. This plug traps sebum and creates an anaerobic, nutrient-rich environment.

This environment favors the proliferation of Cutibacterium acnes, a commensal Gram-positive bacterium. C. acnes does not merely infect but actively contributes to inflammation by activating the innate immune system via multiple pathways. It binds to Toll-like receptor 2 (TLR-2) on monocytes and keratinocytes, stimulating the release of pro-inflammatory cytokines such as IL-1α, IL-8, and TNF-α. C. acnes also produces lipases that break down sebum triglycerides into free fatty acids, which are themselves pro-inflammatory. This inflammatory cascade leads to the recruitment of neutrophils, resulting in the formation of papules and pustules. In severe nodulocystic acne, the follicular wall ruptures, spilling its contents into the dermis and provoking a robust, granulomatous foreign-body reaction.

Factors Affecting Disease Expression and Therapy

The presentation and course of these dermatoses are modulated by numerous endogenous and exogenous factors.

4. Clinical Significance

The translation of pathophysiological understanding into therapeutic strategy is the cornerstone of clinical dermatology and dermatopharmacology. Each class of drug targets specific nodes within the disease pathways.

Relevance to Drug Therapy in Eczema

Therapeutic strategies for atopic eczema are directed at repairing the barrier, suppressing inflammation, and managing pruritus. Emollients are foundational, acting as passive barrier repair devices, reducing transepidermal water loss and diminishing the need for anti-inflammatory therapy. Topical corticosteroids (TCS) remain first-line for active inflammation; their potency is tailored to disease severity and body site. They act via genomic mechanisms to suppress the transcription of multiple pro-inflammatory genes. Topical calcineurin inhibitors (TCIs) such as tacrolimus and pimecrolimus offer a steroid-sparing option, particularly for sensitive areas (face, eyelids). They inhibit calcineurin, blocking T-cell activation and the production of Th1 and Th2 cytokines. For moderate-to-severe disease, systemic immunosuppressants like cyclosporine (a calcineurin inhibitor), methotrexate, and azathioprine are used. The most significant recent advance is the advent of biologic therapies targeting key cytokines. Dupliumab, a monoclonal antibody against the IL-4 receptor alpha subunit, inhibits signaling of both IL-4 and IL-13, effectively breaking the Th2 axis and demonstrating high efficacy with a favorable safety profile.

Relevance to Drug Therapy in Psoriasis

Psoriasis treatment follows a stepwise approach, often conceptualized as a therapeutic ladder. Topical therapies are first-line for limited disease. Vitamin D analogs (calcipotriol, calcitriol) normalize keratinocyte differentiation and inhibit proliferation, while also having immunomodulatory effects. They are frequently combined with TCS for synergistic effect. For more extensive or refractory disease, phototherapy (narrowband UVB, PUVA) and traditional systemic agents are employed. Methotrexate, a folate antagonist, inhibits lymphocyte proliferation. Acitretin, an oral retinoid, normalizes keratinocyte differentiation. Cyclosporine provides rapid immunosuppression by inhibiting T-cell activation. The landscape has been revolutionized by biologic and targeted synthetic therapies. These are often categorized by their target: TNF-α inhibitors (adalimumab, infliximab, etanercept), IL-12/23 inhibitors (ustekinumab), IL-17 inhibitors (secukinumab, ixekizumab, brodalumab), and IL-23 inhibitors (guselkumab, risankizumab, tildrakizumab). Oral small molecules like apremilast (a PDE4 inhibitor) and deucravacitinib (a TYK2 inhibitor) offer systemic options with different safety profiles.

Relevance to Drug Therapy in Acne

Acne management is tailored to the predominant lesion type and severity, targeting the pathogenic pillars. Topical retinoids (tretinoin, adapalene, tazarotene) are cornerstone treatments for comedonal acne. They normalize follicular keratinization, prevent microcomedone formation, and exhibit anti-inflammatory properties. Topical antimicrobials like benzoyl peroxide (BPO) and antibiotics (clindamycin, erythromycin) target C. acnes. BPO is bactericidal via free radical formation and is not associated with resistance, making it an ideal combination partner. To mitigate antibiotic resistance, topical antibiotics are almost always prescribed in combination with BPO or a retinoid. For moderate inflammatory acne, oral antibiotics (tetracyclines like doxycycline, minocycline) are used for their anti-inflammatory and antimicrobial effects, typically for a limited duration (≈3–4 months). Hormonal therapies (combined oral contraceptives, spironolactone) are effective in females by reducing androgen-driven sebum production. For severe, nodulocystic, or scarring acne, oral isotretinoin is the definitive treatment. It is a retinoid that profoundly reduces sebum production (by up to 90%), normalizes follicular keratinization, and has anti-inflammatory effects, often inducing long-term remission.

5. Clinical Applications and Examples

The integration of pharmacological principles into clinical decision-making is best illustrated through structured approaches and case-based scenarios.

Case Scenario 1: Moderate Atopic Eczema in an Adult

A 28-year-old female presents with a 6-month history of worsening eczema affecting the flexures of her elbows and knees, neck, and face. The skin is erythematous, lichenified, and excoriated, with significant pruritus disrupting sleep. She has a history of childhood eczema and allergic rhinitis. Previous use of an over-the-counter hydrocortisone 1% cream provided minimal relief.

Treatment Approach: The foundation is aggressive, frequent emollient use. For active lesions, a medium-potency topical corticosteroid (e.g., betamethasone valerate 0.1% cream) would be prescribed for application once daily to body plaques until clearance (typically 1–2 weeks), followed by weekend-only use or cessation. For the face, a low-potency steroid (hydrocortisone butyrate 0.1%) or a topical calcineurin inhibitor (tacrolimus 0.03% ointment) would be recommended to minimize risks of atrophy and telangiectasia. Patient education on the “finger-tip unit” for dosing and the difference between ointments (better for dry, lichenified areas) and creams (better for weeping or intertriginous areas) is crucial. If control is inadequate with optimized topical therapy, phototherapy or a systemic agent like dupilumab could be considered.

Case Scenario 2: New-Onset Plaque Psoriasis

A 45-year-old male presents with thick, scaly, erythematous plaques on his elbows, knees, and lower back, covering approximately 15% of his body surface area (BSA). He reports associated mild joint stiffness in his fingers. He is otherwise healthy but has a body mass index of 32 kg/m².

Treatment Approach: Given the extent (>10% BSA) and impact, treatment beyond topical therapy alone is warranted. A first step may be a course of narrowband UVB phototherapy. Alternatively, initiation of a traditional systemic agent like methotrexate could be considered, given its efficacy for both skin and joint symptoms. Baseline investigations (full blood count, liver and renal function, hepatitis serology) are required, with ongoing monitoring. The presence of obesity is a consideration, as it can reduce the efficacy of some systemic therapies. If methotrexate is contraindicated or ineffective, or if psoriatic arthritis is confirmed, a biologic agent would be a strong candidate. An IL-17 or IL-23 inhibitor might be selected for high skin clearance rates. The choice is influenced by comorbidities, patient preference (injection frequency), and payer restrictions.

Case Scenario 3: Severe Nodulocystic Acne

A 19-year-old male presents with widespread inflammatory papules, pustules, and several painful, deep nodules on his face, chest, and back. He has scarring from previous lesions. Multiple courses of oral doxycycline and topical clindamycin/BPO gel over the past two years have provided only temporary improvement.

Treatment Approach: This presentation indicates severe, scarring acne that has proven resistant to conventional antibiotic therapy. The most appropriate intervention is oral isotretinoin. A starting dose of ≈0.5 mg/kg/day would be typical, with the goal of achieving a cumulative dose of 120–150 mg/kg over a 5–6 month course to minimize relapse. Mandatory pre-treatment counseling includes the teratogenicity risk (requiring two forms of contraception in females), and common side effects like cheilitis, xerosis, myalgia, and hypertriglyceridemia. Baseline and monthly monitoring of lipids and liver function tests is required. Concomitant use of topical therapy is usually stopped, and aggressive moisturization is advised. The profound reduction in sebum production usually leads to dramatic improvement and often long-term remission.

Problem-Solving: Addressing Therapeutic Challenges

• Topical Steroid Phobia/Withdrawal: Patient fear of TCS can lead to under-treatment. Management involves education on appropriate potency and duration, and the introduction of TCIs for maintenance therapy. True topical steroid withdrawal syndrome, from chronic inappropriate use, requires gradual tapering and supportive care.
• Antibiotic Resistance in Acne: Minimized by avoiding long-term monotherapy with topical or oral antibiotics, using combination therapy with BPO or retinoids, and setting clear treatment durations for oral agents before transitioning to maintenance or isotretinoin.
• Biologic Failure in Psoriasis: Primary failure (no response) or secondary failure (loss of response) may occur. Strategies include dose escalation (if available), switching within the same class (e.g., one TNF inhibitor to another), or switching to a drug with a different mechanism (e.g., from a TNF inhibitor to an IL-17 inhibitor).

6. Summary and Key Points

The management of eczema, psoriasis, and acne requires a systematic approach grounded in an understanding of their distinct pathophysiologies and the pharmacological tools available to modulate them.

Summary of Main Concepts

• Atopic eczema is driven by barrier dysfunction (often filaggrin-related) and a biphasic Th2/Th1 immune response, with pruritus as a central symptom. Therapy focuses on barrier repair with emollients, anti-inflammatory (TCS, TCIs), and advanced immunomodulators (dupilumab).
• Psoriasis is an IL-23/Th17-mediated disease causing keratinocyte hyperproliferation. Treatment escalates from topicals (vitamin D analogs/steroids) to phototherapy, traditional systemics, and highly targeted biologics against TNF-α, IL-17, and IL-23.
• Acne vulgaris involves follicular hyperkeratinization, sebum overproduction, C. acnes colonization, and inflammation. Management is staged: topical retinoids and antimicrobials for mild-moderate disease; oral antibiotics or hormonal therapy for moderate; and oral isotretinoin for severe or resistant cases.
• The vehicle of a topical product is as critical as its active ingredient, influencing drug delivery, acceptability, and adherence.
• Chronic management necessitates consideration of long-term safety, monitoring for adverse effects (e.g., skin atrophy with steroids, hepatotoxicity with methotrexate, teratogenicity with isotretinoin and acitretin), and impact on quality of life.

Clinical Pearls

• Potency Matters: Topical corticosteroid potency must be matched to disease severity and body site. Use potent steroids sparingly on thin skin (face, flexures) and for limited durations.
• Combination is Key: In both psoriasis (vitamin D analog + steroid) and acne (retinoid + antimicrobial), combination topical therapy often yields superior efficacy and can mitigate side effects or resistance.
• Think Beyond the Skin: Psoriasis is associated with significant comorbidities (arthritis, cardiovascular disease). Acne can be a marker of endocrine disorders like PCOS. Eczema severity impacts sleep and mental health.
• Prevention of Relapse: In eczema and psoriasis, proactive therapy (e.g., twice-weekly application of a TCI or a potent TCS to previously affected areas) can significantly reduce flare frequency.
• Patient as Partner: Successful management of these chronic conditions is heavily dependent on clear patient education regarding the nature of the disease, realistic expectations of therapy, and correct application techniques.

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