ECZEMA — DEFINITION, CLASSIFICATION & STASIS ECZEMA

(10-Mark Format — 3rd Year PG Dermatology Theory)

I. DEFINITION OF ECZEMA

• Spongiosis — intercellular oedema of the epidermis (disproportionate to the degree of lymphocytic exocytosis)
• Perivascular lymphoid infiltrate in the superficial dermis
• Exocytosis of lymphocytes into the epidermis

"Virtually all eczematous eruptions share a common denominator: spongiotic dermatitis" — Fitzpatrick's Dermatology, Vol. 1–2

II. CLASSIFICATION OF ECZEMA

A. Exogenous (Contact) Eczemas

B. Endogenous Eczemas

C. Special / Localised Forms

• Hand eczema, Nipple eczema, Ear eczema, Circumostomy eczema
• Infective dermatitis (HTLV-1 associated)

D. By Morphological Stage

III. NOTE ON STASIS ECZEMA

Definition

Epidemiology

• ~15% of the adult population in Central Europe has symptomatic CVI; ~1% suffers venous ulcers
• Prevalence rises with age
• More common in females, obese individuals, and those with prolonged standing occupations

Pathogenesis

• Valvular incompetence of deep leg veins
• Upright posture (gravitational effect)

Venous Hypertension
        ↓
Slowing of microvascular blood flow
        ↓
Distension of capillaries → Capillary permeability barrier damage
        ↓
Extravasation of fluid (oedema) + erythrocytes (haemosiderin deposits)
        ↓
Pericapillary fibrin cuff deposition
        ↓
Microangiopathy → impaired O₂ diffusion + metabolic exchange
        ↓
Neutrophil activation, free radical release, matrix metalloproteinase activation
        ↓
Chronic inflammation → Stasis Dermatitis

• Allergic contact dermatitis to topical agents (neomycin, bacitracin, lanolin, fragrances, preservatives, corticosteroids — patients develop multiple contact allergies)
• Irritant contact dermatitis from wound exudate in ulcerated areas causing maceration

Clinical Features

1. Pitting oedema — cushion-like, medial aspects of shin/calf, worse in evenings, resolves overnight
2. Varicosities including venulectasias of the instep
3. Stasis purpura — petechiae on a yellow-brown background (haemosiderin deposition)
4. Stasis dermatitis — erythema and scaling maximal around inner malleoli; spreads to involve entire distal lower extremity
5. Lipodermatosclerosis — acute (mimics cellulitis/"pseudoerysipelas") → chronic (indurated skin/subcutaneous tissue creating inverted wine-bottle appearance)
6. Venous ulcers — supramalleolar region, spontaneous or trauma-triggered
7. Acroangiomatosis (pseudo-Kaposi sarcoma)
8. Atrophie blanche — porcelain-white stellate scars with telangiectasias

• Markedly pruritic (pruritus may precede the eczema)
• Excoriations, oozing, crusting
• Lichenification in chronic lesions
• Vesiculation episodes raise suspicion of superimposed contact sensitisation
• Once ulcers form: highly irritated, oozing, erosive

Autosensitisation (ID Reaction / Disseminated Eczema)

• Stasis dermatitis is one of the most common causes of secondary disseminated eczema
• ~Two-thirds of patients with contact dermatitis associated with stasis dermatitis develop disseminated eczema
• Distribution: contralateral leg (anterior aspect), anterior thighs, extensor surfaces of upper extremities — strikingly symmetric

Histopathology

Differential Diagnosis

• Nummular eczema
• Asteatotic eczema
• Allergic/irritant contact dermatitis
• Psoriasis (plaques on legs)
• Mycosis fungoides (patch stage)
• Cellulitis (acute lipodermatosclerosis)

Treatment

• Compression therapy — regular compression bandages or stockings to improve venous return (mainstay; must be continued even after surgery)
• Lifestyle changes: leg elevation, exercise of calf muscles
• Surgical strategies if indicated (varicose vein surgery)

• Emollients — liberal use for xerosis
• Topical corticosteroids — judicious use for active dermatitis; avoid long-term use on ulcerated/atrophic skin
• Topical calcineurin inhibitors — steroid-sparing alternative

• Patch testing — mandatory if contact sensitisation suspected (exclude allergic contact dermatitis to topical agents)
• Treat secondary infection with appropriate antibiotics
• Wound care for venous ulcers

• Short courses of systemic corticosteroids
• Dupilumab (for refractory atopic-background eczema)

Summary Box

CONTACT DERMATITIS — PATHOPHYSIOLOGY

(10-Mark Format — 3rd Year PG Dermatology Theory)

I. INTRODUCTION & DEFINITION

II. PATHOPHYSIOLOGY OF IRRITANT CONTACT DERMATITIS (ICD)

Definition

Mechanism

• Chemical irritants (alkalis, acids, detergents, solvents, wet work) disrupt the stratum corneum lipid bilayer and tight junctions
• This increases transepidermal water loss (TEWL) and reduces skin barrier integrity
• Alkalis penetrate deeply by dissolving keratin; acids cause protein precipitation

• The irritant causes direct cytotoxicity to keratinocytes, with cell membrane damage and liberation of preformed proinflammatory mediators
• Key cytokines released: IL-1α, IL-1β, TNF-α, GM-CSF, IL-6, IL-8 (CXCL8)
• IL-1α is constitutively present in keratinocytes and is released immediately upon irritant-induced cell damage — it is the primary initiating cytokine in ICD

• Released cytokines activate endothelial cells → upregulation of adhesion molecules (ICAM-1, E-selectin, VCAM-1)
• This facilitates neutrophil and macrophage recruitment into the dermis
• Mast cell degranulation releases histamine and prostaglandins → vasodilation and oedema
• No hapten–protein conjugate is formed; no T-cell involvement at this stage

• Macrophages and recruited cells release further IL-1β, TNF-α, reactive oxygen species (ROS)
• In acute ICD: erythema, oedema, vesiculation → oozing → crusting
• In chronic/cumulative ICD (repeated low-dose exposure): barrier never fully recovers; persistent subclinical inflammation → lichenification, fissuring
• A hardening effect can develop — repeated mild irritant exposure induces adaptive changes making skin more resistant (unlike ACD where repeat exposure worsens the reaction)

Factors Modifying ICD

• Concentration and type of irritant; duration of contact; occlusion
• Skin thickness (thin skin > thick skin in reactivity)
• Maceration (wet skin > dry skin for acute ICD)
• Atopic diathesis (impaired barrier → increased susceptibility)
• Age, site of exposure

III. PATHOPHYSIOLOGY OF ALLERGIC CONTACT DERMATITIS (ACD)

Phase 1 — SENSITISATION PHASE (Afferent Limb) (~10–14 days; first exposure)

Step 1 — Hapten Entry and Hapten–Protein Conjugate Formation

• Most contact allergens are low-molecular-weight chemicals (<500 Da) called haptens — they are immunologically incomplete by themselves
• Haptens penetrate the stratum corneum (facilitated by their lipophilicity and small size)
• In the epidermis, haptens covalently bind to endogenous skin proteins (carrier proteins) → forming a complete hapten–protein conjugate (complete antigen)
• Examples: Nickel (Ni²⁺) → binds to epidermal proteins; Urushiol (poison ivy) → binds to skin lipids/proteins; DNCB → binds to lysine residues

Step 2 — Innate Immune Activation ("Danger Signals")

• Haptens stimulate keratinocytes and other skin cells to release ATP and DAMPs (danger-associated molecular patterns) and ROS
• These activate the NLRP3 inflammasome → processing and secretion of IL-1β and IL-18 (critical for sensitisation — not seen with irritants or tolerogens)
• Metal ions use distinct pathways:
  • Ni²⁺ directly binds to human TLR4 → induces interferon, IL-1β, IL-18 production
  • Cr⁶⁺ activates both TLR4 and NLRP3 inflammasome pathways
• Also released: TNF-α, GM-CSF, IL-6, TSLP → collectively activate antigen-presenting cells (APCs)

Step 3 — APC Activation and Migration

• Langerhans cells (LCs) in the epidermis and Dermal Dendritic Cells (DDCs) in the dermis take up the hapten–protein conjugate via endocytosis
• Activated by the innate cytokine milieu, these APCs upregulate MHC class II and co-stimulatory molecules (CD80, CD86, CD40)
• APCs migrate via afferent lymphatics to the paracortex of regional (skin-draining) lymph nodes
• Note: Evidence suggests DDCs may be more important than LCs for CD8+ T-cell priming; urushiol uniquely binds to CD1a on LCs

Step 4 — T-Cell Priming and Clonal Expansion (in Lymph Nodes)

• In lymph nodes, APCs present hapten-peptide on MHC class I (for CD8+ T cells) and MHC class II (for CD4+ T cells)
• In contrast to most delayed hypersensitivity responses (which are CD4-dominant), ACD is predominantly mediated by CD8+ cytotoxic T cells; CD4+ T-cell activation provides optimal help for CD8+ priming
• Naïve hapten-specific T cells recognise the conjugate via their T-cell receptor (TCR) → clonal expansion and differentiation into:
  • Effector T cells (circulate immediately)
  • Central memory T cells (TCM) — long-lived, recirculating; cause delayed CHS responses on later challenge
  • Tissue-resident memory T cells (TRM) — distributed throughout the skin surface; mediate rapid local responses on re-exposure
• Simultaneously, regulatory T cells (Tregs) are induced — the sensitisation vs. tolerance outcome depends on the dose of hapten (very low dose → tolerance, not sensitisation)

"The balance between effector T cells and Tregs seems to depend on the dose of antigen applied" — Fitzpatrick's Dermatology, Vol. 1–2

Phase 2 — ELICITATION PHASE (Efferent Limb) (24–72 hours after re-exposure)

Step 1 — Re-exposure to Hapten

• On subsequent contact with the same hapten, the antigen again penetrates the skin and forms a hapten–protein conjugate

Step 2 — Recognition by Memory T Cells

• Hapten-specific TRM cells already resident in skin provide a rapid first-line response
• Circulating TCM cells home to the skin via the skin-homing marker CLA (Cutaneous Lymphocyte Antigen) and CCR4/CCR10
• Antigen presentation in the skin is now less selective — can be performed by keratinocytes, dermal macrophages, mast cells (MHC class I-restricted), not exclusively DCs

Step 3 — T-Cell Activation and Cytokine Release

• Skin-homing CD8+ effector T cells recognise hapten–MHC I complexes on keratinocytes → direct cytotoxic killing via perforin/granzyme B and Fas–FasL pathway
• CD4+ Th1 cells release IFN-γ → macrophage activation; IL-17 (Th17 subpopulation) → neutrophil recruitment
• CD4+ Th2 cells release IL-4, IL-13 (especially in chronic ACD, atopic background)
• TNF-α amplifies the response by upregulating adhesion molecules

Step 4 — Inflammatory Cascade → Spongiotic Dermatitis

Hapten re-exposure
       ↓
TRM/TCM cell activation in skin
       ↓
IFN-γ, TNF-α, IL-17 release
       ↓
Keratinocyte activation + macrophage/neutrophil recruitment
       ↓
Mast cell degranulation → vasodilation, increased permeability
       ↓
Intercellular oedema → SPONGIOSIS (hallmark)
       ↓
Vesicle formation, erythema, pruritus (acute ACD)
       ↓
Chronic: lichenification, acanthosis (with minimal spongiosis)

Step 5 — Resolution

• Regulatory T cells (Tregs) secrete IL-10 and TGF-β → suppress effector T-cell function
• In the absence of re-exposure, the inflammatory response resolves within days to weeks
• Sensitisation persists lifelong (memory T cells); even trace re-exposure can trigger a full reaction

IV. COMPARISON OF PATHOPHYSIOLOGY

V. SPECIAL CONCEPTS

Systemic Contact Dermatitis

Photocontact Dermatitis

• Phototoxic: UV activates a chemical to a cytotoxic state → ICD-like; no prior sensitisation needed
• Photoallergic: UV creates a hapten–protein conjugate → ACD-like; prior sensitisation required

Barrier Disruption–Sensitisation Link

• Patients with atopic dermatitis (filaggrin mutation → impaired barrier) develop ongoing "danger signals" from the disrupted epithelium
• This lowers the threshold for sensitisation to weakly potent allergens (e.g., propylene glycol, neomycin, lanolin)
• Paradoxically, atopic patients are less likely to be sensitised to potent irritant–allergens like urushiol (the strong irritant signal drives tolerance mechanisms)

VI. SUMMARY DIAGRAM

CONTACT DERMATITIS
├── ICD (Innate)
│   Irritant → Barrier disruption → Keratinocyte damage
│   → IL-1α release → Neutrophil recruitment → Inflammation
│   [No sensitisation required; No T-cell memory]
│
└── ACD (Adaptive)
    SENSITISATION (1st exposure, 10–14 days):
    Hapten + Protein → Complete Antigen
    → Inflammasome activation (IL-1β) → APC (LC/DDC) activation
    → APC migration to lymph nodes
    → CD8+ T-cell priming + TRM/TCM generation
    
    ELICITATION (re-exposure, 24–72 hrs):
    Hapten re-entry → TRM recognition → IFN-γ, TNF-α, IL-17
    → Keratinocyte killing + spongiosis → Eczematous dermatitis
    → Tregs → Resolution via IL-10, TGF-β

ATOPIC ECZEMA — DIAGNOSTIC CRITERIA & MANAGEMENT

(10-Mark Format — 3rd Year PG Dermatology Theory)

I. INTRODUCTION

II. DIAGNOSTIC CRITERIA

A. Hanifin and Rajka Criteria (1980)

Major Criteria (must have ≥3):

1. Pruritus
2. Typical morphology and distribution (flexural lichenification in adults; facial and extensor involvement in infants)
3. Chronic or chronically relapsing course
4. Personal or family history of atopy (asthma, allergic rhinitis, atopic dermatitis)

Minor Criteria (must have ≥3):

B. UK Working Party Criteria (Williams, 1994) — Simplified, validated for epidemiology

1. History of involvement of skin creases (antecubital/popliteal fossae, ankles, neck, eyes)
2. Personal history of asthma or hay fever (or history of atopic disease in first-degree relative if child <4 years)
3. History of generally dry skin in the past year
4. Visible flexural dermatitis
5. Onset under the age of 2 years (not used if child <4 years)

C. AAD Consensus Criteria (Eichenfield et al., 2004 — Revised Hanifin & Rajka) (Most clinically applicable — Table 12.1, Dermatology 5e)

Essential Features (must be present; sufficient for diagnosis)

• Pruritus — "the itch that rashes"; often worse in the evening; triggered by sweating, rough clothing
• Typical eczematous morphology and age-specific distribution:
  • Infants/young children: Face (cheeks with sparing of central face), neck, scalp, extensor extremities
  • Children (2–12 yr): Flexural folds (antecubital, popliteal fossae), wrists, ankles
  • Adults/adolescents: Flexural involvement continues; chronic hand dermatitis; facial/eyelid predominance
  • Sparing of groin and axillae at all ages
• Chronic or relapsing course

Important Features (seen in most cases; supports diagnosis)

• Early age of onset (infancy/early childhood)
• Personal and/or family history of atopy (with IgE reactivity)
• Xerosis (dry skin with fine scale; leads to pruritus)

Associated Features (suggestive but less specific)

• Filaggrin-deficiency markers: keratosis pilaris, hyperlinear palms, ichthyosis vulgaris
• Follicular prominence, lichenification, prurigo lesions
• Ocular findings: recurrent conjunctivitis, anterior subcapsular cataract, Dennie–Morgan folds, periorbital darkening
• Regional variants: perioral/periauricular dermatitis, pityriasis alba
• Atypical vascular responses: midfacial pallor, white dermographism, delayed blanch

Exclusionary Conditions

• Scabies, seborrhoeic dermatitis, contact dermatitis, psoriasis, ichthyoses, cutaneous T-cell lymphoma, photosensitivity disorders

D. IgE-Associated vs Non-IgE-Associated AD (WAO Classification)

III. MANAGEMENT OF ATOPIC DERMATITIS

STEP 1 — General Measures & Trigger Avoidance

• Written action plans and disease education significantly improve outcomes
• Identify and avoid individual triggers: extremes of temperature, wool/rough fabrics, perspiration, detergents, solvents, stress
• Psychological support: cognitive-behavioural therapy, biofeedback

• Once daily, 5–10 minutes in warm (not hot) water
• Fragrance-free non-soap cleanser with neutral-to-low pH (syndets preferred)
• Apply moisturiser immediately after bathing ("soak and smear" technique)

STEP 2 — Moisturisers / Emollients (Cornerstone at all steps)

• Daily liberal use of moisturisers is the cornerstone of AD management
• Reduces xerosis, pruritus, erythema, fissuring, and lichenification
• Decreases the total amount of anti-inflammatory medication required
• Recommended quantities: 150–200 g/week (young children), 250–500 g/week (older children/adults)
• Preferred formulations: ointments (petrolatum) > creams > lotions
• Must be free of dyes, fragrances, food-derived proteins (e.g., peanut oil), and sensitising preservatives
• Prescription emollient devices (PEDs) with barrier-restoring ingredients (ceramides, filaggrin breakdown products, fatty acids) are emerging options

STEP 3 — Topical Anti-Inflammatory Therapy

A. Topical Corticosteroids (TCS) (First-line anti-inflammatory)

• Applied immediately after bathing, before moisturiser
• Choose potency based on age, body site, and disease severity:
  • Low potency (e.g., hydrocortisone 1%): face, eyelids, body folds, infants
  • Moderate/high potency (e.g., mometasone, betamethasone valerate): trunk, limbs in adults
  • Very high potency (e.g., clobetasol): lichenified/refractory lesions; short courses only
• Maintenance (proactive) therapy: twice-weekly application to previously affected areas prevents relapse
• Side effects of chronic use: skin atrophy, striae, telangiectasia, tachyphylaxis, HPA-axis suppression (with potent agents over large areas)

B. Topical Calcineurin Inhibitors (TCIs) (Steroid-sparing)

• Tacrolimus 0.03%/0.1% ointment and pimecrolimus 1% cream
• Inhibit calcineurin → block IL-2 transcription and T-cell activation
• Indicated for: sensitive sites (face, eyelids, neck, genitalia), patients with steroid-induced skin atrophy, children ≥2 years
• No skin atrophy; safe for long-term use on sensitive areas
• Side effect: transient burning/stinging initially
• Proactive use twice weekly prevents flares

C. Topical Phosphodiesterase-4 (PDE4) Inhibitor

• Crisaborole 2% ointment — FDA approved for mild-to-moderate AD in patients ≥3 months
• Non-steroidal anti-inflammatory; inhibits PDE4 → reduces cAMP breakdown → dampens inflammatory cytokine production
• Suitable for mild-to-moderate disease and sensitive areas

STEP 4 — Adjunctive Measures

• Application of TCS under wet bandages followed by dry layer
• Enhances penetration, reduces pruritus; used in acute moderate-severe flares, especially in children

• S. aureus colonisation can trigger/worsen AD flares
• Bleach baths (0.005% sodium hypochlorite = 0.5 cup bleach/40-gallon tub, twice weekly) with intranasal mupirocin → reduces bacterial burden
• Systemic antibiotics only when clinical evidence of bacterial superinfection (pustules, purulent exudate, furuncles) — not for routine colonisation
• Systemic antivirals (aciclovir/valaciclovir) for eczema herpeticum

• Non-sedating antihistamines are NOT routinely recommended for AD itch (histamine plays a limited role)
• Sedating antihistamines (hydroxyzine, chlorpheniramine): short-term use during acute flares with significant sleep disturbance

• Improves sleep and reduces disease activity in children with AD (based on RCT evidence)

STEP 5 — Phototherapy (Moderate-Severe AD)

STEP 6 — Systemic Immunosuppressive Therapy (Moderate-Severe, refractory)

STEP 7 — Biologics and Targeted Therapies (Moderate-Severe AD unresponsive to conventional therapy)

Dupilumab (IL-4Rα antagonist) (Game-changer in AD)

• Fully human monoclonal antibody against IL-4 receptor alpha (IL-4Rα)
• Blocks both IL-4 and IL-13 signalling (dual blockade)
• Approved for moderate-to-severe AD in adults and children ≥6 months
• Dosing: 300 mg SC every 2 weeks (adults); weight-based in children
• Rapidly reduces EASI/IGA scores, pruritus NRS, and sleep disturbance
• Side effects: conjunctivitis (most common), injection site reactions

Tralokinumab (Anti–IL-13)

• Monoclonal antibody against IL-13 specifically
• Approved for moderate-to-severe AD in adults

JAK Inhibitors (Oral small molecules)

Management of Special Situations

IV. MANAGEMENT STEPLADDER SUMMARY

SEVERITY          TREATMENT
─────────────────────────────────────────────────────────────
Mild              Emollients + Low-potency TCS / TCIs
                  Trigger avoidance, education
─────────────────────────────────────────────────────────────
Moderate          Moderate-potency TCS + TCIs (proactive)
                  Wet wraps for flares; bleach baths
                  Phototherapy (NB-UVB)
─────────────────────────────────────────────────────────────
Severe            Systemic: Cyclosporine / MTX / Azathioprine
                  Biologics: Dupilumab (first-line biologic)
                             Tralokinumab
                  JAK inhibitors: Upadacitinib, Abrocitinib
─────────────────────────────────────────────────────────────
Throughout        Emollients (cornerstone), education,
all steps         psychological support, comorbidity management

CUMULATIVE IRRITANT CONTACT DERMATITIS (CICD)

(10-Mark Format — 3rd Year PG Dermatology Theory)

I. INTRODUCTION & DEFINITION

"Cumulative ICD is a consequence of multiple sub-threshold skin insults, without sufficient time between them for complete restoration of skin barrier function." — Dermatology 2-Volume Set 5e (Bolognia et al.)

II. EPIDEMIOLOGY

• The most common form of occupational skin disease, predominantly affecting the hands
• Prevalence of hand dermatitis in industrial populations: ~10% (vs ~0.5% in general population)
• Most common in: healthcare workers, hairdressers, caterers, cleaners, metal workers, agricultural workers, food handlers
• Higher risk in atopics, women (especially young, 16–29 years), and individuals with prolonged wet work exposure
• More than half of affected workers eventually change jobs; a large proportion have >1 month off work

III. PATHOGENESIS

The Manifestation (Elicitation) Threshold Concept

Each sub-threshold irritant exposure
           ↓
Partial barrier damage (insufficient to cause clinical ICD alone)
           ↓
Insufficient recovery time between exposures
           ↓
Repeated damage accumulates → Surpasses manifestation threshold
           ↓
CUMULATIVE ICD

• Weak irritants do NOT cause clinical ICD if exposures are spaced far enough apart to allow complete barrier restoration
• If the same weak irritant exposures follow closely in time → cumulative ICD develops
• The manifestation threshold is not fixed — it decreases with disease progression, meaning even trivial exposures can perpetuate established disease
• May result from frequent repetition of one irritant (e.g., repeated handwashing) or, more commonly, from multiple different stimuli (e.g., wet work + detergents + friction + cold)

Molecular/Cellular Mechanisms

• Repeated exposure to water, detergents, and solvents disrupts stratum corneum lipids (ceramides, free fatty acids, cholesterol) and degrades tight junctions
• Results in increased transepidermal water loss (TEWL)
• Physical properties of irritants matter: pH, solubility, detergent action, physical state

• Damaged keratinocytes release IL-1α (constitutively stored, immediately released on cell damage) — the primary initiating cytokine
• Further release of TNF-α, IL-6, IL-8 (CXCL8), GM-CSF

• Proinflammatory cytokines activate endothelial cells → upregulation of ICAM-1, E-selectin, VCAM-1
• Recruitment of neutrophils (early), then macrophages and lymphocytes
• Mast cell degranulation → histamine, prostaglandins → vasodilation and oedema
• No adaptive/T-cell sensitisation component; repeat exposure does NOT generate immunologic memory

• Once the threshold is exceeded, even previously tolerated (sub-threshold) exposures sustain the inflammation
• The ratio of IL-1α (proinflammatory) to IL-1Ra (anti-inflammatory) shifts towards inflammation
• Chronic scratching and rubbing → lichenification → further barrier impairment (vicious cycle)

Factors Reducing the Manifestation Threshold

IV. CLINICAL FEATURES

Symptoms

• Pruritus (predominant in chronic stages)
• Pain, burning, and stinging (especially from fissuring)
• Symptoms often precede visible signs
• Patients often unaware of the causative link (especially when multiple weak exposures are involved — domestic + occupational) → diagnosis considerably delayed

Signs (in chronological order of evolution)

Site Distribution

• Hands (most common) — especially dorsal aspects, finger webs, periungual areas
• Distribution may extend to wrists and forearms in hairdressers/metal workers
• Face and periorbital regions in airborne ICD
• Perioral in lip-lickers

Key Distinguishing Clinical Feature vs Acute ICD

V. HIGH-RISK OCCUPATIONS AND ASSOCIATED IRRITANTS

VI. HISTOPATHOLOGY

The combination of neutrophil-rich superficial perivascular infiltrate + scattered necrotic keratinocytes is most typical of ICD, helping distinguish it from ACD — Dermatology 5e (Bolognia)

VII. DIAGNOSIS

• Primarily a clinical diagnosis and a diagnosis of exclusion
• No diagnostic test definitively confirms ICD
• Patch test: negative to standard allergens (distinguishes from ACD) — but both may coexist
• Repeated open application test (ROAT): may identify weak irritants
• Bioengineering measurements: TEWL, skin hydration, erythema indices — research tools
• Occupation and exposure history is central to diagnosis

Key Differentials

• Allergic contact dermatitis (patch test positive; crescendo pattern; more pruritic)
• Atopic dermatitis (personal/family atopy history; flexural distribution)
• Dyshidrotic eczema (deep-seated palmoplantar vesicles)
• Psoriasis (silvery plaques; nail changes)
• Tinea manuum (fungal KOH/culture positive)

VIII. PROGNOSIS

• In some individuals, ICD resolves spontaneously despite continued exposure — a process called "accommodation" or "hardening" — through:
  • Thicker stratum corneum and stratum granulosum formation + increased ceramide production
  • Increased skin permeability allowing faster removal of irritants
  • Immunological shift: increased IL-1Ra:IL-1α ratio → anti-inflammatory bias
  • Systemic hyporeactive state after repetitive low-dose irritant exposure
• Poor prognostic factors:
  • Pre-existing atopic diathesis
  • Female sex
  • Coexisting allergic contact dermatitis
  • Delayed diagnosis
  • Continued exposure
• Good prognostic factors:
  • Early diagnosis and treatment
  • Patient education and awareness
  • Effective exposure control

IX. TREATMENT AND PREVENTION

Primary Treatment: Eliminate / Reduce Causative Irritants

• Substitution of potent irritants with less irritating alternatives
• Closed or automated systems for hazardous chemicals
• Engineering shielding to minimise skin contact

• Gloves — appropriate material selection crucial; occlusive environment of ill-fitting/low-quality gloves can worsen ICD via maceration
• Protective clothing, barrier creams

Skin Care Programme (3-Stage Approach)

Topical Therapy

Systemic Therapy (Severe/Recalcitrant Cases)

Education and Prevention Programmes

• "Eczema school" programmes run by specialist nurses showed significantly better outcomes in occupational hand dermatitis (Finland study)
• Educating workers to recognise early signs (slight erythema, interdigital scaling) enables timely intervention before chronicity
• Combination of medical treatment + exposure analysis + individual/group training in preventive measures provides optimal outcomes

X. SUMMARY

CUMULATIVE ICD
│
├── CAUSE: Multiple weak irritants; sub-threshold each time;
│         insufficient barrier recovery between insults
│
├── PATHOGENESIS: Threshold model → IL-1α → Neutrophil/Macrophage
│                 → Barrier never fully restores
│
├── RISK FACTORS: Atopy, wet work, occupation, female sex
│
├── CLINICS: Insidious onset; lichenification + hyperkeratosis
│            + fissuring; less demarcated; pruritus + pain
│            Site = HANDS (dominantly)
│
├── DIAGNOSIS: Clinical + exclusion of ACD (patch test negative)
│
├── PROGNOSIS: Can "harden" (IL-1Ra:IL-1α shift) or become chronic
│             Poor if atopic + ACD coexists
│
└── TREATMENT: Eliminate irritant → Emollients → TCS/TCIs
               Systemic: Retinoids, Cyclosporine, MTX
               Biologic: Dupilumab (refractory)
               Education programmes (cornerstone of prevention)

AIRBORNE CONTACT DERMATITIS (ABCD)

(10-Mark Format — 3rd Year PG Dermatology Theory)

I. DEFINITION

• Airborne Allergic Contact Dermatitis (ACD) — Type IV (delayed-type) hypersensitivity mediated by T cells; requires prior sensitisation
• Airborne Irritant Contact Dermatitis (ICD) — non-immunological; due to direct cytotoxic or mechanical damage by airborne particles

"Airborne ICD develops in irritant-exposed sensitive skin of the face and periorbital regions... Dermatoses in exposed areas should raise the possibility of a possible airborne contact allergy" — Dermatology 2-Volume Set 5e (Bolognia et al.)

II. EPIDEMIOLOGY

• Predominantly an occupational disease, though domestic and environmental exposures are also recognised
• Most common in workers handling plants, woods, resins, and chemical dusts
• Rising incidence due to isothiazolinone biocides (methylisothiazolinone/MI, methylchloroisothiazolinone/MCI) — increasing reactions to MI/MCI-containing paints and baby wipes
• Affects both sexes; more common in adults with occupational exposures
• Atopics are at higher risk for the irritant form

III. CAUSATIVE AGENTS / AETIOLOGICAL CLASSIFICATION

A. Plants (Most Common Cause)

Compositae (Asteraceae) Family — Commonest cause of plant-related ABCD

• Ragweed dermatitis is the prototype of airborne contact dermatitis — most noticeable on the face, with seasonal variation (pollinating season)
• SLs are the primary sensitising haptens; they react with skin proteins via α-methylene-γ-butyrolactone groups

Other Plants

• Primula obconica — primin; may become airborne in enclosed spaces
• Tulip — tulipalin (can become airborne from handling bulbs/dust)
• Thyme, garlic — dust in farmers; reported in agricultural workers

B. Woods and Wood Dusts

C. Fragrances and Perfumes

• Fragrance molecules can volatilise and become airborne, especially in enclosed spaces
• Common airborne sensitisers: Myroxylon pereirae (balsam of Peru), cinnamal, eugenol, isoeugenol, Lyral (hydroxymethylpentyl-cyclohexenecarboxaldehyde)
• Aromatherapy-related ABCD from volatilised essential oils is increasingly recognised

D. Epoxy Resins and Acrylates

• Diglycidyl ether of bisphenol A (DGEBA) — prototype epoxy resin allergen; floats as fine dust in workshops
• Acrylates and methacrylates — dental technicians, nail technicians, printers
• Eyelid involvement is characteristic (Fig. 14.21A,B — Dermatology 5e)

E. Isothiazolinones (Biocides)

• MI (methylisothiazolinone) and MCI/MI in water-based paints → ABCD increasingly reported
• MI volatilises during painting, causing facial and eyelid dermatitis in painters and bystanders
• Also in baby wipes — causing facial ABCD in infants and mothers

F. Rubber and Rubber Chemicals

• Antioxidants (e.g., thiurams, carbamates) can become airborne in rubber processing industries

G. Metals

• Nickel dust in metal grinding
• Cobalt and chromate dusts in cement industries

H. Miscellaneous

• Fiberglass (glass wool) — irritant form; causes periorbital and facial ICD
• Volatile solvents and sprays
• Preservatives in sprays (e.g., kathon CG)
• Glues (cyanoacrylate vapours from superglue)
• Animal danders (occupational — veterinarians, farmers)
• Paints — MI/MCI, isocyanates

IV. PATHOGENESIS

A. Airborne Allergic Contact Dermatitis

• Follows the identical immunological pathway as standard ACD (Type IV delayed hypersensitivity)
• Sensitisation Phase: Airborne hapten lands on skin surface → penetrates stratum corneum → binds to carrier proteins → hapten–protein conjugate → taken up by Langerhans cells/dermal DCs → migration to regional lymph nodes → CD8+ T-cell priming → TRM and TCM generation
• Elicitation Phase: On re-exposure, airborne hapten activates memory T cells in skin → IFN-γ, TNF-α, IL-17 release → spongiotic dermatitis
• The very small particle size of airborne allergens facilitates penetration through the stratum corneum — making even brief exposure sufficient for elicitation in sensitised individuals

B. Airborne Irritant Contact Dermatitis

• Non-immunological mechanism
• Airborne dusts (fiberglass, wood dust) mechanically abrade the stratum corneum
• Volatile chemicals (solvents, acids) cause direct cytotoxic damage to keratinocytes
• IL-1α release → neutrophil recruitment → innate inflammatory response
• No prior sensitisation needed; any exposed individual with sufficient concentration is susceptible
• Atopics with pre-existing barrier dysfunction are more vulnerable

V. CLINICAL FEATURES

Distribution — The Hallmark

"In airborne contact dermatitis, all exposed sites can be involved, including the upper eyelids, submental region, and postauricular areas; these sites are frequently spared in photoallergic contact dermatitis" — Dermatology 2-Volume Set 5e

Morphological Features by Stage

Special Clinical Points

• Eyelid involvement is a cardinal feature — eyelids are thin-skinned, highly sensitive, and receive proportionally high airborne deposition
• Seasonal variation with pollen allergens (Compositae — worse in late summer/autumn)
• The distribution may initially appear to mimic a photosensitivity dermatosis — careful examination of shaded and shielded sites is crucial
• In the workplace, the face, neck, V-area, and forearms are primarily affected, with relative sparing of covered areas
• Pronounced upper eyelid involvement with relative sparing of the lower lids and the photoprotected retroauricular creases behind the ear suggest ABCD rather than photo-contact dermatitis

VI. HISTOPATHOLOGY

• Identical to standard spongiotic dermatitis — cannot distinguish ABCD from other forms of ACD histologically
• Acute: Spongiosis, intraepidermal vesiculation, exocytosis of lymphocytes, perivascular lymphocytic infiltrate
• Chronic: Acanthosis, hyperkeratosis, parakeratosis, lichenification, minimal spongiosis; dermal fibrosis
• ICD type: neutrophil-rich infiltrate + scattered necrotic keratinocytes (in more severe reactions)

VII. DIAGNOSIS

1. Clinical Diagnosis

• Careful exposure history — occupational, domestic, hobbies, aromatherapy
• Seasonal pattern → suggests pollen/plant allergens (Compositae)
• Distribution pattern — upper eyelid + submental + postauricular involvement strongly suggestive

2. Patch Testing

• Standard European Baseline Series + Compositae mix (for plant allergy)
• Additional specialised panels based on occupation:
  • Acrylate series (printers, dental technicians, nail technicians)
  • Epoxy resin series (electronics, construction)
  • Wood dust series (carpenters)
  • Fragrance series (perfumers, cosmetologists)
  • Rubber chemicals series
• Patch test to a sample of the workplace dust/substance may be required
• MI and MCI/MI should be included in the series for painters

3. Photopatch Testing

• Required when photocontact dermatitis cannot be excluded clinically

4. Provocation / Open Application Tests

• Open application of suspected airborne material to the antecubital fossa (ROAT — Repeated Open Application Test)

VIII. DIFFERENTIAL DIAGNOSIS

IX. TREATMENT

1. Identification and Avoidance of Causative Agent

• Cornerstone of management
• Identify the specific airborne allergen/irritant via careful history and patch testing
• Seasonal avoidance (Compositae — air filtration, staying indoors during high pollen season)
• Occupational: substitute causative material (e.g., switch to MI-free paints), improve ventilation, enclosed processing systems

2. Personal Protective Equipment

• Respiratory masks and protective goggles — reduce airborne particle contact with face and periorbital skin
• Barrier creams to exposed facial skin (especially workers)
• Full protective clothing to minimise exposed skin area

3. Workplace Modifications

• Improved local exhaust ventilation to reduce airborne particle concentration
• Engineering controls — enclosure of processes generating dust/aerosols
• Worker education and health surveillance

4. Topical Therapy

5. Systemic Therapy (Severe/Extensive Cases)

• Short courses of oral corticosteroids (prednisolone 0.5–1 mg/kg/day, tapering) for acute severe ABCD with marked facial oedema
• Systemic immunosuppressants (cyclosporine, methotrexate, azathioprine) for chronic, recalcitrant ABCD — especially occupational cases where complete avoidance is not possible
• Dupilumab — emerging evidence for biologic therapy in refractory cases with atopic background

6. Specific Considerations

• For Compositae allergy: oral hyposensitisation/immunotherapy is not currently validated; strict allergen avoidance remains primary
• For paint-related MI/MCI ABCD: awareness campaigns and regulatory reduction of MI concentrations in consumer paints have been implemented in Europe
• Regular follow-up and patch testing to re-evaluate sensitisation profile (new sensitisations may develop over time)

X. PROGNOSIS

• Good if the causative allergen is identified and completely avoided
• Poor if occupational exposure is ongoing or multiple sensitisations are present
• Chronicity is common when:
  • Ubiquitous airborne allergens (e.g., Compositae pollen, fragrances)
  • Inability to change occupation
  • Coexisting atopic dermatitis (lower threshold for sensitisation)
• Some patients develop persistent light reactivity if ABCD overlaps with photocontact dermatitis

XI. SUMMARY TABLE

EXFOLIATIVE DERMATITIS (ERYTHRODERMA)

(10-Mark Format — 3rd Year PG Dermatology Theory)

I. DEFINITION

• Exfoliative dermatitis
• Exfoliative erythroderma
• Pityriasis rubra (Hebra)
• Erythroderma (Wilson-Brocq)
• "Red man syndrome" (historical; in idiopathic form only — not to be confused with vancomycin infusion reaction)

"Erythroderma does not represent a defined entity, but rather is a severe clinical presentation that can arise from a variety of diseases" — Dermatology 2-Volume Set 5e (Bolognia et al.)

II. EPIDEMIOLOGY

• Overall incidence: approximately 1 per 100,000 population
• Male predominance: male-to-female ratio 2:1 to 4:1 (even higher in idiopathic form)
• Mean age at onset: 52 years in adults; younger when children are included
• Overall relapse rate at 1 year: 20–30%
• Mortality attributable to erythroderma: approaches 7% in some series

III. AETIOLOGY / CAUSES

A. Causes in Adults (Large Series Data)

• Atopic dermatitis (9%) — most common
• Contact dermatitis (6%)
• Seborrhoeic dermatitis (4%)
• Chronic actinic dermatitis (3%)

B. Mnemonic: "ID PAS" (common causes)

• Idiopathic
• Dermatitis (atopic, contact, seborrhoeic)
• Psoriasis
• Allergic drug reaction
• Sézary syndrome / CTCL

C. Uncommon Causes in Adults

• Pityriasis rubra pilaris (PRP)
• Pemphigus foliaceus (bullous dermatosis)
• Graft-versus-host disease (GvHD)
• Scabies (Norwegian/crusted scabies)
• Ichthyoses
• Sarcoidosis
• Paraneoplastic (lymphoma, solid organ malignancies)
• Hypereosinophilic syndrome
• Autoimmune connective tissue diseases (SLE, dermatomyositis)

D. Drugs Associated with Erythroderma (Table 10.3 — Dermatology 5e)

E. Causes in Neonates / Infants

• Immunodeficiencies (Omenn syndrome, SCID) — ~30%
• Congenital ichthyoses (including Netherton syndrome, ARCI) — ~24%
• Seborrhoeic dermatitis, infantile psoriasis, atopic/nonatopic eczema — ~20%
• Staphylococcal scalded skin syndrome (SSSS)
• Inborn errors of metabolism: holocarboxylase synthetase deficiency, biotinidase deficiency (multiple carboxylase deficiency); essential fatty acid deficiency
• Congenital cutaneous candidiasis

IV. PATHOGENESIS

• Not fully understood for most aetiologies
• The specific pathways of underlying diseases drive the erythroderma
• Common final pathway involves increased keratinocyte turnover:
  • Number of germinative keratinocytes and their mitotic rate are both increased
  • Transit time of epidermal cells is shortened
  • Scales contain material normally retained (nucleic acids, amino acids, soluble proteins)
  • Daily scale loss increases from normal 500–1000 mg → 20–30 g/day
• In acute erythroderma: desquamated material has marginal metabolic significance
• In chronic erythroderma: cumulative protein loss → hypoalbuminaemia → contributes to anaemia of chronic disease and peripheral oedema
• Immune dysregulation likely contributory — supported by peak onset in 6th–7th decade (immune senescence) and high prevalence in immunodeficient children
• Cutaneous vasodilation → massive heat loss → hypothermia; increased blood flow → high-output state → potential cardiac failure

V. CLINICAL FEATURES

A. Onset

• May be acute (drugs, infections) or insidious (pre-existing dermatosis generalising over weeks to months)
• Up to 45% have a prior history of a localised skin disease
• Generalisation of existing patches → confluent erythema → universal involvement

B. General Skin Features

• Erythema — initially patchy, becoming confluent; ultimately dull scarlet colour involving ≥80% BSA
• Scaling — small, laminated, bran-like scales exfoliating profusely
• Pruritus — often severe; may be the dominant symptom (especially in Sézary syndrome)
• Skin feels warm and tight
• Oedema — peripheral, especially legs and face
• Oozing and crusting in acute stages
• Lichenification in chronic stages

C. Hair and Nails

• Telogen effluvium — diffuse hair shedding (seen in most prolonged cases)
• Diffuse alopecia — in chronic erythroderma (Sézary syndrome especially)
• Nail changes — onycholysis, nail dystrophy, Beau's lines
• Palmoplantar keratoderma — in CTCL; painful, fissured

D. Additional Features (Systemic)

• Fever and chills — onset often accompanied by systemic toxicity
• Peripheral oedema (loss of plasma proteins through skin)
• Hypothermia — disruption of thermoregulation (heat loss through vasodilated skin)
• Tachycardia — high-output state; may progress to high-output cardiac failure
• Lymphadenopathy — commonly dermatopathic lymphadenopathy (reactive); or malignant in CTCL
• Ectropion — in chronic erythroderma due to periorbital skin tightening

E. Disease-Specific Clinical Clues

VI. SÉZARY SYNDROME (Erythrodermic CTCL — Special Note)

1. Erythroderma
2. Generalised lymphadenopathy
3. Peripheral blood lymphocytosis with Sézary cells (cerebriform/convoluted nuclei)

• ≥1000 Sézary cells/mm³
• CD4:CD8 ratio ≥10:1
• ≥40% CD4+/CD7− or ≥30% CD4+/CD26− cells on flow cytometry
• Plus: identical T-cell clone in blood AND skin

VII. HISTOPATHOLOGY

• Non-specific in most cases — cannot reliably identify the underlying disease
• Features: hyperkeratosis/parakeratosis, acanthosis, variable spongiosis, perivascular lymphocytic infiltrate
• Disease-specific clues may be retained:
  • Psoriasis: subcorneal pustules, club-shaped rete ridges, neutrophils in epidermis, suprapapillary plate thinning
  • Mycosis fungoides/Sézary: Pautrier's microabscesses, epidermotropic atypical lymphocytes, band-like infiltrate — but diagnostic in only ~2/3 of biopsies
  • Drug reaction: eosinophils in dermis, vacuolar interface changes
  • PRP: alternating ortho- and parakeratosis in chessboard pattern ("checkerboard pattern")
• Multiple biopsies from different sites at different times increase diagnostic yield

VIII. INVESTIGATIONS

Immediate

• Full blood count: eosinophilia (drug reaction, PRP); lymphocytosis + Sézary cell count (CTCL)
• Serum albumin, total protein — hypoalbuminaemia in chronic erythroderma
• Electrolytes and renal function — fluid/electrolyte derangement
• LFTs, ESR, CRP, LDH — elevated in lymphoma-associated erythroderma
• Peripheral blood smear — Sézary cells (cerebriform nuclei)

For Aetiology

• Skin biopsy (multiple) — H&E ± immunohistochemistry
• T-cell receptor gene rearrangement (PCR) in blood and skin — identical clone → CTCL
• Peripheral blood flow cytometry: CD4:CD8 ratio; CD4+/CD7−, CD4+/CD26− population
• Patch testing (after resolution) — if contact dermatitis suspected
• IgE levels — elevated in atopic erythroderma
• Chest X-ray, CT scan, PET-CT — staging for CTCL/lymphoma
• Lymph node biopsy — if lymphadenopathy present
• Bone marrow biopsy — if haematological malignancy suspected

IX. TREATMENT

A. General/Supportive Measures (Priority in all cases)

B. Topical Therapy

• Open wet dressings — soothing; reduce acute inflammation and heat loss
• Bland emollients — liberal, frequent application to restore barrier
• Low-potency topical corticosteroid ointments — for generalised use
• High-potency TCS — restricted to lichenified areas only; use with caution (enhanced transcutaneous absorption in erythrodermic skin)
• Avoid: coal tar preparations and phototherapy in acute stages (may aggravate)

C. Symptomatic Relief

• Sedating antihistamines (hydroxyzine, chlorpheniramine) — for severe pruritus and to aid sleep
• Cool soaks — for comfort

D. Disease-Specific Systemic Treatment

X. COMPLICATIONS

XI. PROGNOSIS

• Overall mortality: ~7% in some series — from sepsis, cardiac failure, or underlying malignancy
• Good prognosis: drug-induced (resolves on withdrawal); contact dermatitis
• Moderate prognosis: psoriatic and atopic erythroderma (chronic but manageable)
• Poor prognosis:
  • Idiopathic (chronic, relapsing)
  • CTCL/Sézary syndrome
  • Malignancy-associated
  • Patients with underlying cardiac/respiratory disease
• ~25% idiopathic cases eventually develop CTCL on long-term follow-up → mandatory serial monitoring

XII. SUMMARY TABLE

AIRBORNE CONTACT DERMATITIS (ABCD)

(10-Mark Format — 3rd Year PG Dermatology Theory)

I. DEFINITION

• Airborne Allergic Contact Dermatitis (ACD) — Type IV delayed hypersensitivity; requires prior sensitisation
• Airborne Irritant Contact Dermatitis (ICD) — non-immunological; direct cytotoxic/mechanical damage

II. EPIDEMIOLOGY

• Predominantly an occupational disease; domestic and environmental exposures also recognised
• Most common in workers handling plants, woods, resins, and chemical dusts
• Rising incidence due to isothiazolinone biocides (MI/MCI) in paints and baby wipes
• Atopics at higher risk for the irritant form
• Both sexes affected; more common in adults with occupational exposures

III. CAUSATIVE AGENTS

A. Plants (Most Common Cause) — Compositae (Asteraceae) Family

• Ragweed dermatitis = prototype of ABCD — predominantly facial; seasonal
• SLs sensitise via α-methylene-γ-butyrolactone groups reacting with skin proteins
• Thyme dust in farmers is a more obscure plant cause

B. Woods and Wood Dusts

C. Fragrances and Essential Oils

• Volatile fragrance molecules (cinnamal, eugenol, Lyral, balsam of Peru)
• Aromatherapy — volatilised essential oils causing facial dermatitis
• Fragrances in sprays, air fresheners

D. Epoxy Resins and Acrylates

• DGEBA (diglycidyl ether of bisphenol A) — floats as fine dust in workshops; eyelid involvement characteristic
• Acrylates and methacrylates — dental technicians, nail technicians, printers
• Increasing reactions to MI/MCI-containing paints and baby wipes

E. Isothiazolinones — Biocides (Rising Cause)

• Methylisothiazolinone (MI) and methylchloroisothiazolinone (MCI/MI) in water-based paints
• Volatilises during painting → facial/eyelid ABCD in painters and bystanders
• Also implicated in baby wipes → facial ABCD in infants and mothers

F. Other Agents

IV. PATHOGENESIS

A. Airborne Allergic Contact Dermatitis (Type IV Hypersensitivity)

Airborne hapten deposits on skin surface
         ↓
Penetrates stratum corneum (facilitated by small particle size)
         ↓
Binds to carrier proteins → Hapten–protein conjugate (complete antigen)
         ↓
Inflammasome activation → IL-1β, IL-18; TLR activation
         ↓
Langerhans cells / Dermal DCs take up antigen → activation
         ↓
DC migration via lymphatics to regional lymph nodes
         ↓
CD8+ T-cell priming (primary) + CD4+ T-cell help
         ↓
TRM (tissue-resident memory T cells) + TCM (central memory T cells) generated

Re-exposure to airborne hapten
         ↓
TRM cells in skin + TCM cells homing via CLA rapidly activated
         ↓
IFN-γ, TNF-α, IL-17 released → keratinocyte activation
         ↓
Spongiotic dermatitis → acute/chronic eczema

B. Airborne Irritant Contact Dermatitis (Innate, Non-immunological)

• Airborne dusts (fiberglass) → mechanical abrasion of stratum corneum
• Volatile chemicals → direct cytotoxic damage to keratinocytes
• IL-1α release (from damaged keratinocytes) → neutrophil recruitment → innate inflammation
• No prior sensitisation needed; anyone with sufficient exposure is susceptible

V. CLINICAL FEATURES

Distribution — The Cardinal Diagnostic Clue

"In airborne contact dermatitis, all exposed sites can be involved, including the upper eyelids, submental region, and postauricular areas; these sites are frequently spared in photoallergic contact dermatitis" — Dermatology 2-Volume Set 5e (Bolognia et al.)

Morphology by Stage

Special Points

• Eyelid involvement — cardinal feature; thin skin + high airborne particle deposition
• Seasonal variation — plant/pollen allergens (Compositae — worse late summer/autumn)
• Distribution initially mimics photosensitivity — careful examination of shaded sites (upper eyelids, submental) is essential
• Pronounced upper eyelid involvement with relatively spared retroauricular creases distinguishes ABCD from photocontact dermatitis

VI. HISTOPATHOLOGY

• Identical to standard spongiotic dermatitis — cannot be distinguished histologically from other ACD types
• Acute: Spongiosis, intraepidermal vesiculation, exocytosis of lymphocytes, perivascular lymphocytic infiltrate
• Chronic: Acanthosis, hyperkeratosis, parakeratosis, lichenification, minimal spongiosis
• ICD type: Neutrophil-rich infiltrate + scattered necrotic keratinocytes

VII. DIAGNOSIS

1. Clinical

• Careful occupational, domestic, and hobby exposure history
• Seasonal pattern → suggests plant/pollen allergens
• Distribution pattern — upper eyelid + submental + postauricular = strong pointer to ABCD

2. Patch Testing

• European Baseline/Standard Series
• Compositae mix — mandatory for suspected plant-related ABCD
• Occupation-specific panels:

• Direct testing with workplace dust or sample where standard panels are negative
• MI and MCI/MI included in standard screening for painters

3. Photopatch Testing

• Required when photocontact dermatitis cannot be clinically excluded

4. ROAT (Repeated Open Application Test)

• Open application of suspected substance to antecubital fossa twice daily for 7 days — useful for weak allergens and borderline reactions

VIII. DIFFERENTIAL DIAGNOSIS

IX. TREATMENT

1. Allergen/Irritant Identification and Avoidance (Cornerstone)

• Identify via patch testing; advise complete avoidance
• Seasonal measures for pollen allergens (air filtration, staying indoors during high pollen season)
• Occupational: substitute MI-free paints, improve ventilation, enclose dust-generating processes

2. Workplace/Environmental Modifications

• Improved local exhaust ventilation
• Engineering enclosure of processes generating aerosols/dusts
• Worker education and health surveillance

3. Personal Protective Equipment

• Respirator masks and protective goggles — reduce facial/periorbital particle deposition
• Barrier creams to exposed skin
• Protective clothing (full sleeves)

4. Topical Therapy

5. Systemic Therapy

X. PROGNOSIS

• Good if causative allergen identified and completely avoided
• Poor/chronic if:
  • Ubiquitous allergens (Compositae pollen, fragrances) — difficult to avoid
  • Inability to change occupation
  • Coexisting atopic dermatitis
  • Multiple sensitisations
• Some develop persistent light reactivity if ABCD overlaps with photocontact dermatitis
• Regulatory/industry impact: EU mandates on MI concentration reduction in consumer paints have begun to reduce incidence of paint-related ABCD

XI. SUMMARY TABLE