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Autoimmune Blistering Diseases: Pemphigus Vulgaris & Bullous Pemphigoid

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The Big Picture: How to Think About These Diseases

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PART 1: PEMPHIGUS VULGARIS (PV)

Epidemiology

• Age of onset: typically 40-60 years
• No sex predilection
• Higher incidence in Ashkenazi Jews and Mediterranean populations
• Associated with HLA-DR4 and HLA-DQ3

Pathogenesis

• DSG3 is expressed predominantly in the lower epidermis (and mucosae)
• DSG1 is expressed throughout the epidermis, but more in the upper layers
• Mucosal-dominant PV: anti-DSG3 only - blisters occur in the lower epidermis (suprabasal) where only DSG3 compensates
• Mucocutaneous PV: anti-DSG3 + anti-DSG1 - both skin and mucosa are involved

1. Direct steric interference with the DSG3 trans-adhesive interface
2. Desmosome disassembly and keratin tonofilament retraction
3. Loss of cell-cell cohesion → intraepidermal blister formation

Clinical Features

Skin Lesions

• Erosions are large, painful, ooze easily, and bleed
• Tend to spread peripherally rather than heal
• Heal with hyperpigmentation but no scarring
• Pruritus is uncommon (unlike BP)

Mucous Membrane Lesions

• Oral mucosa is involved in virtually 100% of patients
• Oral involvement typically precedes skin lesions by months (important: most patients are misdiagnosed as aphthous ulcers initially)
• Erosions at buccal and palatine mucosae, ill-defined borders, extremely painful
• Can involve pharynx, esophagus (sloughing casts reported), nasal mucosa, conjunctivae, vagina, penis, and anus
• Intact blisters in the mouth are rare - they rupture before you see them

Nikolsky Sign

Histopathology

• Suprabasal acantholysis - intraepidermal blister just above the basal cell layer
• The basal cells lose lateral connections but maintain their hemidesmosomal attachment to the basement membrane - classically described as a "row of tombstones"
• A few rounded-up acantholytic keratinocytes float in the blister cavity
• Dermal perivascular mononuclear infiltrate with eosinophils
• No keratinocyte necrosis

Immunofluorescence

• Direct immunofluorescence (DIF): IgG (and often C3) in an intercellular "fishnet/chicken-wire" pattern throughout the epidermis - biopsy from perilesional skin
• Indirect immunofluorescence (IIF): Circulating anti-DSG antibodies detectable in serum
• ELISA: Anti-DSG1 and anti-DSG3 levels correlate with disease activity - useful for monitoring

Diagnosis Summary

1. Clinical presentation (flaccid blisters, oral erosions, Nikolsky positive)
2. Biopsy for H&E (suprabasal acantholysis, tombstoning)
3. DIF of perilesional skin (fishnet IgG)
4. Serology (anti-DSG1, anti-DSG3 by ELISA)

Treatment

Standard Treatment

Steroid-Sparing / Aggressive

Monitoring

• Serum anti-DSG levels track disease activity
• Taper steroids once new blister formation stops (consolidation phase)

Prognosis

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PART 2: BULLOUS PEMPHIGOID (BP)

Epidemiology

• Most common autoimmune blistering disease in Western countries
• Primarily elderly patients (mean onset 65-75 years)
• Risk factors: neurological disorders (dementia, Parkinson disease), psychiatric illness, bedridden state, chronic polypharmacy
• Drug-induced BP: furosemide, penicillamine, captopril, DPP-4 inhibitors (gliptins)

Pathogenesis

• BPAG2 (BP180, type XVII collagen) - the primary pathogenic antigen; transmembrane collagen that spans the lamina lucida
• BPAG1 (BP230) - intracellular plakin protein of hemidesmosomes

1. Anti-BPAG2 IgG binds to the NC16A domain of BP180 at the DEJ
2. Complement activation at the basement membrane zone
3. Recruitment of eosinophils and neutrophils (this is important - BP has prominent eosinophils unlike PV)
4. Protease release (MMP-9, elastase) degrades anchoring proteins
5. Blister forms at the lamina lucida level (subepidermal) - the entire epidermis lifts off intact

Clinical Features

Key: Tense Bullae vs Flaccid Bullae

1. Pre-bullous phase (weeks to months): Intense pruritus, erythematous urticarial papules and plaques - no blisters yet. This phase is often misdiagnosed as urticaria or eczema.
2. Bullous phase: Large, tense blisters on urticarial/erythematous background

Variants to Know

• Gestational pemphigoid (herpes gestationis): Occurs in 2nd-3rd trimester; same BPAG2 antibodies; resolves postpartum, may recur in subsequent pregnancies
• Vesicular pemphigoid: Small, grouped tense blisters (mimics DH)
• Pemphigoid nodularis: Scalp and extremity nodules resembling prurigo nodularis
• Nonbullous variant: Generalized pruritus or urticaria alone - no blisters; difficult to diagnose

Histopathology

• Subepidermal blister - the epidermis lifts off intact as a roof
• No acantholysis (keratinocytes retain intercellular connections - key distinction from pemphigus)
• Prominent eosinophils at the DEJ and within the blister cavity
• Basal cell layer vacuolization in early lesions
• Superficial dermal edema

Immunofluorescence

• DIF: Linear IgG and C3 at the basement membrane zone (linear band pattern along the DEJ) - biopsy from perilesional skin
• IIF: Circulating anti-basement membrane IgG; when salt-split skin is used, antibodies bind to the epidermal side (roof) of the split - this helps distinguish BP from EBA (which binds the dermal floor)
• ELISA: Anti-BP180 ELISA is highly sensitive and specific; correlates with disease activity

Diagnosis Summary

1. Clinical: elderly patient, intense pruritus, tense bullae, flexural distribution
2. Biopsy H&E: subepidermal blister, no acantholysis, eosinophil-rich
3. DIF perilesional: linear IgG + C3 at BMZ
4. ELISA: anti-BP180 and anti-BP230

Treatment

• High-potency topical corticosteroids alone (clobetasol 0.05% BID) - effective even in moderate-severe disease and may be safer than systemic steroids in the elderly

• Oral prednisone 0.75-1 mg/kg/day
• After blisters controlled, taper slowly (5 mg/week down to 30 mg, then alternate-day taper)
• Steroid-sparing agents: azathioprine, mycophenolate mofetil, methotrexate

• Tetracycline (doxycycline) + nicotinamide - effective with fewer steroid side effects; preferred option in trials comparing to prednisone in older patients
• Dapsone - controls 15-44% of BP patients
• Rituximab - for refractory cases
• Omalizumab - used in BP given the IgE-mediated component (eosinophilia, pruritus suggest IgE involvement)
• IVIg, plasmapheresis - severe refractory cases

Prognosis

• Self-limiting in most patients (unlike PV)
• Remitting-relapsing course
• Does not leave scars
• Mortality is associated with disease severity and treatment complications (not the disease itself)
• Children: usually resolves within 5 months

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SIDE-BY-SIDE COMPARISON TABLE

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MEMORY TRICKS

• Pemphigus = Painful mucosa, Potentially fatal, Placid/flaccid blisters, Positivity for Nikolsky
• Bullous pemphigoid = Big tense Bullae, BMZ target, Benign course, older patient Bodies
• The "V" in Vulgaris - think of the Vital mucosa being involved first
• PV splits the epidermis → roof is thin → fragile; BP splits below the epidermis → roof is full epidermis → tough
• DIF pattern: PV = spider web (intercellular); BP = line (at the basement membrane)

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Lichen Planus & Psoriasis

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PART 1: LICHEN PLANUS (LP)

The 6 P's - The Classic Memory Aid

Epidemiology

• Affects ~0.3% of the population worldwide; all races
• Cutaneous LP peaks between ages 40-70 in persons of European descent
• Childhood LP is more common in Asian/Indian/Arab populations (up to 10-20%)
• Associated with HLA-DR/DQ, HLA-A3 alleles
• Oral LP affects women slightly more than men (2.3% vs 1.5%)
• Strong association with hepatitis C virus (HCV) - especially in Mediterranean/Italian populations; screening is warranted

Pathogenesis

1. CD8+ T lymphocytes recognize an (unknown) antigen on basal keratinocytes
2. T cells cluster at the dermoepidermal junction and launch a cytotoxic attack
3. Th1 cytokines (IFN-γ, TNF-α) predominate
4. Basal keratinocytes undergo apoptosis → liquefactive degeneration of the basal cell layer (also called hydropic degeneration or vacuolar alteration)
5. Dead basal cells become eosinophilic globules = Civatte bodies (colloid bodies)
6. The inflammatory infiltrate "hugs" the DEJ like a band = lichenoid reaction pattern

Clinical Features

Classic Skin Lesions

Variants to Know

Oral LP

• Reticular (most common): Asymptomatic interlacing white striae (Wickham striae); buccal mucosa; often bilateral
• Erosive: Painful red erosions; higher malignant transformation risk (~1-2% to oral SCC over 10 years)
• Atrophic: Red/white atrophic patches
• Bullous/plaque/papular: Less common variants

Nail LP (~5-10% of patients)

• Longitudinal ridging and splitting (90% of nail LP cases)
• Onycholysis, subungual debris
• Red lunulae (30%)
• Pterygium - pathognomonic: scarring of the nail fold over the nail plate
• Severe disease leads to permanent anonychia (loss of nail plate)

Scalp LP (Lichen Planopilaris)

• Perifollicular erythema and scale
• Leads to permanent scarring alopecia (unlike LP elsewhere which is non-scarring)
• Associated with frontal fibrosing alopecia variant

Histopathology

1. Band-like ("lichenoid") lymphocytic infiltrate at the DEJ - the infiltrate obscures and "hugs" the basement membrane zone
2. Vacuolar/hydropic degeneration of the basal cell layer - basal keratinocytes are destroyed
3. Civatte bodies (colloid/hyaline bodies) - dead, eosinophilic basal keratinocytes that have undergone apoptosis

• Saw-tooth" (irregular) rete ridges - the inflammatory destruction creates a jagged silhouette
• Hypergranulosis (thickened granular layer) - correlates with Wickham striae clinically
• No significant epidermal hyperplasia (distinguishes from psoriasis)
• DIF: Linear or shaggy fibrinogen deposits at BMZ; IgM in Civatte bodies

Triggers / Associations

• HCV infection (strongest known association, especially erosive oral LP)
• Drugs (lichenoid drug reactions): NSAIDs, beta-blockers, ACE inhibitors, antimalarials, thiazides, gold, penicillamine
• Dental amalgam can trigger oral LP at contact sites
• Hepatitis B vaccination (rare)
• PD-1 inhibitors (pembrolizumab) - checkpoint inhibitor-associated LP
• Stress, trauma (Koebner)

Malignant Potential

Treatment

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PART 2: PSORIASIS

Overview

Epidemiology

• Equal frequency in men and women
• Bimodal age onset: 16-22 years (type I, HLA-linked, more severe) and 57-60 years (type II)
• Genetics: When both parents have psoriasis, ~50% risk in offspring; one parent affected → ~16%
• HLA-Cw6 is the strongest genetic association (type I psoriasis)
• MHC Class I locus confers the largest genetic risk
• Less common in Sub-Saharan African and Native American populations

Pathogenesis

1. An environmental trigger (infection, trauma, drug, stress) activates plasmacytoid and myeloid dendritic cells
2. DCs produce TNF-α, IL-12, IL-23
3. IL-23 drives Th17 cell development and survival
4. Th17 cells produce IL-17A, IL-17F, IL-22
5. IL-17 acts on keratinocytes → neutrophil recruitment (IL-8), antimicrobial peptide production
6. IL-22 causes acanthosis (thickened epidermis) by retarding keratinocyte differentiation
7. Basal keratinocyte transit time falls dramatically (from ~52 days normally to ~8 days) → parakeratosis, poor cornification
8. Vascular changes: papillary capillary loops elongate, dilate, and "kiss" the epidermis → "squirting papillae" (neutrophils and lymphocytes extravasate directly at papillary tips) → Auspitz sign

Triggers and Exacerbating Factors

Clinical Types

Clinical Signs to Know

Histopathology

Nail Psoriasis

• Pitting (most common) - from matrix disease
• Onycholysis - nail separates from nail bed
• "Oil drop" / "salmon patch" sign - yellow-brown discoloration under the nail (pathognomonic)
• Subungual hyperkeratosis
• Leukonychia, red lunulae, splinter hemorrhages

Psoriatic Arthritis

1. Oligoarticular asymmetric (most common)
2. Polyarticular (resembles RA)
3. Distal interphalangeal (DIP) joint predominant (classic psoriatic pattern)
4. Axial (spondylitis/sacroiliitis - HLA-B27 associated)
5. Arthritis mutilans (most severe - "opera glass" deformity)

Systemic Comorbidities

• Cardiovascular disease (increased risk of MI, stroke - especially in young patients with severe psoriasis)
• Metabolic syndrome (obesity, hypertension, dyslipidemia, insulin resistance)
• Psoriatic arthritis
• Depression and anxiety
• Inflammatory bowel disease (Crohn's more than UC)
• Slightly increased risk of lymphoma
• Increased risk of celiac disease

Treatment

Topical (Mild-Moderate, Limited BSA)

Phototherapy

• Narrowband UVB (NB-UVB) - first-line phototherapy; safe in pregnancy
• PUVA (psoralen + UVA) - effective but increases long-term skin cancer risk
• Excimer laser - targeted 308nm UVB for localized plaques

Systemic (Moderate-Severe)

Biologics - The Modern Cornerstones

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COMPARISON TABLE: LP vs PSORIASIS

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Memory Tricks

• LP = "Lacy Purple" - the Wickham striae look like white lace on a purple background
• LP histology = BALL - Band-like infiltrate, Acantholysis absent, Liquefactive degeneration, Lyssa (Civatte) bodies
• Psoriasis = "Silver Scale on Salmon Skin" at extensor surfaces
• Psoriasis histology = PALM - Parakeratosis, Acanthosis, Lost granular layer, Munro microabscesses
• Auspitz sign = A for Auspitz, A for Arteries (the capillaries exposed by scale removal bleed)
• For biologics in psoriasis: TNF → IL-12/23 → IL-23 → IL-17 (progressive refinement of the pathway)

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Systemic Sclerosis, Discoid Lupus Erythematosus & Atopic Dermatitis (Eczema)

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PART 1: SYSTEMIC SCLEROSIS (SSc / Scleroderma)

What It Is in One Sentence

Epidemiology

• Incidence: 9-19 cases per million per year (orphan disease)
• Strong female predominance (F:M = 3-4:1), especially in childbearing years
• Peak onset: 40-60 years
• Black patients: earlier onset, more often diffuse cutaneous form, worse prognosis (more ILD)
• Family history is the strongest risk factor (1.6% of patients have an affected first-degree relative)
• Occupational risk: crystalline silica (sandblasting, mining, ceramics) is the strongest linked exposure; also polyvinyl chloride, aromatic hydrocarbons

The Two Major Subtypes - The Core of SSc

Pathogenesis - Three Interlocking Processes

1. Autoimmunity

• CD4+ T cells (Th2-skewed) accumulate in skin and release IL-13 and TGF-β
• IL-13 and TGF-β → fibroblast activation → excess collagen synthesis
• ANAs are present; specific antibodies have diagnostic and prognostic value (see below)
• Type I interferons (IFN signaling genes STAT4, IRF5) play a role

2. Vascular Damage

• Endothelial injury → platelet aggregation → PDGF and TGF-β release → intimal proliferation and perivascular fibrosis
• Progressive obliterative microangiopathy (vasculature narrows and is lost)
• Raynaud phenomenon is the clinical manifestation of vascular dysfunction
• Pulmonary vasculature involvement → pulmonary arterial hypertension (PAH)

3. Fibrosis

• Culmination of macrophage activation, fibrogenic cytokines (TGF-β is the master regulator), and ischemic scarring
• Fibroblasts become constitutively activated, producing excessive Type I and III collagen

Autoantibodies - Must Know

Skin Manifestations - Stages

• Non-pitting edema of the fingers and hands - the first sign
• Skin is shiny, tight, waxy
• Raynaud phenomenon is typically present
• Patients often complain of "my rings no longer fit"

• Progressive skin thickening and tightening
• Fibrosis of the dermis, bound to subcutaneous structures
• Hyaline thickening of dermal blood vessel walls
• Thinning of the epidermis, loss of rete pegs, atrophy of adnexal structures
• Loss of normal skin folds; reduced range of motion

• Skin becomes atrophic and tightly bound
• Fingers taper and develop "clawlike" appearance (sclerodactyly)
• Face becomes taut and masklike (reduced mouth opening = microstomia)
• Digital ulcers and gangrene from ischemia
• Subcutaneous calcinosis (calcium deposits, especially in CREST)
• Telangiectasia (mat telangiectasias on face, hands, lips)

Organ Involvement

Gastrointestinal (most commonly affected = 90%)

• Esophagus (most severely affected): atrophy of the muscularis → rubber-hose inflexibility of lower 2/3; lower esophageal sphincter dysfunction → GERD, Barrett's esophagus, strictures
• Small bowel: fibrosis → malabsorption, bacterial overgrowth, pseudo-obstruction
• Colon: wide-mouthed diverticula on anti-mesenteric border (characteristic)

Lungs (>50% affected)

• Interstitial lung disease (ILD): NSIP pattern most common (vs UIP in IPF) - insidious dyspnea, bibasal crackles
• Pulmonary arterial hypertension (PAH): especially in lcSSc; progressive dyspnea, cor pulmonale
• ILD + PAH are the leading causes of death in SSc

Kidneys (~30-40%)

• Scleroderma Renal Crisis (SRC): abrupt-onset malignant hypertension + acute renal failure
• Associated with anti-RNA Pol III antibodies and dcSSc (within first 4 years)
• Precipitated by corticosteroids (important!)
• Histology: "onion skin" intimal proliferation of small arteries; fibrinoid necrosis of arterioles
• Treatment: ACE inhibitors (captopril) are life-saving - even in dialysis patients, they can help renal recovery

Heart (1/3 of patients)

• Pericarditis with effusion, myocardial fibrosis, arrhythmias
• Right ventricular failure secondary to pulmonary disease

Musculoskeletal

• Arthralgia and arthritis (early); fibrosis of tendons → tendon friction rubs (leathery crunching on movement) - characteristic of dcSSc
• Inflammatory myositis in ~10%

Raynaud Phenomenon

• Present in >95% of SSc patients
• Classic triphasic: White (vasospasm/ischemia) → Blue (cyanosis/deoxygenation) → Red (reperfusion hyperemia)
• May lead to digital ulcers, pitting scars, and even autoamputation of fingertips
• Distinguish primary Raynaud (benign, common, no autoantibodies) from SSc-associated Raynaud (asymmetric, associated with abnormal nailfold capillaroscopy = dilated/absent capillaries)

Nailfold Capillaroscopy

Treatment

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PART 2: DISCOID LUPUS ERYTHEMATOSUS (DLE)

Where DLE Sits in the Lupus Spectrum

• Acute CLE (ACLE): malar rash, photodistributed erythema - highly associated with SLE
• Subacute CLE (SCLE): annular/papulosquamous photodistributed - moderate systemic risk; anti-Ro/SSA positive
• Chronic CLE (CCLE): DLE, lupus panniculitis, tumid lupus - lower systemic risk; primarily a skin disease

Epidemiology

• Most common form of cutaneous lupus
• Young adults; F:M = 2:1
• Can occur in children (higher rate of SLE association in children - up to 26%)
• Localized DLE (above the neck only): only 5-15% progress to SLE
• Generalized DLE (above and below neck): higher risk of SLE, more lab abnormalities

Clinical Features

Classic Presentation: The Three Zones of DLE

1. Active erythematous/violaceous border (outer) - active inflammation
2. Central atrophy and scarring (middle) - destroyed dermis
3. Dyspigmentation (inner) - hypopigmentation centrally, hyperpigmentation peripherally

Distribution

• Localized DLE: face (malar areas, nose, ears - particularly the concha of the ear and external canal), scalp, lips
• Lesions on the lips are gray/red and hyperkeratotic with a narrow red inflammatory rim
• Oral/nasal/conjunctival/genital mucosa in ~24% of patients

Scalp DLE - Critical Complication

• Active scalp DLE → permanent scarring alopecia
• Active signs: perifollicular erythema, easily extractable anagen hairs
• End-stage: smooth, depressed white patches or dilated follicular openings in isolated remaining follicles
• This scarring is irreversible - early treatment is paramount

The "Carpet Tack" Sign

Malignant Transformation

Histopathology

• Vacuolar interface dermatitis (liquefactive degeneration of basal cells)
• Patchy lymphocytic infiltrate

• Hyperkeratosis with follicular plugging
• Thickening of the basement membrane (PAS-positive, thickened BMZ - a hallmark)
• Superficial and deep perivascular and periadnexal lymphocytic infiltrate (both above and below - contrast with ACLE/SCLE which are superficial only)
• Dermal mucin deposition
• Vacuolar degeneration of basal cells
• Civatte bodies (like LP, but scattered)

• Atrophy, fibrosis
• Sparse or absent infiltrate
• Post-inflammatory pigmentation
• Pilosebaceous units destroyed (only "orphaned" arrector pili muscles remain)

Immunofluorescence

• DIF (direct IF) of lesional skin: positive in >75% of established lesions (must be active for several months)
• Pattern: strong, continuous granular deposition of IgG, IgM, and complement (C3) at the DEJ = the "lupus band"
• Contrast with pemphigus (fishnet intercellular) and BP (linear BMZ)
• DIF of non-lesional skin is typically negative in DLE (unlike SLE where non-lesional sun-exposed skin can be positive)

Laboratory Workup

Differential Diagnosis

Treatment

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PART 3: ATOPIC DERMATITIS (ECZEMA)

The Big Concept: A Broken Skin Barrier + Type 2 Inflammation

Epidemiology

• Affects ~20% of children globally; ~10% of adults
• Prevalence still rising in developing nations (plateaued in developed nations in the 1990s)
• Most common chronic skin disease of childhood
• 50% of cases present in the first year of life, almost all within 5 years
• Girls slightly more affected
• Strongly associated with asthma (50%), allergic rhinoconjunctivitis, food allergy = atopic triad
• Atopic march: AD → food allergy/asthma → allergic rhinitis (AD often precedes and may prime this sequence)

Pathogenesis - Two Interlocking Defects

1. Barrier Defect (Filaggrin)

• FLG is cleaved by caspase-14 into pyrrolidone carboxylic acid + urocanic acid = "natural moisturizing factor" (NMF)
• FLG null mutations → reduced NMF → xerosis (dry skin)
• Defective lamellar body lipid delivery (especially ceramide deficiency) → impaired lipid bilayers → increased transepidermal water loss (TEWL)
• The leaky barrier allows allergen penetration → sensitization through the skin
• FLG mutations: 42-79% of carriers develop AD; associated with early onset, persistence into childhood, and the atopic march (especially asthma)
• Hyperlinear palms (PPV 71%) and ichthyosis vulgaris are cutaneous markers of FLG mutations

2. Immune Dysregulation (Th2/Th22 inflammation)

• TSLP (thymic stromal lymphopoietin) - produced by keratinocytes - is the "master alarm signal" of the skin that activates dendritic cells and drives Th2 differentiation
• Th2 cells produce IL-4, IL-13 → IgE class-switching, mucus production, inhibit filaggrin expression (perpetuating the barrier defect)
• IL-31 binds directly to cutaneous nerves → itch (key cytokine for pruritus in AD)
• IL-22 (Th22 cells) → epidermal hyperplasia
• JAK-STAT pathway is central to this overactive Th2 signaling
• Secondary: CD8+ T cells and innate lymphoid cells type 2 (ILC2) also contribute
• Staphylococcus aureus colonization (universal in AD) secretes superantigens that massively amplify Th2 inflammation

• Elevated total and specific IgE
• Elevated blood eosinophils
• Response to IL-4/IL-13 blockade (dupilumab)

Clinical Features by Age

Stage 1: Infantile AD (birth to 2 years)

• Begins at 2+ months (never at birth - that would suggest ichthyosis or immunodeficiency)
• Cheeks, forehead, scalp, extensor surfaces - the baby's crawling surfaces
• Weeping, crusting, erythematous patches
• Note: Axillary and inguinal folds typically spared (unlike scabies which involves folds)
• Usually improves by end of year 2

Stage 2: Childhood AD (2-10 years)

• Shifts to flexural surfaces - antecubital and popliteal fossae, flexor wrists, behind knees, ankles
• Less weeping, more lichenified plaques from chronic rubbing
• Nummular morphology common

Stage 3: Adolescent/Adult AD

• Flexural distribution continues; also front of neck, periorbital, perioral
• Lichenification prominent; prurigo-like papules (excoriated firm papules)
• Distribution becomes less characteristic in older adults
• Hand eczema is very common in adults (aggravated by wet work)
• "The itch that rashes" - pruritus often precedes lesions

The "Itch-Scratch Cycle"

Diagnostic Criteria (Hannifin and Rajka)

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

Physical Signs of the Atopic Diathesis

Complications

• Eczema herpeticum (Kaposi varicelliform eruption): HSV dissemination through the broken barrier → widespread punched-out erosions, fever, potentially fatal. Contraindication to smallpox vaccination (vaccinia = severe, potentially fatal).
• Staph aureus superinfection: universal colonization; exacerbates AD through superantigen production; treat with mupirocin topically or systemic antibiotics for overt infection
• Molluscum contagiosum: widespread, exuberant in atopics
• Eczema vaccinatum: disseminated vaccinia from exposure to smallpox vaccine

Treatment - Stepwise Approach

Step 1: Skin Care Foundation (All Patients)

• Emollients/moisturizers: applied liberally and frequently, within 3 minutes of bathing ("soak and smear"); ointments preferred (no preservatives, better occlusion)
• Bathing: lukewarm soaks 10-15 min to hydrate skin; gentle non-soap cleansers
• Avoid triggers: wool, harsh soaps, sweat, known allergens, stress
• Reduce Staph colonization: dilute bleach baths (0.005% sodium hypochlorite - "bleach baths")

Step 2: Anti-inflammatory Therapy

• Ointments preferred over creams
• Low-potency for face, genitals, skin folds (hydrocortisone 1-2.5%)
• Mid-potency for body (triamcinolone 0.1%)
• High-potency for thick, lichenified plaques (clobetasol) - short courses only
• Once daily application nearly as effective as twice daily; do not over-apply
• Steroid phobia is common - address parental concerns directly
• Maintenance: 2-5x weekly application to frequently-flaring areas

• Tacrolimus 0.03% / 0.1% ointment (Protopic)
• Pimecrolimus 1% cream (Elidel)
• No skin atrophy (unlike steroids) - preferred for face, eyelids, skin folds
• Safe for long-term use; burning on application common initially
• Not for age <2 years (tacrolimus 0.03%); not for immunocompromised

• Crisaborole - non-steroid, non-TCI option; mild-moderate AD

Step 3: Systemic Therapy (Moderate-Severe)

Dupilumab - The Key Biologic

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THREE-WAY COMPARISON TABLE

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Memory Tricks

• SSc = "Skin becomes Stone"** - fibrosis turns skin into hard, tight stone; remember CREST for limited form
• SSc autoantibodies: lcSSc = "Centromere in CREST"; dcSSc = "Scl-70 in dcSSc" (both start with hard 'S' sounds)
• DLE: Discs, Dyspigmentation, Death of follicles (scarring alopecia), Direct IF positive at DEJ
• AD = "Inside Out": broken barrier lets things IN (allergens), and water escapes OUT (TEWL); Th2 is the T-helper that says "Be Allergic" - type 2 = atopy
• Atopic march: A-A-A-R = AD → Asthma → Allergic rhinitis (in that order)
• Dupilumab = Du-pi = blocks IL-4 and IL-13 (the two Th2 cytokines)

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