Contact Dermatitis

• Irritant Contact Dermatitis (ICD) - Non-immunologic mechanism: ICD occurs through direct cytotoxic effects of irritating substances on keratinocytes without requiring prior sensitization or adaptive immunity. Common irritants (water, detergents, acids, alkalis, solvents) disrupt the stratum corneum lipid barrier, damaging tight junctions and desmosomes. This barrier disruption allows irritants and endogenous proteases to penetrate deeper layers, directly activating innate immune pathways through pattern recognition receptors (particularly TLR2/4) on keratinocytes and resident Langerhans cells. Activated keratinocytes release damage-associated molecular patterns (DAMPs) including HMGB1, S100 proteins, and heat shock proteins, which trigger rapid release of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-8) and chemokines (CXCL8, CXCL10). This results in immediate (within minutes to hours) infiltration of neutrophils and macrophages, producing acute inflammation with erythema and edema. The severity and kinetics depend on irritant concentration, exposure duration, and individual barrier function rather than immunologic memory.

• Allergic Contact Dermatitis (ACD) - Type IV hypersensitivity: ACD represents a Type IV delayed-type hypersensitivity reaction requiring two phases: sensitization and elicitation. During sensitization, haptens (small molecular weight allergens <500 Da, such as nickel, poison ivy urushiol, or paraphenylenediamine) penetrate the skin barrier and covalently conjugate to carrier proteins, forming complete antigens. Langerhans cells (and other dendritic cells) phagocytose hapten-protein complexes via TLR-mediated pattern recognition. These antigen-presenting cells undergo maturation, upregulate MHC-II and co-stimulatory molecules (CD80/86), and migrate to regional lymph nodes via CCR7-mediated migration. In lymph nodes, activated Langerhans cells present processed antigen peptides to naive CD4+ T cells through MHC-II molecules, providing three signals: (1) TCR-MHC-II interaction, (2) CD28-CD80/86 co-stimulation, and (3) cytokine polarization (IL-12, IL-18) that drives Th1 differentiation. Sensitized effector and memory CD4+ T cells (and CD8+ T cells for some allergens) develop and circulate for years to decades. Upon re-exposure (elicitation phase), hapten-antigen enters skin and is presented locally by Langerhans cells and dermal dendritic cells to resident memory T cells. Activated T cells release IFN-γ, TNF-α, and lymphotoxin, recruiting and activating macrophages and additional T cells in a cascade that peaks at 48-72 hours. This explains the delayed kinetics of ACD versus ICD and the characteristic patch test timing.

• Barrier dysfunction and amplification: Both ICD and ACD involve compromise of the skin barrier function, including loss of structural proteins (filaggrin mutations predispose to both conditions), reduced lipid content, and impaired tight junction proteins. Inflammatory mediators (TNF-α, IL-1β) further disrupt claudins and occludin, perpetuating barrier dysfunction and enhancing allergen/irritant penetration. IL-17 produced by activated T cells enhances neutrophil recruitment and barrier disruption. This creates a feed-forward loop where initial inflammation perpetuates barrier damage, explaining why resolution requires complete allergen/irritant avoidance.

• Genetic and individual susceptibility factors: Polymorphisms in filaggrin (FLG), IL-4, IL-13, and other immune-related genes increase ACD susceptibility through impaired barrier function or enhanced Th2/Th1 responses. Atopic individuals with impaired barrier function develop ACD more readily despite comparable allergen exposure. Polymorphisms in detoxification enzymes (glutathione S-transferases) influence individual susceptibility to certain allergens.

• Irritant Contact Dermatitis (ICD) causes: Water (cumulative irritation from repeated wetting/drying cycles, particularly in healthcare workers), soaps and detergents (strip lipid barrier), organic solvents (acetone, chloroform, mineral oil—dissolve lipid bilayer), strong acids and alkalis, metalworking fluids, pesticides, and plants (mechanical irritation from calcium oxalate crystals in Dieffenbachia). Healthcare workers and food handlers develop ICD from frequent handwashing and immersion. Severity correlates with irritant concentration and duration; most individuals develop ICD with sufficient exposure, making it a "universal" reaction.

• Allergic Contact Dermatitis (ACD) allergens - classic associations: Nickel (jewelry, belt buckles, coins, watches, orthopedic implants—most common allergen affecting 10-15% of population, higher in women), poison ivy/oak/sumac (urushiol oil—affects 50% of exposed Americans, most common ACD in North America), chromium (leather tanning, cement), cobalt (jewelry, batteries, pigments—frequently co-sensitized with nickel), fragrance mix and balsam of Peru (cosmetics, topical medications, flavorings), paraphenylenediamine (PPD—hair dyes, particularly in darker-skinned populations), formaldehyde (clothing, cosmetics, nail products), thiuram and dithiocarbamate accelerators (rubber products, including latex gloves—paradoxically, individuals become sensitized to additives rather than latex itself), neomycin (topical antibiotics—causes ACD in 6% of users), and methylchloroisothiazolinone/methylisothiazolinone (MCI/MI—preservative in personal care products and industrial biocides). Occupational allergens include epoxy resins (electronics, construction), adhesives, and wood dusts.

• Risk factors for ACD development: Genetic predisposition (family history of atopy increases risk 2-3 fold), female gender (higher sensitization rates to nickel and fragrance due to jewelry exposure and cosmetic use), occupational exposure (especially in construction, healthcare, metalworking, hairdressing, agriculture—accounts for 10-15% of occupational dermatitis), atopic dermatitis history (impaired barrier function increases allergen penetration), age (peak incidence 40-60 years, though can occur any age), and degree of exposure (frequency and concentration both matter for sensitization).

• ICD risk factors: Impaired barrier function (atopic dermatitis, ichthyosis, filaggrin mutations), age extremes (elderly with thinner stratum corneum, infants with immature barrier), environmental factors (low humidity, cold weather exacerbate), genetic polymorphisms affecting barrier proteins, and occupational/behavioral factors (handwashing frequency, chemical exposure).

• Pruritus (itching) - cardinal symptom present in nearly 100% of cases, often severe and out of proportion to visible findings in early disease. Mediated by histamine release from mast cells, neuropeptides (substance P, CGRP from nerve endings), and pro-inflammatory cytokines (IL-31 produced by Th2 cells). Pruritus often precedes visible erythema by 12-24 hours. Scratching causes lichenification and excoriation, which perpetuates inflammation through trauma.

• Erythema - appears as well-demarcated or poorly demarcated areas of blanching erythema, typically within 24-48 hours of exposure in sensitized individuals. In ICD, erythema may appear within minutes to hours. Intensity correlates with allergen potency and degree of sensitization. Erythema results from vasodilation mediated by histamine, bradykinin, and prostaglandins.

• Edema and vesiculation - fluid accumulation in dermis causes skin swelling and tense edema. In acute severe ACD, characteristic fluid-filled vesicles and bullae develop as inflammatory infiltrate separates epidermal/dermal interface (spongiosis). Vesicles tend to occur in most exposed, thin-skinned areas (face, genitals, hands). Fluid from vesicles contains high concentrations of allergen and inflammatory mediators.

• Xerosis and scaling - as acute phase resolves (typically day 5-7), inflammation decreases but barrier disruption persists, leading to dry skin (xerosis) and fine scale. This phase may last weeks if allergen exposure continues.

• Morphologic patterns reflect exposure pattern: Sharp demarcation at jewelry lines (nickel), linear streaks or drip patterns (plant oils dripping down extremity), glove distribution (occupational), symmetric involvement of eyelids from touching (indirect spread), and facial involvement in seasonal allergies (pollen-induced ACD).

• Physical exam findings:
• Acute phase (day 1-3): Erythema, edema, vesicles/bullae on erythematous base, oozing and crusting if severe
• Subacute phase (day 4-14): Resolving erythema, scaling, lichenification from scratching, crusting
• Chronic phase (weeks to months if allergen continues): Lichenification (thickened, exaggerated skin markings), hyperpigmentation, hypopigmentation, excoriations
• Important distribution clues: Airborne ACD involves face/neck/exposed areas (fragrance, pollen); contact patterns correspond to allergen source; photoallergic contact dermatitis (from sunscreen, fragrances) affects sun-exposed areas

• Clinical variants:
• Airborne contact dermatitis: Occurs from inhaled particles (plant pollens, cosmetic sprays, adhesive dusts) affecting face and exposed skin, sparing intertriginous areas
• Photocontact dermatitis: Allergen requires UV activation (furocoumarins in citrus, sunscreen components) causing exaggerated reaction in sun-exposed areas
• Systemic contact dermatitis: Oral or systemic exposure to allergen causes widespread dermatitis in already sensitized individual (e.g., nickel ingestion causing flare of hand dermatitis in nickel-sensitized patients; poison ivy oral exposure)
• Nummular dermatitis appearance: Coin-shaped plaques, can be secondary to contact allergen
• Severe acute reaction: Extensive edema of face/genitals, high fever, lymphadenopathy, diffuse vesiculation—must distinguish from severe drug reaction or infection

• Clinical history - key diagnostic elements: Temporal relationship between exposure and symptom onset (ICD typically minutes to hours, ACD 24-72 hours after exposure), identification of potential allergen/irritant source (occupational history, product use, recent travel), prior similar reactions, and distribution pattern. Ask specifically about jewelry (nickel), cosmetics and fragrances, topical medications (neomycin), occupational exposures, home cleaning products, plants contacted, and hobbies. Key history point: Can the patient identify the allergen/irritant? Unlike eczema with unknown etiology, contact dermatitis should have identifiable precipitant.

• Physical examination patterns: Demarcation corresponding to allergen application (sharp borders at jewelry contact site vs. less defined edges in airborne/irritant exposure), involvement of exposed areas in airborne dermatitis, and characteristic morphology (acute vesiculation in ACD vs. scaling/erythema in chronic ICD). Important exam sign: Ask patient to demonstrate where reaction started—this often pinpoints exposure source.

• Patch testing - gold standard for ACD diagnosis: Standardized allergens (typically 20-30 allergens in routine panel, up to 100+ in extended panels) applied to aluminum chambers on adhesive tape placed on uninvolved skin (usually upper back) for 48 hours, then read immediately after removal and again at 72-96 hours. Interpretation of patch test reactions:
• Negative (-): No reaction
• Irritant reaction (IR): Faint erythema/erosions developing by 48 hours and diminishing by 72 hours
• Doubtful (+/?): Faint erythema only at 72-96 hours
• Weak positive (+1): Erythema with possible papules at 72-96 hours
• Strong positive (+2/+3): Erythema, papules, vesicles at 48 hours OR intense reaction at 72-96 hours
• Clinical significance: Doubtful reactions are often false positives/irritant; strong positive reactions (+2/+3) are highly specific for clinically relevant sensitization (80-90% specificity). Sensitization history may not indicate current clinical relevance; patient must have compatible exposure history.

• Photopatch testing: For suspected photocontact dermatitis, allergen applied to two identical sites; one site covered from UV, other exposed to UVA 10J/cm² immediately after application. Read at 24/48 and 72/96 hours. Photopatch reaction only on exposed site confirms photoallergy. Sensitivity approximately 60-70%.

• Use testing: Direct application of suspected allergen to small skin area (forearm) for 24-48 hours if patch testing unavailable or to confirm patch test findings with real product. Higher risk of sensitization, mainly used when product is primary suspect.

• Laboratory tests: Generally not needed for diagnosis. Serum IgE testing (specific IgE to allergen) has poor sensitivity/specificity (~50-60%) compared to patch testing and not routinely recommended. Lymphocyte proliferation assays (LPA) and leukocyte migration inhibition tests measure T cell response to allergen but are research tools, not clinically practical.

• Imaging: Not typically needed. Dermoscopy may show nonspecific findings (hyperpigmentation pattern in dark skin). Photography helpful for follow-up assessment but not diagnostic.

• Diagnostic criteria: Diagnosis requires ALL of: (1) compatible clinical presentation (pruritic dermatitis with defined distribution), (2) temporal relationship with known allergen/irritant exposure, (3) exclusion of other diagnoses (infection, other dermatitis), and (4) for ACD: reproducible positive patch test or clinically diagnostic history. Single positive patch test without compatible history/exposure is insufficient.

• Differential diagnosis considerations:
• Allergic drug reaction: Systemic onset (typically all over body), history of new medication. Patch testing negative.
• Atopic dermatitis: Poorly demarcated plaques, personal/family history of atopy, often affects flexural areas, pruritus with dry skin baseline
• Seborrheic dermatitis: Scalp/face involvement, greasy scale, history of similar flares, no clear allergen exposure
• Nummular dermatitis: Coin-shaped plaques, may be secondary to contact allergen (must patch test)
• Dyshidrotic eczema: Pompholyx-type vesicles on palms/soles, unknown trigger (though contact allergen can exacerbate)
• Photodermatitis/phototoxicity: Sun-exposed distribution, history of sun exposure preceding rash, may occur without prior sensitization
• Irritant vs. allergic: ICD develops in anyone with sufficient exposure; ACD requires prior sensitization and occurs in subset of exposed individuals

• Allergen/irritant avoidance - first-line definitive therapy: Complete removal of the offending substance from environment is mandatory. Even with pharmacologic treatment, continued exposure prevents resolution. Provide patient with detailed list of allergen-containing products to avoid (e.g., "avoid

Infectious complications (barrier failure + excoriation)

• Secondary bacterial infection (impetiginization): scratching inoculates Staphylococcus aureus or Streptococcus pyogenes through a disrupted stratum corneum. Signals: honey-colored crust, pustules, purulent oozing, expanding tender erythema. Treat per IDSA skin and soft tissue infection guidance — topical mupirocin for limited impetigo, oral anti-staphylococcal therapy (e.g., cephalexin; doxycycline or trimethoprim-sulfamethoxazole if MRSA is suspected) for cellulitis. Fever, streaking lymphangitis, or systemic toxicity warrants urgent evaluation.
• Eczema herpeticum: HSV disseminating across inflamed, barrier-poor skin, most often in patients with underlying atopic dermatitis. Signals: abrupt monomorphic punched-out erosions with scalloped borders, pain out of proportion, fever. Emergency — start systemic acyclovir and obtain ophthalmology input if periocular.

Complications of the dermatitis itself

• Erythroderma/generalized exfoliative dermatitis: >90% body surface involvement causes transepidermal water and heat loss, high-output vasodilation, and hypoalbuminemia. Signals: diffuse erythema with sheets of scale, hypothermia, tachycardia. Emergency requiring admission and fluid/temperature support.
• Severe periorbital or genital edema (classic with urushiol): loose connective tissue permits dramatic swelling; airway compromise is rare but facial/oropharyngeal involvement warrants urgent assessment.
• **Autoeczematization (id reaction)**: circulating activated T cells seed distant skin, producing symmetric papulovesicles remote from the contact site.
• Chronic hand eczema, lichenification, and postinflammatory hyper- or hypopigmentation: persistent exposure drives fibrosis and melanocyte disruption; a leading cause of occupational disability and job change.

Treatment-related complications

• Topical corticosteroids: dermal collagen catabolism causes atrophy, striae, telangiectasia, and perioral dermatitis; periocular use risks glaucoma and cataract. Potent agents over large surfaces (especially in children) can suppress the HPA axis.
• Systemic corticosteroids: hyperglycemia, insomnia, mood change; abrupt short courses in extensive urushiol dermatitis classically produce rebound flare, so taper over roughly two to three weeks.
• Iatrogenic allergic contact dermatitis: neomycin, bacitracin, topical diphenhydramine, and even corticosteroid molecules themselves (screened with tixocortol pivalate and budesonide) can sensitize — suspect this when a "treated" rash worsens. Bacitracin has caused anaphylaxis on open wounds.
• Topical calcineurin inhibitors: application-site burning; FDA boxed warning regarding theoretical malignancy risk.

• Type IV, not type I: ACD is a delayed, T-cell–mediated hypersensitivity peaking at 48-72 hours. No IgE, no mast-cell degranulation, no role for serum IgE or skin-prick testing. The common distractor is latex: immediate urticaria/anaphylaxis from latex protein is IgE-mediated type I, whereas the dermatitis under a glove is usually type IV to rubber accelerators (thiuram, carbamates).
• Single best next step for recurrent or unexplained dermatitis: patch testing, applied to uninvolved back skin, read at removal (~48 h) and again at 72-96 h. Choosing "prick testing," "serum IgE," or "skin biopsy" is the trap. A positive patch test only counts if exposure history makes it clinically relevant.
• Nickel is the most frequently positive patch-test allergen; look for sharp demarcation under a belt buckle, earlobes, or watch band, and for hand eczema flaring after nickel-rich food in systemic contact dermatitis.
• Urushiol (poison ivy/oak/sumac) gives linear vesicular streaks where the plant brushed the skin. Blister fluid is not contagious and does not spread the rash — apparent "spread" reflects differing doses and skin thickness plus retained oil on clothing, pets, and tools.
• Timing separates the two forms: irritant dermatitis is dose-dependent, burns more than itches, and appears within minutes to hours in anyone; allergic dermatitis itches, requires prior sensitization, and is delayed a day or more.
• Iatrogenic allergens are heavily tested: a wound "failing to heal" on triple antibiotic ointment is often ACD to neomycin or bacitracin. Paraphenylenediamine explains scalp/hairline dermatitis after hair dye or black henna tattoos.
• Treatment pearls: allergen removal is definitive; mid-potency topical corticosteroids for the body, low-potency or a calcineurin inhibitor for face/folds. Reserve tapered systemic steroids for extensive disease, and do not use a short burst — rebound is the classic complication.
• Sedating oral antihistamines help sleep, not the lesions; topical antihistamines and topical anesthetics should be avoided because they sensitize.