# Contact Dermatitis and Patch Testing

## Overview and Classification

Contact dermatitis is an inflammatory skin reaction resulting from direct contact with an exogenous substance. Two principal types are recognized. Allergic contact dermatitis (ACD) is a Type IV (delayed-type) hypersensitivity reaction mediated by antigen-specific T cells and accounts for approximately 20 percent of all contact dermatitis cases. Irritant contact dermatitis (ICD) is a non-immunologic reaction caused by direct chemical damage to the skin barrier and represents the majority, approximately 80 percent, of contact dermatitis. Additional subtypes include photoallergic contact dermatitis, in which ultraviolet radiation activates a hapten to trigger a T cell-mediated response, and protein contact dermatitis, an immediate (Type I) reaction seen in food handlers exposed to intact proteins from latex or foods.

## Allergic Contact Dermatitis (ACD)

### Pathophysiology

The development of allergic contact dermatitis proceeds through two immunologically distinct phases. The sensitization phase occurs during first exposure and is clinically silent, spanning 10 to 14 days. A low-molecular-weight chemical hapten (less than 500 Daltons) penetrates the skin barrier and binds to endogenous carrier proteins, forming a complete antigen. Langerhans cells in the epidermis capture this hapten-protein complex and migrate via afferent lymphatics to regional draining lymph nodes, where they present the processed antigen to naive T cells, including both CD4+ and CD8+ subsets. This results in clonal expansion of allergen-specific memory and effector T cells.

The elicitation phase occurs on subsequent re-exposure to the sensitizing hapten and develops over 24 to 96 hours. The hapten reactivates previously generated memory T cells within the skin. CD8+ cytotoxic T lymphocytes serve as the major effector cells, inducing keratinocyte apoptosis. CD4+ T cells of both Th1 and Th17 lineages contribute by producing interferon-gamma, tumor necrosis factor-alpha, and interleukin-17. The clinical result is eczematous dermatitis localized to the site of contact, which may spread beyond the initial contact area with repeated or prolonged exposure. Some contact allergens function as pre-haptens, requiring metabolic activation within the skin itself (as with urushiol, which is oxidized to a quinone), while pro-haptens require systemic metabolism for activation.

### Common Allergens (NACDG Top 10)

The North American Contact Dermatitis Group (NACDG) has identified the most prevalent contact allergens through large-scale patch testing surveillance. Nickel sulfate leads the list at 18 to 20 percent prevalence, found in jewelry, belt buckles, cell phones, and orthodontic devices. Fragrance mix I ranks second at 11 to 14 percent, present in cosmetics, detergents, and personal care products. Balsam of Peru (Myroxylon pereirae) at 8 to 12 percent serves as a fragrance indicator and flavoring agent. Neomycin sulfate at 8 to 10 percent is found in topical antibiotic preparations and cross-reacts with the aminoglycosides gentamicin and tobramycin. Bacitracin at 7 to 9 percent is notable for its capacity to cause both Type IV contact dermatitis and Type I IgE-mediated anaphylaxis. Formaldehyde at 6 to 8 percent is found in cosmetics, fabric finishes, and formaldehyde-releasing preservatives. Cobalt chloride at 7 to 8 percent is present in metal alloys and paints and frequently co-reacts with nickel. Methylisothiazolinone (MI) at 5 to 8 percent is a preservative in cosmetics and household products that has emerged as an epidemic contact allergen. Quaternium-15 at 4 to 6 percent is a formaldehyde-releasing preservative. Para-phenylenediamine (PPD) at 4 to 6 percent is found in permanent hair dyes and black henna tattoos and cross-reacts with azo dyes, sulfonamides, and para-aminobenzoic acid (PABA).

### Occupation-Related ACD

Certain occupations carry heightened risk for specific contact allergens. Healthcare workers are exposed to latex, glutaraldehyde, acrylates, chlorhexidine, and thiuram (in rubber gloves). Hairdressers encounter PPD, persulfate bleaching agents, and glyceryl monothioglycolate. Construction workers are exposed to chromium in cement, epoxy resins, and rubber chemicals. Dental professionals handle acrylates (methacrylates), glutaraldehyde, and eugenol. Food handlers may develop protein contact dermatitis from garlic, onion, and spices.

<image>An illustrated grid showing the top 10 contact allergens in North America (NACDG data). Each allergen has its own box containing: (1) the chemical name, (2) a photograph-style illustration of common sources (e.g., nickel - jewelry and belt buckles; PPD - hair dye bottles; neomycin - antibiotic tube), (3) positive patch test reaction image showing the typical eczematous response, (4) prevalence rate percentage, and (5) key cross-reactors listed below. The grid is arranged in order of prevalence. A sidebar notes the testing concentration and vehicle for each allergen. Special highlight on methylisothiazolinone as an "emerging epidemic allergen" with upward trend arrow.</image>

## Patch Testing

### Indications

Patch testing is indicated in several clinical scenarios: suspected allergic contact dermatitis that is not responding to empiric treatment or that recurs upon cessation of therapy, chronic or recurrent eczematous dermatitis of unknown etiology, evaluation of occupational dermatitis, hand dermatitis (particularly involving the dorsal surfaces), eyelid and facial dermatitis, perianal and genital dermatitis, and stasis dermatitis with suspected superimposed allergic contact dermatitis.

### Methodology

The standard patch test series in the United States includes the T.R.U.E. Test, which is an FDA-cleared system containing 36 allergens, and the North American Contact Dermatitis Group (NACDG) standard series, which tests 70 to 80 allergens applied in Finn Chambers. Supplemental series are selected based on clinical suspicion and may include cosmetic, hairdressing, dental, corticosteroid, adhesive, or textile series. The patient's own products may also be tested in appropriate dilutions and vehicles.

The application procedure involves loading allergens into Finn Chambers (8 mm aluminum discs) or using T.R.U.E. Test strips, which are then applied to uninvolved skin on the upper back. The patches are left in place under occlusion for 48 hours (from Day 0 to Day 2). A critical aspect of the reading schedule includes: the Day 2 reading at 48 hours, performed 30 to 60 minutes after patch removal to allow pressure-induced erythema to resolve; the Day 4 to 5 delayed reading at 96 to 120 hours, which is essential and must not be omitted, as it captures late reactions that are negative at the initial reading; and an optional Day 7 reading for allergens known to produce late reactions, including metals, corticosteroids, and neomycin.

### Interpretation (ICDRG Scoring)

Patch test reactions are graded according to the International Contact Dermatitis Research Group (ICDRG) scoring system. A negative result shows no reaction. An irritant reaction (IR) appears as a glazed, petechial, pustular, or sharply demarcated burn-like response. A doubtful reaction (?+) shows faint erythema only. A weak positive (+) demonstrates erythema with slight induration and possible papules. A strong positive (++) shows erythema, induration, papules, and vesicles. An extreme positive (+++) produces a bullous or ulcerative reaction. Beyond grading the reaction, clinical relevance must be determined: whether the positive patch test result is relevant to the patient's current dermatitis (current relevance), to a past episode (past relevance), or of unknown relevance.

### Special Considerations

Several factors may affect patch test accuracy. Systemic immunosuppressants, particularly prednisone at doses exceeding 10 mg/day for more than one week, may suppress reactions; these should be held for 2 to 4 weeks before testing when feasible. Topical corticosteroids applied to the test site on the back should be avoided for one week before testing. Recent ultraviolet exposure, including tanning or sunburn, on the back should be avoided for 4 weeks, as UV radiation suppresses the local immune response. Pregnancy is not an absolute contraindication but testing is generally deferred. False-negative results may arise from immunosuppression, testing during a severe flare (anergy), use of incorrect concentrations or vehicles, or insufficient occlusion. False-positive results may occur from irritant reactions, "excited skin syndrome" (also known as "angry back," in which multiple strong positive reactions cause nonspecific positivity at adjacent sites), or edge effects.

<image>A step-by-step visual guide to patch testing procedure. Panel 1: Finn Chambers loaded with allergens in a systematic grid pattern on tape strips, with numbered chambers corresponding to allergen list. Panel 2: Patches applied to upper back of patient (anatomical illustration showing correct placement between scapulae, avoiding spine). Panel 3: Day 2 reading - patches removed, marked sites visible, examiner using magnifying lens. Panel 4: Grading scale illustrated with clinical images of each grade: negative (no reaction), irritant (sharply demarcated redness), doubtful (+/- faint erythema), weak positive (erythema + papules), strong positive (vesicles on erythematous base), extreme positive (bullous reaction). Panel 5: Day 4-5 delayed reading shown with example of a reaction that was negative at Day 2 but positive at Day 5 (metal allergen). Bottom note: "Day 4-5 reading is essential - do not omit."</image>

## Irritant Contact Dermatitis (ICD)

### Pathophysiology

Irritant contact dermatitis results from direct cytotoxic damage to keratinocytes without the involvement of immunologic memory. The mechanism involves innate immune activation, including release of interleukin-1alpha from damaged keratinocytes and NLRP3 inflammasome activation. Common irritants include soaps, detergents, solvents, wet work exposure, friction, and acids and alkalis. The severity of irritant contact dermatitis is dose-dependent, with higher concentration and longer duration of exposure producing more severe reactions. Cumulative irritant contact dermatitis develops from repeated low-grade exposures, such as frequent hand washing or chronic wet work, leading to chronic dermatitis.

### Distinguishing ICD from ACD

| Feature | Allergic Contact Dermatitis (ACD) | Irritant Contact Dermatitis (ICD) |
|---------|----------------------------------|----------------------------------|
| Mechanism | Type IV hypersensitivity (T cell-mediated) | Direct cytotoxic damage (non-immunologic) |
| Prior sensitization | Required | Not required |
| Dose-dependence | Not strictly dose-dependent | Dose-dependent |
| Borders | Irregular, may extend beyond contact area | Sharp, matching contact area precisely |
| Predominant symptom | Pruritus | Burning/stinging |
| Morphology | Vesicles, papules, eczematous | Glazed, dry, fissured |
| Affected individuals | Only sensitized persons | Most exposed at sufficient dose |
| Patch test | Positive (specific allergen) | Negative or irritant reaction |
| Timing | 24-96 hrs after re-exposure | Variable (acute or cumulative) |

Several clinical features help differentiate irritant from allergic contact dermatitis, though overlap and coexistence are common. Irritant contact dermatitis typically presents with sharp borders precisely matching the area of contact, burning sensation more prominent than pruritus, a glazed or dry appearance, and affects most individuals exposed at sufficient dose (dose-dependent). Allergic contact dermatitis tends to show irregular borders that may extend beyond the direct contact area, pruritus that predominates over burning, vesicles and papules, and affects only immunologically sensitized individuals. An important clinical principle is that chronic irritant contact dermatitis impairs the skin barrier, facilitating hapten penetration and thereby increasing the risk of developing subsequent allergic contact sensitization.

## Systemic Contact Dermatitis

Systemic contact dermatitis occurs when a previously contact-sensitized individual is exposed to the relevant allergen through a systemic route, including ingestion, inhalation, intravenous, or intramuscular administration. The clinical presentation may include symmetric involvement in a pattern known as baboon syndrome or symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), widespread eczematous dermatitis, flare at the site of prior contact dermatitis, or pompholyx (dyshidrotic eczema). Clinically relevant examples include nickel-sensitized patients who develop hand dermatitis or diffuse eczema from dietary nickel found in chocolate, oats, and legumes; balsam of Peru-sensitized patients reacting to spice-containing foods, citrus, and tomato; and patients with topical budesonide allergy developing systemic reactions to intravenous methylprednisolone due to Group B corticosteroid cross-reactivity.

## Corticosteroid Contact Allergy

Corticosteroid contact allergy presents a paradoxical situation in which a patient's eczema worsens with the very therapy intended to treat it. Cross-reactivity among corticosteroids follows the Coopman classification system, which organizes corticosteroids into groups based on structural similarity. Group A includes hydrocortisone-type molecules, with tixocortol pivalate serving as the screening marker. Group B includes triamcinolone and budesonide types, with budesonide as the marker. Group C encompasses betamethasone-type corticosteroids. Group D is subdivided into D1 (clobetasol and betamethasone dipropionate types) and D2 (methylprednisolone aceponate and hydrocortisone butyrate). Screening with tixocortol pivalate and budesonide on the standard patch test series captures approximately 90 percent of corticosteroid contact allergies.

## Management of ACD

The most important intervention in allergic contact dermatitis management is identification and avoidance of the causative allergen. Patients should receive detailed allergen-specific avoidance lists, with the Contact Allergen Management Program (CAMP) database providing customized product avoidance guidance. For acute disease, treatment includes cool compresses, mid- to high-potency topical corticosteroids, and a short course of systemic corticosteroids for severe or widespread disease (prednisone 0.5 to 1 mg/kg tapered over 2 to 3 weeks). Chronic disease is managed with topical corticosteroids or calcineurin inhibitors, emollients, and barrier protection such as gloves for hand dermatitis. Occupational allergic contact dermatitis may require workplace modifications, personal protective equipment, occupational health referral, and disability documentation when necessary.

## Key Clinical Pearls
- The Day 4-5 delayed reading is essential in patch testing; metal allergens and corticosteroids commonly show late reactions missed at 48 hours
- Irritant reactions are dose-dependent and affect most exposed individuals; ACD requires sensitization and affects only sensitized individuals
- Methylisothiazolinone (MI) is a rapidly emerging epidemic contact allergen; found in personal care products and household cleaners
- Corticosteroid contact allergy should be suspected when eczema worsens with topical steroid use; screen with tixocortol pivalate and budesonide
- Neomycin cross-reacts with gentamicin and tobramycin (shared aminoglycoside ring structure)
- Bacitracin can cause both Type IV (contact dermatitis) and Type I (IgE-mediated anaphylaxis) reactions
- Excited skin syndrome (angry back) produces false-positive patch test results from multiple strong reactions; repeat testing individually if suspected
- A low-nickel diet may benefit nickel-sensitized patients with chronic hand eczema or diffuse eczema

## References
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2. DeKoven JG, et al. North American Contact Dermatitis Group (NACDG) patch test results 2017-2018. *Dermatitis*. 2021;32(2):111-123.
3. Thyssen JP, et al. The epidemiology of contact allergy in the general population - prevalence and main findings. *Contact Dermatitis*. 2007;57(5):287-299.
4. Ale IS, Maibach HI. Diagnostic approach in allergic and irritant contact dermatitis. *Expert Rev Clin Immunol*. 2010;6(2):291-310.
5. Mowad CM, et al. Allergic contact dermatitis: patient diagnosis and evaluation. *J Am Acad Dermatol*. 2016;74(6):1029-1040.