What is a cutaneous reaction?

What is a Cutaneous Reaction

A cutaneous reaction is an adverse change in the skin, mucous membranes, or skin appendages (hair, nails) caused by medications, allergens, or other external agents, ranging from mild rashes to life-threatening conditions requiring immediate recognition and management. 1, 2

Definition and Scope

Cutaneous reactions encompass a broad spectrum of skin manifestations that can be triggered by various mechanisms:

• Drug-induced cutaneous reactions affect 2-3% of hospitalized patients and occur in 1-3% of multimedicated patients, making the skin the most frequently affected organ by adverse drug reactions 2, 3
• These reactions can present as exanthematous (morbilliform), urticarial, pustular, bullous, papulosquamous, or granulomatous lesions, and may appear in annular, polycyclic, or polymorphous configurations 4
• Immediate cutaneous reactions (occurring within minutes to hours) range from mild eruptions to anaphylaxis and are often mast cell-mediated, while delayed reactions (typically 6-24 hours or longer) are more likely T-cell-mediated 1

Classification by Mechanism

Immune-Mediated Reactions

• Type I (immediate hypersensitivity): IgE-mediated reactions causing urticaria, angioedema, or anaphylaxis within minutes to hours of exposure 5
• Type IV (delayed hypersensitivity): T-cell-mediated reactions including allergic contact dermatitis, which manifests as eczematous lesions after sensitization to environmental chemicals (haptens) that bind to epidermal carrier proteins 1
• Allergic contact dermatitis is clinically indistinguishable from other forms of dermatitis and requires patch testing for definitive diagnosis, with sensitivity of 60-80% 6

Non-Immune-Mediated Reactions

• Irritant contact dermatitis results from direct chemical damage without immune system involvement and is more common than allergic dermatitis 7, 8
• Other mechanisms include cumulative toxicity, photosensitivity, drug interactions, and metabolic pathway variations 2

Clinical Presentation Spectrum

Mild to Moderate Reactions

• Maculopapular rash (most common drug eruption pattern), urticaria/angioedema, and fixed drug eruption are the most frequently reported patterns 3
• Benign delayed exanthems can often be managed symptomatically with oral H1-antihistamines while continuing treatment 1
• In acute phase: erythema and vesiculation; in chronic phase: dryness, lichenification, and fissuring 7

Severe Cutaneous Adverse Reactions (SCARs)

• Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN): characterized by skin pain, skin sloughing, facial edema, blisters, and erosions—potentially lethal and requiring immediate drug discontinuation 1
• Drug reaction with eosinophilia and systemic symptoms (DRESS): presents with fever, widespread rash, and internal organ involvement 1
• Acute generalized exanthematous pustulosis (AGEP): characterized by widespread pustules 1
• These severe T-cell-mediated reactions are not amenable to desensitization and typically indicate complete drug avoidance 1

Common Causative Agents

Medications

• Antibiotics (especially beta-lactams, sulfonamides, fluoroquinolones), NSAIDs, and antiepileptics are most commonly associated with cutaneous reactions, with eruption rates of 1-5% 2, 3
• Chemotherapeutic agents cause cutaneous reactions in up to 71.5% of patients, with immediate reactions ranging from mild eruptions to anaphylaxis 1
• Corticosteroids themselves can cause allergic dermatitis, acneiform eruptions, and various other skin manifestations 9

Contact Allergens

• Most common allergens in atopic dermatitis patients: nickel, neomycin, fragrance, formaldehyde and other preservatives, lanolin, and rubber chemicals 1
• Metals (particularly nickel), fragrances, and topical antibiotics are frequent triggers in the general population 7

Diagnostic Approach

Clinical Assessment

• Detailed exposure history including timing of symptom onset (immediate vs. delayed), location of initial symptoms, and whether symptoms improve with environmental changes 8
• Pattern recognition: facial/eyelid involvement, flexural severity, vesicular lesions on hands/fingertips suggest allergic contact dermatitis 1
• Clinical features alone are unreliable in distinguishing allergic from irritant or endogenous eczema, particularly with hand and facial involvement 7, 8

Diagnostic Testing

• Patch testing is the gold standard for allergic contact dermatitis, with allergens applied to unaffected skin for 48 hours and reactions assessed at removal and up to 7 days later 1
• Skin testing for immediate drug reactions has variable utility depending on the agent; for many drugs (fluoroquinolones, macrolides), testing is not validated or standardized 1
• Drug challenge may be appropriate for mild historical reactions occurring >5 years ago, with graded dosing protocols 1

Critical Management Principles

Immediate Actions

• Discontinue the suspected causative agent immediately for any severe cutaneous reaction or when SJS/TEN is suspected 1, 2
• Complete allergen avoidance is the most critical step for allergic contact dermatitis and offers the best chance for resolution 6

Treatment by Severity

• Mild reactions: Topical mid- to high-potency corticosteroids (e.g., triamcinolone 0.1%) for localized acute reactions 6
• Widespread exanthematous rashes: Short cycles of systemic corticosteroids combined with antihistamines 2
• Severe reactions (SJS/TEN, DRESS): Aggressive corticosteroid regimens or intravenous immunoglobulins with intensive supportive care 2

Special Considerations

• Desensitization protocols can be performed for immediate hypersensitivity reactions when the implicated drug is preferred therapy, but are not appropriate for severe T-cell-mediated delayed reactions 1
• Delayed reactions to contrast media comprise 0.5-23% of all reactions, with >99% manifesting as cutaneous symptoms, most commonly maculopapular exanthem 1
• Immune checkpoint inhibitor-related cutaneous toxicities are the most common immune-related adverse events, occurring in up to 71.5% of patients, with median onset at 4 weeks but ranging from 2-150 weeks 1

Common Pitfalls

• Failing to consider contact dermatitis in atopic dermatitis patients: allergic contact dermatitis occurs in 6-60% of atopic dermatitis patients and is often overlooked 1, 6
• Assuming seafood or iodine allergy increases risk for contrast reactions: no clear association exists, and these should not be used as criteria for premedication 1
• Continuing potentially causative drugs in severe reactions: early recognition and immediate discontinuation of non-essential drugs is life-saving for SCARs 1, 2
• Relying on clinical appearance alone: patch testing is essential when allergic contact dermatitis cannot be ruled out, as morphology is unreliable for distinguishing reaction types 7, 8