Adverse Drug Reactions (ADRs)
An adverse drug reaction (ADR) is any harmful, unintended response to a medicine that occurs at doses normally used in people to prevent, diagnose or treat disease, or to modify a physiological function. In dermatology and medical aesthetics, the skin is the organ where ADRs show up most often (30% to 45% of all systemic ADRs). That is because of its large surface area, rich network of small blood vessels and abundance of antigen-presenting cells (Langerhans cells and dendritic cells).
Drug-related skin reactions range widely, from mild, self-limiting rashes (hives, maculopapular eruptions) to acute, life-threatening syndromes (SJS/TEN, DRESS, AGEP). At Haute-Derma, early recognition, accurate classification of the underlying mechanism and prompt treatment are central to keeping patients safe, and they form the basis of a personal drug allergy record.
Mechanisms and the Rawlins & Thompson Classification
Clinically, ADRs fall into two main groups under the modified Rawlins & Thompson classification, depending on whether the reaction is predictable:
- Type A ADRs (Augmented):
- Mechanism: dose-dependent reactions arising from the drug's known pharmacologic effects. They account for about 80% of clinical ADRs.
- Features: predictable from pharmacokinetics and pharmacodynamics. Common, but rarely fatal.
- Skin examples: dry skin and lips with high-dose isotretinoin, skin thinning and visible vessels from long-term topical steroids, and hair loss from chemotherapy.
- Type B ADRs (Bizarre — idiosyncratic or allergic):
- Mechanism: not dose-dependent; driven by the immune system (drug allergy) or by genetic and individual susceptibility (idiosyncrasy).
- Features: cannot be predicted from the drug's usual pharmacology. Less common, but often severe, with a high death rate. Activated T cells or IgE- or immune complex-mediated responses play the central role.
- Gell & Coombs classification (for type B drug allergy):
- Type I (immediate, IgE-mediated): angioedema, acute hives and anaphylaxis, within minutes to hours of taking the drug.
- Type II (cytotoxic, IgG/IgM): drug-induced thrombocytopenia and hemolytic anemia.
- Type III (immune complex): serum sickness and drug-induced vasculitis.
- Type IV (T cell-mediated): exanthematous (maculopapular) eruptions, DRESS, SJS/TEN and AGEP, appearing days to weeks later.
How We Diagnose and Screen for ADRs at Haute-Derma
- Detailed Drug History and Timeline
- Building a timeline: we record the exact start date, any dose changes and the date the rash appeared for every oral and injected medicine, supplement and herbal product used in the past 2 months.
- Assessing causality with the Naranjo scale or the ALDEN score (specific to SJS/TEN), based on plausible timing, what happens when the drug is stopped (dechallenge) and, where data exist, what happens on re-exposure (rechallenge).
- Clinical Examination and Lab Tests
- Checking the mucous membranes (eyes, mouth, genitals) and the Nikolsky sign (the top layer of skin shearing off with gentle rubbing).
- Complete blood count: looking for a sharp rise in eosinophils, atypical lymphocytes or low platelets.
- Liver (ALT/AST), kidney (urea/creatinine) and muscle enzyme tests to pick up internal organ involvement early.
- Identifying the Culprit After the Acute Phase
- Skin prick and intradermal tests: for type I (IgE) reactions, performed 4–8 weeks after the skin has fully healed.
- Patch testing: chambers containing the suspected drugs are left on the skin for 48 hours to diagnose delayed, T cell-mediated (type IV) allergy.
Principles of ADR Management
- Stop the Suspected Drug Immediately: as soon as an ADR is suspected, stopping the culprit — or all non-essential medicines — is the single most important step in reducing the risk of severe complications and death.
- Supportive and Intensive Care
- Severe cases (SJS/TEN, DRESS) need care in a sterile isolation room or an intensive care or burn unit.
- Correcting fluids and electrolytes, maintaining body temperature, and caring for skin and mucous membranes with non-stick petrolatum gauze dressings.
- Drug Treatment to Calm the Immune Response
- Systemic corticosteroids: IV methylprednisolone (1–2 mg/kg/day) given early in DRESS or in moderate to severe drug reactions to control the excessive inflammatory response (cytokine storm).
- Intravenous immunoglobulin (IVIG) and cyclosporine A: used in SJS/TEN to block the Fas–FasL pathway that drives widespread death of epidermal keratinocytes.
- Second-generation antihistamines: to control itching and hives.
- Formal ADR Reporting and Patient Alerts
- Completing a standard ADR report for the National ADR Reporting Center.
- Giving the patient a personal "Drug Allergy Card" listing the drug that caused the reaction and any cross-reacting drugs to be strictly avoided in the future.