Severe cutaneous adverse reactions
Often harmless but sometimes
life threatening
Severe cutaneous adverse reactions
Often harmless but sometimes
life threatening
SCAR
Cutaneous adverse reactions are among the most common adverse drug reactions and range from benign rashes to life-threatening conditions known as severe cutaneous adverse reactions, or SCARs such as Stevens Johnson syndrom (SJS), Toxic epidermal necrolysis (TEN) and Drug rleated eosiophilia with systemic symptoms (DRESS). While these can pose diagnostic and therapeutic challenges even in resource-rich countries, SCARs place an even greater burden on healthcare systems in low- and middle-income countries (LMICs), particularly in sub-Saharan Africa, due to limited diagnostic capabilities, therapeutics and surveillance systems.
The role of Asitro for SCAR is based on 3 pillars:
- Research on the pathophysiology of SCAR, especially in areas with limited resources where parasites and infections might enhance SCAR
- Establish simple information to recognize danger signs of SCAR for health personal and patients
- Enable access to better treatment of SCAR, including modern drugs such as JAK-inhibitors
Epidemiology
CDRs account for approximately 2–3% of all hospital patients in high-income countries and up to 5% in LMICs. Severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) occur worldwide with an incidence of approximately 1–6 cases per million inhabitants per year. However, in regions such as sub-Saharan Africa, the figures are likely to be significantly higher due to limited diagnostic challenges and a lack of medical personnel, resulting in a considerable number of unreported cases
Risk factors for SCAR, especially in LMICs, include
Polypharmacy (taking multiple medications at the same time)
Genetic predisposition
HIV infection & Tuberculosis (TB)
Other risk factors such as older age & female gender
Limited, and in most cases completely lacking, infrastructure for drug monitoring and reporting of adverse reactions
Severe cutaneous adverse reactions (SCARs):
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe skin reactions characterized by epidermal necrosis (TEN), mucosal involvement, and systemic symptoms. SJS affects less than 10% of the body surface, while TEN involves more than 30%. These conditions typically begin 1 to 3 weeks after starting medication, but can also occur with long-term use. The symptoms can become life threatening due to liquid loss and super infectious.
DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms):
Features: Fever, rash, eosinophilia, lymphadenopathy, and organ involvement (lungs, liver, kidneys, heart).
Onset: 2–6 weeks after starting medication, often later than other drug reactions.
Description: Severe, potentially life-threatening delayed hypersensitivity reaction, marked by widespread rash, fever, facial swelling, and systemic organ effects.
Triggers: Anticonvulsants (e.g., carbamazepine, phenytoin), allopurinol, sulfonamides, certain antibiotics, and antivirals. Genetic factors and viral reactivations also play roles.
Diagnosis: Based on clinical features, lab results, and timing related to drug use, using criteria like RegiSCAR.
Treatment: Immediate withdrawal of the drug, corticosteroids for severe cases, and possibly immunosuppressants, IV immunoglobulins, or biologics targeting eosinophils.
Note: DRESS can cause lasting organ damage, so early diagnosis and follow-up are critical.
AGEP (Acute Generalised Exanthematous Pustulosis):
Features: Rapid onset of numerous small, non-follicular pustules on red, painful skin, usually within 3–5 days of medication intake, often with fever and neutrophilia. Rarely life-threatening.
Description: Sudden, drug-induced skin reaction, often starting on the face or folds and spreading quickly. Common triggers include antibiotics, antifungals, and calcium antagonists; medications are identified in up to 90% of cases.
Additional signs: Fever, malaise, increased white blood cells, and temporary liver or kidney changes. Histology shows sterile pustules.
Prognosis: Good; rash typically resolves in days after stopping the drug, often leaving scaly skin. Symptom relief with antihistamines or topical steroids; systemic steroids are rarely needed.
Diagnosis: Based on clinical features, medication history, and skin biopsy if needed. Must distinguish from pustular psoriasis or infectious rashes.
Common triggers: Sulfonamides, allopurinol, anti-tuberculosis drugs (isoniazid, rifampicin), and others.
Regenerieren
Treatment:
Mild to moderate reactions
Exanthematic/Maculopapular eruptions (MPE):
Most common; symmetrical red macules and papules lasting days to weeks, often itchy but harmless without mucosal involvement or blisters.
Urticaria/angioedema:
Usually IgE-mediated; rapid onset in an hour. Wheals that dissolve quickly, but can last over 24 hours (suggesting urticaria vasculitis). In 30%, mucous membrane swelling occurs (angioedema). Can cause severe reactions like anaphylactic shock.
Fixed drug eruption (FDE):
Well-defined lesions recur at the same site with the same medication, lasting days, possibly itchy, painful, or blistering.z
Diagnostic approach for SCAR
The diagnostic approach for SCAR (Severe Cutaneous Adverse Reactions) includes a thorough clinical examination of skin and mucosal symptoms, a detailed medical and medication history to identify potential trigger drugs, and the assessment of systemic involvement. Diagnostic tools such as skin biopsies can help confirm the specific type of SCAR, like Stevens-Johnson syndrome or toxic epidermal necrolysis. Additionally, laboratory tests including blood work and imaging may be performed to evaluate the severity and rule out other causes. Accurate and prompt diagnosis is essential for effective management and avoiding re-exposure to the offending agents. Severity can be measured in different scores (score-TEN)
Medical history
Chronological course of the rash
Tests
• Complete blood count (CBC) • Skin tests • Skin biopsy • LAB • Liver/kidney function tests
Physical examination
Involvement of the mucous membranes