Delayed cutaneous adverse drug reactions

Cutaneous reactions can develop shortly after the introduction of the drug (a few days) or later in the course (one–two months). Cutaneous reactions may include redness, scaling, blistering, and itching. The maculopapular exanthema (MPE), the most common type of cutaneous adverse drug reaction, is characterized by small confluent redness. In rare cases, MPE can develop into a serious cutaneous adverse drug reaction, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or acute generalized exanthematous pustulosis (AGEP), requiring inpatient care. Drug treatment can also worsen an existing skin disease, the worsening of psoriasis after the introduction of antimalarials is one well-known example. 

The diagnosis is primarily based on the patient’s medical history. The onset of the cutaneous reaction after the introduction of medication, the healing of skin symptoms after discontinuation of medication, and the recurrence of skin symptoms after reintroduction of medication are all factors strongly suggesting that the cutaneous reaction could be drug-induced. When applicable, an epicutaneous test (EC test) is used to investigate a potential drug-induced cutaneous reaction. The EC test is performed by applying small amounts of the specific drug substance onto the patient’s back to induce a local allergic reaction. The EC test should ideally be applied no earlier than six weeks after the suspected cutaneous adverse drug reaction has occurred and no later than six months after the suspected reaction. A positive result of the EC test (redness, blistering) strongly suggests a drug allergy (delayed drug hypersensitivity). A negative result does not exclude a drug allergy, as it could be a false negative result due to the low sensitivity of the EC test.  

The development of an additional diagnostic tool, the lymphocyte transformation test (LTT) for delayed drug hypersensitivity at Karolinska University Hospital (in collaboration with Clinical Immunology), is now ongoing. The LTT is performed by adding a suspected drug substance to a venous blood test from the patient and detecting signs of possible lymphocyte activation. 

The withdrawal of the suspected drug is essential when a drug-induced cutaneous reaction has occurred. In mild cutaneous reactions, treatment with locally administered steroids is sufficient. In moderate cutaneous reactions, the administration of oral steroids is required. Serious cutaneous reactions require inpatient care, and some of the more severe cases of patients with SLS/TEN require specialized care at the burn injury department, BRIVA, at Uppsala University Hospital. 

As a doctor, it is important to assess and take the correct action when encountering a patient with a suspected drug-induced cutaneous reaction. Therefore, we spend much time teaching students, resident doctors, and specialists. This will likely lead to better patient care.