What is a fixed drug eruption (FDE)?

From the Guidelines

A fixed drug eruption is a type of adverse drug reaction characterized by the recurrence of skin lesions at the same site each time a specific medication is taken. According to the most recent study on drug allergy, published in the Journal of Allergy and Clinical Immunology in 2022 1, fixed drug eruptions are one of the phenotypes that can occur in response to sulfonamide antimicrobials, along with other reactions such as urticaria and severe cutaneous adverse reactions (SCARs).

Key Characteristics of Fixed Drug Eruptions

• They typically appear as round or oval, well-defined patches that are reddish-purple or dark brown in color
• These lesions often develop within hours to days after taking the triggering medication and may cause burning, itching, or pain
• Common medications that cause fixed drug eruptions include antibiotics, pain relievers, anticonvulsants, and some oral contraceptives
• The reaction occurs because the drug triggers immune cells in the skin to release inflammatory chemicals in specific areas where these cells have previously been sensitized

Diagnosis and Treatment

• Diagnosis is often based on the patient's history and physical examination, as skin testing has poor sensitivity for fixed drug eruptions 1
• Treatment involves discontinuing the offending medication and sometimes using topical corticosteroids to reduce inflammation
• The lesions usually heal within 7-10 days after stopping the medication but often leave behind hyperpigmentation that can last for months or years

Importance of Avoiding Triggering Medications

• If you experience a fixed drug eruption, it's essential to identify and avoid the triggering medication in the future, as subsequent exposures typically cause more severe and potentially widespread reactions
• Induction of tolerance protocols may be considered in certain cases, but these should be relegated primarily to those with convincing histories of anaphylaxis 1

From the FDA Drug Label

NSAIDs can also cause fixed drug eruption (FDE). FDE may present as a more severe variant known as generalized bullous fixed drug eruption (GBFDE), which can be life-threatening Skin and Appendages: Exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE).

A fixed drug eruption is a type of skin reaction that can be caused by NSAIDs, including ibuprofen tablets. It may present as a more severe variant known as generalized bullous fixed drug eruption (GBFDE), which can be life-threatening 2 2.

From the Research

Definition and Characteristics of Fixed Drug Eruption

• A fixed drug eruption (FDE) is a dermatological manifestation of drug reactions that often occur in the same location upon re-exposure to a drug 3, 4.
• FDEs usually appear as erythematous-violaceous, circular patches, but several different variants have been described 3.
• They can often present without any associated symptoms, but in some cases, patients may complain of pain and pruritus 3, 4.

Diagnosis and Treatment

• The lesions are often underdiagnosed or mistaken for insect bites, urticaria, or erythema multiforme 3.
• The primary approach and treatment for all types of FDEs are to identify and remove the causative agent 4.
• Treatment of localized FDE includes medication removal, patient counseling, and symptomatic relief 4.
• Failure to remove the causative agent in localized FDE can lead to recurrence, which is associated with increased inflammation, hyperpigmentation, and risk of a potentially lethal generalized bullous FDE (GBFDE) 4, 5.

Causes and Triggers

• FDEs are associated with more than 100 medications, with the most frequently implicated drugs including analgesics (nonsteroidal anti-inflammatory drugs [NSAIDs] and paracetamol) and antibiotics 6.
• Newer, novel agents of note include cyclooxygenase-2 specific inhibitors, fluconazole, and phosphidi-9c2 inhibitors 6.
• Ibuprofen is a common cause of FDE, and its widespread availability as an over-the-counter medication can make diagnosis challenging 7.

Generalized Bullous Fixed Drug Eruption

• Generalized bullous fixed drug eruption (GBFDE) is a severe form of FDE that can be confused clinically with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) 4, 5.
• GBFDE has a more rapid onset, less or no mucosal involvement, and a tendency for a more favorable prognosis compared to SJS/TEN 4.
• However, recent experience suggests that GBFDE may be just as life-threatening as SJS/TEN 4.