Fixed Drug Eruption (FDE) is a distinct type of cutaneous adverse drug reaction that presents with unique clinical features. It is characterized by the development of one or more skin lesions that recur at the exact same anatomical site each time the causative drug is administered. This characteristic "fixed" recurrence is the defining feature distinguishing it from other drug-induced skin eruptions.
What Are the Clinical Features of Fixed Drug Eruption?
FDE typically presents as a sharply demarcated, round or oval patch or plaque of erythema and edema, often developing a dusky red or violaceous hue. Lesions commonly occur on the lips, genitals, hands, and face, but any part of the skin can be affected. And they usually appear within minutes to hours after re-exposure to the drug, though the initial episode may take up to a week or more to develop. Once the causative drug is discontinued, the active inflammation gradually resolves, leaving behind a characteristic residual hyperpigmentation—a brown to purple macule—at the previously affected site.
While the most common presentation is the classic pigmenting form, several variants exist, including the non-pigmenting, bullous, and generalized forms. The latter, termed Generalized Bullous Fixed Drug Eruption (GBFDE), is the most severe and extensive variant, clinically mimicking severe conditions like Stevens-Johnson syndrome or Toxic Epidermal Necrolysis (SJS/TEN) due to widespread blistering and skin detachment.
Why Do Fixed Drug Eruptions Occur?
FDE occurs due to the persistence of drug-specific memory T cells in previously affected skin sites. After the initial exposure to a medication, these T cells remain in the epidermis and dermis. Upon re-exposure, they quickly release inflammatory mediators that cause localized tissue damage. The reason these cells preferentially remain in specific anatomical sites is not fully understood. Current hypotheses suggest that local cytokine patterns, keratinocyte vulnerability, and regional microenvironmental factors influence T-cell residence. Genetic factors may also play a role, although no single HLA allele has been found to account for all cases.
Which Medications are the Most Common Causes?
A wide variety of medications have been linked to FDE. Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most frequently implicated drug classes. Antibiotics such as sulfonamides, tetracyclines, fluoroquinolones, and penicillins are also common triggers. Anticonvulsants and antihistamines appear in case series as recognized causes. In some patients, herbal products and food additives have also been reported to provoke similar reactions. Although certain drug categories are more common, virtually any medication can cause FDE in a susceptible individual.
How Is Fixed Drug Eruption Diagnosed?
The diagnosis of FDE is primarily clinical, relying heavily on a detailed medical history and characteristic physical examination findings. Three elements are essential for a strong clinical diagnosis:
(1) Recurrence at the Same Site: This is the pathognomonic feature. The patient reports that the lesion consistently reappears at the exact same location(s) each time they take the specific drug.
(2) Temporal Relationship: The lesion develops within hours (typically 30 minutes to 8 hours) to a few days after re-ingestion of the suspected drug.
(3) Residual Hyperpigmentation: The lesions resolve with the development of post-inflammatory hyperpigmentation.
Can a Dermatoscope Help Detect Fixed Drug Eruption?
A dermatoscope cannot confirm the diagnosis on its own, but it can provide valuable visual clues that support clinical evaluation. Dermatoscopic features commonly associated with FDE include brown or gray-brown dots and globules produced by pigment incontinence, a reddish or violaceous background corresponding to inflammation and vascular dilation, and bluish-gray granules caused by dermal melanophages. Acute lesions may show mild and non-specific vascular structures such as fine dotted or linear vessels, though these patterns are typically subtle. While these findings may suggest FDE, none of them are specific, as similar patterns can appear in other pigmentary or inflammatory dermatoses.
How Is Fixed Drug Eruption Treated?
The cornerstone of treatment is discontinuation of the offending medication. Most lesions improve gradually once exposure stops. Topical corticosteroids are commonly used to reduce inflammation and relieve symptoms such as itching or burning. In cases with significant blistering, wound care includes protecting the skin, preventing secondary infection, and keeping the area clean and dry.
Oral antihistamines may be recommended to help reduce pruritus. The residual hyperpigmentation usually fades slowly over time. Sun protection is often advised to prevent further darkening of the affected skin and to support gradual fading.
Does Fixed Drug Eruption Affect Future Medication Use?
Having an FDE caused by one medication does not necessarily increase the risk of reactions to unrelated drugs. However, cross-reactivity may occur among medications with similar chemical structures. For example, some NSAIDs share similar molecular features that may increase the likelihood of cross-sensitivity in certain patients. Healthcare providers typically review alternative medications and choose options that are structurally distinct from the offending agent. Patients with a history of drug-induced skin reactions should consult clinicians before taking new medications.