Fixed drug eruptions (FDE) are a type of
adverse drug reaction that presents as recurrent lesions in the same location each time the offending drug is administered. These eruptions are characterized by their distinctive clinical and histopathological features. In this article, we will explore various aspects of fixed drug eruptions from a histological perspective.
Histologically, fixed drug eruptions are characterized by a combination of epidermal and dermal changes. The epidermis often shows
necrotic keratinocytes, which are a hallmark of FDE. Additionally, there is often
spongiosis, or intercellular edema, which may be accompanied by vesiculation.
In the dermis, a superficial and deep perivascular infiltrate composed predominantly of
lymphocytes can be observed. There may also be the presence of eosinophils and
melanophages, which are indicative of post-inflammatory pigmentation changes. The infiltrate can extend into the subcutaneous tissue, especially in more severe cases.
Diagnosis of FDE through histology involves identifying the characteristic features mentioned above. A biopsy taken from the edge of a lesion typically reveals a band-like infiltrate of lymphocytes that obscures the dermo-epidermal junction, along with necrotic keratinocytes. The presence of these features, combined with the clinical history of recurrent lesions at the same site following drug exposure, supports the diagnosis of FDE.
Immunohistochemistry can be a valuable tool in distinguishing FDE from other conditions with similar histological features, such as
lichen planus or
discoid lupus erythematosus. Markers like CD3, CD4, and CD8 are useful in characterizing the types of lymphocytes present in the infiltrate. A predominance of CD8+ T cells is typically seen in FDE, which assists in differentiating it from other dermatoses.
FDE can be differentiated from other drug-induced skin reactions histologically by its unique pattern. Unlike
erythema multiforme, which may show similar epidermal necrosis, FDE tends to have more localized and recurrent lesions. Furthermore, the presence of a dense, band-like lymphocytic infiltrate in FDE is distinct from the more diffuse infiltrate seen in other conditions, such as
drug-induced hypersensitivity syndrome (DIHS).
Histological examination alone cannot predict the recurrence of FDE. However, it provides essential information for the initial diagnosis and helps in ruling out other potential causes of skin lesions. The recurrence is primarily a clinical phenomenon, driven by re-exposure to the causative drug.
While histology is invaluable in diagnosing FDE, it has limitations. Histological findings can sometimes overlap with other dermatoses, making it challenging to distinguish between them without comprehensive clinical correlation. Furthermore, the timing of the biopsy can affect the histological findings, as early lesions might not show full-blown features of FDE, and older lesions may show more non-specific post-inflammatory changes.
In conclusion, histology plays a critical role in the diagnosis and understanding of fixed drug eruptions. By identifying key features such as necrotic keratinocytes and lymphocytic infiltrates, histologists can aid clinicians in confirming a diagnosis of FDE. However, it is essential to integrate histological findings with clinical history and presentation to achieve accurate and effective diagnosis and management.
