Acetazolamide and Skin Reactions: What You Need to Know
"A rare case highlights a potential link between acetazolamide, a common medication, and unique skin eruptions. Learn about symptoms, diagnosis, and implications."
Allergic and adverse reactions to sulfonamide medications are relatively common. While acetazolamide, a type of sulfonamide, is generally well-tolerated, it can occasionally lead to cutaneous adverse drug reactions (CADRs). These reactions can manifest in various ways, including maculopapular exanthemas, acute generalized exanthematous pustulosis (AGEP), and Stevens-Johnson syndrome.
This article reports a unique case of a lichenoid and pigmented drug eruption triggered by oral acetazolamide, confirmed through a lichenoid patch test. This is the first documented case of its kind, offering valuable insights into the potential dermatological side effects of this medication.
The case involves a 76-year-old patient who developed a pruriginous maculopapular rash after being prescribed oral acetazolamide to prevent vitreous loss during cataract surgery. The rash initially appeared in the large folds of the skin, specifically in the submammary, inguinal, and axillary areas, without any mucosal involvement.
Reported Skin Reactions
A 2018 Reactions Weekly report described a woman whose biopsy showed vacuolar changes, epidermal keratinocyte necrosis, and a band-like lymphocytic infiltrate without eosinophils, consistent with a lichenoid pattern. After treatment with unspecified emollients, her symptoms healed within a week. A separate retrospective study of 64 patients treated for hypertrophic scars from January 2020 to December 2021 reported hyperpigmentation, wound ulcer, and skin atrophy in individual patients during treatment involving acetazolamide and triamcinolone acetonide injection.
Diagnosis and Testing
Published information describes acetazolamide-related cutaneous adverse drug reactions as uncommon, with few previously reported cases involving oral acetazolamide. The interest of acetazolamide skin tests had not previously been studied in the report indexed by Europe PMC. More broadly, a 2024 review examined delayed patch, prick, and intradermal testing for systemic medications and critically assessed the evidence for their usefulness across drugs and delayed hypersensitivity phenotypes.
Early Clinical Recognition
A Reactions Weekly report described a pruritic maculopapular rash in the inguinal, axillary, and sub-mammary areas after a woman received two 250 mg oral acetazolamide tablets before cataract surgery. The report noted no mucosal involvement. Another cited report identified what its authors described as the first pigmented lichenoid drug reaction to acetazolamide, placing the reaction within the drug's sulphonamide and carbonic anhydrase inhibitor context.
Unusual Symptoms and Diagnosis
The patient's condition evolved rapidly. Although pustules weren't initially observed, the skin lesions progressed to a fine desquamation, a characteristic sign observed during the healing phase of AGEP. Clinical examination revealed the patient was afebrile but presented with bilateral axillary lymphadenopathy and mild facial edema.
- Lichenoid Pattern: Characterized by a band-like infiltrate of lymphocytes in the upper dermis.
- Hyperpigmentation: Development of hyperpigmented skin patches in previously affected areas.
- Patch Test Confirmation: Positive patch tests for acetazolamide confirmed the diagnosis.
Recent Case Evidence
A case report of granuloma annulare following acetazolamide challenge described recurrence of idiopathic intracranial hypertension, after which acetazolamide was restarted at 1 g daily. Three months later, the patient's headaches had improved, but another foot rash clinically consistent with granuloma annulare had appeared. Separately, an FDA adverse-event summary presents charts of the top 100 serious side effects reported for acetazolamide, drawing on 6,266 reports submitted to the FDA.
Limits of the Evidence
The available evidence does not establish that every rash occurring during acetazolamide treatment is caused by the drug. Individual case reports and spontaneous adverse-event reports can identify possible patterns, but they do not by themselves determine frequency or prove causation. Clinical interpretation therefore requires attention to timing, competing explanations, examination findings, and the severity of the reaction.
Interpreting Differences
Acetazolamide-related skin reactions may vary substantially in appearance, distribution, and severity. A cautious comparison should distinguish localized eruptions from potentially serious systemic hypersensitivity rather than treating all rashes as equivalent. Because the supplied evidence does not provide a consistent comparator group or standardized rates, it cannot support a reliable numerical comparison among reaction types.
Implications and Further Considerations
This case underscores the importance of considering acetazolamide as a potential cause of lichenoid and pigmented drug eruptions, even though such reactions are rare. The positive patch test results emphasize the value of patch testing in assessing drug imputability and confirming the diagnosis.
Putting the Findings Together
The reported evidence includes lichenoid and pigmented eruptions, maculopapular rash, granuloma annulare-like lesions, and isolated skin findings such as hyperpigmentation, ulceration, and atrophy. These reports indicate clinical diversity rather than a single characteristic acetazolamide rash. A practical interpretation should combine the medication timeline with physical examination and, when appropriate, specialist assessment rather than relying on the appearance alone.
Questions for Future Research
Future research could clarify how often acetazolamide causes specific cutaneous phenotypes and how reliably testing identifies drug-related delayed reactions. Prospective studies with standardized diagnostic criteria would help address the limitations of isolated case reports and spontaneous reporting systems. Further work is also needed to determine which patients are at greatest risk for recurrence or severe hypersensitivity.
Rare but Serious Reactions
A 2025 report states that acetazolamide has a broad range of side effects and identifies Stevens-Johnson syndrome and toxic epidermal necrolysis as rarer reactions. A separate case report described drug reaction with eosinophilia and systemic symptoms, or DRESS, secondary to acetazolamide, initially mimicking sepsis with markedly raised procalcitonin. These cases illustrate why unusual skin findings may require assessment for systemic involvement rather than being treated as a purely local problem.
Patient Experience and Recognition
A published case described the first lichenoid drug eruption attributed to acetazolamide with pigmented evolution of the lesions, confirmed by a lichenoid patch test. The report also placed acetazolamide among sulphonamide agents and noted that allergy and adverse reactions to sulphonamides are quite common. For patients, recognizing a changing or persistent eruption and communicating its timing after treatment can be important to the clinical evaluation.
While the initial presentation resembled AGEP, the progression to hyperpigmented skin and the lichenoid pattern observed in biopsies differentiated it from typical AGEP cases. This highlights the importance of careful clinical and histopathological evaluation in diagnosing unusual drug reactions.
This case expands the spectrum of known cutaneous side effects associated with acetazolamide and emphasizes the need for clinicians to be aware of these potential reactions. Further research is needed to understand the underlying mechanisms and risk factors associated with acetazolamide-induced lichenoid and pigmented drug eruptions.