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- Presentation
Inpatient Dermatology Cases: Atypical AGEP, DRESS, and Multiple Drug Hypersensitivity
Description
The talk reviewed two main inpatient dermatology cases and highlighted how severe drug reactions can overlap clinically and histologically. In the first case, a woman with new Sjogren’s treatment developed a diffuse targetoid, edematous eruption with facial swelling and marked leukocytosis after starting hydroxychloroquine. Biopsy showed subcorneal neutrophilic pustules, spongiosis, papillary dermal edema, and mixed inflammation without epidermal necrosis, supporting atypical acute generalized exanthematous pustulosis (AGEP) with features overlapping DRESS and Sweet syndrome. Her course was more prolonged than classic AGEP, required high-dose systemic steroids and a slow taper, and ultimately resolved after stopping hydroxychloroquine. The speaker emphasized that hydroxychloroquine can cause delayed, protracted AGEP-like eruptions with overlap features. The second case involved an elderly woman with CKD and gout who initially developed DRESS from allopurinol, likely worsened by renal impairment and rapid dose escalation. She improved on steroids, but later had recurrent rashes and transaminitis after ceftriaxone and then nitrofurantoin, raising concern for flare-ups versus multiple drug hypersensitivity. Workup showed viral reactivation, mild biopsy changes with spongiosis/interface alteration, and later low-titer TIF-1 gamma plus incidental pancreatic cysts that led to a prolonged but ultimately unrevealing malignancy evaluation. The final impression was multiple drug hypersensitivity on a background of DRESS, with recurrent reactions to unrelated drugs and prolonged immune activation. The speaker concluded with lessons about overlap among AGEP, DRESS, and other severe cutaneous adverse reactions, the importance of considering viral reactivation and prolonged steroid risks, and the value of early steroid-sparing therapies such as cyclosporine to reduce morbidity.
View moreConclusions
- Hydroxychloroquine can trigger an atypical, delayed, and prolonged AGEP-like eruption that overlaps clinically and histologically with DRESS, Sweet syndrome, and erythema multiforme.
- In severe hydroxychloroquine reactions, stopping the drug is not always enough, and prolonged systemic steroids or cyclosporine may be needed for remission.
- AGEP can present with vesiculation, facial edema, and diffuse erythema yet still lack epidermal necrosis, which helps distinguish it from SJS/TEN.
- Allopurinol is a common cause of DRESS, especially in patients with renal impairment and rapid dose escalation.
- DRESS may persist or flare long after the initial culprit drug is stopped, particularly when viral reactivation is present.
- Subsequent unrelated antibiotics can trigger recurrent drug eruptions after DRESS, making recurrent disease versus new hypersensitivity difficult to distinguish.
- Multiple drug hypersensitivity can develop after an initial severe drug reaction and lead to reactions to chemically unrelated medications weeks to months later.
- Broad inpatient workups can uncover important diagnoses but can also lead to potentially harmful diagnostic rabbit holes and prolonged hospitalization.
- Long-term systemic steroid treatment can cause major complications, including avascular necrosis and deconditioning, so steroid-sparing strategies should be considered early in DRESS.
- A structured approach using clinical pattern recognition, biopsy, labs, and follow-up is essential because severe drug reactions often overlap morphologically and evolve over time.
- Jörg L, Yerly D, Helbling A, Pichler W. The role of drug, dose, and the tolerance/intolerance of new drugs in multiple drug hypersensitivity syndrome.#10.1111/all.14146
- Pichler WJ, Srinoi Y, Yun J, Hausmann O. Multiple Drug Hypersensitivity.#10.1159/000458725
- Recurrence of drug-induced reactions in DRESS patients.
- Fitzgerald JD, et al. 2020a. (ACR guideline cited on allopurinol dosing in kidney impairment)
- Perez-Ruiz F, et al. 2022. (allopurinol dosing in kidney impairment citation)
- Stamp LK, et al. 2012. (allopurinol dosing in kidney impairment citation)
- Vargas-Santos AB, et al. 2017. (allopurinol dosing in kidney impairment citation)