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A 55-year-old obese African American male presented with a two-month history of erythematous papules initially limited to his back after starting a new thermogenic pre-workout supplement and intense exercise regimen to lose weight. The rash spread to upper and lower extremities sub-acutely and became pruritic with burning vesicles and pustules. He presented to the emergency department a few days later after an episode of near-syncope with diaphoresis and shortness of breath. He was noted to have diffuse non-follicular, ~1mm vesicles and pustules scattered over the back and more concentrated over the upper and lower extremities, proximal more than distal, with sparing of the face, palms, and soles on physical exam (Figure 1).

Figure 1: Arm with scattered non-follicular pustules on an erythematous base.

Initially, the pustular rash was deemed clinically consistent with miliaria pustulosa. Then, with the development of borderline fever, along with leukocytosis, a biopsy was done to explore alternative diagnoses. The biopsy revealed typical histopathologic features for acute generalized exanthematous pustulosis. Biopsy showed subcorneal pustules with neutrophils, mild epidermal spongiosis with some lymphocyte and neutrophil exocytosis, and a superficial perivascular and interstitial lymphohistiocytic infiltrate with scattered neutrophils and rare eosinophils (Figure 2).

Figure 2: H&E of one of the pustules with typical AGEP histologic features.

Psoriasiform hyperplasia was not appreciated, which helped to rule out pustular psoriasis, which is often also included in the differential. With supportive care and the addition of topical triamcinolone to the affected areas, the patient’s symptoms began to improve, and he was discharged with counseling not to take the supplement again.


Acute Generalized Exanthematous Pustulosis (AGEP) is a rare acute eruption of non-follicular sterile pustules on an erythematous base that is usually drug induced, most commonly by antibiotics, antifungals, antimalarials, and calcium channel blockers. Less commonly, AGEP can be caused by bacterial or viral infection, as well as other inflammatory conditions, such as spider bites, contact dermatitis, or contact with mercury.1 Some case reports have even noted a rare association with malignancy or pregnancy.2 One retrospective review in Thailand also implicated the herbal product Andrographis paniculate, a medicinal plant used for various health concerns.3,4

The typical AGEP patient presents with a pustular eruption in the folds that spreads quickly to trunk and extremities, often with associated itching and burning sensation. Occasionally there may be mucosal involvement that is limited if present. Systemic signs may include fever, leukocytosis, and elevated C-reactive protein. Multiorgan involvement has been reported in 17 percent of cases and will usually still result in a mild course, although secondary complications have rarely been associated with a life-threatening reaction.

AGEP can be confused with miliaria, folliculitis, pustular psoriasis, or even toxic epidermal necrolysis (TEN) but can be distinguished based on history and presentation along with characteristic histologic findings of spongiform subcorneal or intraepidermal pustules, papillary edema, and perivascular infiltrate containing neutrophils and eosinophils. Treatment focuses on prompt discontinuation of the causative drug in addition to supportive measures and topical steroids for symptomatic relief.5

Based on the histopathologic findings and in the absence of infectious nidus or typical medication exposures, and despite the slightly atypical presentation with subacute onset and relative sparing of acral areas, we believe this patient had AGEP induced by his recent thermogenic pre-workout supplement ingestion. According to our investigation, thermogenic supplements inducing AGEP has not been previously described in the literature.

The authors have no relevant conflicts of interest or financial disclosures.

1. Bhat YJ, Akhtar S, Ahmad M, Hassan I, Wani R. Etiopathological and Clinical Study of Acute Generalized Exanthematous Pustulosis: Experience from a Tertiary Care Hospital in North India. Indian Dermatol Online J. 2020;11(3):391-397. Published 2020 May 10. doi:10.4103/idoj.IDOJ_232_19

2. De A, Das S, Sarda A, Pal D, Biswas P. Acute Generalised Exanthematous Pustulosis: An Update. Indian J Dermatol. 2018;63(1):22-29. doi:10.4103/ijd.IJD_581_17

3. Thienvibul C, Vachiramon V, Chanprapaph K. Five-Year Retrospective Review of Acute Generalized Exanthematous Pustulosis. Dermatol Res Pract. 2015;2015:260928. doi:10.1155/2015/260928

4. Okhuarobo A, Falodun JE, Erharuyi O, Imieje V, Falodun A, Langer P. Harnessing the medicinal properties of Andrographis paniculata for diseases and beyond: a review of its phytochemistry and pharmacology. Asian Pac J Trop Dis. 2014;4(3):213-222. doi:10.1016/S2222-1808(14)60509-0

5. Feldmeyer L, Heidemeyer K, Yawalkar N. Acute Generalized Exanthematous Pustulosis: Pathogenesis, Genetic Background, Clinical Variants and Therapy. Int J Mol Sci. 2016;17(8):1214. Published 2016 Jul 27. doi:10.3390/ijms17081214

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