A rapidly progressive and fatal case of atypical acute generalized exanthematous pustulosis
Authors: Sheila Krishna, Alex Ortega-Loayza, Navid Malakouti, Nooshin Brinster
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: A 78-year-old African American woman with metabolic syndrome presented with skin sloughing for 2 days. She had no history of skin conditions. Twelve days before the onset of the eruption, levofloxacin and vancomycin were started for presumed pneumonia. Cultures from the oropharynx revealed methicillin-resistant Staphylococcus aureus, and the smear was without neutrophils and contained numerous epithelial cells. No other medications had been started.Initial examination revealed erythematous, dusky plaques and papules with flaccid bullae, and scattered pustules over approximately 40% of the body surface area (Fig 1). The vaginal mucosa appeared erythematous whereas the ocular and oral mucosae were clear. The initial white blood cell count was 32.8/L with an absolute neutrophil count of 28.3/L and a normal eosinophil count. Pending histopathologic examination, a clinical diagnosis of toxic epidermal necrolysis (TEN) was made, and intravenous immunoglobulin was started at 1 g/kg/d. Antibiotics were discontinued.After 24 hours and 1 dose of intravenous immunoglobulin, the patient progressed to diffuse epidermal sloughing with erosions of the oral mucosa and signs of shock. Intravenous immunoglobulin was discontinued because of concern for sepsis or anaphylaxis, and daptomycin, piperacillin-tazobactam, and fluconazole were started, along with stress-dose steroids. Skin biopsy specimen from an area of dusky erythema and pustules demonstrated subcorneal pustules without epidermal necrosis or interface alteration (Fig 2). Direct immunofluorescence, periodic acid–Schiff and Gram stains, and pustule culture revealed negative findings. The patient developed multiorgan failure and disseminated intravascular coagulation, and died on hospital day 4. Her final cause of death at autopsy was deemed multisystem organ failure caused by complications of acute generalized exanthematous pustulosis (AGEP) without internal sources of sepsis.Fig 2Acute generalized exanthematous pustulosis. Histopathology demonstrates subcorneal pustules without evidence of epidermal necrosis. (Hematoxylin-eosin stain; original magnification: ×100.)View Large Image Figure ViewerDownload Hi-res image Download (PPT)We present a case of atypical AGEP with severe mucocutaneous involvement that resulted in death. On initial evaluation, the differential diagnosis was primarily TEN and AGEP. A pathological role for S aureus was not established, as the cultures were consistent with contamination. Furthermore, the temporal relationship of the eruption to the initiation of antibiotics was strongly suggestive of a drug reaction. Therefore, the diagnostic considerations in this case were TEN, AGEP, or an overlap syndrome of the two. In this patient, although a few pustules were present initially, the overwhelming amount of epidermal detachment and mucosal involvement clinically favored TEN. However, with the histopathological findings of subcorneal pustules without epidermal necrosis, the final diagnosis was atypical AGEP with severe mucocutaneous involvement.Severe cutaneous adverse reactions include TEN, AGEP, and drug reaction with eosinophilia and systemic symptoms, which vary in their presentation and prognosis.1Revuz J. Valeyrie-Allanore L. Chapter 21: drug reactions.in: Bolognia J.L. Jorizzo J. Schaffer J. Dermatology. 3rd ed. Elsevier, Philadelphia (PA)2012Google Scholar, 2Harr T. French L.E. Severe cutaneous adverse reactions: acute generalized exanthematous pustulosis, toxic epidermal necrolysis and Stevens-Johnson syndrome.Med Clin North Am. 2010; 94: 727-742Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar Because of the potential clinical overlap in these severe cutaneous adverse reactions, AGEP should be considered in the differential diagnosis of generalized desquamation. However, the expected clinical course and prognosis may vary from what is typically seen.3Cohen A.D. Cagnano E. Halevy S. Acute generalized exanthematous pustulosis mimicking toxic epidermal necrolysis.Int J Dermatol. 2001; 40: 458-461Crossref PubMed Scopus (39) Google Scholar, 4Peermohamed S. Haber R.M. Acute generalized exanthematous pustulosis simulating toxic epidermal necrolysis: a case report and review of the literature.Arch Dermatol. 2011; 147: 697-701Crossref PubMed Scopus (39) Google Scholar, 5Speeckaert M.M. Speeckaert R. Lambert J. Brochez L. Acute generalized exanthematous pustulosis: an overview of the clinical, immunological and diagnostic concepts.Eur J Dermatol. 2010; 20: 425-433PubMed Google Scholar We herein report a case of fulminant AGEP with severe mucocutaneous involvement that resulted in death and highlight the potential for high mortality in this setting. To the Editor: A 78-year-old African American woman with metabolic syndrome presented with skin sloughing for 2 days. She had no history of skin conditions. Twelve days before the onset of the eruption, levofloxacin and vancomycin were started for presumed pneumonia. Cultures from the oropharynx revealed methicillin-resistant Staphylococcus aureus, and the smear was without neutrophils and contained numerous epithelial cells. No other medications had been started. Initial examination revealed erythematous, dusky plaques and papules with flaccid bullae, and scattered pustules over approximately 40% of the body surface area (Fig 1). The vaginal mucosa appeared erythematous whereas the ocular and oral mucosae were clear. The initial white blood cell count was 32.8/L with an absolute neutrophil count of 28.3/L and a normal eosinophil count. Pending histopathologic examination, a clinical diagnosis of toxic epidermal necrolysis (TEN) was made, and intravenous immunoglobulin was started at 1 g/kg/d. Antibiotics were discontinued. After 24 hours and 1 dose of intravenous immunoglobulin, the patient progressed to diffuse epidermal sloughing with erosions of the oral mucosa and signs of shock. Intravenous immunoglobulin was discontinued because of concern for sepsis or anaphylaxis, and daptomycin, piperacillin-tazobactam, and fluconazole were started, along with stress-dose steroids. Skin biopsy specimen from an area of dusky erythema and pustules demonstrated subcorneal pustules without epidermal necrosis or interface alteration (Fig 2). Direct immunofluorescence, periodic acid–Schiff and Gram stains, and pustule culture revealed negative findings. The patient developed multiorgan failure and disseminated intravascular coagulation, and died on hospital day 4. Her final cause of death at autopsy was deemed multisystem organ failure caused by complications of acute generalized exanthematous pustulosis (AGEP) without internal sources of sepsis. We present a case of atypical AGEP with severe mucocutaneous involvement that resulted in death. On initial evaluation, the differential diagnosis was primarily TEN and AGEP. A pathological role for S aureus was not established, as the cultures were consistent with contamination. Furthermore, the temporal relationship of the eruption to the initiation of antibiotics was strongly suggestive of a drug reaction. Therefore, the diagnostic considerations in this case were TEN, AGEP, or an overlap syndrome of the two. In this patient, although a few pustules were present initially, the overwhelming amount of epidermal detachment and mucosal involvement clinically favored TEN. However, with the histopathological findings of subcorneal pustules without epidermal necrosis, the final diagnosis was atypical AGEP with severe mucocutaneous involvement. Severe cutaneous adverse reactions include TEN, AGEP, and drug reaction with eosinophilia and systemic symptoms, which vary in their presentation and prognosis.1Revuz J. Valeyrie-Allanore L. Chapter 21: drug reactions.in: Bolognia J.L. Jorizzo J. Schaffer J. Dermatology. 3rd ed. Elsevier, Philadelphia (PA)2012Google Scholar, 2Harr T. French L.E. Severe cutaneous adverse reactions: acute generalized exanthematous pustulosis, toxic epidermal necrolysis and Stevens-Johnson syndrome.Med Clin North Am. 2010; 94: 727-742Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar Because of the potential clinical overlap in these severe cutaneous adverse reactions, AGEP should be considered in the differential diagnosis of generalized desquamation. However, the expected clinical course and prognosis may vary from what is typically seen.3Cohen A.D. Cagnano E. Halevy S. Acute generalized exanthematous pustulosis mimicking toxic epidermal necrolysis.Int J Dermatol. 2001; 40: 458-461Crossref PubMed Scopus (39) Google Scholar, 4Peermohamed S. Haber R.M. Acute generalized exanthematous pustulosis simulating toxic epidermal necrolysis: a case report and review of the literature.Arch Dermatol. 2011; 147: 697-701Crossref PubMed Scopus (39) Google Scholar, 5Speeckaert M.M. Speeckaert R. Lambert J. Brochez L. Acute generalized exanthematous pustulosis: an overview of the clinical, immunological and diagnostic concepts.Eur J Dermatol. 2010; 20: 425-433PubMed Google Scholar We herein report a case of fulminant AGEP with severe mucocutaneous involvement that resulted in death and highlight the potential for high mortality in this setting.