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When a Rash is Deadly

Fadial, Tom MD

doi: 10.1097/01.EEM.0000578644.10509.d3



A 68-year-old man with hypertension and gout presented with a rash he had had for two to three weeks. He noted some subjective fevers but was otherwise asymptomatic. He had no recent travel or sick contact. When asked about his medications, he reported that his primary care provider started him on allopurinol approximately two months earlier.

He first noted the rash on his face, characterizing it as pimples, which were slightly pruritic. The lesions subsequently spread to his trunk and extremities, and had been growing in size.

Objectively, his vital signs were notable for fever (38.2°C) and tachycardia (108 bpm). Examination demonstrated diffuse blanching erythema, most prominent on the trunk and extremities. The remainder of the physical examination was normal. Laboratory studies were obtained and notable for a complete blood count with peripheral eosinophilia and mildly elevated serum transaminases.

The patient was diagnosed with drug reaction with eosinophilia and systemic symptoms (DRESS), likely caused by the initiation of a xanthine oxidase inhibitor. He improved after withdrawal of the drug and a brief course of systemic corticosteroids.

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Dermatologic Emergencies

Critical dermatologic processes are divided into two categories: cutaneous manifestation of a critical illness and acute skin failure. The presence of a dermatologic abnormality does not itself represent a life threat. Instead, the skin lesion suggests the presence of an underlying critical process. The prototypical example would be the petechiae and purpura in meningococcemia.

As with any other organ system failure, acute skin failure carries significant morbidity and mortality, and is characterized by derangements in normal skin function.

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Critical Functions of Skin

  • Temperature regulation
  • Protection against excess fluid loss
  • Mechanical barrier to prevent penetration of foreign materials
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Pathophysiologic Changes in ASF

  • Increased peripheral vasodilation (dramatic increase in cardiac output to low-resistance circuits) and vascular permeability result in relative hypovolemia and shock.
  • Increased blood flow and dysfunction of the eccrine sweat glands result in altered temperature regulation (usually hypothermia).
  • Fluid imbalances occur, and similar to burns (transepidermal water loss), ASF varies between dry (erythroderma) and wet (vesiculobullous) diseases.
  • Electrolyte imbalance results in an increased basal metabolic rate, hyperglycemia (insulin resistance), hypophosphatemia, and protein depletion.
  • Barrier dysfunction leads to increased risk of infection.
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Treatment at a dermatologic ICU or burn center is preferred, and should include temperature management, early enteral nutrition, fluid or electrolyte management, local wound care, and disease-specific management. Possible complications are sepsis/shock, acute respiratory distress syndrome, high-output CHF, and known complications of critical illnesses (multiorgan failure, GI ulcers, VTE). Long-term complications could be ocular (ectropion, keratitis, ulcer), esophageal (stricture), GU-related (urethral stricture, phimosis, vaginal stenosis), or integumentary (scarring, alopecia).

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Skin Lesions

The objective of this algorithm is to develop a systematic approach to evaluating dermatologic processes, with a focus on the identification of dermatologic emergencies. The foundation of this approach is an understanding of the underlying pathophysiologic mechanisms for each of the four broad categories of dermatologic processes guiding the differential diagnosis: erythroderma, petechiae/purpura, fluid-filled, and maculopapular.

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Erythroderma is characterized by extensive cutaneous capillary dilation, resulting in widespread exfoliation of the epidermis. Inflammatory mediators result in a dramatic increase in the epidermal turnover rate and accelerated mitotic rate as well as an increased number of germinative skin cells. Causes include exfoliative toxin, eosinophils, basophils/histamine, and skin-homing T-cells.

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Petechiae and purpura represent the passage of erythrocytes from the intravascular to the extravascular compartment. They may be the result of the disruption of vascular integrity (trauma, infection, vasculitis) or disorders of primary or secondary hemostasis. If lesions are palpable, this may suggest a more prominent underlying inflammatory process such as vasculitis. When cutaneous manifestations are identified, other small vessels may be affected (commonly renal and pulmonary).

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Pustules more commonly suggest an infectious process (bacterial, fungal), but vesiculobullous lesions are generally more concerning. They involve the loss of basic structural elements maintaining the cohesion among the keratinocytes in the epidermis or that between the epidermal layer and the dermis (near the basement membrane zone). Intraepidermal blisters tend to be flaccid, fragile, and thin-roofed. Subepidermal blisters have a thick roof and can remain intact when compressed. Vesiculobullous are often due to autoantibodies targeting structural proteins in the skin.

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Maculopapular is a catch-all term for a wide range of potential pathophysiologic mechanisms and causative etiologies. It refers to any process resulting in erythroderma, petechiae, or fluid-filled lesions that may start as a macule or papule. Pathophysiology is of little guidance in this category, where we must instead rely on the patient's history and identification of red flags to exclude dermatologic emergencies.

The high-risk features, which are identified by dermatologists to stratify the urgency of inpatient consultations, include:

  • Ill-appearing, vital sign instability
  • New-onset fever with rash
  • Mucocutaneous or ocular lesions
  • Recent introduction of an anticonvulsant or a sulfa-drug
  • Skin pain
  • Immunocompromised
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Review References

  • Wolf R, Parish LC, Parish JL. Emergency Dermatology, Second Edition. August 2017:1-369.
  • Usatine RP, Sandy N. Dermatologic emergencies. Am Fam Physician 2010;82(7):773;
  • Shilpi Khetarpal, MD, Anthony Fernandez, MD, PhD. Dermatological Emergencies. Cleveland Clinic. August 2014;
  • McQueen A, Martin SA, Lio PA. Derm Emergencies: Detecting Early Signs of Trouble. J Fam Pract 2012;61(2):71.
  • Browne BJ, Edwards B, Rogers RL. Dermatologic Emergencies. Prim Care 2006;33(3):685.
  • Drage LA. Life-threatening Rashes: Dermatologic Signs of Four Infectious Diseases. Mayo Clinic Proceedings 1999;74(1):68;
  • Baibergenova A, Shear NH. Skin Conditions that Bring Patients to Emergency Departments. Arch Dermatol 2011;147(1):118;
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Erythroderma References:

  • Tan TL, Chung WM. A Case Series of Dermatological Emergencies–Erythroderma. Med J Malaysia 2017;72(2):141;
  • Karakayli G, Beckham G, et al. Exfoliative Dermatitis. Am Fam Physician 1999;59(3):625;
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Petechiae/Purpura References:

  • Stevens GL, Adelman HM, Wallach PM. Palpable Purpura: An Algorithmic Approach. Am Fam Physician 1995;52(5):1355.
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Algorithm References:

  • Lynch PJ, Edminster SC. Dermatology for the Nondermatologist: A Problem-Oriented System. YMEM 1984;13(8):603.
  • Nguyen T, Freedman J. Dermatologic Emergencies: Diagnosing and Managing Life-Threatening Rashes. Emerg Med Prac 2002;4(9):1.
  • Murphy-Lavoie H, LeGros TL. Emergent Diagnosis of an Unknown Rash: An Algorithmic Approach Emergency Medicine. 2010;42(3):6;
  • Dean S. “Emergency Medicine Dermatology.” 2017:1-20. doi:10.21980/J8DW21.
  • Talley NJ, O'Connor S. Clinical Examination, 7th Edition. Philadelphia: Elsevier Health Sciences; 2013.
  • Jack AR, Spence AA, et al. A Simple Algorithm for Evaluating Dermatologic Disease in Critically Ill Patients: A Study Based on Retrospective Review of Medical Intensive Care Unit Consults. J Am Acad Dermatol 2009;61(4):728;
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DRESS References:

  • McQueen A, Martin SA, Lio PA. Derm Emergencies: Detecting Early Signs of Trouble. J Fam Pract 2012;61(2):71.
  • Cardoso CS, Vieira AM, Oliveira AP. DRESS Syndrome: A Case Report and Literature Review. BMJ Case Rep 2011;2011:bcr0220113898.
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Evidence-Based Algorithm References:

  • David CV, Chira S, et al. Diagnostic Accuracy in Patients Admitted to Hospitals with Cellulitis. Dermatol Online J 2011;17(3):1.
  • Chou W-Y, Tien P-T, et al. Application of Visually Based, Computerised Diagnostic Decision Support System in Dermatological Medical Education: A Pilot Study. Postgrad Med J 2017;93(1099):256.

Dr. Fadialis an assistant professor of emergency medicine at McGovern Medical School in Houston. As the educational technology and innovation officer there, he develops unique educational tools, including algorithms that can be found at His other medical education projects can be found at

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