Fever and Rash

History, Epidemiology

The list of potential causes of fever and rash (also called pyrexia or febrile illness) is lengthy. It includes viruses, bacteria, spirochetes, rickettsiae, medications, and rheumatologic diseases, among other potential causes.¹

Fever and Rash Causes and Risk Factors

Fever with rash can have infectious or noninfectious causes and can occur in both children and adults.¹ The severity can range from minor to life-threatening. Patients who have weakened immune systems are at heightened risk for more severe illness.

A rash that develops while fever is still present can be caused by a variety of infectious diseases. Some illnesses involving both rash and fever include scarlet fever, measles, mononucleosis, and shingles.

Risk factors for fever or and rash may include recent travel, any contact with animals, medication usage, potential environmental exposures, and a weakened immune system.²

Prognosis

The prognosis for fever and rash depends on many variables including underlying immune system function, age, access to care, and the infectious agent or vector causing the disease. The cause may be minor, such as roseola, or life-threatening, as with meningococcemia. The sooner the origin of the fever and rash is identified and treated, the better a patient’s prognosis. Pediatric viral exanthems are typically self-limited and rarely serious.

Fever and Rash Diagnosis and Presentation

The first step in the diagnostic process of the febrile patient with dermatitis is usually a thorough physical exam with a detailed medical, travel, and social history. It’s important to determine what medications the patient is currently taking, and any recent vaccinations they received. As part of the physical exam, lesions should be examined along with assessment of lymph nodes, liver and spleen enlargement, and jointswelling.³

The next step is to accurately characterize the main skin lesion. Several potential categories exist including⁴:

● Macule or flat discoloration

● Papule or solid, raised lesion, less than 5 mm in diameter

● Plaque or flat, elevated lesion, more than 5 mm, that occupies a relatively large area

● Nodule or round, elevated lesions greater than 5 mm located deeper in the dermis or subcutaneous tissue

● Generalized diffuse erythema

● Vesicle or fluid-filled, elevated lesion

● Bulla or fluid-filled lesion that is larger than a vesicle

● Pustule or pus-filled lesion

● Petechiae or tiny, less than 3 mm, broken capillaries

● Purpura or pink or purple patches just underneath the skin

Classification of eruptions include centrally distributed maculopapular, peripheral, confluent, desquamative, erythematous, vesiculobullous, urticaria-like, nodular, purpuric, ulcerated, or with eschars.⁴ Rashes can be described by the pattern of the spread, the shape, and whether they are painful or pruritic. Timing of the rash’s appearance is also important to record when characterizing the rash.

For example, monkeypox symptoms start with fever and flu-like symptoms, and within one to three days, people develop pustules on the face or vesicles on the legs.⁵ Many viral exanthems begin similarly, with a prodrome of fever and malaise, followed by the development of a rash.

Maculopapular rashes are most common with a viral infection. Chickenpox and herpes zoster are examples of vesicular rash. Scarlet fever, toxic shock syndrome, or Kawasaki are typically characterized by diffuse erythema. Erysipelas can manifest as an area of sharply demarcated erythema, and petechiae and purpura could indicate late-stage meningitis and/or sepsis, along with other symptoms.

Lab tests such as a complete blood count, a chemistry panel, erythrocyte sedimentation rate, liver function tests, and blood and urine screens may also help narrow down the differential diagnosis of fever and rash. Analyzing aspirates, scrapings, and/or pustular fluid may also help identify the cause of the fever and rash.²

Differential Diagnosis

There is an extensive list of potential differential diagnosis for febrile patients with rash.² It includes:

● Acute febrile neutrophilic dermatosis

● Acute generalized exanthematous pustulosis (AGEP)

● Arbovirus (recent travel)

● Arthritis

● Bullous drug eruption

● Calciphylaxis

● Cellulitis

● Cholesterol emboli

● Drug hypersensitivity syndrome

● Eczema herpeticum

● Endocarditis

● Erysipelas

● Erythema marginatum

● Erythema nodosum

● Erythroderma

● Erythema multiforme

● Fifth disease

● Folliculitis/furunculosis

● Fournier gangrene

● Generalized pustular psoriasis

● Hand, foot, and mouth disease (mainly seen in young children.)

● Herpes simplex

● Herpes zoster

● Impetigo or ecthyma

● Kawasaki disease

● Lyme disease

● Measles

● Meningococcal disease

● Monkeypox

● Mycoplasma

● Necrotizing fasciitis

● Necrotizing spider bite

● Neutrophilic dermatosis of dorsal hands

● Panniculitis

● Purpura fulminans

● Roseola

● Rubella (seen in the unvaccinated)

● Scarlet fever (Streptococcus pyogenes)

● Septic emboli

● Staphylococcal scalded skin

● Stevens-Johnson / toxic epidermal necrolysis

● Toxic shock syndrome

● Typhoid fever

● Varicella

● Vascular occlusion

● Vasculitis

There’s a helpful mnemonic to help keep the seven rapidly fatal causes of fever and rash at top of mind during the diagnostic process. SMARTTT⁷ refers to:

● Sepsis

● Meningococcemia

● Acute endocarditis

● Rocky Mountain spotted fever

● Toxic erythema (toxic shock syndrome, staphylococcal scalded skin syndrome, scarlet fever, and scarlatiniform eruptions)

● Toxic epidermal necrolysis is caused by a reaction to drugs

● Travel-related infection

The SNAP⁷ mnemonic is a good way to recall drugs that commonly cause toxic epidermal necrolysis:

● Sulfonamides

● Nonsteroidal anti-inflammatory drugs (NSAIDs)

● Allopurinol

● Phenytoin

Other patient symptoms can help inform the diagnosis. For example, joint pain and swelling may suggest arthritis or Lyme disease. Co-occurrence of certain symptoms can also aid the diagnostic process. For example, rash and conjunctivitis may suggest Kawasaki disease, measles, or toxic shock syndrome, while fever, rash, and abdominal pain may indicate typhoid fever, scarlet fever, cholesterol emboli syndrome, or systemic lupus erythematosus.⁶

References

1. Kang JH. Febrile illness with skin rashes. Infect Chemother. 2015;47(3):155-166. doi:10.3947/ic.2015.47.3.155

2. Antimicrobe. Approach to the patient with fever and rash. Infectious Disease and Antimicrobial Agents. Accessed June 23, 2022.

3. Mckinnon HD, Howard T. Evaluating the febrile patient with a rash. Am Fam Physician. 2000;62(4):804-816.

4. Kaye ET, Kaye KM. Fever and Rash. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. eds. Harrison’s Principles of Internal Medicine, 19e. McGraw Hill; 2014. Accessed July 07, 2022.

5. Centers for Disease Control and Prevention. Social gatherings, safer sex, and monkeypox. Reviewed June 24, 2022. Accessed June 24, 2022.

6. Oakley, A. Fever and a rash. New Zealand Dermatological Society Incorporated. Published May 2016.Accessed June 23, 2022.

7. Shuman E. Fever and rash. In: Saint S, Chopra, V, The Saint-Chopra Guide to Inpatient Medicine. 4th ed. Oxford University Press; 2018:1-6.

Author Bio

Denise Mann, MS, is a veteran freelance health writer in New York. Her work has appeared on HealthDay, among other outlets. She was awarded the 2004 and 2011 journalistic Achievement Awards from the American Society for Aesthetic Plastic Surgery. She was also named the 2011 National Newsmaker of the Year by the Community Anti-Drug Coalitions of America. She has also been awarded the Arthritis Foundation’s Northeast Region Prize for Online Journalism, the Excellence in Women’s Health Research Journalism Award, the Gold Award for Best Service Journalism from the Magazine Association of the Southeast, a Bronze Award from The American Society of Healthcare Publication Editors, and an honorable mention in the International Osteoporosis Foundation Journalism Awards. She was part of the writing team awarded a 2008 Sigma Delta Chi award for her part in a WebMD series on autism. Mann has a graduate degree from the Medill School of Journalism at Northwestern University in Evanston, Ill.