Rashes and Fever

Published on 22/03/2015 by admin

Filed under Critical Care Medicine

Last modified 22/04/2025

Print this page

This article have been viewed 2529 times

26 Rashes and Fever

Cheston B. Cunha, Burke A. Cunha

Clinical Approach

The clinical diagnostic approach to rash and fever in the intensive care unit (ICU) depends on whether the rash and fever were community or nosocomially acquired. Community-acquired rash and fever is best approached by considering the distribution/characteristics of the rash.¹^–⁵ Rashes are visible clues to infectious or noninfectious disorders. In addition to rash and fever, often associated findings such as history, physical examination, and laboratory abnormalities are keys to the correct diagnosis.^1,^4,⁶^–⁸

Nosocomially acquired rashes have more limited differential diagnostic possibilities.⁶ The clinician should determine whether the rash and fever represents the primary clinical problem or is a superimposed finding unrelated to another process—for example, ICU patients admitted for acute myocardial infarction can develop a drug rash from an antiarrhythmic medication, beta-blocker, diuretic, or sulfa-containing stool softener (Colace).^1,³

Acutely ill patients with rash and fever in the ICU should have the benefit of an infectious disease consultation by an experienced infectious disease clinician.^1,³ Both community and nosocomial acquired rash/fever are best diagnosed using the clinical syndromic approach; associated clinical findings, not the appearance of the rash per se, are the main determinants of arriving at the correct diagnosis.^5,⁷

Community-Acquired Rash and Fever

Patients admitted to the ICU from the community with rash/fever are best approached by the type/distribution of the rash.² The degree of fever relative to the pulse rate, and fever pattern are also important diagnostic considerations.^3,⁹

Petechial/Purpuric Rashes and Fever

While petechial/purpuric rashes are common causes of community-acquired rash/fever, petechiae can accompany a variety of systemic infections as well as a variety of noninfectious disorders.¹⁰^–¹² Rash/fever are often potentially life-threatening (e.g., meningococcemia [MC] with or without meningitis, Rocky Mountain spotted fever [RMSF], dengue fever [DF], and arboviral hemorrhagic fevers), and patients should have the benefit of a diagnostic evaluation by an experienced infectious disease consultant.^1,^4,^10,¹¹

The two most common infectious diseases presenting with a petechial/purpuric rash are MC and RMSF. RMSF should be suspected with a recent tick exposure history and/or a characteristic location/distribution of the rash. Importantly, RMSF is the only infectious exanthem that begins on the wrists and/or ankles.¹³^–¹⁵ In contrast, the rash of MC is asymmetrical with irregularly shaped painful petechial/purpuric lesions.^1,^8,¹¹

Post-splenectomy sepsis (PSS) can resemble meningococcemia but only occurs in patients with impaired/absent splenic function.^1,^4,¹¹ Clinicians should be familiar with the disorders associated with diminished splenic function. A key clinical clue to impaired splenic function is the presence of Howell-Jolly bodies or “pocked/pitted” red blood cells in the peripheral smear. The number of Howell-Jolly bodies or “pocked/pitted” RBCs is inversely proportional to splenic function.^1,⁸

High-grade/continuous Staphylococcus aureus bacteremias (methicillin sensitive/methicillin resistant [MSSA/MRSA]) from abscesses or acute bacterial endocarditis (ABE) are often accompanied by splinter hemorrhages and petechial/purpuric rashes on the distal extremities.^1,^10,¹¹

Maculopapular Rashes and Fever

The most common maculopapular rashes/fever associated with serious systemic diseases are toxic shock syndrome (TSS) and systemic lupus erythematosus (SLE). SLE flares can mimic infectious diseases.^1,^4,¹¹ Thus, SLE pneumonitis can mimic community-acquired pneumonia (CAP), and SLE cerebritis can mimic acute bacterial meningitis (ABM). Laboratory studies can differentiate an SLE flare in the absence of infection from an SLE flare with infection. Typically, SLE flares without infection are accompanied by leukopenia, decreased complement levels, and elevated α₁/α₂ globulins on serum protein electrophoresis (SPEP).^1,⁸

TSS can occur in any patient colonized/infected with a TSS-1-producing strain of S. aureus. TSS may not come to mind when there are no overt signs of clinical infection (e.g., staphylococcal colonization of the nares). TSS also may be due to group A streptococci or Clostridium sordelli.^2,^4,¹¹

Vesicular/Bullous Rashes and Fever

Vesicular eruptions limit the diagnostic possibilities to chickenpox or herpes zoster (shingles) due to varicella zoster virus (VZV). Herpes zoster may be localized (dermatomal) or disseminated.⁵^–⁷ Before the appearance of the vesicular rash/fever, dermatomal herpes zoster, depending on dermatomal distribution, can be a difficult diagnostic problem, mimicking many disorders.⁶ Herpes zoster involving the head and/or neck may be associated with VZV meningitis/encephalitis. Disseminated shingles can resemble chickenpox, but patients with herpes zoster have a prior history of chickenpox.^1,^4,¹¹

Community-acquired bullous lesions in the ICU may be due to S. aureus soft-tissue infection, Vibrio vulnificus, or gas gangrene (clostridial myonecrosis). Except when due to S. aureus, all the causes of bullae/fever are painful and tense and accompanied by diarrhea. Clostridial myonecrosis, (i.e., gas gangrene) may be present after a crush injury or trauma. The commonest cause of bullae/fever is S. aureus cellulitis/pyoderma.¹⁰^–¹²

The differential diagnostic features of community-acquired rash/fever are presented in tabular form in Tables 26-1 to 26-16.¹^–¹⁹

TABLE 26-1 Community-Acquired Rash and Fever in the ICU

TABLE 26-2 Community-Acquired Rash and Fever in the ICU

TABLE 26-3 Community-Acquired Rash and Fever in the ICU

TABLE 26-4 Community-Acquired Rash and Fever in the ICU

TABLE 26-5 Community-Acquired Rash and Fever in the ICU

TABLE 26-6 Community-Acquired Rash and Fever in the ICU

TABLE 26-7 Community-Acquired Rash and Fever in the ICU

TABLE 26-8 Community-Acquired Rash and Fever in the ICU

TABLE 26-9 Community-Acquired Rash and Fever in the ICU

TABLE 26-10 Community-Acquired Rash and Fever in the ICU

TABLE 26-11 Community-Acquired Rash and Fever in the ICU

TABLE 26-12 Community-Acquired Rash and Fever in the ICU

TABLE 26-13 Community-Acquired Rash and Fever in the ICU

TABLE 26-14 Community-Acquired Rash and Fever in the ICU

TABLE 26-15 Community-Acquired Rash and Fever in the ICU

TABLE 26-16 Community-Acquired Rash and Fever in the ICU

Nosocomial-Acquired Rash and Fever

Petechial/Purpuric Rashes and Fever

Staphylococcal bacteremia (high-grade/continuous) is usually related to an intravascular/interventional procedure/device.^1,³ Staphylococcal bacteremias or ABE present initially with petechial/purpuric lesions that later can become hemorrhagic and/or gangrenous. The diagnosis is suggested by the peripheral location of the irregular painful petechial/purpuric lesions in the setting of high-grade and/or continuous staphylococcal bacteremia.^1,^4,¹¹

An underrecognized but important cause of nosocomial rash/fever is cholesterol emboli syndrome (CES).²⁰ Cholesterol emboli may be released into the systemic circulation during or following cardiovascular procedures. CES presents as a petechial/purpuric rash with a livedo reticularis–like appearance.^1,⁸ The rash occurs on the trunk and/or extremities and may be accompanied by signs of cholesterol emboli to other organs such as the heart (myocardial infarction), pancreas (acute pancreatitis), kidneys (acute renal failure), or central nervous system (stroke). Excluding drug rash/fever, cholesterol emboli syndrome is the only acute rash in the ICU associated with peripheral eosinophilia.^8,²⁰

Drug rashes are drug hypersensitivity reactions with rash/fever. Most patients who develop drug rashes do so after receiving new medications in the hospital, but some develop drug rash/fever years after being on sensitizing chronic medications. Drug rashes are generalized, maculopapular/petechial, and may be pruritic. Fever is usually present and may be high (>102°F); it is regularly accompanied by relative bradycardia.^8,⁹ Mild increases of serum transaminase levels and eosinophiles in the blood smear are common findings.⁸ The clinical difficulty with drug rash/fever is distinguishing it from underlying medical disorders. Even after discontinuing the sensitizing drug, rash/fever may take days/weeks to resolve.^1,^3,^4,⁹

Maculopapular Rashes and Fever

Maculopapular rash due to surgical TSS is uncommon. Typical surgical TSS occurs from wound infection several days after surgery. A key clinical clue is that drainage from the wound is serosanguineous rather than purulent.^5,^7,^11,¹²

Vesicular/Bullous Rashes and Fever

Particularly following distant extremity trauma or distal abdominal surgery, gas gangrene should be considered in the differential diagnosis.^3,⁶ In patients with gas gangrene (i.e., clostridial myonecrosis), the vesicular/bullous eruptions spread rapidly (over minutes/hours). The skin near the bullous lesions is tense and extremely tender, and the fluid in the lesions is not foul smelling. Patients with gas gangrene are afebrile or have only a low-grade fever, but these patients often have watery diarrhea.^1,³ A key clinical clue to gas gangrene is rapidly progressive hemolytic anemia due to lysis of red blood cells by clostridial lethicinases.^1,^4,¹¹ On physical examination, gas in tissues is not clinically detectable or obvious and is not a feature of gas gangrene. On computed tomography (CT) scan, small gas bubbles may be visible along muscle planes.^1,³ Large collections of gas in the soft tissues on imaging studies should suggest a mixed aerobic-anaerobic infection by nonclostridial gas-producing organisms. Mixed aerobic-anaerobic soft-tissue infections are most common in diabetics and do not involve muscle (myonecrosis).^1,^3,¹⁰

Fever is usually prominent with mixed aerobic/anaerobic soft-tissue infections, but clostridial gas gangrene characteristically is associated with little or no fever. The differential diagnosis of nosocomial rashes/fever is presented in Tables 26-17 to 26-22.^1,^4,^10,¹¹

TABLE 26-17 Hospital-Acquired Rash and Fever in the ICU

TABLE 26-18 Hospital-Acquired Rash and Fever in the ICU

TABLE 26-19 Hospital-Acquired Rash and Fever in the ICU

TABLE 26-20 Hospital-Acquired Rash and Fever in the ICU

TABLE 26-21 Hospital-Acquired Rash and Fever in the ICU

TABLE 26-22 Hospital-Acquired Rash and Fever in the ICU

The diagnostic approach to rash/fever depends on correctly correlating the location/characteristic of the rash with associated non-dermatologic features such as physical examination findings or laboratory findings, or both, to arrive at a clinical syndromic diagnosis (Tables 26-23 and 26-24).¹^–²⁰

TABLE 26-23 Differential Diagnostic Clinical Features of Fever and Rash in the ICU

	Infectious Causes	Noninfectious Causes
Rash with Shock	TSS MC PSS Overwhelming Staphylococcus aureus bacteremia/ABE Arboviral hemorrhagic fevers Hemorrhagic smallpox Vibrio vulnificus Gas gangrene Dengue fever	SLE (on steroids)
Rash with Mental Changes	RMSF MC (with meningitis) S. aureus ABE (with CNS bleeding) Chikungunya fever Typhus	SLE
Rash with Conjunctival Suffusion	RMSF Dengue fever Arboviral hemorrhagic fevers TSS	Adult Kawasaki’s disease
Rash with Relative Bradycardia	RMSF Typhus Dengue fever Typhoid Arboviral hemorrhagic fevers	Drug rash
Rash with Abdominal Pain	V. vulnificus Gas gangrene Clostridium sordelli Scarlet Fever	Cholesterol emboli syndrome SLE
Rash on Palms and Soles	RMSF TSS Chickenpox Smallpox Monkeypox Scarlet fever	Drug rash
Rash with Diarrhea	V. vulnificus Gas gangrene TSS Dengue fever Arboviral hemorrhagic fevers	None
Rash with Edema of Dorsum of Hands/Feet	RMSF TSS	Adult Kawasaki’s disease
Rash with Bullae	V. vulnificus S. aureus cSSSI Gas gangrene	None
Rash with Heart Murmur	ABE	SLE
Rash with Gangrene of Nose Tip	S. aureus ABE	SLE Vasculitis
Rash with CVA	Cholesterol emboli syndrome S. aureus ABE	None
Rash with Splenomegaly	RMSF Typhus	SLE Adult Kawasaki’s disease
Rash with Deafness	RMSF Typhus Meningococcal meningitis	None
Rash with Hepato splenomegaly	RMSF Typhus	Atypical measles
Rash with Hepatomegaly	Typhus	None

ABE, acute bacterial endocarditis; cSSSI, complicated skin/skin structure infection; CVA, cerebrovascular accident; DF, dengue fever; MC, meningococcemia; PSS, postsplenectomy sepsis; RMSF, Rocky Mountain spotted fever; SLE, systemic lupus erythematosus; TSS, toxic shock syndrome.

TABLE 26-24 Differential Diagnostic Laboratory Features of Fever and Rash in the ICU

	Infectious Causes	Noninfectious Causes
Rash with Elevated SGOT/SGPT	RMSF PSS Arboviral hemorrhagic fevers TSS Dengue fever	Drug rash Adult Kawasaki’s disease
Rash with Relative Lymphopenia	RMSF Chikungunya fever Dengue fever	SLE Adult Kawasaki’s disease
Rash with Leukocytosis	RMSF ABE (Staphylococcus aureus) MC Chikungunya fever	Drug rash
Rash with Eosinophilia	Scarlet fever	Cholesterol emboli syndrome Drug rash
Rash with Leukopenia	TSS PSS Dengue fever Smallpox Arboviral hemorrhagic fevers	SLE Atypical measles
Rash with Generalized Adenopathy	Arboviral hemorrhagic fevers Dengue fever Scarlet fever Measles Rubella	SLE Adult Still’s disease

ABE, acute bacterial endocarditis; DF, dengue fever; MC, meningococcemia; RMSF, Rocky Mountain spotted fever; SLE, systemic lupus erythematosus; TSS, toxic shock syndrome.

Annotated References

Cunha BA, editor. Infectious diseases in critical care medicine, 3rd ed, New York: Informa, 2010.

The only text on infectious diseases in critical care, this book presents a clinical diagnostic and therapeutic approach to infectious and noninfectious disorders with fever and rash in the ICU.

Cunha BA. The diagnostic approach to rash and fever in the critical care unit. Crit Care Clin. 1998;8:35-54.

The classic clinical syndromic approach for clinicians for rash and fever encountered in the ICU.

Schlossberg D. Fever and rash. Infect Dis Clin North Am. 1996;10:101-110.

Classic review on the clinical approach to rash and fever.

Schneiderman PI, Grossman ME, editors. A clinician’s guide to dermatologic differential diagnosis. New York: Informa, 2006.

Two-volume tome on dermatologic differential diagnosis. This is the definitive reference work in the field and should be consulted for the most difficult rash/fever problems.

Lopez FA, Sanders CV. Rash and fever. In: Cunha BA, editor. Educational review manual in infectious disease. 4th ed. New York: Castle Connolly; 2009:15-72.

Intended for infectious fellow board review, the chapter on rash and fever is excellent and reviews the rash/fever from a clinician’s standpoint.

Cunha CB. Differential diagnosis in infectious diseases. In Cunha BA, editor: Antibiotic essentials, 9th ed, Sudbury, MA: Jones & Bartlett, 2010.