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Fever and Rash 

Fever and Rash
Fever and Rash

Emily Shuman

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date: 20 May 2022

  1. A. Introduction. Like chest pain, the symptom complex of fever and rash may represent an acute, life-threatening disease or a benign condition.

  2. B. Seven Killer Causes of Fever and Rash. Although there are many causes of fever and rash, you must first consider the diseases that may kill the patient within hours. A SMARTTT physician can easily remember these seven killer causes:

    MNEMONIC: Seven Killer Causes of Fever and Rash (“SMARTTT”)



    Acute endocarditis

    Rocky Mountain spotted fever

    Toxic erythemas

    Toxic epidermal necrolysis (TEN)

    Travel-related infections

    1. a. Sepsis. Fever accompanied by a generalized erythematous rash may signal impending sepsis (often caused by gram-negative organisms).

    2. b. Meningococcemia. Patients usually appear acutely ill. A petechial rash develops in most patients.

      Hot Key

      Disseminated gonococcal infection (DGI) is a less dangerous Neisseria infection that may also produce fever and rash. DGI often presents with palpable purpuric pustules and may be associated with fever, tenosynovitis, polyarthralgias, or septic arthritis.

    3. c. Acute bacterial endocarditis should be considered in all patients with fever and a petechial rash. A careful cardiac examination is always necessary.

    4. d. Rocky Mountain spotted fever. After 3–5 days of an influenza-like febrile illness, a macular rash usually appears over the ankles or wrists. The rash spreads centrally and may evolve into a petechial rash.

    5. e. Toxic erythemas include toxic shock syndrome (TSS), staphylococcal scalded skin syndrome (SSSS), scarlet fever, and scarlatiniform eruptions.

      Hot Key

      Common features of toxic erythemas include fever and an erythematous rash that is most significant in the flexural folds and later desquamates; mucocutaneous involvement occurs frequently.

      1. i. TSS results in a diffuse erythematous rash that blanches easily; desquamation occurs after 1–2 weeks (see Chapter 89). Both Staphylococcus aureus and Streptococcus pyogenes (group A Streptococcus) can cause TSS.

      2. ii. SSSS results in generalized erythema and desquamation.

      3. iii. Scarlet fever follows S. pyogenes pharyngitis. Although it may not be immediately life-threatening, scarlet fever should always be considered when a patient presents with toxic erythema. Scarlatiniform eruptions resemble the rash of scarlet fever and are usually caused by S. aureus.

      4. iv. Toxic epidermal necrolysis (TEN) is caused by a reaction to drugs. It results in large areas of erythema and desquamation and may be clinically indistinguishable from SSSS.

      • MNEMONIC: It is a “SNAP” to remember the drugs that commonly cause TEN if you remember this mnemonic.

      • Sulfonamides

      • Nonsteroidal antiinflammatory drugs (NSAIDs)

      • Allopurinol

      • Phenytoin

    6. f. Travel-related infections. Fever and rash in a recent traveler should alert you to the possibility of a potentially life-threatening viral illness. Most of these dangerous viruses are acquired in Latin America, Africa, or Asia.

      1. i. Hemorrhagic fevers are the most worrisome and include Ebola virus, Lassa virus, and Hantavirus infection. These disorders are often characterized by petechiae or purpura, as well as other types of bleeding, and are associated with a high mortality rate.

  3. C. Approach to the Patient

    1. a. Rule out the seven killer causes of fever and rash. In general, you will be able to rule out these life-threatening causes of fever and rash by taking a careful history and paying attention to clinical manifestations of disease, including the rash.

      1. i. Patient history. Always remember to obtain a medication and travel history. A negative drug and travel history usually rules out TEN and hemorrhagic fever as potential etiologies.

      2. ii. Clinical manifestations

        1. 1. Ill appearance. Patients with meningococcemia, Rocky Mountain spotted fever, or sepsis usually appear systemically ill.

        2. 2. Cardiac murmur. Acute endocarditis is usually accompanied by a cardiac murmur (see Chapter 54).

        3. 3. Rash

          • a. Desquamating rashes often signal toxic erythema or TEN.

          • b. Petechial rashes should always alert you to the possibility of meningococcemia, Rocky Mountain spotted fever, or endocarditis.

      3. iii. Helpful data

        1. 1. Laboratory evaluation to assess other organ systems may be necessary when toxic shock is still a consideration (e.g., in a patient who appears ill or has low blood pressure).

        2. 2. Most of the toxic erythemas (with the exception of SSSS) can usually be ruled out on clinical grounds; however, a skin biopsy is always indicated to differentiate SSSS from TEN. A split epidermis (i.e., intraepidermal separation) is found in SSSS, whereas total epidermal separation (i.e., subepidermal separation) is seen in TEN.

    2. b. Address other diagnostic possibilities

      1. i. Types of lesions. One way to establish a concise differential diagnosis of a fever and rash is to first determine the type of primary skin lesion (Table 50.1).

        Table 50.1 Types of Cutaneous Lesions




        Discolored, flat lesions


        Raised lesions; <0.5 cm in diameter


        Lesions filled with clear fluid; <0.5 cm in diameter


        Large vesicles (i.e., >0.5 cm in diameter)


        Pus-filled vesicles


        Raised lesions >0.5 cm in diameter and depth


        Raised lesions >0.5 cm in diameter, but without depth


        Purple, nonblanchable lesion


        Purpuric lesions <3 mm in diameter


        Purpuric lesions >3 mm in diameter

      2. ii. Differential diagnoses. Some common etiologies for each primary lesion associated with a fever are:

        1. 1. Macules and papules (or a maculopapular rash)

          • a. Drug reactions commonly present with a pruritic, confluent eruption over the trunk and back. Fever is usually absent.

          • b. Viral infections (e.g., measles and other childhood viral exanthems, infectious mononucleosis, primary HIV) usually result in rashes that are nonpruritic. Fever and other viral symptoms are often present.

          • c. Toxic erythemas are usually accentuated in the flexural folds, are not pruritic, and may have mucous membrane involvement.

          • d. Connective tissue diseases (e.g., systemic lupus erythematosus [SLE], Still’s disease) often present with rash in association with other characteristic symptoms (e.g., arthralgias).

          • e. Bacterial infections are less likely causes.

            • i. Lyme disease may cause erythema chronicum migrans.

            • ii. Secondary syphilis most often results in scaling papules that are present on the palms and soles.

            • iii. Typhoid fever can cause “rose spots,” which are usually seen as an individual papule on the trunk that fades with pressure.

        2. 2. Vesicles and bullae

          MNEMONIC: Differential Diagnoses for Vesicles and Bullae Accompanied by Fever (“VESICLES”)

          Viral infections (e.g., varicella-zoster, herpes simplex, Coxsackie)

          Erythema multiforme


          Impetigo (bullous)

          Contact dermatitis

          LESs likely etiologies (e.g., porphyria cutanea tarda, bullous pemphigoid, pemphigus vulgaris, dermatitis herpetiformis)

        3. 3. Pustules

          MNEMONIC: Differential Diagnoses for Pustules Accompanied by Fever (“Very Full of PUS”)

          Viral infections (e.g., varicella-zoster, herpes simplex)

          Fungal infections (e.g., candidiasis)

          Pustular psoriasis

          Urethritis related (i.e., DGI)


        4. 4. Nodules and plaques

          • a. Nonpainful

            • i. Fungal infections

            • ii. Lymphoma

          • b. Painful

            • i. Erythema nodosum presents with tender nodules on the lower legs. It is often associated with another systemic illness (e.g., tuberculosis, coccidioidomycosis, sarcoidosis, post-streptococcal infection) or pregnancy.

            • ii. Sweet’s syndrome should be suspected in patients with fever, neutrophilia, and red-brown skin lesions (usually on the head and upper extremities). The syndrome may be associated with leukemias (usually acute myelogenous leukemia), lymphomas, myelodysplasia, or other malignancies. Infiltration of neutrophils into the dermis is seen on biopsy.

        5. 5. Purpura

          • a. Palpable purpura is pathognomonic for vasculitis (see Chapter 75).

          • b. Nonpalpable purpura. Petechiae usually indicate a bleeding disorder (e.g., thrombocytopenia), and ecchymoses often result from vessel fragility (e.g., actinic purpura); however, overlap does exist (e.g., necrotic ecchymoses may occur with disseminated intravascular coagulation [DIC]).

Hot Key

Purpuric lesions in a patient with fever may be the harbinger of a life-threatening illness. Hemorrhagic fever, meningococcemia, Rocky Mountain spotted fever, endocarditis, sepsis, and vasculitis all need to be considered carefully and ruled out.

Suggested Further Readings

Chung W-H, Wang C-W, Dao R-L. Severe cutaneous adverse drug reactions. J Dermatol 2016;43:758–66.Find this resource:

Cunha BA. Rash and fever in the critical care unit. Crit Care Clin 1998;14:35–53. (Classic Article.)Find this resource:

Gastañaduy PA, Budd J, Fisher N, et al. A measles outbreak in an underimmunized Amish community in Ohio. N Engl J Med 2016;375:1343–54.Find this resource:

Schlossberg D. Fever and rash. Infect Dis Clin North Am 1996;10:101–10. (Classic Article.)Find this resource: