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Skin Signs of Systemic Disease


Fever and Rash

Key Points

  • 1.

    Characterize the rash to limit the differential diagnosis

  • 2.

    Do laboratory tests based on the history and physical examination

A wide spectrum of diseases can present with fever and rash, including infections, drug reactions (e.g., DRESS; Fig 23.1 ), collagen vascular diseases, and vasculitis. These causes are listed in Table 23.1 , according to the primary cutaneous lesions: macules and papules, purpura, nodules and plaques, vesicles and bullae, and pustules. Some of these diseases (e.g., meningococcemia; Fig. 23.2 ) are life threatening and require prompt diagnosis and treatment.

Figure 23.1, DRESS – d rug r eaction with e osinophilia and s ystemic s ymptoms.

Table 23.1
Fever and Rash
Macules and papules (erythematous rashes)
  • ●

    Infections

    • ●

      Viral

      • Measles (rubella, rubeola)

      • Adenovirus

      • Echovirus

      • Infectious mononucleosis

      • Human immunodeficiency virus (HIV)

      • West Nile

      • Ebola

      • Chikungunya

      • Zika

    • ●

      Bacterial

      • Staphylococcus – toxic shock syndrome

      • Streptococcus – erysipelas, rheumatic and scarlet fever

      • Typhoid fever

      • Typhus – endemic

      • Rat-bite fever

    • ●

      Treponemal

      • Erythema migrans (Lyme disease)

      • Secondary syphilis

    • ●

      Fungal

      • Cryptococcosis

  • ●

    Drug reaction with eosinophilia and systemic symptoms (DRESS)

  • ●

    Connective tissue disease

    • Systemic lupus erythematosus

    • Dermatomyositis

    • Juvenile rheumatoid arthritis

    • Adult Still disease

  • ●

    Erythema multiforme

  • ●

    Kawasaki syndrome

  • ●

    Tumor necrosis factor receptor-associated periodic syndrome (TRAPS)

  • ●

    Familial Mediterranean fever

  • ●

    Hyperimmunoglobulinemia D syndrome (HIDS)

  • ●

    Interferonopathies

Purpura
  • ●

    Infections

    • ●

      Viral

      • Ebola

      • Enterovirus

      • Dengue

      • Hepatitis

    • ●

      Bacterial

      • Gonococcemia

      • Meningococcemia

      • Pseudomonas septicemia

      • Bacterial endocarditis

    • ●

      Rickettsial

      • Typhus – epidemic

      • Rocky Mountain spotted fever

    • ●

      Ehrlichiosis

    • ●

      Fungal

      • Candidal septicemia

    • ●

      Drug reaction

    • ●

      Vasculitis

    • ●

      Connective tissue disease

      • Systemic lupus erythematosus

      • Rheumatoid arthritis

    • ●

      Thrombotic thrombocytopenic purpura

Nodules and plaques
  • ●

    Infections

    • ●

      Bacterial

      • Tuberculosis

    • ●

      Fungal

      • Histoplasmosis

      • Blastomycosis

      • Coccidioidomycosis

  • ●

    Lymphoma

  • ●

    Erythema nodosum

  • ●

    Sweet syndrome

Vesicles and bullae
  • ●

    Infections

    • ●

      Viral

      • Herpes simplex (primary, disseminated)

      • Herpes zoster (disseminated)

      • Coxsackie (hand, foot, and mouth syndrome)

      • Varicella

      • Monkeypox

      • Orf

      • Smallpox

    • ●

      Rickettsial

      • Rickettsialpox

    • ●

      Bacterial

      • Staphylococcal scalded skin syndrome

      • Drug reaction (toxic epidermal necrolysis—TEN)

  • ●

    Erythema multiforme

Pustules
  • ●

    Infections

    • ●

      Viral

      • Herpes simplex and zoster

      • Varicella

    • ●

      Treponemal

      • Congenital syphilis

    • ●

      Bacterial

      • Gonococcemia

    • ●

      Fungal

      • Candidal septicemia

      • Blastomycosis

  • ●

    Drug eruption (acute generalized exanthematous pustulosis-AGEP)

  • ●

    Pustular psoriasis

Figure 23.2, Meningococcemia – purpura in an acutely ill patient.

The methods used to diagnose the cause of fever and rash are similar to those used for fever of unknown origin. Clues are sought in the history and physical examination (e.g., Sweet syndrome) ( Fig. 23.3 ). The type of eruption is particularly important, as noted in Table 23.1 .

Figure 23.3, Sweet syndrome (acute febrile neutrophilic dermatosis) manifest by a bullous appearing hemorrhagic plaque. This patient had fever, neutrophilia, and acute myelogenous leukemia.

Diagnostic laboratory tests are directed by the history and physical examination. Simple procedures such as a potassium hydroxide preparation, a Gram stain, and a Tzanck smear should not be overlooked. These “bedside” tests can quickly establish an infectious cause. A skin biopsy with appropriate stains and cultures may be diagnostic. Further work-up is dictated by the clinical setting.

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