The Acutely Ill Patient With Fever 57 and Rash Jonathan J. Juliano, Myron S. Cohen, and David J. Weber SHORT VIEW SUMMARY Definition bioweapon (e.g., anthrax, smallpox, plague, lesions are suggestive of mycobacterial or } Skin lesions are frequently present in acutely viral hemorrhagic fevers). fungal infections. Diffuse erythema suggests scarlet fever, TSS, Kawasaki disease, or ill patients with serious infectious diseases and Microbiology may provide important clues that aid in early Stevens-Johnson syndrome/toxic epidermal } Serious bacterial infections with skin lesions diagnosis and treatment. necrolysis. Bullous lesions suggest include Staphylococcus aureuss (toxic shock streptococcal erysipelas with necrotizing Epidemiology syndrome [TSS], scalded skin syndrome), fasciitis, ecthyma gangrenosum, and Vibrio Acutely ill patients with a potential infectious Streptococcus pyogeness (TSS), Salmonella } infections. Petechial eruptions suggest disease and skin lesions (or rash) should have entericaa serovar Typhi, Neisseria meningitidis, gram-negative sepsis, invasive N. meningitidis a history obtained that elicits the following: and Rickettsia rickettsii. infection, rickettsial infections, and viral recent drug ingestion; travel outside the local } Potentially serious viral infections with skin hemorrhagic fever. area; potential occupational exposures; recent lesions include measles, rubella, Epstein-Barr } Consideration should be given to biopsy of immunizations; risk factors for sexually virus infection, cytomegalovirus, human skin lesions, if present, in acutely ill transmitted infections, including human herpesvirus 6, and viral hemorrhagic fevers immunocompromised patients for appropriate immunodeficiency virus infection; factors (e.g., dengue hemorrhagic fever, Ebola, stains (e.g., Gram stain, fungal stain) and affecting host resistance or Marburg, Lassa). cultures and for pathologic study. immunocompromising conditions; prior } Life-threatening drug reactions may result allergies to antibiotics; recent exposures to from antibiotic therapy for disorders such as Therapy febrile or ill persons; exposure to rural Stevens-Johnson syndrome/toxic epidermolysis } Empirical therapy should often be initiated in habitats, insects, arthropods, and wild animals; necrosis and from drug reaction with acutely ill patients with skin lesions based on and exposure to pets or animals. eosinophilia and systemic symptoms (DRESS). the clinical diagnosis. Most acutely ill patients with skin lesions will } Patients with skin lesions or rashes consistent Diagnosis } with a communicable infectious disease (e.g., require systemic therapy. } Key aspects of skin lesions that aid in a proper invasive meningococcal infection) should be diagnosis include (1) primary type(s) of skin Prevention immediately placed on appropriate isolation lesions, (2) distribution of the lesions, (3) } Standard vaccines should be provided to precautions (i.e., contact, droplet, airborne, or pattern of progression of the rash, and (4) children and adults because many special precautions for highly communicable timing of onset of the rash relative to the vaccine-preventable diseases produce rashes diseases, such as Lassa and Ebola virus onset of fever and other systemic signs. (e.g., measles, rubella, varicella). infections). } The appearance of skin lesions may be very } Underlying noninfectious diseases that lead to Infectious disease physicians should be } useful in the diagnosis of specific infectious disruption of skin should be treated because familiar with the skin lesions (or rash) that diseases. Maculopapular rashes are usually the damaged skin serves as a risk factor for might accompany a patient with disease that seen in viral illnesses, drug eruptions, and infection. could be the result of the intentional use of a immune complex–mediated diseases. Nodular A recognizable rash can lead to immediate diagnosis and appropriate immediate institution of isolation precautions. Isolation is required therapy. Material isolated from involved skin, when properly handled, primarily for patients whose illnesses allow droplet or airborne spread can confirm a specific diagnosis. Unfortunately, rashes often present a of the pathogen, including both viral (e.g., possible viral hemorrhagic bewildering array of diagnostic possibilities. Dermatologists, who are fever) and bacterial diseases (e.g., possible invasive meningococcal generally more comfortable with evaluation of the skin, are not always infection). Isolation precautions should be adhered to scrupulously. available for immediate consultation. Furthermore, dermatologists and Health care personnel should exercise caution in all interactions with infectious disease specialists frequently differ in their approach to the patients with undiagnosed infectious diseases, and they should use patient with a rash. standard precautions, including the avoidance of direct contact with all A framework is provided in this chapter for investigation of the excretions and secretions with the exception of sweat.1–4 Although the cause of rash, with emphasis on the following: (1) a diagnostic approach vast majority of skin eruptions are noninfectious, gloves should always to patients with fever and rash, (2) categories of skin lesions, and (3) be worn during the examination of the skin whenever an infectious brief descriptions of the most important febrile illnesses characterized cause is being considered because some infections (e.g., syphilis, herpes by a rash. simplex virus [HSV]) may be acquired via direct skin contact. In the event of potential exposure to a pathogen, health care personnel should APPROACH TO THE PATIENT be evaluated by their occupational health service for postexposure pro- In the initialinitial evaluationevaluation of a patientpatient withwith feverfever and rash, four concerns phylaxis or the need for work restrictions or both.4–7 The third concern must be addressed immediately. The first is if the patient is well enough to is if skin lesions suggest a life-threatening infection, such as bacterial provide further history or whether cardiorespiratory support is required. sepsis, staphylococcal or streptococcal toxic shock, Kawasaki disease, The second is whether the nature and presentation of the rash demands necrotizing fasciitis, toxic epidermal necrolysis, or Rocky Mountain 801 802 spotted fever (RMSF).8–11 Early diagnosis is important because prompt 3. Signs of toxicity initiation of appropriate therapy may improve survival.12,13 If skin lesions 4. Presence and location of adenopathy are consistent with meningococcal disease (see later discussion), the 5. Presence and morphology of genital, mucosal, or conjunctival s immediate institution of antibacterial therapy is crucial.14,15–17 Finally, lesions consideration must be given to the possibility that the patient has an 6. Detection of hepatosplenomegaly exotic disease acquired as a result of travel or the intentional release of 7. Presence of arthritis ndrome 18 y an agent of bioterrorism. Bioterrorist agents that may be acquired via 8. Signs of nuchal rigidity, meningismus, or neurologic dysfunction person-to-person transmission and characteristically cause a general- Key ingredients in arriving at a correct diagnosis, or at least a useful, ized rash include smallpox1,19 and the viral hemorrhagic fevers (i.e., limited, “working” list of likely diagnoses, include determination of (1) Ebola, Lassa, Marburg, Crimean-Congo, Bolivian, and Argentinean).1,20 the primary type(s) of skin lesions present, (2) the location and distribu- Patients with plague1,21 and anthrax1,22 may present with localized tion of the eruption, (3) the number and size of the lesions, (4) the or Clinical S j skin lesions. pattern of progression of the rash, and (5) the timing of the onset of The history obtained from the patient should elicit the following the rash relative to the onset of fever and other signs of systemic Ma 23–31 I information: illness. It is important for physicians who observe a rash to carefully 1. Drug ingestion within the past 60 days document the characteristics or take images of the skin lesions in the art I 2. Travel outside the local area medical record to aid other providers in the later care of the patient. P 3. Occupational exposure Although histologic findings from lesional skin biopsies may help to 4. Sun exposure confirm some diagnoses,29 the patterns observed are frequently not 5. Immunizations specific for a single organism, the presence of infectious agents may 6. Sexually transmitted disease exposure, including risk factors for not always be detectable, and laboratory studies often require at least infection with human immunodeficiency virus (HIV) 24 hours to complete. Thus the clinician must attempt to use other 7. Factors affecting immunologic status, including chemotherapy, diagnostic skills during the early evaluation of a patient with fever and corticosteroid use, use of immune modulators, hematologic rash. As discussed elsewhere, specific types of primary skin lesions malignancy, solid-organ or stem cell transplantation, and frequently suggest different infectious disorders in patients with fever functional or anatomic asplenia and rash. For example, palpable purpura, the hallmark feature of 8. Valvular heart disease, including heart valve replacement leukocytoclastic vasculitis, is the prototypic early finding in meningococ- 9. Prior illnesses, including a history of drug or antibiotic allergies cemia and RMSF, whereas rapidly enlarging but asymptomatic