Current Diagnosis & Treatment in Infectious Diseases

Section II - Clinical Syndromes

19. Fever & Rash

Peter K. Lindenauer MD, MSc

Merle A. Sande MD

Essentials of Diagnosis

  • The combination of fever and rash is not a specific finding and can be seen in a variety of infectious and noninfectious disorders. Adverse reactions to drugs are the most common noninfectious cause of fever and rash.
  • Because of the life-threatening nature of many of the illnesses causing fever and rash, a thorough, yet rapid, evaluation is required.
  • Rule out treatable but immediately life-threatening causes of fever and rash early on.
  • Diagnosis is best made by a thorough history and a proper classification of the rash. Laboratory testing is useful and specific for some diseases but of limited value for many others.
  • An empiric approach to therapy is warranted when patients appear ill and a definitive diagnosis has not been made.
  • Isolation is often warranted for patients with fever and rash when meningococcemia or varicella is being considered, as these illnesses can be transmitted by respiratory droplets.

General Considerations

The combination of fever and rash is a dramatic finding and can often reflect a life-threatening illness. Because of the variety of infectious and noninfectious disease processes that can present in this manner, an organized and thoughtful approach to patients with this syndrome is essential (Table 19-1).

More than for many other clinical problems, the history obtained from patients with fever and rash is critical in establishing an accurate diagnosis and embarking on effective treatment. Essential historical elements to review include the following: drug and dietary history, human and animal contacts (including a detailed sexual history), occupational exposures, travel, and immunizations. Reviewing the patient's prior medical history is vital as is a review of prior adverse drug reactions. Both the season and geographic location should be factored into the differential diagnosis. Special populations to consider include hospitalized patients as well as the immunosuppressed, especially those with HIV infection. Finally, a careful review of the time course and distribution of the rash can provide extremely valuable diagnostic clues.


Drug Use

Patients should be asked about all drug use: both prescription and over the counter, traditional and alternative, licit and illicit in the preceding weeks. Prescription drugs are common causes of fever and rash, and almost any drug may lead to this syndrome (Figure 19-1). Mechanisms underlying the development of adverse drug reactions can be either immunologically or nonimmunologically mediated, but in many instances the pathogenesis is not understood. Hospitalized patients who often begin treatment with multiple medications over a short time period are an extremely susceptible group. Because of the variety of mechanisms underlying the development of such adverse reactions, the cutaneous manifestations range from simple maculopapular to petechial or desquamating.

Frequently implicated medications include penicillins, sulfonamides, phenytoin, allopurinol, barbiturates, and occasionally nonsteroidal anti-inflammatory agents. Serum sickness is a multisystem illness that presents with fever, rash, arthritis, and glomerulonephritis and results from the deposition of circulating immune complexes throughout the body. It can be caused by exposure to sera but more commonly is induced by medications such as the ones listed above. Vasculitis syndromes can be caused by medications as well as by infections and malignancies. Photosensitivity is a property of certain drugs including tetracyclines, thiazide diuretics, and selected NSAIDS; as such, sun exposure should be reviewed. Because the preceding comments are, for the most part, equally applicable to over-the-counter as well as alternative medicines, use of both is important to document.

Illicit drug use, and injection drug use in particular, exposes the user to a range of bacterial and viral pathogens. Fever and rash in an injection drug user should raise the immediate possibility of infective endocarditis or acute hepatitis B infection. Moreover, because skin and soft tissue infections are common in this patient population, they are at higher risk of developing toxic shock and toxic streptococcal syndromes.


Diet is occasionally found to be the cause of fever and rash. Food allergies to such substances as eggs, nuts, chocolate, and shellfish can cause both immediate, immunoglobulin E-mediated reactions and delayed hypersensitivity. The ingestion of undercooked pork or beef can result in trichinosis that may present with rash. Raw seafood and shellfish have been associated with vibrio vulnificus infections in patients with underlying liver disease. Typhoid fever is commonly associated with rash and is frequently seen in patients returning from the developing world where it is transmitted by the fecal oral route.

Table 19-1. Diagnostic approach to fever and rash.

· Obtain a thorough history, reviewing all drugs and medications used in the preceding weeks, travel, contacts with sick children and adults, exposure to pets, wild animals or insects, sexual history, prior immunizations, past medical history paying particular attention to rheumatic diseases, valvular heart disease or immunosuppression, and onset and distribution of the rash and associated symptoms.

· On physical examination, note the overall severity of the patient's illness, the form and distribution of the rash, and the presence of any associated physical findings.

· Rashes should be grouped as (a) macular and maculopapular, (b) vesicular and vesiculobullous, or (c) petechial, purpuric, and pustular. Each of these categroies has a fairly unique differential diagnosis.

· Petechial, purpuric, and pustular lesions that can be aspirated should be gram stained and sent for culture. Vesicular and vesiculobullous lesions should be unroofed, scraped, and examined for the presence of multinucleated giant cells or inclusion bodies. Punch biopsy is a useful method for diagnosing both infectious and noninfectious disorders and should be considered whenever Rocky Mountain Spotted Fever is suspected or whenever a diagnosis is in doubt. Aerobic and anaerobic blood cultures should be obtained for all patients.

· In the acute setting, serologic studies are of limited usefulness for most of the disorders that cause fever and rash.

· Polymerase chain reaction-based assays are rapidly emerging as the diagnostic tests of choice for a number of infections that cause fever and rash, but their use is limited by availability.


Figure 19-1. Drug-induced rash.


Contacts with sick individuals or with animals are important modes of transmission for many of the diseases that can cause fever and rash (Box 19-1). Viral illnesses are commonly transmitted this way, especially the classic childhood exanthems varicella zoster, rubella, measles, “fifth disease” (erythema infections resulting from parvovirus B-19), along with mononucleosis and cytomegalovirus. Bacterial infections, notably streptococcal and meningococcal, are usually associated with contact with an afflicted individual. Sexual contact is a mode of transmission of hepatitis B and is the source of gonococcal, chlamydial, and syphilis infection. Acute HIV infection obtained sexually or through injection drug use often presents with fever, pharyngitis, and generalized rash.

Insect and Animal Exposure

Insect and animal contacts are another important source of exposure to microbial pathogens that cause fever and rash in the setting of severe illness. Ticks are the vectors for Rocky Mountain Spotted Fever and Lyme disease; however, in only one-half of patients with Rocky Mountain Spotted Fever and one-third of patients with Lyme disease is a history of tick exposure obtainable. Capnocytophagia is an infection strongly associated with dog and cat bites in patients who are immunosuppressed, usually in the setting of splenectomy. Contact with livestock or contaminated water should raise the possibility of leptospirosis, whereas tularemia is seen in patients exposed to infected wild rabbits.


Travel to endemic regions is usually described in cases of coccidioidomycosis and in viral hemorrhagic fever and scrub typhus. Malaria may present in travelers returning from an endemic area, and severe Plasmodium falciparum infections should be considered for those with petechial rashes accompanied by hemolysis, thrombocytopenia, and acute renal failure.

Occupational Exposure

Occupational exposures should not be overlooked. Florists and gardeners are prone to sporotrichosis as a result of their extensive contact with soil and vegetation. Erysipelothrix, or fishmonger's cellulitis, is an unusual cause of fever and rash seen in patients with occupational or recreational fish contact.

Prior Medical History

The prior medical history is the source of much valuable information when the clinician is confronted with a patient with fever and rash. Those with a history of valvular heart disease are at high risk for infective endocarditis. Immunosuppression from steroids, chemotherapy, or HIV is an important risk factor for the development of many of the infections previously discussed. Patients with a prior history of rheumatologic diseases or inflammatory bowel disease are often subject to flares that can include fever and rash as part of the presentation.

BOX 19-1 Microbiology of Fever and Rash1




More Frequent

· Varicella

· Enteroviruses

· Epstein-Barr virus

· Parvovirus B-19

· Group A sterptococci4

· Sepsis

· Other viruses

· Sepsis2

· Infective endocarditis3

· Varicella zoster

· Neisseria meningitidis

Less Frequent

· Neisseria meningitidis

· Borellia burgdorferi

· Measles

· Rickettsia rickettsii

· Rickettsia rickettsii

· Borellia burgdorferi

· T pallidum

· Plasmodium falciparum

· Disseminated fungal disease

· Salmonella typhi

· Dengue

1Many of the causes of fever and rash discussed in this chapter are not infectious in origin.

2Bacterial sepsis from S pneumonia, enteric gram negatives, and Pseudomonas aeruginosa.
3Infective endocarditis most commonly caused by viridans streptococci. Parenteral drug users and hospitalized patients with vascular catheters are at high risk of Staphylococcus aureus endocarditis.
4Scarlet fever in association with group A streptococcal pharyngitis.


Season and geographic setting are important factors influencing the diagnosis in patients with fever and rash. Rocky Mountain spotted fever is a disease of late spring to early fall, coinciding with increased exposure to the tick vectors Dermacentor variabilis or Dermacentor andersoni. Like Rocky Mountain spotted fever, Lyme disease occurs most commonly in the spring and summer months following contact with the infected tick nymph Ixodes dammini or Ixodes pacificus. Outbreaks of the exanthems caused by enteroviruses occur in warmer months, whereas streptococcal and meningococcal disease occurs in late winter and early spring. Lyme disease cases cluster into three distinct geographic regions: the Northeast, the Upper Midwest, and the Far West. However, Rocky Mountain spotted fever has been reported in all states with the exception of Hawaii and Vermont, although its highest prevalence centers in the eastern and southern plains regions.



Hospitalized patients are a special population and should be separately considered. As previously discussed, their high exposure to antibiotics and other new medications makes drug reaction a common cause of fever and rash. Neutropenic and immunosuppressed patients are at high risk of bacterial infection with pseudomonas aeruginosa, Clostridium spp., and alpha hemolytic streptococci. Disseminated candidiasis, Aspergillus, and herpesvirus infections are common complications of neutropenia. Patients receiving broad-spectrum antibiotics or parenteral nutrition are at heightened risk of developing systemic candidiasis. Finally, indwelling catheters, shunts, prosthetic valves, and pacemakers place patients at risk of endovascular infections from recurrent transient bacteremic episodes.


Acute HIV infection may present with fever, rash, headache, pharyngitis, and aseptic meningitis. Dermatologic problems are common in this population and include eosinophilic folliculitis, papular dermatitis, and psoriasis. Pyoderma furunculosis and folliculitis can complicate HIV disease. Cutaneous manifestations of systemic infections may occur, and cutaneous infections may occur in severe forms. Varicella zoster and herpes simplex lesions are common and sometimes severe in HIV-infected patients. All disseminated fungal infections may involve the skin, and mycobacterial infection can present this way as well. Bacillary angiomatosis caused by Bartonella species is increasingly recognized as an important source of systemic illness (fever, hepatosplenomegaly, lymphadenopathy) accompanied by friable papules or nodules.

Clinical Findings

  1. Signs and Symptoms.

Appearance. The appearance and distribution of the rash often provides valuable clues toward a diagnosis, and associated physical findings are characteristic of many of the entities described here.

The skin has a limited repertoire of responses to infections and immunologic challenges. Rashes can generally be divided into the following groups: (1) macular and maculopapular; (2) vesicular or bullous; and (3) pustular, petechial, or purpuric. Although this classification scheme can help limit the differential diagnosis, it must be understood that these distinctions are not absolute. Not only do many processes present with a similar rash, but each disease or process can produce more than one type of rash (Table 19-2). Moreover, exanthems may change over the course of several hours or several days. Rocky Mountain spotted fever, which initially appears as an erythematous maculopapular eruption, often evolves into a petechial rash.

  1. Macular rashes.A macular or maculopapular rash is the most common exanthem caused by the nonherpetic viruses such as enteroviruses (Figure 19-2), rubella, rubeola, and parvovirus B-19. Nevertheless, many serious infections can present this way including Rocky Mountain spotted fever, meningococcemia, disseminated gonococcal infection, typhoid fever, and Pseudomonassepsis. Lyme disease is associated with a characteristic rash termed erythema migrans, which is observed in > 60% of patients. Erythema migrans typically begins as a small red papule arising anywhere between 1 and 30 days after tick exposure and gradually expands to a ring of erythema with central clearing. Any site may be affected, but the axilla, groin, and thigh are most common. Some patients develop similar appearing secondary lesions at distant sites.
  2. Toxic shock syndromeis characterized by a diffuse erythroderma (large macules) likened to a severe sunburn. The dermatologic findings are typically accompanied by fever, hypotension, and diffuse arthralgias and myalgias. Group A streptococci, which elaborate exotoxin, are capable of causing a similar syndrome, sometimes referred to as “toxic strep syndrome.” While the skin is the portal of entry of most cases of toxic shock, in only a minority of cases can the actual source be identified. Although tampon use during menses was initially described in the majority of patients, this now accounts for less than half of the 300 or so annual reported cases. Whereas the skin infections resulting in toxic shock syndrome are often minor, those associated with toxic streptococcal infections are often severe. Myositis and necrotizing fasciitis are common sequelae of these infections, and this virulence is reflected in a case fatality rate for toxic streptococcal infections that is some fivefold higher than that seen in toxic shock. Secondary syphilis occurs some 6–8 weeks after healing of the chancre seen in primary syphilis, although some patients may progress to secondary syphilis while a chancre remains present. The lesions are erythematous and macular or maculopapular, are symmetrically distributed, and often involve the palms and soles (Figure 19-3). The rash is frequently accompanied by constitutional symptoms and lymphadenopathy. Drugs often produce maculopapular exanthems that are “cherry-red” in appearance. The “target lesions” of erythema multiforme and the “slapped cheeks” of parvovirus B-19 are both examples of maculopapular lesions distinctive enough to be almost pathognomonic.

Table 19-2. Diagnosis of fever and rash based on rash appearance

Rash Category





Scarlet fever, Pseudomonas sepsis, secondary syphilis, toxic shock syndrome, Lyme disease, Chlamydia, leptospirosis


Measles, rubella, enteroviruses, parvovirus B-19, mononucleosis, cytomegalovirus, hepatitis B, roseola, human immunodeficiency virus


Rocky Mountain spotted fever (early), murine and scrub typhus


Disseminated candidiasis, coccidioidomycosis, histoplasmosis, blastomycosis, sporotrichosis


Drug reactions, serum sickness, erythema multiforme, systemic lupus erythematosus, dermatomyositis, Behçet's disease, Reiter's syndrome, inflammatory bowel disease



Staphylococcal scalded skin syndrome, Pseudomonas sepsis, bullous impetigo


Herpes simplex, Varicellazoster, eczema herpeticum, hand-foot and mouth disease


Ricketsial pox


Drug reactions, Mycoplasma pneumonia, Stevens-Johnson syndrome, inflammatory bowel disease, pemphigus, pemphigoid

Petechiae, Purpura, or Pustules


Meningococcemia, sepsis with disseminated intravascular coagulation, gonococcemia, Pseudomonas sepsis, staphylococcal sepsis, infective endocarditis, listeriosis


Viral hemorrhagic fevers, enteroviruses


Rocky Mountain spotted fever, epidemic typhus


Drug reactions, Henoch-Schönlein purpura, thrombotic thrombocytopenic purpura


Figure 19-2. Enterovirus.


Figure 19-3. Palmar lesions of secondary syphilis.

  1. Vesicular rashes.Vesicular lesions are caused by a number of viruses including varicella-zoster, herpes simplex, vaccinia, and the enteroviruses. The staphylococcal scalded skin syndrome is characterized by large bullae that rupture, leaving behind beefy red areas of denuded skin. Pseudomonassepticemia can be associated with vesicles that rapidly become hemorrhagic or with the centrally necrotic lesions of ecthyma gangrenosum. Stevens-Johnson syndrome causes vesicular lesions of both the skin and mucosa. Ulcerative colitis and Crohn's disease can cause vesicular lesions that progress to chronic ulceration and may have prominent mucosal involvement.
  2. Petechial, purpuric, or pustular rashes.Petechial, purpuric, or pustular skin lesions often indicate life threatening illness. The identification of such a rash should call immediate attention to the treatable bacterial or rickettsial infections that may be responsible for its appearance. Most prominent among these illnesses are meningococcemia, Rocky Mountain spotted fever (Figure 19-4), infective endocarditis, or sepsis with associated disseminated intravascular coagulation. Disseminated gonococcal infection produces a less severe illness often associated with migratory polyarthritis and tenosynovitis (Figure 19-5). Atypical measles can produce a petechial rash that may mimic that seen in Rocky Mountain spotted fever and is seen in that cohort of patients previously vaccinated with a killed measles vaccine. Occasionally, enteroviral infections can produce petechial lesions, and other viruses including dengue and Epstein-Barr virus may do so as well. Many noninfectious causes of fever and rash present with petechial lesions, the most important of which are systemic lupus erythematosus, Henoch-Schönlein purpura, thrombotic thrombocytopenic purpura, and many of the vasculitides.

Figure 19-4. Rocky Mountain spotted fever.


Figure 19-5. Pustular lesion of disseminated gonococcal infection.

  1. Distribution.The distribution of the rash may also aid in diagnosis. A macular or petechial rash involving the palms or soles should suggest Rocky Mountain spotted fever, meningococcemia, infective endocarditis, Mycoplasmainfection, scarlet fever, or bacteremia. The lesions of secondary syphilis, atypical measles, Kawasaki's disease, and many drug exanthems may present similarly. Maculopapular rashes caused by viruses usually spare the palms and soles, whereas these sites may be involved in vesicular exanthems caused by herpesvirus and certain coxsackie virus strains. Exanthems with a tendency to involve the extremities preferentially include gonococcemia, Henoch-Schönlein purpura, dermatomyositis, and sporotrichosis. The “rose spots” of typhoid fever and the maculopapular lesions of Pseudomonas sepsis are usually confined to the trunk. Scarlet fever begins on the face and neck and spreads to the trunk and extremities within 36 hours. Rubeola usually begins behind the ears and spreads throughout the body within the first day.
  2. Laboratory Findings.As a general rule, diagnostic procedures that are likely to yield immediate results should be carried out on any lesion. Pustular, purpuric, or petechial lesions should be aspirated or scraped and the fluid obtained examined microscopically and cultured. Many patients with meningococcemia can be diagnosed by this simple procedure, which will demonstrate gram-negative biscuit-shaped cocci. Vesicular lesions should be unroofed, and the contents should be examined microscopically using a Wright or Giemsa stain to look for multinucleated giant cells or inclusion bodies characteristic of herpes virus infection (Tzanck test).

Needle aspiration can be used to diagnose group A streptococcal infections in patients with necrotizing fasciitis and should be considered as a means of diagnosing pseudomonal sepsis in immunosuppressed patients with maculopapular rashes. These techniques can provide immediate diagnosis long before a blood culture has had sufficient time to yield an organism. Punch biopsy can be used to identify fungal and mycobacterial disease involving the skin and is diagnostic of vasculitis and erythema multiforme. Immunofluorescent antibody staining is useful in skin biopsy specimens of patients with suspected Rocky Mountain spotted fever and is also used to diagnose systemic lupus erythematosus and pemphigus vulgaris.

In cases where genitourinary, articular, or neurologic symptoms coexist with rash, urethral and cervical swabbing and culturing is mandatory as is arthrocentesis and examination of the cerebrospinal fluid. Blood cultures should be routinely performed in all patients since bacteremia is an especially common cause of fever and rash.

Serologic testing is limited in its usefulness in the acute setting but can be important for confirming a diagnosis and for disease reporting purposes. For example, serologic tests for Lyme disease, especially early in the course of disease, are hampered by an unacceptably high false negative rate and the diagnosis of Lyme disease is largely a clinical one. Polymerase chain reaction–based assays are emerging as an accurate method for diagnosing many of the diseases discussed in this chapter, but today, their limited availability and relatively high cost makes them a poor choice for the typical patient with fever and rash.

  1. Imaging.A chest radiograph is a useful adjunct in the evaluation of patients with fever and rash since it can be used to detect pulmonary infiltrates or hilar adenopathy. Other imaging tests cannot be recommended on a routine basis.

Differential Diagnosis

Because the differential diagnosis of fever and rash is so broad and because of the urgency involved in a small number of cases, it is useful to divide the disorders into the following categories: immediately life-threatening, treatable infectious, nontreatable infectious, and noninfectious causes (Table 19-3).

Associated physical findings are seen in many of the disorders that cause fever and rash, and their recognition is helpful in limiting one's differential diagnosis. Enathems are mucous membrane eruptions, and many of the processes that involve the skin can involve the mucous membrane as well. Koplik's spots are diagnostic of rubeola and are found on the buccal mucosa opposite the second molar (Figure 19-6). They are blue-gray specks on a red base resembling a grain of sand. “Strawberry tongue” is characteristic of Kawasaki's disease, toxic shock syndrome, or scarlet fever. Palatal petechia is observed in 50% of patients with infectious mononucleosis and is also seen in infective endocarditis. Ulcerative mucosal lesions are observed in hand-foot and mouth disease, Behçet's syndrome, Reiter's syndrome, inflammatory bowel disease, and the Stevens-Johnson syndrome.

Table 19-3. Differential diagnosis of fever and rash.


Possible Causes

Immediately Life-threatening

· Meningococcemia

· Rocky Mountain spotted fever

· Bacterial or candidal sepsis syndromes

· Infective endocarditis

· Toxic shock syndrome

· Toxic streptococcal syndromes

· Staphylococcal scalded skin syndrome

· Stevens-Johnson syndrome

Treatable Infectious

· Disseminated gonococcal infection

· Syphilis

· Lyme disease

· Epidemic typhus

· Rat-bite fever

· Mycoplasma

· Human ehrlichioses

· Trichinosis

· Vibrio vulnificus

· Toxoplasmosis

· Varicella zoster

· Herpes simplex

· Acute HIV

· Disseminated fungal infections

Nontreatable Infectious

· Enteroviral infections

· Classic childhood exanthems

· Hepatitis B

· Epstein-Barr virus

· Cytomegalovirus

· Dengue

· Viral hemorrhagic fevers


· Adverse drug reactions

· Rheumatologic disorders [systemic lupus erythematosus, dermatomyositis, Behçet's disease, Reiter's syndrome, Still's disease, vasculitis (various forms)]

· Serum sickness

· Thrombotic thrombocytopenic purpura

· Henoch-Schönlein purpura

· Inflammatory bowel disease

· Pemphigus, pemphigoid


Meningitis and other neurologic changes may be observed in meningococcemia, Rocky Mountain spotted fever, staphylococcal bacteremia leptospirosis, Kawasaki's disease, toxic shock syndrome, Lyme disease, and as part of the aseptic meningitis seen in acute HIV and enteroviral infections. Lymphadenopathy is prominent in mononucleosis, syphilis, sarcoidosis, and drug hypersensitivity. Cervical adenopathy is seen in streptococcal pharyngitis in the setting of scarlet fever and with rubella. The finding of a heart murmur should raise the possibility of infective endocarditis even if findings such as Osler nodes, Janeway lesions, or splinter hemorrhages are absent. Fever and rash associated with pneumonia is seen in Mycoplasma infection, atypical measles, Rocky Mountain spotted fever, coccidioidomycosis, or sepsis associated with staphylococcal or pseudomonal pneumonia.


Figure 19-6. Koplik's spots of measles.


Complications relate to the specific pathogen responsible for the syndrome of fever and rash, and no complications are common to the group. Patients with meningococcemia are at risk for the development of the sepsis syndrome, disseminated intravascular coagulation, or death unless appropriate antibiotics are promptly begun. Rocky Mountain spotted fever is a multisystem disease that can cause encephalitis in approximately one quarter of cases. Infective endocarditis, if left untreated, rapidly progresses and is associated with valve destruction and incompetence as well as complications from septic emboli, such as stroke. Toxic shock syndrome is associated with profound hypotension, and it is this aspect of the illness that results in the vast majority of its complications. The complications from toxic epidermal necrolysis and staphylococcal scalded skin syndrome relate primarily to the degree of epidermal necrosis and include metabolic derangement and severe immunosuppression.


Treatment of fever and rash may be specific (as in the case of a recognized bacterial infection presenting in a classic fashion), empiric (as for the toxic appearing patient with petechial skin lesions), or supportive (as in most viral infections). A general approach to patients with fever and rash depending on whether the illness was nosocomially acquired or in a community is found in Box 19-2. While this can provide a useful starting place, the clinician is strongly encouraged to tailor decisions regarding the need for, and type of, antibiotic therapy only after a careful review of the factors discussed earlier in this chapter.


Mortality in patients with fever and rash is closely tied to the organism or process responsible for the syndrome and to the timeliness of recognizing and instituting appropriate therapy.

BOX 19-2 Empiric Therapy of Fever and Rash1,2


Community Acquired

Hospital Acquired3

First Choice

Ceftriaxone 2 g IV every 24 h PLUS doxycycline4 100 mg IV every 12 h

Ceftazidime 2 g IVevery 8 h PLUS APAG PLUS vancomycin 1 g IV every 12 h

Second Choice

Chloramphenicol 100 mg/kg/d IV divided every 6 h

Piperacillin PLUS APAG PLUS vancomycin 1 g IV every 12 h

Penicillin Allergic

Ciprofloxacin5 500 mg IV every 12 h PLUS doxycycline 100 mg IV every 12 h

Ciprofloxacin 500 mg IV every 12 h PLUS APAG PLUS vancomycin 1 g IV every 12 h

1Because of the diverse causes of fever and rash, it is of limited value to suggest empiric antibiotic therapy in a blanket way.

2In immunocompromised patients, Varicella zoster infections should be treated aggressively with intravenous acyclovir.
3Hospitalized patients and those with immunosuppression are at higher risk of developing pseudomonal sepsis syndromes and disseminated staphyloccal infections and should have antibiotic coverage extended with a third-generation cephalosporin with activity against Pseudomonas spp., or an extended spectrum penicillin (piperacillin, ticarcillin) and an aminoglycoside, as well as vancomycin. However, antibiotics themselves may cause fever and rash, and discontinuation of drugs may be the treatment of choice. APAG, Antipseudomonal aminoglycoside. Dosing of gentamicin and tobramycin is 5 mg/kg every 24 h or 1.5 mg/kg every 12 h.
4Patients with a history compatible with Rocky Mountain spotted fever should be treated empirically with doxycycline because the laboratory diagnosis of this infection cannot be relied on.
5Ciprofloxacin should not be used in children.


Prevention and Control

Isolation is useful to reduce the risk of spread of meningococcemia and varicella zoster. Care in the avoidance of tick exposure is the only method of preventing Rocky Mountain spotted fever and Lyme disease. The practice of safe sex can eliminate the possibility of obtaining syphilis or gonococcal infections.


Lindenauer PK, Sande MA: Fever and rash. In Stein JH: Internal Medicine, Mosby, 1998.

Meyers SA, Sexton DJ: Dermatologic manifestations of arthropod-borne diseases. Infect Dis Clin North Am 1994;8(3):689.

McCauliffe DP, Sontheimer RD: Dermatologic manifestations of rheumatic disorders. Primary Care 1993;20(4): 925.

Walker DH: Rocky mountain spotted fever: a seasonal alert, Clin Infect Dis 1995;20:1111.

Weber DJ, Cohen MS: The acutely ill patient with fever and rash. In Mandell GL, Douglas RG, Bennett JE: Principles and Practice of Infectious Disease, 4th ed. Churchill Livingstone, 1995.