FEVER AND SKIN RASH
Toxic Shock Syndrome
Rocky Mountain Spotted Fever
The acutely ill, febrile patient with a generalized skin rash presents a diagnostic challenge; the list of disorders in the differential diagnosis is extensive and includes both infectious and noninfectious causes. The skin is capable of reacting only in a limited way, and disease may be manifested by macules or papules; vesicles, bullae, or pustules; or purpuric macules, papules, or vesicles. The clinical features of the various disorders causing a skin rash are similar, and one infection may readily mimic another. Misdiagnosis and delay in starting specific therapy can be disastrous in patients with Rocky Mountain spotted fever, toxic shock syndrome (TSS), or meningococcal or staphylococcal bacteremia. It is critical to make a presumptive etiologic diagnosis rapidly and identify treatable infections for which immediate therapy is required to prevent death.
Certain diagnostic procedures can be used to obtain a diagnosis in the acutely ill, febrile patient with a rash. Skin lesions can be aspirated, and the material obtained should be examined with Gram’s stain. Gram-positive organisms in clusters are staphylococci, and gram-negative diplococci are either meningococci or gonococci. Organisms can sometimes be seen by Gram’s-staining a smear of the buffy coat. Meningococci can also be identified by latex particle agglutination tests of the serum, cerebrospinal fluid, or other body fluids. A Tzanck preparation is useful in the diagnosis of a number of vesiculobullous disorders. This test consists of several steps: (a) selecting an intact vesicle, (b) swabbing the lesion with 70% isopropyl alcohol, (c) opening the vesicle with a scalpel blade, (d) scraping the base very gently to avoid bleeding, (e) placing the specimen on a glass slide, and (f) staining it with Giemsa or Wright’s stain. Multinucleated, syncytial giant cells are present with varicella-zoster viral infection and herpes simplex but are absent in vaccinia and variola. A dark-field examination of material from a mucous membrane or skin lesion may reveal spirochetes. A cutaneous biopsy can be helpful in identifying rickettsiae; it provides material for an immunofluorescence technique that produces results before the results of serologic tests are positive. A vasculitis secondary to a noninfectious cause can also be identified by a cutaneous punch biopsy. Acute serum (at the time of presentation and 2 weeks later) should be drawn and frozen for various serologic tests. In addition, several sets of blood cultures are prepared, as well as cultures of throat, urine, and other tissues and fluids as indicated. Table 49-1 lists some of the conditions in which fever and a generalized rash may be prominent symptoms.
Table 49-1. Conditions in which rash and fever are prominent
Toxic Shock Syndrome
In 1978, an illness was described in seven children ages 8 to 17 years. It was characterized by high fever, generalized erythroderma, hypotension, and conjunctival hyperemia, with involvement of the kidneys, liver, and gastrointestinal system. This disease was called toxic shock syndrome (TSS) and was attributed to toxins produced by Staphylococcus aureus. The illness was similar to staphylococcal scarlet fever, which had been described in 1927. Not until late in 1979 and 1980, however, did the syndrome attract widespread attention when studies demonstrated a statistically significant association between use of tampons and the development of TSS. The peak incidence to date occurred in August 1980, when 135 cases were reported to the Centers for Disease Control (CDC). The number of new cases reported to the CDC has declined to approximately 20 per month. The majority of cases are nonmenstrual and occur in patients with staphylococcal infections associated with wounds, vaginal delivery, or cesarean section. In addition to patients with staphylococcal skin and soft-tissue infections, patients with primary staphylococcal bacteremia are at risk for TSS. Rarely, cases are associated with the use of vaginal contraceptive diaphragms.
The diagnosis of TSS still requires use of the CDC case definition because no laboratory test has been developed to confirm the diagnosis. The initial CDC case definition has been modified to include orthostatic dizziness as evidence of hypotension and staphylococcal bacteremia. S. aureus isolated from patients with TSS can be studied for the production of toxic shock syndrome toxin 1 (TSST-1) and staphylococcal enterotoxins A and B. The absence of antibody to the toxin indicates susceptibility to the development of TSS. These toxins appear to activate T cells, resulting in the production of macrophage-derived mediators such as interleukin-1 and tumor necrosis factor, which cause shock-like symptoms. The toxins interact with cells of the immune system and act as superantigens.
The diagnosis of TSS should be considered in any patient, particularly a postoperative or postpartum patient, and any menstruating woman who has unexplained fever, hypotension, and a diffuse rash resembling sunburn. Initially, the rash may be absent in patients with hypotension and may appear only after fluid replacement, or it may go unnoticed or be attributed to the flush of fever. The surgical wound infection often appears clinically trivial, and the patient may be discharged from the hospital before the onset of toxic shock symptoms. The menstrually related disease typically begins abruptly during the menstrual period. Sore throat or vomiting and diarrhea may be prominent complaints and suggest other diagnoses, such as group A streptococcal pharyngitis or gastrointestinal infection.
Criteria to establish a diagnosis of TSS are listed in Table 49-2. Neurologic examination usually reveals a confused, disoriented patient without focal symptoms. Until a specific laboratory test is developed, cases of mild toxic shock are excluded by the strict case definition. A vaginal examination should be performed to remove any tampon and obtain cultures for S. aureus. Normally, 10% of women have vaginal cultures positive for S. aureus, but 98% of vaginal cultures are positive in patients with menstrually associated TSS.
Table 49-2. Case criteria for toxic shock syndrome
Acute management of a patient with TSS requires aggressive treatment for shock with massive IV fluids (up to 12 L/d) and vasopressors to maintain blood pressure and renal output. In a retrospective study, use of high-dose corticosteroids for 3 days reduced the severity of illness and duration of fever if they were administered within 2 to 3 days of TSS onset, but there was no difference in mortality. High doses (400 mg/kg) of IV immune globulin given as a single dose may be useful, as high levels of TSST-1 antibody are present in commercial sera. Immune globulin is preferred to corticosteroids. A b-lactamase-resistant penicillin such as nafcillin should be administered to eradicate staphylococci and lessen the chance of recurrence. Rifampin, which may be useful to eradicate the staphylococcal carrier state, is given in combination with nafcillin or dicloxacillin if nafcillin administration alone fails to eliminate the organism. The recurrence rate is 2% to 30%, depending on the study and criteria for TSS. The case-fatality rate is about 5%. Women who have had TSS should not resume using tampons until more is known about the disease. Recurrent disease is more common with menstrual than nonmenstrual cases.
Numerous reports have described a life-threatening illness caused by group A streptococci that mimics TSS. Several streptococcal exotoxins (including streptococcal pyrogenic exotoxins A, B, and C) activate T cells, resulting in the production of various cytokines, such as tumor necrosis factor and interleukin-6. Various clinical manifestations include bacteremia, hypotension, pneumonia, myositis, and fasciitis. Patients may have renal failure, adult respiratory distress syndrome, and delirium or confusion; they lack the typical rash of scarlet fever or staphylococcal TSS. Petechial or maculopapular rashes may occur. Penicillin is the drug of choice, and clindamycin should be used in the penicillin-allergic patient.
Rocky Mountain Spotted Fever
Several life-threatening illnesses are included in the differential diagnosis of patients with fever and a petechial or purpuric rash. Rocky Mountain spotted fever should be suspected in any patient living where this disease is endemic. A seasonal variation—most cases are seen from April to October—corresponds to the tick season and recreational exposure. In states with a warmer climate, the disease can occur throughout the year. The history of a tick bite can be elicited in about 75% of patients. The incubation period is 3 to 12 days. The illness begins with a nonspecific syndrome of headache, malaise, myalgias, and fever. The rash, which is the most characteristic feature, is usually delayed until the fourth day of fever (but ranges from the second to sixth day). The initial lesions are on the wrists, ankles, palms, and soles. After 6 to 12 hours, the rash spreads centripetally to the trunk and face. At first, the rash is macular and blanches with pressure, but it becomes maculopapular and petechial or purpuric after 2 to 3 days.
The pathologic changes, such as thrombus formation, are a result of rickettsial invasion of the endothelial cells of blood vessels. Disseminated intravascular coagulation and thrombocytopenia also account for the clinical observations. In addition to the rash, which occurs in 90% of patients, nonpitting edema is common, especially in the periorbital area. Other features are intense headache, myalgias with muscle tenderness, nausea, vomiting, constipation, and sometimes splenomegaly or hepatomegaly. Neurologic complications (stiff neck, mental confusion, seizures, hemiplegia, coma) may occur. Myocarditis, hepatitis, and interstitial pneumonitis are occasionally seen. The WBC count and differential are normal, in contrast to the findings of leukocytosis in meningococcal infection. Thrombocytopenia is common.
A presumptive diagnosis must be made and specific antimicrobial therapy started based solely on the clinical observations, as the results of complement fixation and the Weil-Felix test usually are not positive until the eighth to the twelfth day of the illness. With an immunofluorescence test, rickettsiae can be identified in a skin biopsy specimen as early as the fourth day of illness.
Therapy with tetracycline or parenteral chloramphenicol is started and continued until improvement occurs (usually for 5 afrebrile days). A response is seen in 24 to 48 hours if treatment is begun before the sixth day of illness. Sulfonamides can make the illness worse. Usually, by the end of the second week of illness, rickettsial antibodies can be detected by complement fixation or the more sensitive indirect fluorescent antibody and microagglutination tests. Polymerase chain reaction may be used to identify the organism, but this procedure is not readily available at most centers.
Kawasaki disease, or mucocutaneous lymph node syndrome, is an illness of unknown cause. High fever lasting at least 5 days and an erythematous rash are prominent symptoms. The disease occurs predominantly in children under the age of 5 years, with a peak incidence between 1 and 2 years of age. The disease rarely occurs in persons more than 8 years old. Outbreaks continue to occur in the United States, particularly in the winter and spring. Person-to-person transmission has not been demonstrated. The case-fatality rate is 1% to 2%. Therapy consists of aspirin, other antiplatelet drugs (e.g., dipyridamole), and IV immunoglobulin.
Lyme disease is caused by a spirochete, Borrelia burgdorferi, which is transmitted by various ixodid ticks. In the United States, the disease occurs most frequently in areas where Ixodes scapularis or Ixodes pacificus can be found. The disease has been described in many other countries around the world. After an incubation period of about 1 week, with a range of 3 to 32 days, the characteristic skin lesion, erythema migrans, appears. Fever is usually low-grade and intermittent and is reported in half the patients. The fever may be high (up to 40°C) and persistent in children. Multiple skin lesions can develop, and erythema migrans usually lasts 2 to 3 weeks. Intense headache, malaise, fatigue, and regional lymphadenopathy are frequent early clinical features. Weeks to months later, neurologic manifestations, including meningoencephalitis, cranial nerve palsies (particularly of the facial nerve), and motor and sensor radiculoneuropathy, develop in 10% of patients. Neurologic abnormalities may persist for months but usually resolve completely. Weeks after onset, cardiac symptoms develop in 8% of patients, most commonly various degrees of atrioventricular block. Still later, weeks to several years after onset, migratory arthritis develops in some patients. Arthritis usually begins months after the onset of Lyme disease, affects primarily the large joints, such as the knees, and in 10% of patients becomes chronic, with destruction of cartilage and bone. (The diagnosis of Lyme disease is discussed in Chapter 40.)
A guide to the differential diagnosis of fever and a skin rash is given in Table 49-1; it includes treatable infectious disease emergencies (e.g., Rocky Mountain spotted fever, meningococcal or staphylococcal septicemia, and TSS). Failure to institute appropriate therapy based on the epidemiologic history and results of rapid diagnostic tests, such as the Gram’s stain, can be disastrous. (N.M.G.)
Ackerman AB, Miller RC, Shapiro L. Gonococcemia and its cutaneous manifestations. Arch Dermatol 1965;91:227.
Anderson LJ, Torok TJ. The clinical spectrum of human parvovirus B19 infections. In: Remington JS, Swartz MN, eds. Current clinical topics in infectious diseases. Cambridge, MA: Blackwell Science, 1991.
In adults, rash and arthralgias often occur. The arthritis can be present without a rash.
Baker RC, et al. Fever and petechiae in children. Pediatrics 1989;84:1051.
Of children with fever and petechiae, 7% had meningococcal disease.
Bergman SJ, Kundin WD. Scrub typhus in South Vietnam. Ann Intern Med 1973; 79:26.
The characteristic features are fever (100%), adenopathy (85%), eschar (46%), and maculopapular eruption (34%).
Bodey GP. Dermatologic manifestations of infections in neutropenic patients. Infect Dis Clin North Am 1994;8:655–675.
Review. Sweet’s syndrome, or acute febrile neutrophilic dermatosis, is often misdiagnosed as cellulitis.
Burns JC, et al. Clinical and epidemiologic characteristics of patients referred for evaluation of possible Kawasaki disease. J Pediatr 1991;118:680.
Measles, group A b-hemolytic streptococcal infection, and drug reaction may mimic Kawasaki disease.
Cale DF, McCarthy MW. Treatment of Rocky Mountain spotted fever in children. Ann Pharmacol 1997;31:492–494.
Doxycycline can be given safely to children less than 9 years of age for Rocky Mountain spotted fever.
Case records of the Massachusetts General Hospital (case 26-1973). N Engl J Med 1973;288:1400.
Discusses the differential diagnosis of an acutely ill patient with a rash and fever.
Case records of the Massachusetts General Hospital (case 16-1978). N Engl J Med 1978;298:957.
Presentation of the case of a fish cutter with fever and a skin rash caused by Erysipelothrix rhusiopathiae (erysipeloid).
Case records of the Massachusetts General Hospital (case 27-1985). N Engl J Med 1985;313:36.
Discussion of fever, rash, and pulmonary infiltrates in a veterinarian with tularemia.
Case records of the Massachusetts General Hospital (case 30-1990). N Engl J Med 1990;323:254.
Discussion of a patient with fever and pustular skin lesions (neutrophilic dermatosis, or Sweet’s syndrome).
Case records of the Massachusetts General Hospital (case 32-1997). N Engl J Med 1997;337:1149–1156.
A fatal case of Rocky Mountain spotted fever.
Centers for Disease Control. Follow-up on toxic shock syndrome. MMWR Morb Mortal Wkly Rep 1980;29:441.
Chambers HF, Korzoniowski OM, Sande MA. Staphylococcus aureus endocarditis: clinical manifestations in addicts and nonaddicts. Medicine (Baltimore) 1983;62:170.
A murmur was absent in about 25% of addicts on the initial presentation.
Cherry JD. Contemporary infectious exanthems. Clin Infect Dis 1993;16:199–207.
Pictures of classic exanthems. Epidemiologic clues (e.g., season) are key to diagnosis.
Clinicopathological Conference. A 54-year-old woman with fevers, arthralgias, myalgias, and rash. Am J Med 1988;85:84.
A discussion of leukocytoclastic vasculitis (allergic).
Clinicopathologic Conference. Abdominal pain, fever, and rash in a 39-year-old male. Am J Med 1994;97:300–306.
Diagnosis of Henoch-Schönlein purpura by skin biopsy in an adult with fever, abdominal pain, and rash.
Duma RJ, et al. Epidemic typhus in the United States associated with flying squirrels. JAMA 1981;245:2318.
Clinical features include headache, fever, myalgias, and rash.
Dumler JS, Bakken JS. Human ehrlichioses: newly recognized infections transmitted by ticks. Annu Rev Med 1998;49:201–213.
In this tick-borne disease, rash is present in up to one third of patients. Treatment with doxycycline usually results in cure.
Dumler JS, Taylor JP, Walker DH. Clinical and laboratory features of murine typhus in south Texas, 1980 through 1987. JAMA 1991;266:1365.
The features often include fever, headache, chills, myalgias, and rash.
Fichtenbaum CJ, Peterson LR, Weil GJ. Ehrlichiosis presenting as a life-threatening illness with features of the toxic shock syndrome. Am J Med 1987;95:351.
Patients with ehrlichiosis may fulfill the criteria for TSS, including a rash and conjunctival hemorrhage or erythema.
Gentry LO, Zeluff B, Kielhofner MA. Dermatologic manifestations of infectious diseases in cardiac transplant patients. Infect Dis Clin North Am 1994;8:637–654.
A skin lesion in a transplant recipient may be a primary infection site or indicate another, occult focus of infection.
Gersony WM. Diagnosis and management of Kawasaki disease. JAMA 1991;265:2699.
Reviews cardiovascular features. Although coronary artery aneurysms were noted in 20% of patients, aneurysms may also occur in other arteries, most often axillary, iliac, or renal.
Haynes RE, Sanders DV, Cramblett HG. Rocky Mountain spotted fever in children. J Pediatr 1970;76:685.
Classic. A clinical diagnosis requiring empiric therapy.
Hill WR, Kinney TD. The cutaneous lesions in acute meningococcemia. JAMA 1947; 134:513.
Discusses the clinical and pathologic features of meningococcal skin lesions.
Kain KC, Schulzer M, Chow AW. Clinical spectrum of nonmenstrual toxic shock syndrome (TSS): comparison with menstrual TSS by multivariate discriminant analyses. Clin Infect Dis 1993;16:100.
S. aureus from patients with nonmenstrual TSS produced TSST-1 with a frequency comparable with that of strains from patients with menstrual TSS (62% vs. 84%). Nonmenstrual TSS was often nosocomial.
Kato H, et al. Long-term consequences of Kawasaki disease. A 10- to 21-year follow-up study of 594 patients. Circulation 1996;94:1379–1385.
The incidence of coronary aneurysms in acute Kawasaki disease was 25%, with half of cases showing regression.
Kennedy NJ, Duncan AW. Acute meningococcaemia: recent advances in management (with particular reference to children). Anaesth Intensive Care 1996;24:197–216.
Review. No vaccine is available for group B meningococci.
Kingston ME, Mackey D. Skin clues in the diagnosis of life-threatening infections. Rev Infect Dis 1986;8:1.
Examination of a Gram’s-stained smear of a scraping from the base of an ulcer or of a skin biopsy specimen may establish the diagnosis. Cutaneous manifestations are illustrated in color.
Kirk JL, et al. Rocky Mountain spotted fever: a clinical review based on 48 confirmed cases, 1943–1986. Medicine (Baltimore) 1990;69:35.
Review. The classic triad of fever, headache, and rash were present in only 62% of patients. Two thirds of patients noted an exposure to ticks.
Lee VTP, Chang AH, Chow AW. Detection of staphylococcal enterotoxin B among toxic shock syndrome (TSS) and non–TSS-associated Staphylococcus aureus isolates. J Infect Dis 1992;166:911.
Staphylococcal enterotoxin B was found in 62% of patients with nonmenstrual TSS who were negative for TSST-1.
Levin S, Goodman LJ. An approach to acute fever and rash (AFR) in the adult. In: Remington JS, Swartz MN, eds. Current clinical topics in infectious diseases. Boston: Blackwell Science, 1995:19–75.
Litwack KD, Hoke AW, Borchardt KA. Rose spots in typhoid fever. Arch Dermatol 1972;105:252.
Illustrates rose spots.
Mackowiak PA, LeMaistre CF. Drug fever: a critical appraisal of conventional concepts. Ann Intern Med 1987;106:728.
Fever patterns were not helpful, and a rash was present in only 18% of patients.
Marrack P, Kappler J. The staphylococcal enterotoxins and their relatives. Science 1990;241:705.
Various staphylococcal toxins, TSS toxin, and streptococcal toxins activate T cells, resulting in the production of mediators such as interleukin-1 and tumor necrosis factor.
Martin DB, et al. Atypical measles in adolescents and young adults. Ann Intern Med 1979;90:877.
Rash may be vesicular, petechial, and purpuric.
Mawhorter SD, et al. Cutaneous manifestations of toxoplasmosis. Clin Infect Dis 1992;14:1084.
Acute toxoplasmosis may be associated with fever and a maculopapular rash.
Melish ME. Kawasaki syndrome. Pediatr Rev 1996;17:153–162.
Peak incidence occurs between the ages of 1 and 2 years, with 80% of cases seen in children less than 4 years of age.
Miller JQ, Price TR. The nervous system in Rocky Mountain spotted fever. Neurology 1972;22:561.
Most frequent findings were headache and lethargy. Cerebral spinal fluid pleocytosis, usually less than 50 cells per cubic millimeter, may occur.
Parsonnet J. Nonmenstrual toxic shock syndrome: new insights into diagnosis, pathogenesis and treatment. In: Remington JS, Swartz MN, eds. Current clinical topics in infectious diseases. Boston: Blackwell Science, 1996: 1–20.
Review. Testing for TSST-1 and its antibody may be helpful in menstrual but not in nonmenstrual cases of TSS.
Perez CM, et al. Adjunctive treatment of streptococcal toxic shock syndrome using intravenous immunoglobulin: case report and review. Am J Med 1997;102:111–113.
IV immunoglobulin was useful for streptococcal TSS.
Procop GW, et al. Immunoperoxidase and immunofluorescent staining of Rickettsia rickettsii in skin biopsies. A comparative study. Arch Pathol Lab Med 1997;121:894–899.
Immunoperoxidase and immunofluorescent staining of skin biopsy specimens were useful in diagnosing Rocky Mountain spotted fever (senstivity of 73% and specificity of 100%).
Pruksananonda P, et al. Primary human herpesvirus 6 infection in young children. N Engl J Med 1992;326:1445.
An important cause of an acute febrile illness in young children.
Reingold AI, et al. Nonmenstrual toxic shock syndrome. Ann Intern Med 1982;96 (Pt 2):871.
Clinical features are identical to those seen in menses-related cases, but the epidemiology differs.
Sexton DJ, Corey GR. Rocky Mountain “spotless” and “almost spotless” fever: a wolf in sheep’s clothing. Clin Infect Dis 1992;15:439.
Rash may be absent or minimal in male and black patients, making the diagnosis difficult in these populations.
Shands KN, et al. Toxic shock syndrome in menstruating women. N Engl J Med 1980; 303:1436.
Classic. Associated TSS with tampon use and isolated S. aureus from vaginal cultures.
Shrestha M, Grodzicki RL, Steere AC. Diagnosing early Lyme disease. Am J Med 1985;78:235.
Blood cultures were positive for the spirochete in one of 40 patients (2.5%).
Silpapojakul K, et al. Scrub and murine typhus in children with obscure fever in the tropics. Pediatr Infect Dis J 1991;10:200.
Scrub typhus in children was characterized by fever, diarrhea, vomiting, and hepa-tosplenomegaly. Rash was rare.
Spach DH, et al. Tick-borne diseases in the United States. N Engl J Med 1993;329:936.
Illustrated review. To remove a tick, use a tweezer and pull slowly.
Steere AC, et al. Lyme carditis: cardiac abnormalities of Lyme disease. Ann Intern Med 1983;99:8.
The most common abnormality is atrioventricular block of various degrees, especially complete heart block.
Steere AC, et al. Treatment of the early manifestations of Lyme disease. Ann Intern Med 1983;99:22.
Penicillin is an alternative drug for treating early Lyme disease.
Steere AC, et al. The early clinical manifestations of Lyme disease. Ann Intern Med 1983;99:76.
Color pictures of erythema chronicum migrans.
Steere AC, et al. The spirochetal etiology of Lyme disease. N Engl J Med 1983;308:733.
Isolated the spirochete from the blood, skin lesions, and cerebrospinal fluid of patients, and also from the ticks.
Stevens DL. Invasive group A Streptococcus infections. Clin Infect Dis 1992;14:2.
Review. Discusses virulence factors and clinical features.
Stevens DL. Streptococcal toxic shock endrome. Emerging Infect Dis 1995;1:69–78.
Stevens DL. The toxic shock syndromes. Infect Dis Clin North Am 1996;10:727–746.
Review of streptococcal and staphylococcal TSS.
Stevens DL, et al. Severe group A streptococcal infections associated with a toxic shock-like syndrome and scarlet fever toxin A. N Engl J Med 1989;321:1.
Patients with this life-threatening illness did not have the typical rash of scarlet fever or the erythroderma of staphylococcal TSS. Petechial and maculopapular rashes were noted.
Stevens FA. The occurrence of Staphylococcus aureus infection with a scarlatiniform rash. JAMA 1927;88:1957.
Todd JK. Therapy of toxic shock syndrome. Drugs 1990;39:856.
Reviews management of TSS.
Todd J, et al. Toxic shock syndrome associated with phage group 1 staphylococci. Lancet 1978;2:1116.
Todd JK, et al. Corticosteroid therapy for patients with toxic shock syndrome. JAMA 1984;252:3399.
Corticosteroid therapy may be beneficial, but the trial was not controlled.
Toews WH, Bass JW. Skin manifestations of meningococcal infection. Am J Dis Child 1974;127:173.
Color pictures. Mortality was high (44%) in patients with purpuric or ecchymotic skin lesions.
Torok TJ. Parvovirus B19 and human disease. Adv Intern Med 1992;37:431.
Toxic shock syndrome. Ann Intern Med 1982;96:831.
Entire issue on TSS.
Van Nguyen O, Nguyen EA, Weiner LB. Incidence of invasive bacterial disease in children with fever and petechiae. Pediatrics 1984;74:77.
Twenty percent of patients with fever and petechiae had bacterial infections.
Walker DH. Rocky mountain spotted fever: a seasonal alert. Clin Infect Dis 1995;20: 1111–1117.
A history of a tick exposure with a 3- to 12-day incubation period is key to diagnosis.
Wolfson JS, Sober AJ, Rubin RH. Dermatologic manifestations of infections in immunocompromised patients. Medicine (Baltimore) 1985;64:115.
Diagnosis is usually established by skin biopsy for culture and histologic examination. The gross appearance of the skin lesions is of limited value.
Woodward TE, et al. Prompt confirmation of Rocky Mountain spotted fever: identification of rickettsiae in skin tissues. J Infect Dis 1976;134:297.
An immunofluorescence technique identified rickettsiae in a skin biopsy specimen in 4 hours.
Working Group on Severe Streptococcal Infections. Defining the group A streptococcal toxic shock syndrome. JAMA 1993;269:390–391.
Cases are defined by isolation of group A streptococci from a sterile site, presence of hypotension, and presence of two or more of the following: renal impairment, coagulopathy, liver abnormalities, acute respiratory distress syndrome, tissue necrosis, and an erythematous rash.