Four infectious diseases that are associated with high rates of morbidity and mortality are Rocky Mountain spotted fever, meningococcal disease, staphylococcal toxic shock syndrome, and streptococcal toxic shock syndrome. These diseases necessitate a timely diagnosis and treatment, which may be facilitated by recognition of the characteristic cutaneous findings. Herein the clinical manifestations, diagnosis, and management are presented, with emphasis on the dermatologic signs of each disease. A dermatology consultation can be valuable, but all physicians should be familiar with the cutaneous findings of these potentially life-threatening diseases.
Most dermatologic conditions are diagnosed and treated in the outpatient setting; however, a subset of diseases with prominent cutaneous features are first encountered by physicians other than dermatologists in an emergency department, hospital, or critical-care setting. These diseases can be life threatening; thus, prompt diagnosis and treatment are crucial. Management may be expedited by recognition of the associated cutaneous manifestations. This review focuses on four serious infectious illnesses and their associated cutaneous findings, with the goal of enhancing the diagnostic repertoire of non-dermatologists.
Rocky Mountain Spotted Fever
Rocky Mountain spotted fever (RMSF) is caused by Rickettsia rickettsii, an obligate intracellular coccobacillus. The organism is transmitted by a tick, Dermacentor variabilis (American dog tick) in the eastern United States or D. andersoni (Rocky Mountain wood tick) in the western United States. From an epidemiologic standpoint, the term “Rocky Mountain spotted fever” is deceiving because, although first described in Idaho and Montana, most cases are concentrated in the south central and southeastern United States. The disease has been reported in almost every state.
RMSF is a seasonal disease; most cases occur during the spring and summer when the ticks are most active and human-tick contact is most likely. Outdoor recreationalists, children, and farmers are most frequently affected. The mortality rate ranges from 5 to 25%.
1Prognosis depends heavily on prompt recognition of the disease and early initiation of appropriate antibiotic therapy.
Fever, malaise, myalgia, and severe .headache are the most common initial features of RMSF. The rash classically begins on day 4 of the illness (range, 1 to 15 days) on the wrists and ankles, then spreads to the palms and soles. Subsequently, it spreads centrally to involve the proximal extremities and trunk (Fig. 1). Although not discernible in all cases, this classic centripetal spread is a hallmark of RMSF. Initially, the rash consists of small pink or red macules that blanche with pressure. Over time, the rash evolves into petechia and purpura. Gangrenous areas may develop on the fingers, toes, nose, ears, scrotum, or vulva. Involvement of the scrotum or vulva is a diagnostic clue.
The absence of a rash does not exclude the diagnosis because 10% of patients never have development of a rash; this type of manifestation is called Rocky Mountain “spotless” fever.
1In addition, the dermatologic signs may develop late during the course of disease. The rash may be more difficult to appreciate or may be atypical in deeply pigmented patients, and this situation may contribute to a higher fatality rate.
During the acute stage of RMSF, laboratory tests will not aid in the diagnosis. Recognition is based purely on appreciation of the clinical and epidemiologic findings: fever, headache, and rash in a person with a known or potential tick exposure. A history of tick bite, travel to an endemic area, or recent outdoor activity should be sought. Unfortunately, the classic triad of fever, rash, and history of a tick bite is found in only 60 to 70% of patients on initial examination.
1Although serology is confirmatory, it does not help in guiding immediate therapeutic decisions. The Weil-Felix agglutination test is no longer used because of poor specificity and sensitivity. Direct immunofluorescence staining of a skin biopsy specimen can be helpful in the acute setting but is only 70% sensitive and is not widely available.
3In the future, polymerase chain reaction may be a valuable diagnostic tool; currently, its sensitivity is sub-optimal.
Doxycycline (intravenous or oral administration) is the mainstay of therapy for RMSF. Chloramphenicol may be used in a pregnant patient or a young child.
1Supportive care may be needed for the severely ill patient. Of importance, typical broad-spectrum antibiotic coverage will not treat RMSF. Appropriate therapy should be initiated when clinical and epidemiologic clues suggest RMSF. Failure to consider this diagnosis can be a fatal error.
Acute meningococcemia and meningococcal meningitis are caused by Neisseria meningitidis, an encapsulated gram-negative diplococcus. Serogroups B and C cause most cases in the United States. Ten to 20% of healthy people are nasopharyngeal carriers of this organism, but the percentage increases during outbreaks in crowded conditions, such as military settings or college dormitories. Colonization usually leads to protective antibodies and immunity from the disease. Transmission is through respiratory droplets; hence, close contact is necessary. Most cases occur during the winter and spring in patients younger than 20 years of age. The mortality rate of meningococcal disease ranges from 10 to 20%.
4Outcome depends on early diagnosis and institution of appropriate antibiotics and support measures.
Typically, patients with meningococcal disease have fever, headache, nausea, vomiting, and myalgia. Altered consciousness and signs of meningeal inflammation signal meningococcal meningitis. Skin lesions are common and are an important early diagnostic clue to this rapidly progressive illness. Classically, the rash appears as a petechial eruption that is scattered on the trunk and extremities and then evolves into the pathognomonic palpable purpura with gunmetal gray necrotic centers. Urticarial, macular, and papular lesions may also occur. Clusters of petechia may develop at areas of pressure, such as under blood pressure cuffs or elastic bands. Adults with meningococcal disease are less likely to have cutaneous findings.
5Fulminant meningococcemia (Waterhouse-Friderichsen syndrome) can be complicated by purpura fulminans, a cutaneous manifestation of disseminated intravascular coagulation.
Meningococcal disease should be suspected when a petechial rash develops in the setting of fever, headache, and myalgias. Diagnosis is traditionally made by Gram stain and culture of the blood and cerebrospinal fluid. Microbiologic analysis of the skin lesions may be a helpful diagnostic adjunct. Gram stain of smears from the petechial skin lesions can show the characteristic gramnegative diplococci in up to 70% of cases.
6Furthermore, Gram stain and culture of a characteristic skin lesion may be positive even after antibiotic therapy has been initiated and other specimens are sterile.
Early treatment is the highest priority in any suspected case of meningococcal disease. Appropriate antibiotic treatment should not await transfer or hospitalization of the patient. When a definitive diagnosis is made, penicillin G is appropriate in susceptible isolates.
7Rifampin or ciprofloxacin (in nonpregnant adults) or ceftriaxone is used for chemoprophylaxis of close household contacts, day-care contacts, and hospital personnel with exposure to secretions.
Staphylococcal Toxic Shock Syndrome
Staphylococcal toxic shock syndrome is caused by infection or colonization with toxin-producing Staphylococcus aureus. The key toxins causing this multisystem disease are toxic shock syndrome toxin 1 and staphylococcal enterotoxins B and C. Although staphylococcal toxic shock syndrome was originally associated with menstruation and tampon use, nonmenstrual cases have occurred among both sexes and are currently more common.
8Nonmenstrual associations include influenza, childbirth, tracheitis, surgical wound infections, nasal packing, barrier contraceptives, and any localized staphylococcal infection. The mortality rate has decreased to less than 5% in menstrual-related cases but is twofold to threefold higher in nonmenstrual cases,
Prodromal features of patients with staphylococcal toxic shock syndrome include fever, malaise, myalgia, nausea, vomiting, diarrhea, and prominent confusion. The cutaneous signs are often striking and include a sunburn like diffuse macular erythroderma followed by desquamation, especially of the hands and feet, within 5 to 14 days (Fig. 4). Conjunctival injection, mucosal hyperemia (oral and genital), and a strawberry tongue (Fig. 5) are appreciable and are important diagnostic signs in deeply pigmented patients in whom the erythroderma may be subtle or overlooked. Less frequent manifestations are edema of the hands and feet, petechiae, and delayed loss of nails and hair.
Diagnostic criteria include fever, desquamative erythroderma, mucous membrane hyperemia, hypotension, and multiorgan involvement. Multiorgan involvement may include gastrointestinal, hepatic, musculoskeletal, renal, cardiopulmonary, central nervous system, and metabolic findings. Evidence for exclusion of other causes of sepsis is imperative. S. aureus is only rarely isolated from blood cultures.
Treatment involves identification and removal of the source of S. aureus (surgical débridement or drainage or removal of nasal packing or tampon), initiation of effective antistaphylococcal antibiotic therapy, and appropriate supportive care. Additional treatments to consider are intravenous immunoglobulin to neutralize circulating toxins and clindamycin to reduce toxin production.
Streptococcal Toxic Shock Syndrome
Streptococcal toxic shock syndrome is caused by infection with group A streptococcus (Streptococcus pyogenes- “the flesh-eating bacteria”) and the production of streptococcal pyrogenic exotoxins A, B, and C. This syndrome occurs most commonly in the setting of invasive soft tissue infections, such as necrotizing fasciitis, myonecrosis, and cellulitis; however, association with streptococcal pneumonia, sinusitis, and pharyngitis have also been reported. In many patients, the portal of entry for the bacterium can be discerned: burn site, laceration, surgical incision, decubitus ulcer, childbirth trauma, or varicella lesion. Of interest, cases also occur in association with blunt trauma or muscle strain. The age range of most patients is 20 to 50 years. The absence of protective immunity is thought to be a risk factor for this age-group. The mortality rate ranges from 30 to 70%.
Streptococcal toxic shock syndrome usually occurs in a young, previously healthy person who seeks medical attention because of fever, hypotension, cutaneous findings, and severe local pain. Both dramatic and rapid progression of local and systemic findings are hallmarks of streptococcal toxic shock syndrome. The pain is typically localized to an extremity and is often disproportionate to the findings on examination. The cutaneous signs are protean and may be subtle or absent. A thorough examination of the skin will often detect subtle evidence of a soft tissue infection such as localized swelling, tenderness, or erythema or the more distinctive violaceous bullae that may be seen in necrotizing fasciitis (Fig. 6). Desquamating erythroderma may be present but is less common than in staphylococcal toxic shock syndrome.
Diagnostic criteria include isolation of group A streptococcus from a sterile body site, hypotension, and multiorgan involvement Multiorgan involvement may include renal impairment, coagulopathy liver abnormalities, adult respiratory distress syndrome, generalized red rash, or soft tissue necrosis. Intraoperative Gram stain, culture, and biopsy are often necessary to make a definitive diagnosis. In contrast to staphylococcal toxic shock syndrome, more than 60% of patients with streptococcal toxic shock syndrome have bacteremia.
The most important management tenet in streptococcal toxic shock syndrome is early and aggressive surgical exploration and débridement of any associated soft tissue infection. Surgical exploration may also facilitate a definitive diagnosis through acquisition of tissue for culture, Gram stain, and histopathologic examination. Empiric treatment includes broad-spectrum antimicrobial coverage until the streptococcus is positively identified. Once the diagnosis is confirmed, definitive treatment consists of both penicillin G and clindamycin. The latter agent suppresses bacterial toxin synthesis and inhibits protein synthesis.
10Intravenous immunoglobulin may be used to neutralize circulating toxins. Aggressive supportive care is necessary.
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Questions About Life-Threatening Rashes (See article, pages 68 to 72)
- 1.Which one of the following is most helpful in the early diagnosis of Rocky Mountain spotted fever?
- a.Clinical and epidemiologic manifestations
- b.Direct immunofluorescence testing of skin lesions
- c.Polymerase chain reaction
- e.Serologic testing
- 2.Which one of the following statements is true regarding the rash of Rocky Mountain spotted fever?
- a.It has a centrifugal pattern
- b.It occurs only on the palms and soles
- c.It is seen in a minority of patients
- d.It classically occurs on the wrists and ankles, proceeds to the palms and soles, and then spreads to the trunk
- e.It is usually present at the onset of initial symptoms
- 3.Which one of the following is not a cutaneous sign of meningococcemia?
- a.Palpable purpura with gunmetal gray centers
- b.Sunburn like erythroderma
- c.Clusters of petechiae at sites of pressure
- d.Purpura fulminans
- e.Urticarial, macular, or papular lesions
- 4.Which one of the following is not a cutaneous sign of staphylococcal toxic shock syndrome?
- b.Edema of the hands
- c.Desquamation of the palms and soles
- d.Mucosal hyperemia
- 5.Which one of the following is not a cutaneous sign of streptococcal toxic shock syndrome?
- a.Localized swelling
- b.Desquamative erythroderma
- c.Red plaques with silver scale
- d.Violaceous bullae
- e.Pronounced tenderness
1. a, 2. d, 3. b, 4. a, 5. c
© 1999 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.