Sepsis, most commonly from Gram-positive bacteria, is the 10th leading cause of death in the United States. A review of approximately 750 million hospitalizations over 22 years in the United States showed that sepsis accounts for 1.3% of all hospital admissions. The incidence of sepsis has been steadily increasing since 1971 although the mortality rate has been dropping.8
Etiology and Pathogenesis
The prevailing presumption has been that sepsis is a result of uncontrolled activation of the inflammatory response to pathogens. This increased inflammation leads to uncontrolled coagulation, which in turn causes the release of more inflammatory mediators. Sepsis is often characterized by an initial burst of immunologic activation, including a surge in TNF-α production. This is thought to be mediated by binding of specific pathogen-associated molecules to toll-like receptors found on cells of the immune system. Toll-like receptors activate signaling through transcription factors such as nuclear factor-κB (NF-κB) that activate the expression of a cascade of inflammatory cytokines. However, this is followed by a relative decrease in immunity with impaired delayed type hypersensitivity, a loss of critical cells of the immune response including B cells, CD4+ helper T cells, and dendritic cells, and the inability to clear infection.9
Sepsis is often complicated by impaired organ function. Autopsy studies revealed that even in the setting of profound organ dysfunction, cell death is minimal and not sufficient to account for the clinical picture. Thus, sepsis appears to activate a state of cellular hibernation in which cells reduce their activities to only those required for cell survival. This would explain why organ function is often regained in those patients who recover from sepsis.
The septic patient is usually febrile, or in some cases hypothermic, with tachycardia and tachypnea. Patients with severe sepsis can also have dysfunction of major organ systems and those in septic shock develop hypotension that is refractory to the administration of fluid.
The causative organism in sepsis is not always identifiable by routine culture. In some cases, the cutaneous exam can provide clues to the identity of the responsible pathogen, providing a valuable clinical tool in the management of the septic patient.
Erythroderma in the septic patient suggests staphylococcal or streptococcal toxic shock syndrome (TSS). Patients with TSS are usually young and otherwise healthy. Patients with staphylococcal TSS are much more likely to be erythrodermic but much less likely to have positive blood culture than are patients with streptococcal TSS. Streptococcal TSS is commonly associated with a soft tissue infection.
The finding of pustules on the skin of a septic patient, particularly in the neonate or immunocompromised individual, may be suggestive of fungal infection, particularly with Candida species. Congenital candidiasis, most often seen in infants born to mothers with vaginal candidiasis, is generally a skin-limited disease. However, in the septic infant with pustules, candidemia should be considered.
The vasculitis and coagulopathy that can occur in the septic patient may cause purpura, sometimes prominent in the nail fold small capillaries (Fig. 181-2). Purpura is particularly prominent in those patients with thrombocytopenia. Such infections are seen most commonly in oncology patients undergoing bone marrow transplantation. In the immunocompromised host, opportunistic fungal infection, such as with Aspergillus sp., Fusarium sp., and Candida sp., often presents as erythematous papules, petechiae, or pustules that progress to purpuric lesions (Fig. 181-3).
Proximal nail fold purpura from leukocytoclastic vasculitis due to Clostridium difficile sepsis.
Petechiae from Fusarium sepsis in an immunosupprressed patient.
Pustules due to disseminated gonococcemia are acrally located, typically tender and a characteristic gun-metal gray color, hemorrhagic or black, and are most commonly seen in the otherwise healthy adolescent or young adult (eFig. 181-3.1). Gram stain of the pustule will reveal intracellular Gram-negative diplococci. In its most extreme form, meningococcemia can cause purpura fulminans (see below). Pustules may also be secondary to a local inoculation site, as in the case of staphylococcal sepsis.
Disseminated gonococcal infection. Hemorrhagic, painful pustules on the palm and fingers.
Cellulitis is characterized by intense local inflammation in the presence of relatively few infectious organisms and blood cultures are rarely positive (see Chapter 179). Most commonly occurring on the legs, the affected extremity is typically erythematous, hyperemic, and edematous. The most common causes of cellulitis are S. aureus and Group A Streptococcus. Rarely, anaerobic organisms including clostridial species and other anaerobic bacteria species such as Bacteroides, Peptostreptococcus, or Peptococcus are the causative organism. In immunosuppressed patients, Cryptococcus neoformans can also cause cellulitis, particularly in the setting of AIDS. Patients with liver compromise can develop cellulitis from Vibrio vulnificus, a Gram-negative bacterium that lives in warm marine environments and becomes concentrated in filter-feeding shellfish. Infection occurs either via consumption of contaminated organisms such as raw oysters, or through contact with infected waster. Mortality rates exceed 40% in those with V. vulnificus sepsis.10
A more aggressive local soft tissue infection, necrotizing fasciitis, can be associated with positive blood cultures later in the course of the disease due to hematogenous seeding by the organisms. Clinically, necrotizing fasciitis is rapidly progressive, initially painful, and accompanied by fever and leukocytosis (see Chapter 179). Blood cultures are frequently positive. After several days, the involved area may become anesthetic secondary to destruction of cutaneous nerves.11
Ecthyma gangrenosum (see Chapter 180) begins as an erythematous papule that expands and eventually becomes a necrotic bulla. Lesions are most commonly seen between the umbilicus and the knees. Classic ecthyma gangrenosum represents cutaneous seeding of bacteria, usually Pseudomonas aeruginosa, from a hematogenous source, and is seen almost exclusively in neutropenic patients, often in association with an underlying malignancy. Nonclassical cases have been reported with Aeromonas hydrophila, Escherichia coli, Citrobacter freundii, and Corynebacterium diptheriae, fungal infection including Candida, Aspergillus, Fusarium, and mucormycosis-causing species, and even herpes simplex virus.12
Related Physical Findings
Sepsis is defined as infection plus systemic inflammation and is characterized by hyper- or hypothermia, tachycardia and tachypnea. Sepsis is further subdivided into severe sepsis, which is defined as infection with systemic inflammation and organ dysfunction. The organ systems commonly affected in sepsis include the renal, hepatic, central nervous, pulmonary, gastrointestinal, and cardiovascular systems. Septic shock occurs when patients with severe sepsis also have hypotension (SBP <90) refractory to fluid administration.
The septic patient will generally have a white blood cell count greater than 12 × 109/L or less than 4 × 109/L, or a bandemia of greater than 10%. Elevated CRP and procalcitonin levels are common. Organ dysfunction can manifest as low cardiac output, elevated creatinine, thrombocytopenia, and elevated INR or PTT, or hyperbilirubinemia.13 Blood cultures can be helpful in guiding treatment of the septic patients, however, only 30%–50% of septic patients will have positive blood cultures.14
Special tests including imaging studies and culture of suspected involved tissue can sometimes be helpful in identifying the source of infection in the septic patient.
The differential diagnosis of skin findings in the septic patient is reviewed in Box 181-3.
Box 181-3 Differential Diagnosis of Skin Findings in the Septic Patient ||Download (.pdf)
Box 181-3 Differential Diagnosis of Skin Findings in the Septic Patient
- Staphylococcal or streptococcal scalded skin syndrome
- Drug reaction
- Cutaneous T cell lymphoma
- Drug reaction
- Contact Dermatitis
- Disseminated gonococcemia
- Steroid acne
- Acute generalized exanthematous pustulosis
- Invasive fungal infection, especially in thrombocytopenic patient
- Disseminated intravascular coagulation
- Vasculitis (infectious, neoplastic, drug induced, or autoimmune)
- Trauma induced
- Heparin or coumadin necrosis
- Thrombotic thrombocytopenic purpura
- Infectious cellulitis
- Necrotizing fasciitis
- Stasis dermatitis
- Ecthyma gangrenosum
- Pseudomonal ecthyma gangrenosum
- Nonpseudomonal bacterial or fungal ecthyma gangrenosum
- Herpes simplex infection in immunosupressed patient
- Necrotizing vasculitis
Complications of sepsis include death, loss of limbs due to hypoperfusion and permanent organ dysfunction.
Prognosis and Clinical Course
There are over 750,000 cases of sepsis each year in the United States and mortality rate from severe sepsis and septic shock is 30%–60%.15
Treatment of sepsis is usually done in an intensive care unit and involves the use of antimicrobial drugs, chosen empirically or on the basis of the culture of a particular microorganism started as soon as possible, but no longer than one hour after the diagnosis of severe sepsis or septic shock is mad. Choice of antibiotic therapy should be reevaluated on a daily basis to minimize toxicity and maximize efficacy. The administration of activated drotrecogin-α has been shown to reduce mortality in cases of sever sepsis. Patient outcomes in sepsis haven been shown to improve with the use of standardized treatment protocols. Supportive care is important to preserve organ function.
The prevention of sepsis in a hospital setting is achieved by the implementation of basic infection control measures including routine hand washing and the minimization and regular replacement of indwelling catheters. In patients who are immunocompromised, particularly in the setting of organ transplantation or AIDS, the use of prophylactic antibiotics can help to reduce the incidence of sepsis.