ACUTELY ILL INFECTED FEBRILE PATIENT 2

SEPSIS WITH SKIN MANIFESTATIONS

Maculopapular rashes may reflect early meningococcal or rickettsial disease but are usually associated with nonemergent infections. Exanthems are usually viral.

Petechiae Petechial rashes caused by viruses are seldom associated with hypotension or a toxic appearance, although severe measles can be an exception. In other settings, petechial rashes require more urgent attention.

Meningococcemia Almost three-quarters of patients with bacteremic N. meningitidis infection have a rash. Meningococcemia most often affects young children (i.e., those 6 months to 5 years old, often in daycare). However, sporadic cases and outbreaks occur in schools (grade school through college) and army barracks. Between 10 and 20% of all cases have a fulminant course, with shock, DIC, and multiorgan failure. Of these patients, 50 to 60% die, and survivors often require extensive debridement or amputation of gangrenous extremities. Patients may exhibit fever, headache, nausea, vomiting, myalgias, change in mental status, and meningismus. However, the rapidly progressive form of disease is not usually associated with meningitis. The rash is initially pink, blanching, and maculopapular, appearing on the trunk and extremities, but then becomes hemorrhagic, forming petechiae. Petechiae are first seen at the ankles, wrists, axillae, mucosal surfaces, and palpebral and bulbar conjunctiva, with subsequent spread to the lower extremities and trunk. A cluster of petechiae may be seen at pressure points, e.g., where a blood pressure cuff has been inflated. In rapidly progressive meningococcemia, the petechial rash quickly becomes purpuric and patients develop DIC. Hypotension with petechiae for <12 h is associated with significant mortality. The mortality rate can exceed 90% in patients without meningitis who have rash, hypotension, and a normal or low white blood cell count and erythrocyte sedimentation rate. A better prognosis has been reported in cases where antibiotics are given before admission by the primary care provider. This observation suggests that early initiation of treatment may be life-saving.

Rocky Mountain spotted fever RMSF occurs throughout the United States. A history of tick bite is common; however, if such a history is lacking, a history of travel or outdoor activity (e.g., camping in tick-infested areas) can be ascertained. RMSF is caused by Rickettsia rickettsii. For the first 3 days, headache, fever, malaise, myalgias, nausea, vomiting, and anorexia are present. By day 3, half of patients have skin findings. Blanching macules develop initially on the wrists and ankles and then spread over the legs and trunk. The lesions become hemorrhagic and are frequently petechial. The rash spreads to palms and soles later in the course (Plate IID-45). The centripetal spread is a classic feature of RMSF. However, 10 to 15% of patients with RMSF never develop a rash. The patient can be hypotensive and develop noncardiogenic pulmonary edema, confusion, lethargy, and encephalitis progressing to coma. The cerebrospinal fluid (CSF) contains 10 to 100 cells/uL, usually with a predominance of mononuclear cells. The CSF glucose level is often normal; the protein concentration may be slightly elevated. Renal and hepatic injury and bleeding secondary to vascular damage are noted. Untreated infection has a mortality rate of 30%.

Purpura Fulminans This is the cutaneous manifestation of DIC and presents as large ecchymotic areas and hemorrhagic bullae. Progression of petechiae to purpura and ecchymoses is associated with congestive heart failure, septic shock, acute renal failure, acidosis, hypoxia, hypotension, and death. Purpura fulminans has primarily been associated with N. meningitidis but, in the splenectomized patient, has been described in association with S. pneumoniae and H. influenzae.

Ecthyma Gangrenosum Septic shock caused by P. aeruginosa and A. hydrophila can be associated with ecthyma gangrenosum: hemorrhagic vesicles surrounded by a rim of erythema with central necrosis and ulceration. These gram-negative bacteremias are most common among patients with neutropenia, extensive burns, and hypogammaglobulinemia.

Other Emergent Infections Associated with Rash Vibrio vulnificus and other noncholera Vibrio bacteremic infections can cause focal skin lesions and overwhelming sepsis in the host with liver disease. After ingestion of contaminated shellfish, there is a sudden onset of malaise, chills, fever, and hypotension. The patient develops bullous or hemorrhagic skin lesions, usually on the lower extremities, and 75% of patients have leg pain. The mortality rate can be as high as 50%. Capnocytophaga canimorsus can cause septic shock in asplenic patients. Infection with this fastidious gram-negative rod typically presents after a dog bite as fever, chills, myalgia, vomiting, diarrhea, dyspnea, confusion, and headache. Findings can include an exanthem or erythema multiforme, cyanotic mottling or peripheral cyanosis, petechiae, and ecchymosis. About 30% of patients with this fulminant form die of overwhelming sepsis and DIC, and survivors may require amputation to treat gangrene.

Erythroderma TSS is usually associated with erythroderma. The patient presents with fever, malaise, myalgias, nausea, vomiting, diarrhea, and confusion. There is a sunburn-type rash that may be subtle and patchy but is usually diffuse and is found on the face, trunk, and extremities. Erythroderma, which desquamates after 1 to 2 weeks, is more common in Staphylococcus-associated than in Streptococcus-associated TSS. Hypotension develops rapidly after onset of symptoms, often within hours. Multiorgan failure is seen. Often there is no indication of a primary focal infection. Colonization rather than overt infection of the vagina or a postoperative wound, for example, is typical with staphylococcal TSS, and the mucosal areas appear hyperemic but not infected. Early renal failure may distinguish this syndrome from other septic shock syndromes. Clinical evaluation constitutes the diagnosis because TSS is defined by the clinical criteria of fever, rash, hypotension, and multiorgan involvement. The mortality rate is 5% for menstruation-associated TSS, 10 to 15% for nonmenstrual TSS, and 30 to 70% for streptococcal TSS.

SEPSIS WITH A SOFT TISSUE/MUSCLE PRIMARY FOCUS

Necrotizing Fasciitis This infection may arise at a site of minimal trauma or postoperative incision and may also be associated with recent varicella, childbirth, or muscle strain. The most common causes of necrotizing fasciitis are group A streptococci alone and a mixed facultative and anaerobic flora. Diabetes mellitus, peripheral vascular disease, and intravenous drug use are associated risk factors. Use of nonsteroidal anti-inflammatory agents adversely affects granulocyte chemotaxis, phagocytosis, and bacterial killing, allowing progression of skin or soft tissue infections. The patient may have bacteremia and hypotension without other organ-system failure. Physical findings are minimal compared to the severity of pain and the degree of fever. The examination is often unremarkable except for soft tissue edema and erythema. The infected area is red, hot, shiny, swollen, and exquisitely tender. In untreated infection, the overlying skin develops blue-gray patches after 36 h, and cutaneous bullae and necrosis develop after 3 to 5 days. Necrotizing fasciitis due to a mixed flora, but not that due to group A streptococci, can be associated with gas production. Without treatment, pain decreases because of thrombosis of the small blood vessels and destruction of the peripheral nerves¾an ominous sign. The mortality rate is >30% overall, >70% in association with TSS, and nearly 100% without surgical intervention. Life-threatening necrotizing fasciitis may also be due to Clostridium perfringens; in this condition, the patient is extremely toxic and the mortality rate is high. Within 48 h, rapid tissue invasion and systemic toxicity associated with hemolysis and death ensue. The distinction between this entity and clostridial myonecrosis is made by muscle biopsy.

Clostridial Myonecrosis Myonecrosis is often associated with trauma or surgery but can be spontaneous. The incubation period is usually 12 to 24 h long, and massive necrotizing gangrene develops within hours of onset. Systemic toxicity, shock, and death can occur within 12 h. The patient's pain and toxic appearance are out of proportion to physical findings. On examination, the patient is febrile, apathetic, tachycardic, and tachypneic and may express a feeling of impending doom. Hypotension and renal failure develop later, and hyperalertness is evident preterminally. The skin over the affected area is bronze-brown, mottled, and edematous. Bullous lesions with serosanguineous drainage and a mousy or sweet odor can be present. Crepitus can occur secondary to gas production in muscle tissue. The mortality rate is >65% with spontaneous myonecrosis, which is often associated with C. septicum and underlying malignancy. The mortality rates associated with trunk and limb infection are 63% and 12%, respectively, and any delay in surgical treatment increases the risk of death.