++
Although leptospirosis is a potentially fatal disease with bleeding and multiorgan failure as its clinical hallmarks, the majority of cases are thought to be relatively mild, presenting as the sudden onset of a febrile illness. The incubation period is usually 1–2 weeks but ranges from 1 to 30 days. (Figure 80-3 indicates a slightly different range, but an incubation period of up to 1 month has now been documented.) Leptospirosis is classically described as biphasic. The acute leptospiremic phase is characterized by fever of 3–10 days’ duration, during which time the organism can be cultured from blood. During the immune phase, resolution of symptoms may coincide with the appearance of antibodies, and leptospires can be cultured from the urine. The distinction between the first and second phases is not always clear: milder cases do not always include the second phase, and severe disease may be monophasic and fulminant. The idea that distinct clinical syndromes are associated with specific serogroups has been refuted, although some serovars tend to cause more severe disease than others.
++
Most patients are asymptomatic or only mildly ill and do not seek medical attention. Serologic evidence of past inapparent infection is frequently found in persons who have been exposed but have not become ill. Mild symptomatic leptospirosis usually presents as a flu-like illness of sudden onset, with fever, chills, headache, nausea, vomiting, abdominal pain, conjunctival suffusion (redness without exudate), and myalgia. Muscle pain is intense and especially affects the calves, back, and abdomen. The headache is intense, localized to the frontal or retroorbital region (resembling that occurring in dengue), and sometimes accompanied by photophobia. Aseptic meningitis may be present and is more common among children than among adults. Although Leptospira can be cultured from the cerebrospinal fluid (CSF) in the early phase, the majority of cases follow a benign course with regard to the central nervous system; symptoms disappear within a few days but may persist for weeks.
++
Physical examination may include any of the following findings, none of which is pathognomonic for leptospirosis: fever, conjunctival suffusion, pharyngeal injection, muscle tenderness, lymphadenopathy, rash, meningismus, hepatomegaly, and splenomegaly. If present, the rash is often transient; may be macular, maculopapular, erythematous, or hemorrhagic (petechial or ecchymotic); and may be misdiagnosed as due to scrub typhus or viral infection. Lung auscultation may reveal crackles, and mild jaundice may be present.
++
The natural course of mild leptospirosis usually involves spontaneous resolution within 7–10 days, but persistent symptoms have been documented. In the absence of a clinical diagnosis and antimicrobial therapy, the mortality rate in mild leptospirosis is low.
++
Although the onset of severe leptospirosis may be no different from that of mild leptospirosis, severe disease is often rapidly progressive and is associated with a case–fatality rate ranging from 1 to 50%. Higher mortality rates are associated with an age >40, altered mental status, acute renal failure, respiratory insufficiency, hypotension, and arrhythmias. The classic presentation, often referred to as Weil's syndrome, encompasses the triad of hemorrhage, jaundice, and acute kidney injury.
++
Patients die of septic shock with multiorgan failure and/or severe bleeding complications that most commonly involve the lungs (pulmonary hemorrhage), gastrointestinal tract (melena, hemoptysis), urogenital tract (hematuria), and skin (petechiae, ecchymosis, and bleeding from venipuncture sites). Pulmonary hemorrhage (with or without jaundice) is now recognized as a widespread public health problem, presenting with cough, chest pain, respiratory distress, and hemoptysis that may not be apparent until patients are intubated.
++
Jaundice occurs in 5–10% of all patients with leptospirosis; it can be profound and give an orange cast to the skin but usually is not associated with fulminant hepatic necrosis. Physical examination may reveal an enlarged and tender liver.
++
Acute kidney injury is common in severe disease, presenting after several days of illness, and can be either nonoliguric or oliguric. Typical electrolyte abnormalities include hypokalemia and hyponatremia. Loss of magnesium in the urine is uniquely associated with leptospiral nephropathy. Hypotension is associated with acute tubular necrosis, oliguria, or anuria, requiring fluid resuscitation and sometimes vasopressor therapy. Hemodialysis can be life-saving, with renal function typically returning to normal in survivors.
++
Other syndromes include (necrotizing) pancreatitis, cholecystitis, skeletal muscle involvement, rhabdomyolysis (with moderately elevated serum creatine kinase levels), and neurologic manifestations including aseptic meningitis. Cardiac involvement is commonly reflected on the electrocardiogram as nonspecific ST- and T-wave changes. Repolarization abnormalities and arrhythmias are considered poor prognostic factors. Myocarditis has been described. Rare hematologic complications include hemolysis, thrombotic thrombocytopenic purpura, and hemolytic-uremic syndrome.
++
Long-term symptoms following severe leptospirosis include fatigue, myalgia, malaise, and headache and may persist for years. Autoimmune-associated uveitis, a potentially chronic condition, is a recognized sequela of leptospirosis.