Leptospirosis，常被忽略的、可治癒的致命感染

From Journal
of Medical Case Reports

Fulminant Leptospirosis (Weil's Disease)
in an Urban Setting as an Overlooked Cause of Multiorgan Failure: A Case Report

Elias Maroun; Anurag Kushawaha; Elie El-Charabaty; Neville
Mobarakai; Suzanne El-Sayegh

Authors and
Disclosures

Posted: 03/06/2011; J Med Case Reports. 2011;5(1) © 2011
BioMed Central, Ltd.

Abstract Introduction: Leptospirosis has recently come to international attention as a globally important re-emerging infectious disease. Our case is unusual given the season, location and setting in which leptospirosis occurred. According to the New York City Board of Health, there were only two other cases of leptospirosis in New York City in the year that our patient was diagnosed. Case presentation: A 49-year-old healthy Chinese man presented to our hospital with sepsis and multiorgan failure. The patient did not respond to antibiotics and his multiorgan failure worsened. His workup did not show any significant findings except for a positive nasopharyngeal swab result for influenza A. Later the patient developed hemoptysis with evidence of bilateral infiltrates on radiography. His status mildly improved after he was started on steroids. Eventually, a microagglutination test confirmed the presence of antibodies against Leptospira icterohaemorrhagiae. The patient subsequently recovered after a course of intravenous antibiotics. Conclusion: The case of fulminant leptospirosis presented here should serve to alert health care providers and the general public to the clinical importance of this severe, sometimes fatal, disease. Leptospirosis should be considered early in the diagnosis of any patient with acute, non-specific febrile illness with multiorgan system involvement or high fever in a returning traveler. In addition, not only should it be considered in tropical and rural areas between late summer to early fall, but also in any location or time if the risk factors are present

Discussion

Leptospirosis is a zoonosis of worldwide distribution
caused by infection with L. interrogans, a
pathogenic spirochete. The organism infects a variety of animals, especially
rodents and animals associated with farming. Humans represent only incidental
infection usually through work-related contact through skin or mucous
membranes, typically after exposure to water or soil contaminated with urine
from an infected animal or via drinking of or bathing in contaminated water.
The main occupational groups at risk are farm workers, field agricultural
workers, plumbers, sewer workers, sanitation workers and military troops.

Leptospira are spiral-shaped, thin, motile organisms
with flagella. The most common serovars are icterohaemorrhagiae,
which are usually found in rats (Rattus norvegicus).
Urinary shedding of organisms from infected animals is the most significant
source of Leptospira spp. because the
spirochetes can persist for long periods of time in the renal tubules.

The natural course of leptospirosis comprises of two
distinct clinical phases: septicemic and immune. Humans typically become ill
seven to 12 days after exposure to leptospires. The first stage is called the
septicemic phase (leptospiremic phase) because the bacteria may be isolated
from blood cultures and cerebrospinal fluid (CSF). This phase is characterized
by a nonspecific flulike illness with sudden onset of high fever, headache,
myalgias (classically involving the paraspinal, calf and abdominal muscles)^[1] and
conjunctival suffusion. Conjunctival suffusion (reddening of the eye surface)
is a characteristic physical finding in leptospirosis, and its presence in a
patient with a nonspecific febrile illness should raise suspicion for
diagnosis.

The second stage is called the immune phase
(leptospiruric phase) when circulating antibodies can be detected and the
bacteria can be isolated from the urine. This stage occurs as a result of the
body's immunologic response by producing immunoglobulin M antibodies and can
last longer than one month. During this stage, specific organ damage can be
observed. Aseptic meningitis is one of the most important clinical syndromes
that can occur in 80% of patients during the immune phase. Renal symptoms, such
as uremia, azotemia, pyuria and hematuria, may occur. Pulmonary manifestations,
although usually benign, can be potentially life threatening and range from
chest pain, cough and dyspnea to pulmonary hemorrhage or acute respiratory
distress syndrome. An increase in liver enzymes (up to five times normal) with
a disproportionately high total bilirubin has been described as a prognostic
indicator in leptospirosis.^[2] Varying
degrees of jaundice, pancreatitis, hepatomegaly and myocarditis can also occur.

Weil's disease is the most severe form of
leptospirosis. Patients can present with high fever (>40°C), significant
jaundice, renal failure, hepatic necrosis, pulmonary involvement,
cardiovascular collapse, neurologic changes and hemorrhagic diathesis, with a
variable clinical course. Weil's disease can occur at the end of the first
stage and peaks during the second stage but can occur at any time during acute
leptospirosis as a single, progressive illness.

Acute renal failure is one of the most common
complications of severe leptospirosis. Renal leptospirosis is usually described
as a combination of acute tubular damage and interstitial nephritis.

A particularly serious type of lung involvement called
severe pulmonary hemorrhagic syndrome is considered to be a major cause of
death in patients with Weil's disease in developing countries, with profuse
lung hemorrhage dominating the clinical picture.^[3]

Hepatic dysfunction is usually mild and reversible.
Liver dysfunction in severe leptospirosis can be seen as conjugated serum
bilirubin levels may increase to above 80 mg/dL, accompanied by modest
elevations in transaminases, which rarely exceed 200 U/L.^[4]

Variable degrees of thrombocytopenia have been
reported with leptospirosis. The pathogenesis of thrombocytopenia and
hemorrhagic diathesis in leptospirosis is not well understood.

Overall, Weil's syndrome has a mortality rate of 5% to
10%. Important causes of death include renal failure, cardiopulmonary failure
and widespread hemorrhage.^[5]

The diagnosis of leptospirosis requires a high degree
of clinical suspicion because the disease's numerous manifestations can mimic
other tropical infections or other nonspecific febrile illnesses, as well as
noninfectious diseases such as small vessel vasculitides, systemic lupus
erythematosus or even malignancies. The initial diagnosis of leptospirosis
remains a clinical one, a presumed analysis in the appropriate epidemiologic
and clinical context. Routine laboratory testing is nondiagnostic but may show
elevated erythrocyte sedimentation rate, peripheral leukocytosis, variable
degrees of cytopenias, mildly increased aminotransferases and increased serum
bilirubin and ALP.

Isolation of the organism by culture of clinical
specimens (blood, CSF, urine) during the first seven to 10 days of the illness
is considered the gold standard of diagnosis. However, this method is
difficult, requires longer than 16 weeks because initial growth may be slow and
has a low sensitivity and specificity. The majority of leptospirosis cases are
diagnosed by serologic testing of which MAT is most common

The vast majority of infections with leptospira are
self-limiting, and it remains controversial if antimicrobials produce benefit
in cases of mild leptospirosis without end-organ damage. The current choices of treatment for mild leptospirosis include oral
doxycycline and amoxicillin. Parenteral
high-dose penicillin G has long been considered the treatment of choice of
fulminant leptospirosis. Recent trials have demonstrated that the
broad-spectrum third generation cephalosporins cefotaxime and ceftriaxone are
also acceptable agents for patients with severe leptospirosis.^[6,7]

The use of steroids in patients with leptospirosis has
not been well established. In the
current case, the improvement of the patient's renal dysfunction,
thrombocytopenia and hemoptysis may be attributed to the introduction of
steroids. Several case reports have described the beneficial effects of
glucocorticoids in severe leptospirosis with pulmonary hemorrhage,^[8]
thrombocytopenia^[9]
and renal failure.^[10,11]

Public health measures to prevent and reduce
leptospirosis include identification of contaminated water sources, rodent
control, prohibition of swimming in waters where risk of infection is high and
informing persons of the risk involved in recreational water activities.

In the case of our patient, the diagnosis of
leptospirosis was not initially considered because potential risk factors were
not identified at the outset. The majority of cases of leptospirosis occur in
the tropics, with infrequent incidences in temperate regions. Adding another
atypical facet to the patient's presentation, in the United States, the
majority of cases occur in the Southern and Pacific coastal states, with Hawaii
having the most reported cases. Also, our patient presented in the wintertime.
Most cases of leptospirosis occurring in temperate areas occur in the late
summer to early fall.^[1]
According to the NYC Board of Health, between 2008 and summer 2009, there were
only three cases of leptospirosis in NYC (including our patient).