Here, we report of a patient who presented with fever, shock and thrombocytopenia followed by diffuse pulmonary hemorrhage caused by leptospirosis. The patient also had elevated levels of CRP, PCT, IL-6, lactate, Cr, urine RBC and WBC. Because acute pyelonephritis often leads to serious conditions including sepsis and septic shock, the patient was diagnosed with acute pyelonephritis with septic shock on the day of hospitalization. However, antibiotic treatment with meropenem was ineffective. To our knowledge, this is not the first case of leptospirosis which went undiagnosed. Similar clinical presentations with thrombocytopenia and shock in acute febrile illnesses often lead to a diagnostic and therapeutic dilemma. Correctly evaluation of thrombocytopenia in acute febrile illnesses plays a crucial role in reducing disease complication and mortality.
Leptospirosis is a worldwide infection of zoonotic origin caused by spirochetes of the genus Leptospira [1]. Transmission of leptospirosis usually occurs through contact with the urine or tissue of carrier mammals and contaminated water, soil, or vegetation [4]. Portals of entry can be either skin, the respiratory tract or the gastrointestinal tract. Intact skin is an important barrier against leptospiral infection, and skin breakdown is one of the main ways to cause infection[5]. The clinical spectrum of the disease ranges from a mild anicteric leptospirosis manifesting as an influenza-like presentation of fever and myalgia, to multi organ dysfunction including thrombocytopenia, diffuse pulmonary hemorrhage, acute kidney injury, hepatic dysfunction and shock [1, 2, 6]. As a result of its broad range of clinical manifestations that mimic a wide variety of acute infectious diseases, leptospirosis can potentially lead to a misdiagnosis or delay in diagnosis.
The degree of thrombocytopenia in infections has an important value. It can also help in differential diagnosis and clear identification of aetiology of acute febrile illnesses.
Sepsis, zoonotic diseases (including malaria, dengue, scrub typhus, and leptospirosis), and Thrombotic Thrombocytopenic Purpura (TTP) are some of the common causes of fever with thrombocytopenia. Thrombocytopenia occurs in around 18% of patients with sepsis, however, severe thrombocytopenia (platelets < 20000/mm3) is less common in patients with sepsis [7]. Meanwhile, in a cohort of adults with severe malaria in Asia, 95% of patients with severe malaria were thrombocytopenic (platelets < 150000/mm3) and 51% had a platelets < 50000/mm3 [8]. Furthermore, acute febrile patients with thrombocytopenia should be considered for the presence of atypical pathogens such as dengue and epidemic hemorrhagic fever infections [9]. Dircio Montes, et al. concluded that one sixth of the patients initially diagnosed with dengue fever were actually leptospirosis [10]. Moreover, scrub typhus is one of the differential diagnoses for fever with thrombocytopenia, and the mainstay of diagnosing scrub typhus, immuno-florescence antibody test, or indirect immuno-peroxidase assay is the gold standard [11]. In our study, the patient's platelets were only 7×109/L on admission, combined with fever, anemia, renal failure, elevated lactate, so the possibility of TTP cannot be excluded. There are some methods that can be employed to identify TTP, such as peripheral blood morphology, bone marrow aspiration, ADAMTS13 activity test, and inhibitor titer test [12]. Therefore, the infectious and non-infectious causes mentioned above should be actively considered in acute febrile patients with thrombocytopenia.
Several diagnostic tests are available for leptospirosis including detection of the pathogen and antibodies. Leptospira culture is an aetiological test with high specificity, and considered as the gold standard test for diagnosis [13, 14]. However, it can take up to about 13 weeks and does not contribute early diagnosis of Leptospira[15].Enzyme-linked immunosorbent assay (ELISA) for detecting IgM, IgG, or both antibody types have been developed to detect specific antibodies in leptospirosis, while the method is prone to false-positive diagnosis[15, 16].As a complementary approach to conventional methods, mNGS is increasingly being applied in clinical laboratories for the diagnosis of leptospirosis, and can accurately detect Leptospira DNA during the early stage of the infection[15, 17]. Early diagnosis of leptospirosis is crucial to provide early and appropriate empiric antibiotics. Therefore, mNGS is recommended when leptospirosis infection is suspected, especially in patients with a history of contacting with contaminated water or animals.
Treatment of severe leptospirosis patients is supportive management, and use of appropriate antibiotics. Penicillin, doxycycline, ceftriaxone, and cefotaxime have been recommended for the treatment of leptospirosis [6, 18]. In the study, the patient received TZP plus doxycycline for 7 days along with supportive care. He improved dramatically, and became asymptomatic.
Overall, Leptospirosis is easily overlooked in cities, and can have serious complications such as septic shock. When a patient presents with unexplained fever, shock, thrombocytopenia, and diffuse pulmonary hemorrhage, mNGS should be considered to identify any special infection including Leptospirosis during the early stage.