Hemorrhagic fever with renal syndrome with concurrent aortic dissection: a case report

Hemorrhagic fever with renal syndrome (HFRS) is caused by hantaviruses presenting with high fever, hemorrhage, acute kidney injury. Microvascular injury and hemorrhage in mucus was often observed in patients with hantavirus infection. Infection with bacterial and virus related aortic aneurysm or dissection occurs sporadically. We present a previously unreported case of hemorrhagic fever with concurrent Stanford B aortic dissection.

diagnosed with Hemorrhagic fever with renal syndrome and Stanford B aortic dissection. The patient recovered completely after surgery with other support treatments.

Conclusion
We present a case of HFRS complicated with aortic dissection,and no study has reported the association of HFRS with aortic disease. However, we suppose that hantavirus infection not only cause microvascular damage but may be risk factor for acute macrovascular detriment. A causal relationship has yet to be con rmed.

Background
Hemorrhagic fever with renal syndrome (HFRS) is caused by hantaviruses (such as Hantaan, Seoul and Puumala virus) which are carried by a speci c rodent host species and transmitted through their saliva, urine, feces and blood [1]. In China, the hantaan virus and Seoul virus infection are two main pathogens for HFRS, with more than 11,000 cases reported annually [2]. The most commonly classic HFRS presents with high fever, loin or abdominal pain, nausea and vomiting, malaise, conjunctival hemorrhage and progressing to acute kidney injury. Hantavirus cardiopulmonary syndrome is another life-threatening clinical syndromes infected by Sin Nombre virus in the United States and Andes virus circulating in south America [3].Since hantavirus primarily infects endothelial cells, it had been investigated that hantavirus infection induce the leakage of the vascular endothelia cells and present with pleural or perirenal effusion in patients [4]. The clinical course, from fever to abrupt hypotension with oliguria, can be extremely variable and some patients were asymptomatic. AD is a lethal and critical disease, presenting with the separation of the aortic wall layers and subsequent formation of a false lumen [5]. The Stanford B aortic dissection is de ned as the appearance of a false lumen at the segment distal to the left subclavian artery. Risk factors of AD include hypertension, genetic disorders and in ammation of the aortic wall, etc. [6]. Infected AD is a rare life threatening condition because of the possibility of rupture as well as perforation to surrounding organs. Although less common, infective aortic disease due to bacteria (such as staphylococcus, salmonella, mycobacteria) and virus (such as Zoster Virus,) have been reported [7][8]. The infection related in ammatory response in the vascular media may lead to aortic dilation and formation of aneurysm [9].
In this report, we present a case of HFRS with concurrent aortic dissection during the convalescent period.
To our knowledge, the hantavirus infection could cause microvascular in ammation and endothelium damage [10], however, hemorrhagic fever complicated with aortic dissection was no report before, and a causal relationship has yet to be con rmed.

Case Presentation
In December 16, 2018, a previously healthy 56 year old man presented to our emergency department complaining of high fever(the highest recorded oral temperature 39.7℃) ,fatigue and generalized body ache for 3 days. The local clinic blood test showed an increased WBC (11.1 × 10^9 /L) with dramatically decreased platelets (36 × 10^9/L). He lived in rural area and worked in a place overrun with rats. On admission, his oral temperature was 38.0℃, respiratory rate 19/min, heart rate 78/min, blood pressure 129/86 mmHg. Physical examination found a poor general condition, petechiae in the oral and neck. His blood tests revealed as followed: leukocyte count 14.9 × 10^9 /L, hemoglobin 212 g/L, platelets 10 × 10^9/L, alanine aminotransferase 66 U/L, aspartate aminotransferase 108 U/L, lactic dehydrogenase 1079 IU/L, creatinine 187 µmol/L, C-reactive protein 33.3 mg/L(reference 0-5). The coagulation function test showed the prothrombin time 15.5 s (reference 11.5-14.5), the partial thromboplastin time 91.2 s. The clinical course and manifestations were summarized in Fig. 1. The laboratory results and reference range were listed in Table 1. The computed tomography scan of chest and abdomen showed pleural effusion, perinephric effusion extended to paracolic sulcus, slight peritoneal and pelvic effusion ( Fig. 2A-D). Enzymelinked immunosorbent assays (ELISA) of IgM and IgG antibodies for HFRS were both positive and the serotype was hantaan virus. Based on clinical symptoms and signs, along with his platelets count, creatinine level, urine volume changes, the patient was eventually diagnosed as HFRS. The treatment mainly includes transfusion of platelets and fresh frozen plasma, hemodialysis, antibacterial drug Piperacillin/Tazobactam empirically in dealing with abdomen effusion and other supportive therapies. His condition was recovered gradually after treatment.
On hospital day 10, he complained sudden onset acute chest pain radiating to the back when eating lunch.
After consulting a cardiologist, he was sent for a computed tomography angiography (CTA) of the aorta. The CTA revealed an AD of the descending aorta extending to iliac artery with the left subclavian artery involved (Fig. 3A-D). On hospital day 26, when the platelets were recovered to normal level and the creatinine to 122 µmol/L, he received an angiography of aortic and surgery of thoracic endovascular aortic repair (Fig. 3.E, F). A week after operation, the patient was discharged and followed up as outpatient.

Discussion And Conclusion
Hantaviruses are negative sense single stranded ribonucleic acids viruses, which can survive for more than ten days as a virion type at room temperature [11]. The exposure to aerosolized rodent excreta containing pathogenic virus is the main cause of human infection with hantaviruses. The classical manifestation of HFRS includes high fever, conjunctival hemorrhage, and gastrointestinal symptoms like abdominal pain, malaise, nausea and vomiting. Some patients develop severe oliguric acute kidney injury and need hemodialysis. Patients typically have abnormal laboratory values including a leukocytosis, thrombocytopenia, elevation of serum creatinine and lactate dehydrogenase. The diagnosis of hantavirus infection can be con rmed by serum speci c antibody or viral RNA. We were not able to perform reverse transcription-polymerase chain reaction to make a molecular test because of condition limitations. But the clinical symptoms and signs, platelets count, creatinine level, urine volume changes, all indicated HFRS.
Increased vascular permeability appears to be a dramatic expression of this patient, which had pleural and perinephric effusion according to the CT scan (Fig. 2.). In patients, hantaviruses replicate primarily in the endothelium, which cause damage to vascular endothelium, tubular and interstitial, and further increasing the permeability [1]. The increased vescular permeability is mediated in part by bradykinin and cytokines such as tumor necrosis factor and interleukin-6 [3]. All of these pathogenesis can increase the possibility of vascular in ammation, damage, and hemorrhage in HFRS.
Infection with virus or bacterial related aortic aneurysm or dissection were reported sporadically. Staphylococcus aureus and Salmonella species were reported to cause AD [5]. Virus infection such as herpes zoster, human immunode ciency virus and varicella-zoster virus, can also lead to vascular dissection [12]. However, the exact mechanisms of infection related vascular dissection are still far from clear. Prior report suggested that virals might lead to in ammatory injury of the arterial wall that subsequently developed artery dissection [13]. During the recovery period of HFRS, our patient developed a sudden AD on day 10 in hospital. A multivariate analysis con rmed that the dissection was independently associated with a diagnosis of recent infection [9]. Availability of data and materials The datasets supporting the conclusions of this article are included within the article.
Competing interests: The authors declare that they have no competing interests.
Funding: No funding was obtained for this case report The patients' manifestation and main treatment according to day of illness and hospitalization, December 13, 2018 to January 17, 2019. BP, blood pressure, FFP, fresh frozen plasma, PLT, Platelets, RRT, renal replacement therapy, CTA, computed tomography angiography, AD, aortic dissection, MAP, mean atrial blood pressure.

Figure 2
Computed tomography of the thorax and abdomen on hospital day 1 showing pleural effusion (A, B), perinephric effusion extended to paracolic sulcus, slight peritoneal and pelvic effusion(C, D).