SCCM Resource Library-52-Lone Star Tick Bites Big Apple: Ehrlichia chaffeensis-Induced Hemophagocytic Lymphohistiocytosis

Video Transcription

Hello all, my name is Shashkant Ambati and I'm one of the Pediatric Intensive Care Physicians at Albany Medical Center, Albany, New York.  I would like to thank the Critical Care Congress for giving me this opportunity to do this presentation.  Today, I'll be presenting to you an interesting case that we have encountered in our pediatric ICU. So, the title of my presentation is Lone Star Tech Bites Big Apple.  It's a case about ehrlichia chafensis-induced hemophagocytic lymphohistiocytosis. I don't have any disclosures.  A brief introduction about HLH, HLH or hemophagocytic lymphohistiocytosis is a term given to a group  of disorders of the mononuclear phagocyte system where there is an uncontrolled activation of the cellular immune system.  Although HLH is rare, it can be life-threatening as it can result in multi-organ failure and irreversible tissue damage. Its mortality rate can go as high as 75%.  There are two types of HLH, primary and secondary. The primary type, also called familial type, which is due to genetic defects in cytotoxic T cells and natural killer cells.  The secondary type is due to mainly infections, malignancies, certain rheumatological disorders, medications, and some immunodeficiency states.  Viruses are the most frequent cause of infectious triggers for HLH, of which EBV, Epstein-Barr virus, is the most common.  Here we describe a case of HLH triggered by infection caused by ehrlichia chafensis. Sorry for the busy slide, a little information about ehrlichia chafensis.  Ehrlichia chafensis is an intracellular obligate organism which is transmitted to humans through a tick bite. And the name of the tick is Amblyomma americanum.  It's also called Lone Star tick. It's predominantly found in southeastern and south central part of the United States. Its primary reservoir host is a white-tailed deer.  Ehrlichia preferentially infects leukocytes. The incubation period can range anywhere from one to two weeks before the symptoms of fever, headache, fatigue, and mausoleum develop.  This slide depicts the life cycle of a Lone Star tick. As you can see on the right-hand side, all the uninfected larvae, when they feed on the  blood of a white-tailed deer, which is infected with ehrlichia pathogen, all the larvae get infected and they can start infecting humans. Let's go into our case.  Our patient is a nine-year-old male who presented to our hospital with a two-day history of rash and fever.  He was originally from Tennessee, but he was visiting New York when he developed his symptoms.  A week before he arrived in New York, he fell off a motorbike close to his home and suffered  an aberration on his left thigh, which resulted in localized cellulitis for which he was being treated with trimethoprim-sulfamethoxazole combination, which is Bactrim.  A week later after starting Bactrim, he developed a full body macular rash with subsequent fever while he was in New York and so was brought into the hospital.  There had been no symptoms of difficulty breathing, cough, chest pain, confusion or lethargy, neither nausea, vomiting or diarrhea.  Parents denied any known recent tick bites, although they live in a rural part of Tennessee that is near wooded areas.  His initial labs on presentation showed a leukopenia with a white cell count of 900,  thrombocytopenia with a platelet count of 59,000, and elevated liver enzymes with AST in thousands.  So our initial differential diagnosis in our patient included a Bactrim-induced allergic reaction, sepsis secondary to viral bacterial infection, or Steven-Johnson syndrome, which  we thought to be less likely in our patient as he did not have any significant mucosal involvement.  Due to his persistent fevers and rash, the following labs were ordered, which came back up with prolonged prothrombin time and INR was at more than 9.  He had super high level of ferritin, which was close to 55,000 and his fibrinogen was low and he had elevated triglyceride level.  So based on the elevated ferritin, decreased fibrinogen, abnormal coagulation panel, and transaminitis in the setting of a rash and fever, HLH was diagnosed on this patient with  the help of pediatric hematology oncology. So he was started on high-dose dexamethasone.  So plan was also made to start him on atoposide or anakinra, which is a type of antiretroviral in the next few days.  On day two of hospitalization, his ehrlichia PCR came back positive and doxycycline was started.  During the course, he also received intravenous immunoglobulin before the tick panel came back positive for ehrlichia.  His fever and rash improved by day three of doxycycline and steroids and his ferritin significantly decreased.  His overall clinical status improved and his elaborative studies ultimately returned to almost normal.  His total hospital duration was eight days and he was discharged home with doxycycline to complete a total two-week course with tapering steroids.  Some of the labs that resulted during his course, his soluble interleukin-2 receptor level came back elevated at 2659 units per ml.  He also had a flow cytometry done, which showed markedly decreased natural killer cell function.  We deferred the bone marrow study in our patient as he responded dramatically to doxycycline.  His two-week post-discharge follow-up labs showed completely normal coagulation labs as well as ferritin and liver enzymes.  So HLH secondary to ehrlichia chathensis is very rare.  Our review of literature showed only six pediatric reported cases of ehrlichia-induced HLH so far.  So the initial presentation in our patient was thought to be a drug reaction secondary to Bactrim, but symptoms continued even after stopping the drug.  So our patient's presentation of elevated ferritin, decreased fibrinogen, abnormal coagulation panel, transaminitis in the setting of a rash and fever were consistent with a  clinical diagnosis of HLH.  So drug-induced HLH is rare and is usually caused by anti-epileptics and anti-cancer drugs. And a review of literature showed no reports of HLH secondary to Bactrim.  There was no known history of recent tick bites in our patient, however, his history of living in a rural part of Tennessee has led us to test for tick-borne diseases.  Thus, it is very important to take the geographical location into consideration while considering the causes for HLH.  HLH is typically due to pathological immune activation due to genetic defects, but secondary causes such as infections must be ruled out.  Due to the high mortality associated with HLH, our case stresses the importance of recognizing and evaluating for potential infectious causes when encountered with HLH.  The prognosis of Ehrlichia-induced HLH is excellent if diagnosed early with prompt initiation of treatment.  It should be noted that although infections alone can lead to secondary HLH, they are also the common trigger for overwhelming immune activation in Fabelia HLH, and children with  secondary HLH may also have potentially pathogenic polymorphisms in an HLH-associated gene.  So, our patient has been recommended to follow up with a complete genetic analysis to identify  mutations in genes that encode proteins critical to the lymphocyte granule-mediated cytotoxic pathway. So, this brings to the end of my presentation. These are my references.  So, I would like to thank all the audience for listening to my presentation, and have a nice day.

Video Summary

This presentation discusses a case of hemophagocytic lymphohistiocytosis (HLH) triggered by an infection caused by ehrlichia chafensis, a tick-borne pathogen. The patient, a nine-year-old male, presented with a rash and fever and was initially thought to have a drug reaction. However, further testing revealed abnormal lab results consistent with HLH. The patient was treated with high-dose dexamethasone and doxycycline, and his condition improved. Ehrlichia-induced HLH is rare, and this case highlights the importance of considering infectious causes and geographic location in diagnosing and treating HLH. The patient is recommended for genetic analysis to identify potential mutations.

Asset Subtitle

Immunology, Pediatrics, 2021

Asset Caption

The Society of Critical Care Medicine's Critical Care Congress features internationally renowned faculty and content sessions highlighting the most up-to-date, evidence-based developments in critical care medicine. This is a presentation from the 2021 Critical Care Congress held virtually from January 31-February 12, 2021.

Shashikanth Reddy Ambati, MD

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a group of disorders of the mononuclear phagocyte system in which there is uncontrolled activation of the cellular immune system. While HLH is a rare disorder it can be a life-threatening condition with an overall mortality of 58-75%. HLH disease can be due to genetic defects but can also be triggered by infections, of which Ehrlichia is one rare cause. E.Chaffeensis is transmitted to humans through an infected lone star tick. Here we describe a case of HLH induced by Ehrlichia.

Description: A 9-year-old male presented with two-day history of rash and fever. He was visiting New York from his home in rural Tennessee and was previously healthy, except with a recent abrasion on his thigh with localized cellulitis being treated with trimethoprim-sulfamethoxazole (TMP-SMX). A week after starting TMP-SMX, he developed a full body macular rash and subsequently fever and hepatosplenomegaly. His blood tests showed leukopenia, anemia, thrombocytopenia, and transaminitis. His coagulation studies were also abnormal, ferritin was elevated to >50,000 and fibrinogen was low. Based on the above clinical and laboratory data, HLH was diagnosed. He was started on high dose dexamethasone. On Day 2 of hospitalization, E. chaffeensis was detected by PCR and doxycycline was started. His fever and rash improved by Day 3 of doxycycline and steroids and his ferritin significantly decreased. His overall clinical status improved, and laboratory studies ultimately returned to normal. He was discharged with doxycycline to complete a total 2-week course with tapering steroids.

Discussion: Drug induced rash from TMP-SMX was the initial impression in our patient. There was no known history of recent tick bites, however, his history of living in a rural part of Tennessee led us to test for tick borne diseases. HLH is typically due to pathological immune activation due to genetic defects but secondary causes such as infections must be ruled out. Due to the high mortality associated with HLH, this case highlights the importance of recognizing and evaluating for potential infectious causes when encountered with HLH. The prognosis of Ehrlichia induced HLH is excellent if diagnosed early with prompt initiation of treatment.

Meta Tag

Content Type Presentation

Knowledge Area Immunology

Knowledge Area Pediatrics

Knowledge Level Advanced

Membership Level Select

Tag Infectious Diseases

Year 2021

Keywords

hemophagocytic lymphohistiocytosis

ehrlichia chafensis

tick-borne pathogen

infection

genetic analysis

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