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Chatterjee R, Chandra A, Mukherjee S, Chatterjee N, Dasgupta S. Secondary haemophagocytic lymphohistiocytosis associated with scrub typhus: A case report with a brief review of literature. J R Coll Physicians Edinb 2025; 55:23-27. [PMID: 39648451 DOI: 10.1177/14782715241303969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/10/2024] Open
Abstract
Scrub typhus is a very important cause of acute undifferentiated febrile illness in the Asia-Pacific region. Haemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition characterised by widespread immune system activation, resulting in tissue damage throughout multiple organ systems. HLH is categorised into primary HLH, arising from intrinsic defects in lymphocytes and macrophages, and secondary HLH, primarily triggered by infections or connective tissue disorders. HLH is one of the rarest complications of scrub typhus. We present the case of a previously healthy young man who presented to our facility with a history of acute febrile illness. Clinical examination revealed an eschar and subsequent laboratory investigations confirmed the diagnosis of scrub typhus. The patient's haematological parameters showed pancytopenia, raising suspicion of this rare association. Confirmatory tests established the diagnosis of HLH, and the patient achieved an uneventful recovery following treatment for the underlying illness and supportive care.
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Affiliation(s)
- Rupak Chatterjee
- Department of Tropical Medicine, Calcutta School of Tropical Medicine, Kolkata, India
| | - Atanu Chandra
- Department of Internal Medicine, Bankura Sammilani Medical College, Bankura, India
| | - Sumana Mukherjee
- Department of Pathology, Calcutta School of Tropical Medicine, Kolkata, India
| | - Nandini Chatterjee
- Department of Internal Medicine, IPGMER and SSKM Hospital, Kolkata, India
| | - Sugata Dasgupta
- Department of Critical Care Medicine, IPGMER and SSKM Hospital, Kolkata, India
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Jevtic D, da Silva MD, Haylock AB, Nordstrom CW, Oluic S, Pantic N, Nikolajevic M, Nikolajevic N, Kotseva M, Dumic I. Hemophagocytic Lymphohistiocytosis (HLH) in Patients with Tick-Borne Illness: A Scoping Review of 98 Cases. Infect Dis Rep 2024; 16:154-169. [PMID: 38525759 PMCID: PMC10961790 DOI: 10.3390/idr16020012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 02/15/2024] [Accepted: 02/18/2024] [Indexed: 03/26/2024] Open
Abstract
Hemophagocytic lymphohistiocytosis (HLH) secondary to tick-borne infections is a rare but potentially life-threatening syndrome. We performed a scoping review according to PRISMA guidelines to systematically analyze the existing literature on the topic. A total of 98 patients were included, with a mean age of 43.7 years, of which 64% were men. Most cases, 31%, were reported from the USA. Immunosuppression was present in 21.4%, with the most common cause being previous solid organ transplantation. Constitutional symptoms were the most common, observed in 83.7% of the patients, while fever was reported in 70.4% of cases. Sepsis was present in 27.6%. The most common laboratory abnormalities in this cohort were thrombocytopenia in 81.6% of patients, while anemia, leukopenia, and leukocytosis were observed in 75.5%, 55.1%, and 10.2%, respectively. Liver enzyme elevation was noted in 63.3% of cases. The H-score was analyzed in 64 patients, with the mean value being 209, and bone marrow analysis was performed in 61.2% of patients. Ehrlichia spp. was the main isolated agent associated with HLH in 45.9%, followed by Rickettsia spp. in 14.3% and Anaplasma phagocytophilum in 12.2%. Notably, no patient with Powassan virus infection or Lyme borreliosis developed HLH. The most common complications were acute kidney injury (AKI) in 35.7% of patients, shock with multiple organ dysfunction in 22.5%, encephalopathy/seizure in 20.4%, respiratory failure in 16.3%, and cardiac complications in 7.1% of patients. Treatment included antibiotic therapy alone in 43.9%, while 5.1% of patients were treated with immunosuppressants alone. Treatment with both antibiotics and immunosuppressants was used in 51% of patients. Appropriate empiric antibiotics were used in 62.2%. In 43.9% of cases of HLH due to tick-borne disease, patients received only antimicrobial therapy, and 88.4% of those recovered completely without the need for immunosuppressive therapy. The mortality rate in our review was 16.3%, and patients who received inappropriate or delayed empiric therapy had a worse outcome. Hence, we suggest empiric antibiotic treatment in patients who are suspected of having HLH due to tick-borne disease or in whom diagnostic uncertainty persists due to diagnostic delay in order to minimize mortality.
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Affiliation(s)
- Dorde Jevtic
- Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (D.J.); (A.B.H.)
- Department of Medicine, NYC Health + Hospitals/Elmhurst, New York, NY 11373, USA
| | | | - Alberto Busmail Haylock
- Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (D.J.); (A.B.H.)
- Department of Medicine, NYC Health + Hospitals/Elmhurst, New York, NY 11373, USA
| | - Charles W. Nordstrom
- Department of Hospital Medicine, Mayo Clinic Health System, Eau Claire, WI 54703, USA;
- Mayo Clinic College of Medicine and Science, Rochester, MN 55902, USA
| | - Stevan Oluic
- Department of Internal Medicine, Mayo Clinic Health System, Mankato, MN 56001, USA;
| | - Nikola Pantic
- Clinic of Hematology, University Clinical Center of Serbia, 11000 Belgrade, Serbia;
| | - Milan Nikolajevic
- School of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (M.N.); (N.N.)
| | - Nikola Nikolajevic
- School of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (M.N.); (N.N.)
| | - Magdalena Kotseva
- Internal Medicine Residency, Franciscan Health, Olympia Fields, Chicago, IL 60461, USA;
| | - Igor Dumic
- Department of Hospital Medicine, Mayo Clinic Health System, Eau Claire, WI 54703, USA;
- Mayo Clinic College of Medicine and Science, Rochester, MN 55902, USA
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Muacevic A, Adler JR, Upadhyay A, Dubey K. Disseminated Intravascular Coagulation Manifesting as Diffuse Alveolar Hemorrhage in a Scrub Typhus Patient: A Rarely Thought of Complication. Cureus 2022; 14:e32974. [PMID: 36712722 PMCID: PMC9879597 DOI: 10.7759/cureus.32974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/26/2022] [Indexed: 12/28/2022] Open
Abstract
Scrub typhus is a common cause of an acute, unexplained febrile illness. Without proper treatment, it can lead to life-threatening complications and even death. We present the case of a 16-year-old girl who presented with complaints of fever with reddish spots all over her body for 10 days and breathing difficulty for three days. She had an episode of gum bleeding just prior to admission and two episodes of hemoptysis after admission. She had severe thrombocytopenia, a low serum fibrinogen level, raised D-dimer levels, a raised activated partial thromboplastin time as well as a raised prothrombin time, and an international normalized ratio. Her chest radiograph showed diffuse bilateral interstitial infiltrates. A diagnosis of disseminated intravascular coagulation and diffuse alveolar hemorrhage secondary to possible hematological malignancy or vector-borne infectious disease was made. She was treated with intravenous doxycycline and broad-spectrum antibiotics, along with other supportive measures. Bone marrow aspiration and biopsy showed normal trilineage differentiation, normal erythropoiesis, myelopoiesis, and megakaryopoiesis. Finally, a positive immunoglobulin M (IgM) antibody for scrub typhus clinched the diagnosis. Her condition improved over the next week, and she was discharged with the advice to continue oral doxycycline for a week. This case highlights one of the rare complications of scrub typhus, disseminated intravascular coagulation, and the importance of timely initiation of treatment in such patients.
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Chen IH, Fong CM, Chang HHS, Lin JH. Successful Application of Team Resource Management in Scrub Typhus Infection with Septic Shock. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph191710683. [PMID: 36078399 PMCID: PMC9518151 DOI: 10.3390/ijerph191710683] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 08/24/2022] [Accepted: 08/26/2022] [Indexed: 05/20/2023]
Abstract
The fatality rate of scrub typhus infection with septic shock is quite high if timely and correct diagnosis and treatment are not obtained. There are few studies in the literature on the subject of holding TRM conferences to discuss the condition and reach a consensus on treatment. A TRM conference has the significance of early intervention by the medical team and consensus on therapy from the medical doctors and family members. We report the case of scrub typhus infection with septic shock. On the day the patient was hospitalized, the medical team held a TRM conference and invited family members to attend. We found that the eschar on the patient may be related to scrub typhus, which was later confirmed by a positive Weil-Felix test and PCR analysis. Under the consensus treatment, the patient's condition improved considerably within the next day. The most significant difference between the TRM conference and the clinical specialist's consultation is that it can quickly narrow the cognitive gap between doctors and family members and reach a consensus on the patient's therapy strategy, truly avoid medical disputes, and effectively share the stress of attending physician. In this case report, we highlight the significance of the TRM conference.
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Affiliation(s)
- I-Hung Chen
- Department of Internal Medicine, Pingtung Branch of Kaohsiung Armed Forces General Hospital, Pingtung 90092, Taiwan
- Department of Business Management, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan
- Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan
- Correspondence:
| | - Cher-Min Fong
- Department of Business Management, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan
| | - Hsing-Hua Stella Chang
- International Master of Business Administration, National Taichung University of Education, Taichung 40359, Taiwan
| | - Jen-Hsien Lin
- Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, Taiwan
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Abstract
PURPOSE OF REVIEW Scrub typhus, caused by Orientia tsutsugamushi, is a widely neglected disease which is gaining global momentum because of its resurgence patterns. The disease is now being reported in newer regions as well as areas previously endemic areas. In this review, we aim to comprehensively review the data available to assist physicians in making an accurate diagnosis and appropriate management of the disease. RECENT FINDINGS Several diagnostic tests have been developed for confirming scrub typhus. However, there is lack of clarity on which tests are most appropriate in a given clinical scenario. A recent study has demonstrated that in early disease (<7 days) when serological tests remain negative, the quantitative polymerase chain reaction is the most sensitive test. Among the serological tests, both IgM enzyme-linked immunosorbent assay as well as rapid diagnostic tests revealed excellent sensitivities and specificities. SUMMARY With the reemergence of scrub typhus, a high degree of clinical suspicion is required to appropriately diagnose this disease which presents as an acute febrile illness. It can progress to develop various complications leading to multi-organ dysfunction syndrome. Mild illness responds well to antibiotic treatment with doxycycline and azithromycin. Further studies are required to determine the most optimal therapy in severe scrub typhus infections and superiority of one drug over the other.
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Gupta S, Grover S, Gupta M, Kaur D. Cerebellitis as a rare manifestation of scrub typhus fever. BMJ Case Rep 2020; 13:13/5/e233993. [PMID: 32414774 DOI: 10.1136/bcr-2019-233993] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Scrub typhus is a mite-borne rickettsial disease caused by Orientia tsutsugamushi, a gram-negative coccobacilli transmitted through the bite of chigger mite. Scrub typhus has diverse clinical manifestations, often presenting either as a simple febrile illness or as a complicated multi-organ dysfunction. Neurological complications in scrub typhus are diverse but their exact incidence is unknown. Cerebellitis is another rare neurological manifestation associated with scrub typhus. Here, we report the case of a 26-year-old woman with serologically confirmed scrub typhus presenting with fever and gross cerebellar dysfunction. MRI was normal. She was managed with antimicrobials and made an uneventful recovery.
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Affiliation(s)
- Samiksha Gupta
- Department of General Medicine, Government Medical College and Hospital, Chandigarh, India
| | - Sahil Grover
- Department of General Medicine, Government Medical College and Hospital, Chandigarh, India
| | - Monica Gupta
- Department of General Medicine, Government Medical College and Hospital, Chandigarh, India
| | - Daljinderjit Kaur
- Department of General Medicine, Government Medical College and Hospital, Chandigarh, India
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Kotwal M, Vaish E, Gupta KK, Ozair A. Scrub typhus manifesting with intracerebral hemorrhage: Case report and review of literature. J Family Med Prim Care 2020; 9:2535-2537. [PMID: 32754539 PMCID: PMC7380763 DOI: 10.4103/jfmpc.jfmpc_284_20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 03/14/2020] [Accepted: 03/23/2020] [Indexed: 12/04/2022] Open
Abstract
Scrub typhus (ST), hitherto absent from many parts of India, is now recently being recognized as a significant cause of morbidity and mortality throughout the country. Its diverse clinical presentations, low of the index of suspicion by the treating physician, and lack of diagnostic testing in many parts of the country result in delayed treatment, leading to a host of complications. We here report such a complication, where ST manifested with a large intracerebral hemorrhage, of which, to the best of our knowledge, only nine cases have been reported in the English language worldwide. Family physicians, who are the often first point of contact for treatment of febrile illness, as ST typically manifests, need to be aware of this entity to prevent such catastrophic consequences.
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Affiliation(s)
- Mudit Kotwal
- Department of Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
| | - Esha Vaish
- Department of Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
| | - K. K. Gupta
- Department of Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
| | - Ahmad Ozair
- Department of Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
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Abstract
Japanese spotted fever (JSF) is an uncommon but potentially fatal infection transmitted by tick bites. We herein report a fulminant case of JSF infection that occurred in an immunocompetent adult that was complicated by disseminated intravascular coagulation and hemophagocytic lymphohistiocytosis (HLH). We discuss the difficulty in making the diagnosis and identifying the complication of HLH in our patient. HLH is a rare complication of rickettsiosis, and this is the first reported case in English of JSF complicated by HLH in an immunocompetent adult. Secondary HLH caused by rickettsiosis requires a different treatment from primary HLH. Rickettsiosis must therefore be considered in patients with HLH.
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Affiliation(s)
- Masahiro Kaneko
- Department of General Internal Medicine, Akashi Medical Center, Japan
| | - Naoto Ishimaru
- Department of General Internal Medicine, Akashi Medical Center, Japan
| | - Takahiro Nakajima
- Department of General Internal Medicine, Akashi Medical Center, Japan
| | - Yohei Kanzawa
- Department of General Internal Medicine, Akashi Medical Center, Japan
| | - Hiroyuki Seto
- Department of General Internal Medicine, Akashi Medical Center, Japan
| | - Saori Kinami
- Department of General Internal Medicine, Akashi Medical Center, Japan
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Akagi T, Mukai T, Tsuji S, Morita Y. Scrub typhus (Tsutsugamushi disease) in a patient presenting with hemophagocytic syndrome. Immunol Med 2018; 41:82-84. [PMID: 30938265 DOI: 10.1080/13497413.2018.1481581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022] Open
Abstract
Scrub typhus is a mite-borne infectious disease caused by Orientia tsutsugamushi, which is found mainly in East and Southeast Asia and in Australia. The disease presents with a variety of non-specific symptoms, including fever, headache, cough, myalgia, and rash. Delay in starting appropriate antimicrobial therapy may lead to serious complications and even death. We report the case of an 84-year-old Japanese patient with scrub typhus who developed hemophagocytic syndrome (HPS) and was successfully treated with minocycline in addition to corticosteroids. A pathognomonic skin ulcer on her right buttock, which was initially covered with black eschar, prompted us to consider the possibility of scrub typhus. Blood polymerase chain reaction and antibody assays confirmed the diagnosis. Scrub typhus must be considered as one of the underlying diseases that may cause HPS in patients living in the Asia-Pacific region and in those who have recently returned from endemic areas.
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Affiliation(s)
- Takahiko Akagi
- a Department of Rheumatology , Kawasaki Medical School , Kurashiki , Japan
| | - Tomoyuki Mukai
- a Department of Rheumatology , Kawasaki Medical School , Kurashiki , Japan
| | - Shoko Tsuji
- a Department of Rheumatology , Kawasaki Medical School , Kurashiki , Japan
| | - Yoshitaka Morita
- a Department of Rheumatology , Kawasaki Medical School , Kurashiki , Japan
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Rajapakse S, Weeratunga P, Sivayoganathan S, Fernando SD. Clinical manifestations of scrub typhus. Trans R Soc Trop Med Hyg 2018; 111:43-54. [PMID: 28449088 DOI: 10.1093/trstmh/trx017] [Citation(s) in RCA: 75] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Accepted: 04/11/2017] [Indexed: 01/10/2023] Open
Abstract
The mite-borne rickettsial zoonosis scrub typhus is widely prevalent in parts of Southeast and Far East Asia, and northern Australia. The disease is an acute febrile illness, associated with rash and often an eschar, which responds dramatically to treatment with antibiotics. In some cases it results in a serious illness leading to multiple organ involvement and death. The disease manifestations are thought to result from a systemic vasculitis, caused by both direct effects of the organisms as well as an exaggerated immune response, although little is understood about its pathogenesis. A wide spectrum of clinical manifestations, affecting nearly every organ system, have been described with scrub typhus. Some of these manifestations are serious and life threatening. In this systematic review, we summarise the typical and atypical manifestations of scrub typhus reported in the literature. Awareness of these unusual manifestations will hopefully guide clinicians towards diagnosing the condition early, and initiating early appropriate antibiotics and other supportive measures.
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Affiliation(s)
- Senaka Rajapakse
- Tropical Medicine Research Unit, Department of Clinical Medicine, Faculty of Medicine, University of Colombo, 25, Kynsey Road, Colombo 08, Sri Lanka
| | - Praveen Weeratunga
- University Medical Unit, National Hospital, Regent Street, Colombo 08, Sri Lanka
| | - Sriharan Sivayoganathan
- Tropical Medicine Research Unit, Department of Clinical Medicine, Faculty of Medicine, University of Colombo, 25, Kynsey Road, Colombo 08, Sri Lanka
| | - Sumadhya Deepika Fernando
- Department of Parasitology, Faculty of Medicine, University of Colombo, 25, Kynsey Road, Colombo 08, Sri Lanka
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Hemophagocytic Lymphohistiocytosis Associated with Scrub Typhus: Systematic Review and Comparison between Pediatric and Adult Cases. Trop Med Infect Dis 2018; 3:tropicalmed3010019. [PMID: 30274417 PMCID: PMC6136620 DOI: 10.3390/tropicalmed3010019] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Revised: 01/31/2018] [Accepted: 02/06/2018] [Indexed: 12/16/2022] Open
Abstract
Background: Scrub typhus is a mite-borne bacterial infection caused by Orientia tsutsugamushi. Hemophagocytic lymphohistiocytosis (HLH) is a potential severe complication. Most reported cases of HLH associated with scrub typhus were single cases or case series with a small sample sizes. Thus, no clear consensus exists on clinical manifestations and differences between pediatric and adult cases of this condition. Methods: a systematic search of English and Japanese articles from PubMed, PubMed Central, and Directory of Open Access Journals databases was performed from 3 December 2016 to 28 December 2017. The primary outcome was mortality in patients with HLH associated with scrub typhus; secondary outcomes were differences in clinical symptoms, laboratory findings, and treatment between pediatric and adult patients with HLH associated with scrub typhus. Results: thirty cases of HLH associated with scrub typhus were identified (age range: 2 months to 75 years; median age: 21.5 years, male:female ratio, 1:1). Eschar was frequently observed in the pediatric group (p = 0.017), whereas acute kidney injury was more prevalent in the adult group (p = 0.010). Two patients died of intracranial hemorrhage complicated with multiple organ failure; overall mortality rate was 6.7%. Conclusions: HLH associated with scrub typhus could be cured with remarkable improvement using single antibiotic therapy in approximately half the cases, with the mortality rate being relatively lower than that of HLH associated with other secondary causes.
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Liu D, Hu X, Jiang X, Gao B, Wan C, Chen C. Characterization of a novel splicing mutation in UNC13D gene through amplicon sequencing: a case report on HLH. BMC MEDICAL GENETICS 2017; 18:135. [PMID: 29157204 PMCID: PMC5696762 DOI: 10.1186/s12881-017-0489-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Accepted: 11/02/2017] [Indexed: 11/23/2022]
Abstract
Background Hemophagocytic lymphohistiocytosis (HLH) is a rare but fatal disease caused by uncontrolled proliferation of activated lymphocytes and macrophages. Six genes including SH2D1A, PRF1, UNC13D, STX11, STXBP2 and XIAP were reported as causative genes in most cases. Case presentation Here we report a novel splicing mutation in UNC13D gene, which was identified in an 18-year-old female. Patient was diagnosed as HLH base on HLH-2004 guidelines, no history of inherited diseases was revealed in this family, parents were healthy and non-consanguineous. Splenomegaly and hemophagocytosis in bone marrow were observed in clinical examination. Amplicon sequencing for the whole coding region of 6 HLH-related genes was performed on Ion S5XL genetic analyzer. In all, four heterozygous mutations were detected, including 2 nonpathogenic SNPs (PRF1:c.900C > T, STX11:c.*70G > A) and 2 splicing mutations in UNC13D gene (UNC13D:c.1299 + 1G > A and UNC13D:c.2709 + 1G > A), both of which were predicted to be potentially pathogenic by human splicing finder (HSF3) tool. The result was confirmed by two-generation pedigree analysis base on sanger sequencing. Conclusions Two compound heterozygous splicing mutations in UNC13D gene were identified and considered to be potential pathogenesis in a female patient of HLH. The mutation UNC13D:c.1299 + 1G > A was reported in HLH for the first time. The inheritance mode and source of the mutation in the proband was examined by family analysis. Our data suggest that further studies of the spectrum of HLH-related mutations in China are warranted. Electronic supplementary material The online version of this article (10.1186/s12881-017-0489-1) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Dongling Liu
- School of Nursing, Zhengzhou University, Zhengzhou, Henan, 450052, China
| | - Xijiang Hu
- Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430016, China
| | - Xiwen Jiang
- DaAn Gene Co., Ltd. Of Sun Yat-sen University, The Medicine and Biological Engineering Technology Research Center of the Ministry of Health, Guangzhou, Guangdong, China
| | - Bo Gao
- Department of Laboratory Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Cheng Wan
- Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, 100871, China.
| | - Changying Chen
- School of Nursing, Zhengzhou University, Zhengzhou, Henan, 450052, China.
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Chen H, Ning Z, Qiu Y, Liao Y, Chang H, Ai Y, Wei Y, Deng Y, Shen Y. Elevated levels of von Willebrand factor and high mobility group box 1 (HMGB1) are associated with disease severity and clinical outcome of scrub typhus. Int J Infect Dis 2017; 61:114-120. [PMID: 28652214 DOI: 10.1016/j.ijid.2017.06.015] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Revised: 06/11/2017] [Accepted: 06/16/2017] [Indexed: 01/15/2023] Open
Abstract
OBJECTIVES This study aimed to investigate whether von Willebrand factor (vWF) and high mobility group box 1 (HMGB1) are associated with the severity and clinical outcome of scrub typhus and to seek novel biomarkers for surveillance and prediction of the prognosis of this infection. METHODS Serum concentrations of vWF and HMGB1 were measured twice by ELISA for scrub typhus patients (n=103), once prior to doxycycline therapy and then on day 7 of doxycycline therapy; concentrations were measured once for healthy controls (n=32). RESULTS Among the total 103 patients enrolled, 38 had disease complicated by multiple organ dysfunction syndrome (MODS). Serum concentrations of vWF and HMGB1 were significantly higher in all the patients than in the healthy controls, both prior to doxycycline treatment and on day 7 of doxycycline treatment (p<0.01). Furthermore, serum levels of vWF, HMGB1, and creatinine (SCr) in the patients with MODS increased distinctly, while the platelet (PLT) count diminished markedly compared to the levels in patients without MODS (p<0.01). The concentration of vWF was positively correlated with that of HMGB1 (r=0.764, p<0.001) and SCr (r=0.528, p<0.001), but negatively correlated with the PLT count (r=-0.632, p<0.001). Both HMGB1 and vWF were significantly associated with mortality in scrub typhus (area under the curve (AUC)=0.864, p=0.001, and AUC=0.862, p=0.001, respectively). CONCLUSIONS Elevated levels of vWF and HMGB1 are associated with the severity and clinical outcome of scrub typhus. These represent possible new biomarkers for use in the assessment and prognostic prediction of this infection.
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Affiliation(s)
- Hongliu Chen
- Department of Emergency, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, 530021, China
| | - Zong Ning
- Department of Emergency, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, 530021, China
| | - Ying Qiu
- Department of Emergency, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, 530021, China
| | - Yuanli Liao
- Department of Emergency, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, 530021, China
| | - Haihua Chang
- Department of Emergency, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, 530021, China
| | - Yuanyuan Ai
- Department of Emergency, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, 530021, China
| | - Yinghua Wei
- Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, 530021, China
| | - Yiming Deng
- Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, 530021, China
| | - Ying Shen
- General Practice School of Guangxi Medical University, Nanning, Guangxi Province, 530021, China.
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Zhou S, Ma H, Gao B, Fang G, Zeng Y, Zhang Q, Qi G. Characterization of a novel disease-causing mutation in exon 1 of SH2D1A gene through amplicon sequencing: a case report on HLH. BMC MEDICAL GENETICS 2017; 18:15. [PMID: 28196537 PMCID: PMC5310059 DOI: 10.1186/s12881-017-0376-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Accepted: 02/03/2017] [Indexed: 02/03/2023]
Abstract
BACKGROUND Hemophagocytic lymphohistocytosis (HLH) is a rare but fatal hyperinflammatory syndrome caused by uncontrolled proliferation of activated macrophages and T lymphocytes secreting high amounts of inflammatory cytokines. Genetic defect is a common cause of HLH. HLH is complicated to be diagnosed as there are many common symptoms with other disorders. CASE PRESENTATION Here we report on an HLH case caused by 1 bp deletion in gene SH2D1A. Patient was a 3-years-old boy and had fever for more than 8 days. Splenomegaly and hemophagocytosis in bone marrow were observed in examination. The results of the blood analysis suggested the diagnosis of HLH. Genetic test based on high throughput amplicon sequencing was then conducted by targeting all six known HLH-causing genes simultaneously. It took only one single day to accomplish the amplicon sequencing library preparation, sequencing and data analysis. Finally, a novel 1 bp deletion in gene SH2D1A was discovered. The result was also confirmed by Sanger sequencing. The result of the genetic test served as a good basis for further diagnosis of HLH. CONCLUSION This is the first case that the disease-causing genetic defect of HLH was quickly determined by high throughput amplicon sequencing. This diagnosis was also confirmed by Sanger sequencing and cross-validated by blood analysis and other clinical criteria. This case suggests that genetic test based on amplicon sequencing is a powerful tool for diagnosis of HLH and other diseases caused by genetic defect.
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Affiliation(s)
- Shiyuan Zhou
- Henan Research Institute for Population and Family Planning, Zhengzhou, China.,Key Laboratory of Birthdefects Prevention, National Health and Family Planning Commission, #26 Jingwu Road, Zhengzhou, Henan, China
| | - Hongyu Ma
- Thermo Fisher Scientific, Building 6, N0.27, Xin Jinqiao Rd, Pudong, Shanghai, China
| | - Bo Gao
- Department of Laboratory Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Guangming Fang
- Department of Clinical Medicine, Zhengzhou University, No.100 Science Avenue, Zhengzhou, China
| | - Yi Zeng
- Department of Clinical Medicine, Zhengzhou University, No.100 Science Avenue, Zhengzhou, China
| | - Qing Zhang
- Thermo Fisher Scientific, Building 6, N0.27, Xin Jinqiao Rd, Pudong, Shanghai, China.
| | - GaoFu Qi
- Institute of System Biology, Jianghan University, Sanjiaohu Rd, Wuhan, Hubei, China.
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Hong JW, You HS, Lee TW, Jo WY, Kim BR, Suh YS, Bae IG, Cho OH. Epstein-Barr Virus Associated Hemophagocytic Syndrome after Scrub Typhus Infection. Infect Chemother 2016; 48:330-333. [PMID: 27883370 PMCID: PMC5204013 DOI: 10.3947/ic.2016.48.4.330] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2016] [Accepted: 05/05/2016] [Indexed: 11/24/2022] Open
Abstract
There have been a small number of cases of scrub typhus-associated hemophagocytic syndrome (HPS), most of which were treated successfully using adequate antibiotics. Here, we report a case of Epstein-Barr virus (EBV)-associated HPS after scrub typhus infection that was not improved using antirickettsial treatment. A 73-year-old male who had been diagnosed with scrub typhus according to an eschar and a positive serology was transferred to our institution because of a persistent fever despite 7-day doxycycline therapy. Physical and laboratory data showed hepatosplenomegaly, bicytopenia, hyperferritinemia, and hypofibrinogenemia. A bone marrow examination (BM) revealed hypercellular marrow with hemophagocytosis and histiocyte infiltration. EBV was detected in BM aspirates using polymerase chain reaction. After a diagnosis of HPS was made, the patient was treated successfully using high-dose steroids.
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Affiliation(s)
- Jeong Woo Hong
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Hyun Seon You
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Tae Won Lee
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Won Yong Jo
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Bo Ra Kim
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Young Sun Suh
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
| | - In Gyu Bae
- Division of Infectious Diseases, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Oh Hyun Cho
- Division of Infectious Diseases, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea.
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16
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Zhou YH, Xia FQ, Van Poucke S, Zheng MH. Successful Treatment of Scrub Typhus-Associated Hemophagocytic Lymphohistiocytosis With Chloramphenicol: Report of 3 Pediatric Cases and Literature Review. Medicine (Baltimore) 2016; 95:e2928. [PMID: 26937940 PMCID: PMC4779037 DOI: 10.1097/md.0000000000002928] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Revised: 01/28/2016] [Accepted: 01/29/2016] [Indexed: 11/26/2022] Open
Abstract
Scrub typhus is caused by Orientia tsutsugamushi. Any delay in diagnosis can result in delayed treatment and severe complications, including secondary hemophagocytic lymphohistiocytosis, which is rare but potentially fatal.In this paper, the authors present 3 cases of secondary hemophagocytic lymphohistiocytosis associated with scrub typhus, successfully treated with chloramphenicol without additional antineoplastic therapy. All patients cured and achieved complete resolution.This report highlights the effectiveness of chloramphenicol without the need for chemotherapy in the treatment of scrub typhus-associated hemophagocytic lymphohistiocytosis in a pediatric population under the age of 8 years.
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Affiliation(s)
- Yong-Hai Zhou
- From the Department of Pediatrics (Y-HZ, F-QX), The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Anesthesiology (SVP), Intensive Care, Emergency Medicine and Pain Therapy, Ziekenhuis Oost-Limburg, Genk, Belgium; Department of Infection and Liver Diseases (M-HZ), Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University; and Institute of Hepatology (M-HZ), Wenzhou Medical University, Wenzhou, China
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17
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Abstract
Scrub typhus is associated with various clinical symptoms. However, the pathogenesis of scrub typhus infection remains to be elucidated. A 73-year-old man was admitted to our hospital with consciousness disturbance and suspected meningoencephalitis. The patient's laboratory data showed deterioration and were indicative of hemophagocytic lymphohistiocytosis (HLH). A whole body examination to detect the trigger disease revealed an eschar, which is a characteristic of scrub typhus, on his back. His symptoms showed dramatic improvement after the administration of minocycline (MINO). This case report highlights that the clinical course of a case of scrub typhus meningoencephalitis that was cured with MINO.
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Affiliation(s)
- Tameto Naoi
- Division of Neurology, Department of Internal Medicine, Shin-Oyama City Hospital, Japan
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Peter JV, Sudarsan TI, Prakash JAJ, Varghese GM. Severe scrub typhus infection: Clinical features, diagnostic challenges and management. World J Crit Care Med 2015; 4:244-250. [PMID: 26261776 PMCID: PMC4524821 DOI: 10.5492/wjccm.v4.i3.244] [Citation(s) in RCA: 85] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2014] [Revised: 01/27/2015] [Accepted: 04/09/2015] [Indexed: 02/06/2023] Open
Abstract
Scrub typhus infection is an important cause of acute undifferentiated fever in South East Asia. The clinical picture is characterized by sudden onset fever with chills and non-specific symptoms that include headache, myalgia, sweating and vomiting. The presence of an eschar, in about half the patients with proven scrub typhus infection and usually seen in the axilla, groin or inguinal region, is characteristic of scrub typhus. Common laboratory findings are elevated liver transaminases, thrombocytopenia and leukocytosis. About a third of patients admitted to hospital with scrub typhus infection have evidence of organ dysfunction that may include respiratory failure, circulatory shock, mild renal or hepatic dysfunction, central nervous system involvement or hematological abnormalities. Since the symptoms and signs are non-specific and resemble other tropical infections like malaria, enteric fever, dengue or leptospirosis, appropriate laboratory tests are necessary to confirm diagnosis. Serological assays are the mainstay of diagnosis as they are easy to perform; the reference test is the indirect immunofluorescence assay (IFA) for the detection of IgM antibodies. However in clinical practice, the enzyme-linked immuno-sorbent assay is done due to the ease of performing this test and a good sensitivity and sensitivity when compared with the IFA. Paired samples, obtained at least two weeks apart, demonstrating a ≥ 4 fold rise in titre, is necessary for confirmation of serologic diagnosis. The mainstay of treatment is the tetracycline group of antibiotics or chloramphenicol although macrolides are used alternatively. In mild cases, recovery is complete. In severe cases with multi-organ failure, mortality may be as high as 24%.
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