Pandiarajan Vignesh1, Sathish Kumar Loganathan1, Murugan Sudhakar1, Himanshi Chaudhary1, Amit Rawat2, Megha Sharma3, Aravind Shekar4, Kim Vaiphei4, Narender Kumar5, Man-Updesh Singh Sachdeva5, Ankur Kumar Jindal1, Deepti Suri1, Anju Gupta1, Pallab Ray3, Kohsuke Imai6, Osamu Ohara7, Shigeaki Nonoyama6, Yu Lung Lau8, Surjit Singh1. 1. Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India. 2. Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Electronic address: rawatamit@yahoo.com. 3. Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. 4. Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. 5. Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. 6. Department of Pediatrics, National Defense Medical College, Tokorozawa, Saitama, Japan. 7. Department of Applied Genomics, Kazusa DNA Research Institute, Kisarazu, Chiba, Japan. 8. Department of Pediatrics and Adolescent Medicine, Queen Mary Hospital, LKS Faculty of Medicine, the University of Hong Kong, Hong Kong, Hong Kong Special Administrative Region, China.
Abstract
BACKGROUND: Chronic granulomatous disease (CGD) is an inherited defect in components of the nicotinamide adenine dinucleotide phosphate oxidase complex that results in potential life-threatening infective and noninfective complications. Hemophagocytic lymphohistiocytosis (HLH) is an unusual but important inflammatory complication of CGD. Optimal management strategies have not yet been identified in children with CGD who develop HLH. OBJECTIVE: To analyze clinical and laboratory features of HLH in CGD from a tertiary-care center in North India. METHODS: A retrospective review of medical records of children with CGD diagnosed in the last 20 years was performed. Clinical and laboratory features of children with CGD who developed HLH were analyzed. RESULTS: Of 80 patients diagnosed with CGD, 5 (6.25%) had evidence of HLH. All 5 were males; 4 had X-linked CGD and 1 had autosomal recessive CGD (NCF2 defect). Two children with CGD had HLH as the predominant presenting manifestation mimicking the clinical presentation of congenital HLH. Infectious triggers identified were bloodstream infections (n = 3) (Candida albicans, Burkholderia cenocepacia, Francisella noatuensis), pneumonia (n = 4), and splenic abscess (n = 1). We document the first human infection with a fish pathogen, F. noatuensis, in a child with X-linked CGD. Although mortality was seen in 3 children who received only intravenous (IV) immunoglobulin therapy, the other 2 who received IV methylprednisolone pulse therapy survived. CONCLUSION: HLH can be a presenting manifestation of CGD, and workup for CGD must be considered in children with HLH. Early recognition with optimal management of both infectious trigger and HLH is very important to prevent mortality.
BACKGROUND:Chronic granulomatous disease (CGD) is an inherited defect in components of the nicotinamide adenine dinucleotide phosphate oxidase complex that results in potential life-threatening infective and noninfective complications. Hemophagocytic lymphohistiocytosis (HLH) is an unusual but important inflammatory complication of CGD. Optimal management strategies have not yet been identified in children with CGD who develop HLH. OBJECTIVE: To analyze clinical and laboratory features of HLH in CGD from a tertiary-care center in North India. METHODS: A retrospective review of medical records of children with CGD diagnosed in the last 20 years was performed. Clinical and laboratory features of children with CGD who developed HLH were analyzed. RESULTS: Of 80 patients diagnosed with CGD, 5 (6.25%) had evidence of HLH. All 5 were males; 4 had X-linked CGD and 1 had autosomal recessive CGD (NCF2 defect). Two children with CGD had HLH as the predominant presenting manifestation mimicking the clinical presentation of congenital HLH. Infectious triggers identified were bloodstream infections (n = 3) (Candida albicans, Burkholderia cenocepacia, Francisella noatuensis), pneumonia (n = 4), and splenic abscess (n = 1). We document the first humaninfection with a fish pathogen, F. noatuensis, in a child with X-linked CGD. Although mortality was seen in 3 children who received only intravenous (IV) immunoglobulin therapy, the other 2 who received IV methylprednisolone pulse therapy survived. CONCLUSION: HLH can be a presenting manifestation of CGD, and workup for CGD must be considered in children with HLH. Early recognition with optimal management of both infectious trigger and HLH is very important to prevent mortality.
Authors: Milica Miladinovic; Boris Wittekindt; Sebastian Fischer; Elise Gradhand; Steffen Kunzmann; Stefanie Y Zimmermann; Shahrzad Bakhtiar; Thomas Klingebiel; Rolf Schlösser; Thomas Lehrnbecher Journal: Front Immunol Date: 2021-03-29 Impact factor: 7.561
Authors: Koon-Wing Chan; Chung-Yin Wong; Daniel Leung; Xingtian Yang; Susanna F S Fok; Priscilla H S Mak; Lei Yao; Wen Ma; Huawei Mao; Xiaodong Zhao; Weiling Liang; Surjit Singh; Mohamed-Ridha Barbouche; Jian-Xin He; Li-Ping Jiang; Woei-Kang Liew; Minh Huong Thi Le; Dina Muktiarti; Fatima Johanna Santos-Ocampo; Reda Djidjik; Brahim Belaid; Intan Hakimah Ismail; Amir Hamzah Abdul Latiff; Way Seah Lee; Tong-Xin Chen; Jinrong Liu; Runming Jin; Xiaochuan Wang; Yin Hsiu Chien; Hsin-Hui Yu; Dinesh Raj; Revathi Raj; Jenifer Vaughan; Michael Urban; Sylvia van den Berg; Brian Eley; Anselm Chi-Wai Lee; Mas Suhaila Isa; Elizabeth Y Ang; Bee Wah Lee; Allen Eng Juh Yeoh; Lynette P Shek; Nguyen Ngoc Quynh Le; Van Anh Thi Nguyen; Anh Phan Nguyen Lien; Regina D Capulong; Joanne Michelle Mallillin; Jose Carlo Miguel M Villanueva; Karol Anne B Camonayan; Michelle De Vera; Roxanne J Casis-Hao; Rommel Crisenio M Lobo; Ruby Foronda; Vicky Wee Eng Binas; Soraya Boushaki; Nadia Kechout; Gun Phongsamart; Siriporn Wongwaree; Chamnanrua Jiratchaya; Mongkol Lao-Araya; Muthita Trakultivakorn; Narissara Suratannon; Orathai Jirapongsananuruk; Teerapol Chantveerawong; Wasu Kamchaisatian; Lee Lee Chan; Mia Tuang Koh; Ke Juin Wong; Siew Moy Fong; Meow-Keong Thong; Zarina Abdul Latiff; Lokman Mohd Noh; Rajiva de Silva; Zineb Jouhadi; Khulood Al-Saad; Pandiarajan Vignesh; Ankur Kumar Jindal; Amit Rawat; Anju Gupta; Deepti Suri; Jing Yang; Elaine Yuen-Ling Au; Janette Siu-Yin Kwok; Siu-Yuen Chan; Wayland Yuk-Fun Hui; Gilbert T Chua; Jaime Rosa Duque; Kai-Ning Cheong; Patrick Chun Yin Chong; Marco Hok Kung Ho; Tsz-Leung Lee; Wilfred Hing-Sang Wong; Wanling Yang; Pamela P Lee; Wenwei Tu; Xi-Qiang Yang; Yu Lung Lau Journal: Front Immunol Date: 2022-07-08 Impact factor: 8.786