Fatal hemophagocytic lymphohistiocytosis in X-linked chronic granulomatous disease associated with a perforin gene variant

2009 ◽  
Vol 52 (4) ◽  
pp. 527-529 ◽  
Author(s):  
Joris M. van Montfrans ◽  
Eva Rudd ◽  
Lisette van de Corput ◽  
Jan-Inge Henter ◽  
Peter Nikkels ◽  
...  
Keyword(s):  
Chronic Granulomatous Disease ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Granulomatous Disease ◽  
Gene Variant

scholarly journals Case Report: Secondary Hemophagocytic Lymphohistiocytosis With Disseminated Infection in Chronic Granulomatous Disease—A Serious Cause of Mortality

2020 ◽  
Vol 11 ◽  
Author(s):  
Jacqueline D. Squire ◽  
Stephanie N. Vazquez ◽  
Angela Chan ◽  
Michele E. Smith ◽  
Deepak Chellapandian ◽  
...  
Keyword(s):  
Immune Deficiency ◽  
Chronic Granulomatous Disease ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Fungal Infections ◽  
Primary Immune Deficiency ◽  
Granulomatous Disease ◽  
Simultaneous Treatment ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Life Threatening

Chronic granulomatous disease (CGD) is a primary immune deficiency due to defects in phagocyte respiratory burst leading to severe and life-threatening infections. Patients with CGD also suffer from disorders of inflammation and immune dysregulation including colitis and granulomatous lung disease, among others. Additionally, patients with CGD may be at increased risk of systemic inflammatory disorders such as hemophagocytic lymphohistiocytosis (HLH). The presentation of HLH often overlaps with symptoms of systemic inflammatory response syndrome (SIRS) or sepsis and therefore can be difficult to identify, especially in patients with a primary immune deficiency in which incidence of infection is increased. Thorough evaluation and empiric treatment for bacterial and fungal infections is necessary as HLH in CGD is almost always secondary to infection. Simultaneous treatment of infection with anti-microbials and inflammation with immunosuppression may be needed to blunt the hyperinflammatory response in secondary HLH. Herein, we present a series of X-linked CGD patients who developed HLH secondary to or with concurrent disseminated CGD-related infection. In two patients, CGD was a known diagnosis prior to development of HLH and in the other two CGD was diagnosed as part of the evaluation for HLH. Concurrent infection and HLH were fatal in three; one case was successfully treated, ultimately receiving hematopoietic stem cell transplantation. The current literature on presentation, diagnosis, and treatment of HLH in CGD is reviewed.

Chronic Granulomatous Disease Presenting as Hemophagocytic Lymphohistiocytosis: A Case Report

PEDIATRICS ◽  
2014 ◽  
Vol 134 (6) ◽  
pp. e1727-e1730 ◽  
Author(s):  
Gregory Valentine ◽  
Tessy A. Thomas ◽  
Trung Nguyen ◽  
Yi-Chen Lai
Keyword(s):  
Case Report ◽  
Chronic Granulomatous Disease ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Granulomatous Disease

Hemophagocytic lymphohistiocytosis in children with chronic granulomatous disease

2010 ◽  
Vol 56 (3) ◽  
pp. 460-462 ◽  
Author(s):  
Chintan Parekh ◽  
Thomas Hofstra ◽  
Joseph A. Church ◽  
Thomas D. Coates
Keyword(s):  
Chronic Granulomatous Disease ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Granulomatous Disease

scholarly journals Case Report: BCG-Triggered Hemophagocytic Lymphohistiocytosis in an Infant With X-Linked Recessive Mendelian Susceptibility to Mycobacterial Disease Due to a Variant of Chronic Granulomatous Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Suleiman Al-Hammadi ◽  
Amal M. Yahya ◽  
Abdulla Al-Amri ◽  
Amar Shibli ◽  
Ghazala B. Balhaj ◽  
...  
Keyword(s):  
Chronic Granulomatous Disease ◽  
United Arab Emirates ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Young Infant ◽  
Scale Up ◽  
Mendelian Inheritance ◽  
Granulomatous Disease ◽  
Mycobacterial Disease ◽  
Cervical Lymphadenitis ◽  
Live Attenuated Vaccine

In the United Arab Emirates, BCG (Bacillus Calmette-Guérin) is administered to all newborns. We present here a young infant with an inborn error of immunity (IEI) who developed fatal adverse events to this live-attenuated vaccine. This male infant received BCG (Serum Institute of India Pvt., Ltd., India) on Day 11 of life. On Day 25, he developed fever, followed by cervical lymphadenitis and bilateral otitis media with fluid drainage. On Day 118, he was admitted with severe hemophagocytic lymphohistiocytosis (HLH), and passed away on Day 145. The diagnostic exome sequencing test identified a hemizygous nonsense variant, NM_000397.3(CYBB):c.676C>T, p.Arg226* (rs137854592). Pathogenic variants of CYBB [cytochrome b(-245), beta subunit; Mendelian Inheritance in Man [MIM] accession code, 300481] are known to cause “immunodeficiency 34, mycobacteriosis, X-linked” (IMD34, MIM#300645) and “chronic granulomatous disease, X-linked” (CGDX, MIM#306400). The natural history of his illness is consistent with “X-linked recessive Mendelian susceptibility to mycobacterial disease (MSMD).” This entity is responsible for his BCG disease and is a likely trigger of his HLH. This disastrous event underlines the importance of developing worldwide policies that target BCG disease prevention, especially in communities with high prevalence of IEI. Moreover, screening for genetic causes of MSMD in the community could pave the way, at least partially, for scale-up of tuberculosis (TB) prevention.

scholarly journals Undiagnosed Chronic Granulomatous Disease,Burkholderia cepacia complexPneumonia, and Acquired Hemophagocytic Lymphohistiocytosis: A Deadly Association

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Maxime Maignan ◽  
Colin Verdant ◽  
Guillaume F. Bouvet ◽  
Michael Van Spall ◽  
Yves Berthiaume
Keyword(s):  
Nadph Oxidase ◽  
Chronic Granulomatous Disease ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Burkholderia Cepacia ◽  
Autosomal Recessive ◽  
Dna Analysis ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Multiple Organ ◽  
Burkholderia Cepacia Complex ◽  
Granulomatous Disease

Background. Chronic granulomatous disease is a rare inherited disorder of the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The clinical course of the disease is marked by recurrent infections, includingBurkholderia cepacia complexinfection.Case Report. Here we report the case of a 21-year-old male hospitalized for aBurkholderia cepacia complexpneumonia. Despite the broad spectrum antibiotic treatment, fever continued and patient’s condition worsened. Anemia and thrombocytopenia developed together with hypofibrinogenemia. The patient died of multiple organ dysfunction 17 days after his admission. Autopsy revealed hemophagocytosis, suggesting the diagnosis of acquired hemophagocytic lymphohistiocytosis. DNA analysis showed a deletion in the p47phox gene, confirming the diagnosis of autosomal recessive chronic granulomatous disease.Discussion. In addition to chronic granulomatous disease, recent findings have demonstrated thatBurkholderia cepacia complexcan decrease activity of the NADPH oxidase. Interestingly, hemophagocytic lymphohistiocytosis is characterized by an impaired function of the T-cell mediated inflammation which is partly regulated by the NADPH oxidase. Physicians should therefore pay particular attention to this deadly association.

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