Hemophagocytic Lymphohistiocytosis in Activated PI3K Delta Syndrome: an Illustrative Case Report

Zhou, Zijun; Zondag, Timo; Hermans, Maud A.W.; Hagen, P. Martin van; Laar, Jan A M van

doi:10.1007/s10875-021-01080-w

Cited by 4 publications

(2 citation statements)

References 12 publications

(13 reference statements)

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“…This review included 108 studies ( Figure 1 ) for a total of 178 patients ( 4 , 5 , 11 – 116 ). Through database search and reference lists screening, 4570 records were identified.…”

Section: Resultsmentioning

confidence: 99%

HLH as an additional warning sign of inborn errors of immunity beyond familial-HLH in children: a systematic review

Ricci,

Sarli,

Lodi

et al. 2024

Front. Immunol.

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BackgroundHemophagocytic Lymphohistiocytosis (HLH) is a rare and life-threatening condition characterized by a severe impairment of the immune homeostasis. While Familial-HLH (FHL) is a known cause, the involvement of other Inborn Errors of Immunity (IEI) in pediatric-HLH remains understudied.ObjectiveThis systematic review aimed to assess the clinical features, triggers, laboratory data, treatment, and outcomes of pediatric HLH patients with IEI other than FHL (IEInotFHL), emphasizing the importance of accurate identification and management.MethodsA systematic search for studies meeting inclusion criteria was conducted in PubMed, EMBASE, MEDLINE, and Cochrane Central. Quality assessment was performed through JBI criteria.ResultsA comprehensive search yielded 108 records meeting inclusion criteria, involving 178 patients. We identified 46 different IEI according to IUIS 2022 Classification. Combined immunodeficiencies, immune dysregulation disorders, and phagocyte defects were the IEI most frequently associated with HLH. In 75% of cases, HLH preceded the IEI diagnosis, often with an unrecognized history of severe infections. Triggers reflected the specific infection susceptibilities within IEI groups. Liver and central nervous system involvement were less common than in FHL cases. Treatment approaches and outcomes varied, with limited long-term follow-up data, limiting the assessment of therapeutic efficacy across IEI groups.ConclusionA comprehensive evaluation encompassing immunological, infectious, and genetic aspects is essential in pediatric-HLH. Relying solely on FHL or EBV susceptibility disorders tests is insufficient, as diverse other IEI can contribute to HLH. Early recognition of HLH as a potential warning sign can guide timely diagnostic investigations and facilitate tailored therapeutic interventions for improved outcomes.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=371425, PROSPERO, CRD42022371425.

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“…This review included 108 studies ( Figure 1 ) for a total of 178 patients ( 4 , 5 , 11 – 116 ). Through database search and reference lists screening, 4570 records were identified.…”

Section: Resultsmentioning

confidence: 99%

HLH as an additional warning sign of inborn errors of immunity beyond familial-HLH in children: a systematic review

Ricci,

Sarli,

Lodi

et al. 2024

Front. Immunol.

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“…There is poor information regarding the relationship between HLH and the downregulation of the PI3K/AKT/mTOR signaling pathway. Mutation in the PIK3CD gene (NM_005026.3) is associated with activated PI3K delta syndrome, which is a primary immunodeficiency that could cause HLH ( 9 ). Secondary HLH is associated with infections, particularly Herpes viruses, malignancies, and autoimmune disorders.…”

Section: Introductionmentioning

confidence: 99%

Hemophagocytic lymphohistiocytosis in gastric cancer: A rare syndrome for the oncologist. Case report and brief review

Monti

Marconi²,

Ambrosini-Spaltro³

et al. 2023

Front. Oncol.

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Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition characterized by uncontrolled activation of the immune system. HLH is a reactive mononuclear phagocytic response that occurs in association with a constellation of conditions such as malignancies and infections. The clinical diagnosis of HLH remains challenging because HLH can present with symptoms that significantly overlap with other causes of cytopenia, such as sepsis, autoimmune diseases, hematological cancers, and multiorgan failure. A 50-year-old man went to the emergency room (ER) for hyperchromic urine, melena, gingivorrhagia, and spontaneous abdominal wall hematomas. The first blood tests showed severe thrombocytopenia, alteration of the INR, and consumption of fibrinogen, and therefore, a diagnosis of disseminated intravascular coagulation (DIC) was made. A bone marrow aspirate showed numerous images of hemophagocytosis. With the suspicion of immune-mediated cytopenia, oral etoposide, intravenous immunoglobulin, and intravenous methylprednisolone were administered. Then, a diagnosis of gastric carcinoma was performed with a lymph node biopsy and gastroscopy. On the 30th day, the patient was transferred to the oncology ward of another hospital. On admission, he had serious piastrinopenia, anemia, hypertriglyceridemia, and hyperferritinemia. He was supported with a platelet transfusion and underwent a bone biopsy that showed a picture compatible with myelophthisis from diffuse medullary localization of a carcinoma of gastric origin. A diagnosis of HLH secondary to solid neoplasm was formulated. The patient started chemotherapy with oxaliplatin, calcium levofolinate, 5-fluorouracil bolus, 5-fluorouracil for 48 h (mFOLFOX6), and methylprednisolone. Six days after the third cycle of mFOLFOX6, the patient was discharged with the stabilization of his piastrinopenia condition. The patient continued chemotherapy with an improvement in his clinical conditions and normalization of hematological values. After 12 cycles of mFOLFOX, it was decided to start maintenance chemotherapy with capecitabine but, unfortunately, after only one cycle, HLH reappeared. The oncologist has to keep in mind the existence of HLH when there is an unusual clinical presentation of cancer, such as cytopenia affecting ≥2 lineages and alterations of ferritin and triglycerides other than fibrinogen and coagulation. Increased attention and additional research as well as a close collaboration with hematologists are needed to benefit patients with solid tumors complicated by HLH.

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Inborn Errors of Immunity and Cytokine Storm Syndromes

Reid,

Romberg

2024

Advances in Experimental Medicine and Biology

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Hemophagocytic Lymphohistiocytosis in Activated PI3K Delta Syndrome: an Illustrative Case Report

Cited by 4 publications

References 12 publications

HLH as an additional warning sign of inborn errors of immunity beyond familial-HLH in children: a systematic review

HLH as an additional warning sign of inborn errors of immunity beyond familial-HLH in children: a systematic review

Hemophagocytic lymphohistiocytosis in gastric cancer: A rare syndrome for the oncologist. Case report and brief review

Inborn Errors of Immunity and Cytokine Storm Syndromes

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