Hemophagocytic Lymphohistiocytosis and Infection: A Literature Review

Koumadoraki, Evgenia; Madouros, Nikolaos; Sharif, Shayka; Saleem, Amber; Jarvis, Sommer; Khan, Safeera

doi:10.7759/cureus.22411

Cited by 18 publications

(26 citation statements)

References 34 publications

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“…So, in addition to considering lung and abdominal infection, the possibility of SPTCL combined with hemophagocytic syndrome (HPS, also known as hemophagocytic lymphocytosis, HLH) should also be considered as the potential cause of fever. SPTCL is often complicated by HPS (around 20% of cases) (4,19), which is mainly characterized by the following clinical manifestations: hepatosplenomegaly, persistent high fever, and abnormal coagulation function (20)(21)(22). A lymphokine, possibly produced by malignant cells, activates monocytemacrophages, causing macrophages in the bone marrow, liver, spleen and lymph nodes to engulf blood cells (20,23).…”

Section: Discussionmentioning

confidence: 99%

A case report and literature review: subcutaneous panniculitis-like T-cell lymphoma with liver failure as the main manifestation

He¹,

Wang²,

Feng³

et al. 2022

Ann Transl Med

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Background: Subcutaneous lipofuscinosis-like T-cell lymphoma (SPTCL) is a rare cutaneous lymphoma that often presents as recurrent subcutaneous nodules and may progress to hemophagocytic syndrome with fever and hepatic impairment in some patients. However, no cases of progression to hepatic failure have been reported. Here, we present a case of an adult diagnosed with fever and liver failure as the main manifestation, which was eventually confirmed as SPTCL by skin biopsy, but the patient eventually died due to disease progression.Case Description: This study retrospectively reports a rare case of SPTCL in a 34-year-old female patient who was admitted with scleral jaundice for 1 month and fever for 20 days. Examination revealed multiple small subcutaneous nodules on the skin of the chest and tibial surface and an enlarged liver and spleen. Laboratory tests revealed hepatic impairment, and common causes of liver failure (viral infection, fatty liver, immune liver damage, etc.) were excluded. We continued to refine the positron emission tomography-computed tomography (PET-CT) examination, which revealed multiple flocculent and nodular hyperdense shadows with increased metabolism in the subcutaneous fat interstices. And then, we performed a skin biopsy and the final pathological diagnosis was SPTCL, but the patient died 1 month after diagnosis due to poor treatment outcome because the disease progressed too rapidly. With this case report, we hope to improve clinicians' understanding of liver injury caused by SPTCL. A review of the literature revealed that this is the first case report in the literature of SPTCL leading to severe liver failure.Conclusions: For patients presenting with fever and liver injury, primary liver disease cannot simply be assumed, as this presentation may be a manifestation of some extra-hepatic diseases, including SPTCL. For this condition, early detection and early diagnosis may improve the prognosis of patients.

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Section: Discussionmentioning

confidence: 99%

A case report and literature review: subcutaneous panniculitis-like T-cell lymphoma with liver failure as the main manifestation

He¹,

Wang²,

Feng³

et al. 2022

Ann Transl Med

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“…Author details 1 Children's Medical Center, Pediatrics Center of Excellence, Tehran, Iran. 2 Pediatric Rheumatology Society of Iran, Tehran, Iran. 3 Department of Pediatrics, Isfahan University of Medical Sciences, Isfahan, Iran.…”

Section: Abbreviationsmentioning

confidence: 99%

“…HLH can be sporadic or happen in the context of a genetic disorder. In both circumstances, infection is the most common trigger [ 2 ]. Some genes are found to be associated with familial HLH [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

TNFAIP3 mutation causing haploinsufficiency of A20 with a hemophagocytic lymphohistiocytosis phenotype: a report of two cases

et al. 2022

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Background A20 haploinsufficiency (HA20) is a newly introduced autosomal dominant autoinflammatory disorder, also known as Behcet’s-like disease. Some of the most common symptoms of the disease are recurrent oral, genital, and/or gastrointestinal (GI) ulcers, episodic fever, musculoskeletal symptoms, cutaneous lesions, and recurrent infections. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of multi-organ failure due to excessive immune activation. HLH has been reported in a few HA20 patients. Herein, we report two children with the primary presentation of HLH, with a mutation in TNFAIP3, in favor of HA20. Case presentations Our first patient was a 4-month-old boy who presented with fever, irritability, pallor, and hepatosplenomegaly. Pancytopenia, elevated ferritin, and decreased fibrinogen levels were found in laboratory evaluation. He was diagnosed with HLH and was treated with methylprednisolone and cyclosporine. Two years later, whole exome sequencing (WES) indicated a mutation in TNFAIP3 at NM_001270507: exon3: c.C386T, p.T129M, consistent with A20 haploinsufficiency. Etanercept, a TNF inhibitor, was prescribed, but the parents were reluctant to initiate the therapy. The patient passed away with the clinical picture of cerebral hemorrhage. The second patient was a 3-month-old boy who presented with a fever and hepatosplenomegaly. Laboratory evaluation found pancytopenia, hyperferritinemia, hypoalbuminemia, hypertriglyceridemia, and hypofibrinogenemia. With the establishment of the HLH diagnosis, he was treated with etoposide, dexamethasone, and cyclosporine, and recovered. WES results revealed a heterozygous de novo variant of TNFAIP3 (c. T824C in exon 6, 6q23.3) that leads to a proline to leucine amino acid change (p. L275P). He was treated with etanercept and has been symptom-free afterward. Conclusions This report is a hypothesis for developing of the HLH phenotype in the presence of TNFAIP3 mutation. Our results provide a new perspective on the role of TNFAIP3 mutation in HLH phenotypes, but more extensive studies are required to confirm these preliminary results.

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“…Besides, familial hemophagocytic lymphohistiocytosis may be associated with primary immunodeficiency syndromes as Chédiak-Higashi syndrome, Griscelli syndrome type 2, Hermansky-Pudlak syndrome type 2 or X-linked lymphoproliferative disorder subtype 1 and subtype 2 [1,2].Familial hemophagocytic lymphohistiocytosis predominantly incriminates young children whereas acquired hemophagocytic lymphohistiocytosis is commonly encountered within adolescents or adults. A specific racial or gender predilection is absent.Secondary or acquired hemophagocytic lymphohistiocytosis arises in response to immune triggers comprised of infection, malignant conditions, rheumatologic disorders or inflammatory disorders and is preponderantly denominated as Macrophage Activation Syndrome (MAS) [1,2]. Secondary or acquired hemophagocytic lymphohistiocytosis is frequently associated with immunodeficiency, normal or decimated quantifiable NK cells and normal manifestation of perforin.…”

mentioning

confidence: 99%

“…The condition may be induced by exposure to infectious agents, malignant neoplasms, graft versus host disease or exceptionally with HELLP syndrome constituted of haemolysis, elevated liver enzymes and decreased platelet count.Hemphagocytic lymphohistiocytosis commonly incriminates reticuloendothelial organs as the bone marrow, spleen, hepatic parenchyma and lymph nodes. Infrequently, sites such as cutaneous surfaces, subcutaneous tissue, pulmonary parenchyma, meninges or cerebrospinal fluid may be implicated [1,2].…”

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confidence: 99%

Inundate and Deluge-Hemophagocytic Lymphohistiocytosis

Bajaj¹

2023

JCIM

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Hemophagocytic lymphohistiocytosis is categorized into congenital, genetic or primary and acquired or secondary subtypes. Immune activation with consequent hyper-cytokinemia induces histiocytic infiltration within reticuloendothelial organs along with hemophagocytosis of erythrocytes, leukocytes, platelets and precursor cells. Untreated primary and secondary hemophagocytic lymphohistiocytosis is invariably associated with disease associated mortality. However, adoption of contemporary therapeutic protocols document 5 year survival rates of ~ 54%. Familial or primary hemophagocytic lymphohistiocytosis is a progressive, autosomal recessive condition characteristically occurring within young age. The disorder exemplifies decimated NK cell function and frequently detected mutations within perforin gene.

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Hemophagocytic Lymphohistiocytosis and Infection: A Literature Review

Cited by 18 publications

References 34 publications

A case report and literature review: subcutaneous panniculitis-like T-cell lymphoma with liver failure as the main manifestation

A case report and literature review: subcutaneous panniculitis-like T-cell lymphoma with liver failure as the main manifestation

TNFAIP3 mutation causing haploinsufficiency of A20 with a hemophagocytic lymphohistiocytosis phenotype: a report of two cases

Inundate and Deluge-Hemophagocytic Lymphohistiocytosis

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