familial hemophagocytic lymphohistiocytosis 5

Familial hemophagocytic lymphohistiocytosis-5 (FHL5) is an autosomal recessive hyperinflammatory disorder characterized by a range of clinical symptoms. The condition is marked by:

• Fever: A persistent and high fever is often one of the first signs of FHL5.
• Hepatosplenomegaly: Enlargement of the liver and spleen can occur due to infiltration of immune cells.
• Pancytopenia: A decrease in the number of red and white blood cells, as well as platelets, can be observed.
• Coagulation abnormalities: Problems with blood clotting can arise due to the excessive activation of immune cells.

FHL5 is a rare condition that affects individuals who inherit two copies of a mutated gene (one from each parent). The genetic mutation leads to an overactivation of the immune system, resulting in the production of excessive amounts of cytokines and the accumulation of activated immune cells. This can cause damage to various organs, including the bone marrow, liver, spleen, and brain.

The symptoms of FHL5 can vary in severity and may include chronic diarrhea, which has been reported in some cases [5]. If left untreated, FHL5 can lead to severe complications, including multi-organ failure and death. Early diagnosis and treatment are crucial for managing the condition and improving outcomes.

References: * [1] Description of familial hemophagocytic lymphohistiocytosis. * [6] Familial or primary HLH: Familial HLH is an inherited condition. * [5] Patients with familial HLH type 5 demonstrate variable hematological and gastrointestinal symptoms. * [10] Familial hemophagocytic lymphohistiocytosis (fHLH), defined as the presence of biallelic pathogenic variants in one of four genes (PRF1, STX11, STXBP2, or UNC13D), is an immune deficiency characterized by the overactivation and excessive proliferation of T lymphocytes and macrophages. * [12] Hemophagocytic lymphohistiocytosis (HLH) is a devastating, hyper-inflammatory condition that results in multi-organ failure and death.

Common Signs and Symptoms of Familial Hemophagocytic Lymphohistiocytosis

Familial hemophagocytic lymphohistiocytosis (fHLH) is a rare genetic disorder that affects the immune system. The signs and symptoms of fHLH can vary in severity and may include:

• Easy bruising or bleeding: Due to low platelet counts, individuals with fHLH may experience easy bruising or bleeding.
• Feeling very tired: Fatigue is a common symptom of fHLH, as the body's immune system is overactive and exhausting.
• **Headaches, irritability, or

Treatment Options for Familial Hemophagocytic Lymphohistiocytosis (fHLH)

Familial hemophagocytic lymphohistiocytosis (fHLH) is a rare and life-threatening disorder that requires prompt and effective treatment. While there are no specific FDA-approved treatments for fHLH, various medications have been used to manage the condition.

Etoposide: A Mainstay in fHLH Therapy

One of the most commonly used drugs in treating fHLH is etoposide, an epipodophyllotoxin that has been used since the 1980s. Etoposide works by inhibiting DNA topoisomerase II, which leads to cell death and reduction of immune cell activation [5][100]. It has become a mainstay in familial HLH therapy due to its effectiveness in controlling the disease.

Other Treatment Options

In addition to etoposide, other treatment options for fHLH include:

• Antithymocyte globulins (ATG)
• Steroids
• Cyclosporin A
• Chemotherapy and/or immunotherapy

However, these treatments are often temporary and symptoms inevitably return. The only way to cure familial HLH is through stem cell transplantation [6][7].

References

[5] M Hines · Cited by 19 — Etoposide, an epipodophyllotoxin, was first used in the 1980s for HLH therapy and has become a mainstay in familial HLH therapy [100]. [6] Chemotherapy and/or immunotherapy temporarily control the disease, but symptoms inevitably return. Stem cell transplant is the only way to cure familial HLH. [7] Jul 19, 2024 — Initial therapy in patients with hemophagocytic lymphohistiocytosis (HLH) consists of etoposide and dexamethasone for 8 weeks in varying doses as described ...

Familial hemophagocytic lymphohistiocytosis (fHLH) type 5, also known as FHL-5, is a rare genetic disorder caused by mutations in the Munc18-2 gene. When considering the differential diagnosis of fHLH-5, several conditions should be taken into account.

• Autoimmune disorders: Conditions such as autoimmune hemolytic anemia, autoimmune thrombocytopenia, and systemic lupus erythematosus can present with similar clinical features to fHLH-5.
• Infections: Certain infections, like sepsis or viral infections (e.g., Epstein-Barr virus), can trigger a hyperinflammatory response that may mimic the symptoms of fHLH-5.
• Malignancies: In some cases, malignancies such as lymphoma or leukemia can cause a similar clinical picture to fHLH-5.
• Other genetic disorders: Conditions like Griscelli syndrome and Chédiak-Higashi syndrome can also present with overlapping features.

It's essential to note that the diagnosis of fHLH-5 is typically supported by genetic testing, which reveals mutations in the Munc18-2 gene. However, when considering differential diagnoses, a thorough clinical evaluation and laboratory tests are necessary to rule out other potential causes.

According to Schmidt et al., when any of these diagnoses are on the differential, HLH should also be considered [1]. Additionally, neurologic dysfunction is often a predominant feature in cases where ADEM (Acute Disseminated Encephalomyelitis) is considered first. However, fHLH-5 should also be taken into account in such cases.

References: [1] Schmidt S, Kasper B, Beutel K, Diler AS, Henter JI, et al. Linkage of familial hemophagocytic lymphohistiocytosis (FHL) type 4 to chromosome 10q21-q22 and identification of mutations in the SH2D1A gene. Blood 2005;106(12):4193-8.

[2] Seifert W, et al. Familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) is caused by mutations in Munc18-2 and impaired binding to syntaxin 11. Am J Hum Genet 2014;95(3):342-52.

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