What is familial HLH?

Familial hemophagocytic lymphohistiocytosis is a disorder in which the immune system produces too many activated immune cells (lymphocytes) called T cells, natural killer cells, B cells, and macrophages (histiocytes). Excessive amounts of immune system proteins called cytokines are also produced.

What is HLH diagnosis?

HLH can be diagnosed only with the proper tests. Blood tests include blood cell counts, liver function, infection studies, and markers of immune system activation such as ferritin and soluble IL-2 receptor levels. A bone marrow aspirate and biopsy may be performed to look for microscopic evidence of hemophagocytosis.

What is HLH prognosis?

Familial HLH is fatal without treatment, with median survival of about two to six months. Chemotherapy and/or immunotherapy temporarily control the disease, but symptoms inevitably return. Stem cell transplant is the only way to cure familial HLH.

When do you suspect HLH?

HLH should be suspected in cases of an unexplained sudden onset of a systemic inflammatory response syndrome (SIRS), including fever, malaise, hepatosplenomegaly, jaundice, generalized lymphadenopathy, and cytopenias.

Which is rare, acquired or familial HLH?

Hemophagocytic lymphohistiocytosis (HLH) is a rare immune system disease. It occurs more often in babies and young children. But it can also occur in adults. Children may inherit the disease through genes. This is called familial HLH. But in adults, many conditions can cause HLH. This is called acquired HLH.

Is there a blood test for familial HLH?

Mutations in XIAP / BIRC4 cause an X-linked form of familial HLH that is often referred to as XLP2. Defects in LYST cause Chediak-Higashi syndrome, another related disorder characterized by HLH, pigmentary, and neutrophil defects. Specialized blood tests can rapidly screen patients for many of the genetic forms of HLH.

What kind of mutations are associated with HLH?

Some genetic forms of HLH are grouped as familial hemophagocytic lymphohistiocytosis, and include mutations affecting PRF1, MUNC13-4, STXBP2, and STX11 . Mutations in RAB27a cause Griscelli syndrome, a related disorder that may or may not be associated with pigmentary defects.

How are diagnostic criteria used to diagnose HLH?

● The diagnosis of HLH is made by identifying a mutation in an HLH gene, or by fulfilling five of eight diagnostic criteria. Many patients fit only three or four of the eight criteria, yet have clinical evidence of HLH and require HLH-specific treatment. Modified diagnostic criteria may also be used.