Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder of the immune system that primarily affects young infants and children. Although physicians have written about the disorder over the years, it has been only in the last few years that it has received more widespread attention.
HLH occurs either on the basis of a genetic defect or as a secondary form with underlying diseases such as infections, cancer, or rheumatic diseases. In the primary form, also known as familial hemophagocytic lymphohistiocytosis (FHL or FHLH), defective genes are inherited from both the mother and the father (autosomal recessive inheritance). FHL is diagnosed if there is more than one affected child in the family and/or a gene defect has been determined. FHL should be suspected if the symptoms do not disappear with treatment or if symptoms recur when therapy has been stopped. The onset of FHL is usually early in life, and a persistent cure can only be achieved with BMT (bone marrow transplantation). It is important to know that infections can trigger both the familial and the secondary disease.
Without treatment, FHL is usually rapidly fatal with a median survival of about 2 months. The current treatment protocol, HLH 2004, provides recommendations for HLH therapy with a combination of immunosuppressive drugs and chemotherapy. The protocol has been accepted internationally and is used in many countries worldwide. In order to prevent early death or severe persisting organ damage, therapy must be initiated in a timely manner. In FHL cases, only temporary remission will be achieved. For a definite cure, the patient must undergo BMT.
With the former HLH-94 protocol and the now active HLH-2004 protocol, high remission rates and cure rates with BMT have been reported.
Secondary HLH sometimes resolves spontaneously or after treatment of the underlying disease. In some cases, modified immunochemotherapy can be applied, while in others, full immunochemotherapy is required.
The disease usually presents with fever and sometimes other symptoms of an infection. In many cases, a pathogen (viral, bacterial, etc.) can be identified. The human body contains many cells including T-cells and histiocytes that fight infection. The activation of these cells causes an inflammatory reaction in the body. Normally, when the pathogen has been eliminated, the inflammatory reaction is turned off, and the immune system returns to its steady state. In HLH patients, due to defect of the immune system, the inflammatory reaction persists and causes the symptoms of HLH.
Typical symptoms besides persistent fever are pallor (paleness), jaundice, liver and spleen enlargement, and neurological symptoms, such as irritability or even seizures. The involvement of the bone marrow, the site of blood cell production, can lead to severe decline of the blood cell counts (red and white blood cells and platelets). On bone marrow examination, histiocytes that are "eating" other blood cells (also known a phagocytosis) can be detected. Although the disease was named after this phenomenon, it can be absent at the onset or even throughout the course of the disease.
Because symptoms can vary widely, it is sometimes difficult for the physician to make a diagnosis of HLH early in the course of the disease without the help of specialized laboratory tests. To facilitate a rapid and accurate diagnosis, the Histiocyte Society has created diagnostic guidelines and recommendations concerning the treatment of HLH.