What is hemophagocytic lymphohistiocytosis?

Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder primarily affecting young children at a very early age, but it is found in patients of all ages. Although physicians have written about the disorder over the years, it has only been recently that it has received much attention.

In 1985, physicians from all over the world, interested in studying the histiocyte and disorders related to this cell, formed the Histiocyte Society. Thanks to their work and the financial support of the Histiocytosis Association of America, we understand the disease better and have improved treatments. However, this disease remains difficult to fully understand and difficult to treat.

The human body contains many types of cells which help fight infection. One type of cell is called the histiocyte. Histiocytes are produced by the bone marrow, and they may travel throughout the body. At a later stage, these cells remain in place within various tissues in the body. Their job is to help destroy certain foreign materials and to fight infections. This is done in cooperation with other important cells.

Patients with active HLH have too many of these histiocytes, as well as lymphocytes (another kind of infection-fighting cell), both of which are so-called white blood cells that may cause inflammation (swelling, redness, heat, pain, and loss of function). These cells then begin to penetrate and accumulate in good tissue and can cause damage to a variety of organs. Some possible sites of involvement include:

• bone marrow
• lymph nodes
• liver
• spleen
• skin
• membranes surrounding the brain, spinal cord or, more rarely, the brain itself

What causes this disease?

Scientists do not yet know all the complicated processes involved in this disease.

There are two major forms of HLH. One, known as the primary form, is inherited. The other is known as the secondary form. In the secondary form, the disease develops secondary to inappropriate (abnormal) activity of the immune system. This can occur after the use of immunosuppressive therapy and/or infections.

What does familial mean?

Familial hemophagocytic lymphohistiocytosis (also known as FHL, FEL or FHLH) means that the particular form of the disease is genetic. Families who have had more than one child with HLH will have the diagnosis changed to FHL. Because this form is genetic, there is a 25% chance that each young sibling will have FHL. The onset of FHL usually occurs within the first two years of life.

How will I know if it is familial?

It is extremely difficult, if not impossible, to distinguish by testing between a primary (familial) and secondary form of HLH in each patient. However, onset at an early age is suggestive of a familial form, whereas onset later than 6 years of age is rare in the familial form. Discussion with your child's physician concerning family medical history and past infections of your child sometimes, but rarely, may offer clues. If there is a brother or sister who also has or acquires the same disease, it is usually familial. It is important to know that even if the disease has been triggered by a virus, it may still be familial.

The uncertainty of not knowing whether your child has a familial form of this disease adds to the frustration of parents and physicians. Scientists are focusing on ways that a genetic test can be developed, but no such test now exists.

What can we expect to happen?

HLH is a life-threatening disease.

Exactly how the disease will progress is a difficult question for anyone to answer. You can expect your child to receive extensive testing and aggressive treatment with various types of chemotherapy and/or other drugs.

The first aim of treatment is to try to get the disease controlled, that is, into remission. Control of the disease, if achieved, is temporary in the primary inherited form (FHL); the disease always returns sooner or later if treatment is discontinued. Bone marrow transplantation offers the best possibility of a cure for these patients, but many children are not well enough for this procedure. Also, for some, a suitable bone marrow donor cannot be found. In secondary HLH, the underlying cause of the disease is identified and, if possible, treated. In some cases, remission may be temporary, and similar treatment for FHL may be required.

Your child's physician is best able to tell you what you can expect, although no one can say for certain all that will happen. You should, of course, discuss you child's symptoms, treatment, progress, treatment options, and outlook with the treating physician.

Is it cancer?

No. Over the years cancer treatments have been used in patients with HLH/FHL. Consequently, hematologists and oncologists who treat cancer also treat children with HLH/FHL. However, the disease is not a cancer.

Rarely, HLH may develop in association with ongoing treatment for cancer, or in the association with the onset of cancer, particularly in older patients.

Although the histiocyte is part of the immune system, the disease is not related to AIDS.

What resources are available to us?

There are several resources available to you. Your child's physician can answer questions best concerning treatment of your child and the effects of the disease. Other resources that can be helpful to you include:

• Nurses may inform you about treatments that are administered, and psychologists or social workers at the hospital can assist with family counseling.
• You may wish to consider genetic counseling services, and your physician or other hospital personnel can help you make this contact.
• If a bone marrow transplant is a possibility, your physician or other members of the medical staff can help you in the search for a suitable bone marrow donor, when needed.
• The Histiocytosis Association of American maintains a networking directory specifically for HLH and FHL families who wish to share information and mutual support.