Now that I’ve attempted to lay out some basic information for understanding HLH, I’d like to take a look at the real issue: the difference between FHL and HLH.
When I began reading up on this disease it took quite some time to understand where FHL, or Familial HLH, fit in to the picture. When literature or doctors talk about the disease, they tend to refer to it simply as HLH. Over time I’ve come to realize there are a variety of reasons for this, not least of which is the difficulty in diagnosing which of the forms of HLH a patient has. So, let’s take a look at the two forms side by side.
HLH, or Hemophagocytic Lymphohistiocytosis, is the name for the immune disorder. It can come in one of two forms: Familial HLH, also called FHL, and Acquired HLH, usually referred to simply as HLH.
- Is the primary, or most common, form of HLH
- Is also known as Familial HLH
- Is caused by a genetic defect passed to the child by parents who are carriers; children of parents who each are carriers (as they must be for the child to have the disease) have a 1 in 4, or 25%, chance of getting FHL.
- Is rare for two reasons primarily: because it requires two parents who both carry the recessive genetic defect to mate and pass on the gene (only a 25% chance); and because it goes undiagnosed often enough with 100% fatality, so as to seem more rare than it likely is.
- Is generally found in very young children; this is because it manifests itself when the child has an immune response (such as to a cold) and once it manifests is fatal if untreated. Kids who have FHL get sick as kids always do at some point, and they don’t survive unless treated. So, it’s not usually found in older kids — it’s either treated successfully or it is fatal.
- Is fatal if uncured. This means that the disease can be put in remission temporarily through the HLH-2004 protocol, but will return worse and likely with fatal results if uncured.
- Can only be cured with a Bone Marrow Transplant, or a Stem Cell Transplant.
- Requires genetic testing to positively confirm
- Is the secondary, or less common, form of HLH
- Is also known as Acquired HLH
- Is caused by an immune disorder resulting from another condition putting the immune system under severe strain
- Patients who have HLH are usually slightly older children (>1yr), though it has been seen in infants as well
- Is able to be treated successfully with HLH-2004, and often resolves itself permanently once it and the underlying condition are treated
- Cannot be positively confirmed through genetic testing
The Diagnosis Problem
HLH, in either form, is rapidly fatal. Within two months of the disease manifestation, an untreated (undiagnosed) child will die 100% of the time.
Therefore, diagnosis of the particular form of the disease is not the most pressing issue, but instead the focus is on treating the patient as soon as possible to control the immune response before it destroys the body.
Once the disease is under control, a determination has to be made as to whether a Bone Marrow Transplant (BMT) or Stem Cell Transplant (SCT) will be needed. This is where it really gets tricky, and why distinguishing between the two forms is so vital. FHL requires a BMT/SCT to be cured, whereas Acquired HLH does not.
Both BMT and SCT are highly dangerous procedures, not due to the transplant itself but to the difficulty the patient has with accepting the new cells and surviving the side effects. Survival rates for children appear to be in the neighborhood of 70%, with some variation depending on the type of transplant cells used. The numbers never look “good” though, for these procedures — the risk is always too high.
Therefore deciding to get a BMT or SCT is a tough decision, and unfortunately diagnosis of FHL is not always able to be positively confirmed. What has to happen is the tests must be done, and the overall picture must be looked at.
Factors that are considered:
- Results of genetic testing: Sometimes will positively confirm the disease, however because we do not yet know all of the genes to test it does not always confirm it
- Results of Soluble IL-2 test: Over 10,000 tends to be a marker for FHL
- Results of NK cell count test: Low or absent counts are a marker for HLH in general, but not specifically FHL or HLH
- Age of the patient: due to the manner in which Acquired HLH manifests, very young patients without an underlying condition tend to be assumed to have FHL
It is unfortunately not possible to positively confirm Acquired HLH, only FHL. Therefore, to make a decision the doctor and parents will need to look at all of the information and test results before deciding on the need for the transplant.
Here is a chart sometimes used to understand the process for diagnosing FHL. Please note: HCT is the acronym for the medical term for Bone Marrow or Stem Cell Transplant