HLH- lesson one

I am a decently smart person and this diagnosis is difficult to understand in its pathology. I will try to explain it the best that I can.

Let’s look at the name, it tells a lot:

Hemophagocytic- latin for “eating blood” Lymphohistiocytosis- lymph- part of the immune system,   histio- histiocytes- the type of cell that we are discussing- it is their job to “eat” diseased cells, cytosis- movement of molecules in and out of cells

HLH involves over-production and activation of normal infection-fighting cells called histiocytes and T cells (part of your immune system and white blood cells). The immune system starts to attack healthy tissue leaving behind a necrotic area. Because of this, the immune system becomes overstimulated and over activated, creating a feedback loop known as a “cytokine storm”.  The cytokine storm produces the fevers, nausea, and fatigue that I first noticed in December. Ultimately, the immune system begins to damage the patient’s own tissues and organs, including the bone marrow, the liver and the brain. Death occurs from multi-system organ failure, often in just a couple of months. My initial lesions were in the spleen, lungs and liver.

In simple terms, when your body gets an infection, the body releases infection-fighting cells to kill the infectious organisms. Normally, when the infection is eliminated, proteins are expressed by the body that cause the infection-fighting process to turn off. In patients with HLH, the infection-fighting process continues unabated, which allows the infection-fighting cells to destroy healthy organ tissue.

HLH is often referred to as either the “primary” form which is hereditary, or the “secondary” form which is associated with infections, viruses, autoimmune diseases, and malignancies (or cancers).

HLH is not cancer, but cancer-like in its nature and requires chemotherapy for treatment. Symptoms and severity of HLH are on a spectrum. This disorder is deadly if not treated promptly and unfortunately death oftens occurs before diagnosis is made. There are laboratory criteria and physical findings that should be met before a diagnosis is made.

Labs that are affected are:

Complete blood counts (CBC): Pancytopenia, which I had, where all three blood components (white blood cells, hemoglobin, and platelets) are below normal is a diagnostic criteria of HLH. Most often this is because HLH involves the bone marrow. In my case it was the spleen.

Liver function numbers, such as ALT, AST, Alkaline Phosphatase, and LDH (mine were only slightly elevated)

Markers of inflammation such as ferritin (the diagnostic criteria for ferritin is >500, but values above 10,000 are common for full-blown HLH – at my sickest in February my ferritin was only 369) and soluble IL-2 receptor levels (again my markers were abnormal but not as high as what is needed to make the diagnosis). A sample of bone marrow may be obtained to look for hemophagocytosis (mine was negative). Doctors may collect some fluid from the spinal canal to look for HLH affecting the brain (I do not have neurologic involvement).

My case is a mild presentation, which is very unusual for HLH. Most of my doctors had only diagnosed HLH in patients that were near death in the ICU. According to my labs and presentation, I wasn’t “sick enough” to have HLH. At this point, my blood was drawn and sent to Cincinnati for evaluation by the Children’s hospital there. Unfortunately this disorder primarily strikes infants due to the fact that is primarily genetic (inherited- like I have my dad’s lips and my Mom’s eyebrows). Dr. Yoda thought I mostly like had secondary HLH, since primary HLH is rare in adults. However, since I did not have a known trigger for my HLH, he wanted to test for genetic mutations just to rule it out.

Class dismissed.