Hemophagocytic lymphohistiocytosis (HLH)

Hemophagocytic lymphohistiocytosis (HLH) is a severe, systemic inflammatory syndrome that can be fatal. This syndrome can sometimes occur in people with medical problems that cause a strong activation of the immune system, such as an infection or cancer. HLH in these settings is called secondary HLH. Patients with secondary HLH may also have medical conditions that contribute to the predisposition to HLH, such as rheumatologic diseases or primary immune deficiencies.

HLH occurs in other patients because they have specific genetic variants that more directly cause HLH, in which case it is called primary or familial HLH. The genetic variants that cause primary HLH are present at birth, and patients often become ill with HLH in the first few years of life. If not detected and treated, primary HLH is usually fatal, typically within a few months. Even with treatment, the prognosis is sometimes only a few years, unless a bone marrow transplant can be successfully performed. If secondary HLH is detected promptly and treated aggressively, the prognosis may be better.

HLH occurs when histiocytes and lymphocytes become overactive and attack the body rather than just microorganisms, or germs. Histiocytes are phagocytes—cells that engulf and destroy pathogens. Lymphocytes are a form of white blood cell with several subtypes. Two subtypes are T cells and NK cells, which normally produce cytokines to orchestrate the immune system, and also directly kill cells that are infected with pathogens. When histiocytes and lymphocytes are overactive in HLH, they overproduce cytokines, which can lead to a “cytokine storm.” These cells also attack blood cells and bone marrow, in particular, as well as the spleen, liver, lymph nodes, skin, and even the brain.

Initial clinical features are typically a high and unremitting fever, rash, hepatitis, jaundice, an enlarged liver and spleen, pancytopenia (low counts of all blood types), and lymphadenopathy (enlarged lymph nodes). Neurological components such as confusion, seizures, and even coma may also occur.

Primary HLH is a rare disease, reported in about 1 per 50,000 births worldwide per year. These numbers seem to be increasing slightly, possibly due to increased success in detecting the disorder.