Haemophagocytic Lymphohistiocytosis (HLH)

HLH is a rare disorder of the immune system where there is an over-production and activation of normal immune cells. These over activated immune cells cause inflammation and damage of healthy tissues including the liver, spleen, brain and other tissues.There are two forms of HLH, one is the primary or familial form where the condition is inherited (genetic cause) and the other is the secondary or acquired form where the cause is not genetic but is instead due to an underlying condition (examples include immunodeficiency, systemic infection, etc). In familial HLH the blood-producing cells in the the bone marrow are also attacked, a process known as haemophagocytosis. This results in lower numbers of red blood cells (anaemia) and a reduction in the number of platelets (cells involved in the formation of blood clots). A reduction in platelet numbers may result in the individual bruising easily and experiencing abnormal bleeding.

Left untreated, affected individuals survive for around two months due to progressive multi-organ failure.

Signs & Symptoms

The signs and symptoms of HLH are often mistaken for other common infections, eg flu

  • Persistent fever, often high
  • Respiratory issues (coughing etc)
  • Low red/white blood cell count
  • Low platelets
  • Enlarged spleen
  • Enlarged lymph nodes
  • Anaemia
  • Rash

If the brain is involved:

  • Irritability
  • Seizures
  • Fatigue
  • Low or abnormally increased muscle tone
  • Difficulty with coordination
  • Weakness of face/eye nerves
  • Sudden blindness
  • Paralysis and coma (very rare)

Who is affected?

Familial HLH is estimated to occur in 1 in 50,000 individuals worldwide, and affects males and females equally.

Treatment

Early diagnosis and administration of an appropriate treatment is essential to the individuals survival. Treatment involves a combination of chemotherapy, immunotherapy and steroids, as well as antibiotics and antiviral drugs with the aim to suppress the life threatening inflammatory process due to HLH. The patient is weaned off the intense medication and placed on a continuation therapy. The only cure to a diagnosis of familial HLH is a bone marrow transplant, which comes with its own risks of graft vs host disease, etc. There is a medium survival rate after treatment of 54% at 6.2 years after diagnosis.

References:

Trottestam, H. et al., 2011, 'Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the HLH-94 treatment protocol', Blood, 118:4577-4584.

Henter, J et al., 2002, 'Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation', Blood, 100:2367-2373.

Disclaimer:
Information on this page is not intended to replace medical advice and any questions regarding a medical diagnosis or treatment should be directed to a medical practitioner.