HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS: A SCARCE FORM OF NEOPLASIA

Hemophagocytic Lymphohistiocytosis (HLH) , also known as Hemophagocytic Syndrome, is an

Bone marrow smear of a patient with HLH

unconventional form of hematologic disorder seen more often in children than in adults. Unlike previously nowadays, HLH is prevalent among all age groups, including adults. This is a hyper inflammatory Syndrome which is caused by the uncontrolled proliferation of activated lymphocytes and macrophages, characterized by proliferation of morphologically benign lymphocytes and macrophages that secrete high amounts of inflammatory cytokines that makes it classified as one of the Cytokine Storm Syndrome. That is, it’s an anomalous feedback of the immune system.  Based on their etiologies, HLH can be classified broadly into two types - Primary and Secondary. Primary type expressly inherited form which is the Familial Hemophagocytic Lymphohistiocytosis and Secondary type that can be caused due to viral infections (Epstein-Barr virus), autoimmune diseases, Malignancy, Macrophage Activation Syndrome (MAS) etc.

The clinical presentations of HLH maybe difficult to find out as they are lot of symptoms that can mimic other conditions which bring up a way for many other differential diagnoses. However, the initial Signs and symptoms of HLH may include: Rash, Anaemia, Low Platelets and White Blood Cells, Enlarged Liver, Spleen and Lymph Nodes, Diligent Fever, Seizures, Liver Failure, Hepatitis, Jaundice etc.

Familial HLH, which is the Primary HLH maybe acquired from parents to children, but the Acquired HLH can be caused by,

• Viral infections, mainly Epstein-Barr virus
• Autoimmune diseases
• Bacterial or Fungal Infections
• Cancers, such as T-cell lymphoma

There are chances of being conditioned with X-linked lymphoproliferative disease (XLP), if one has an acquired HLH spawned by a virus.

The pathophysiology of the condition is due to an abnormally activated immune system can result in multiple organ damage and severe adverse events. NK cell cytotoxicity is centric in the development of HLH. Familial HLH presents with granule related cytotoxicity. An inability to properly recruit immune cells to the antigen site causes the cytokine storm. With an impending immune system, the release of excessive cytokines threatens the organs with a paramount cytokine infiltration. The clinical presentation of HLH can be attributed to such mechanisms operating behind it. Fever is primarily caused due to IL-6, TNF-alpha and IL-1. TNF-alpha also has other important role where in, it inhibits lipoprotein lipase and stimulates the synthesis of TG. TNF-alpha in conjunction with TNF-gamma promotes cytopenia with an attenuation in haematopoiesis. These pathways culminate in HLH. Ferritin and Plasminogen activator  which is secreted by activated macrophages may lead to hyperfibrinolysis.

The diagnosis for HLH is instituted through blood tests which include blood cell counts, liver function, markers of immune system activation such as ferritin and soluble IL-2 receptor levels. A bone marrow aspirate and biopsy may be performed to look for microscopic evidence of hemophagocytosis. A lumbar puncture may be performed to collect cerebrospinal fluid and to make sure the HLH is not affecting the brain. X-rays, CT scans, ultrasounds or MRIs may be performed.   

The therapy of the ailment maybe approached by:

·        Chemotherapy (cancer drugs)

·   Suppress the severe inflammation: Steroids- Dexamethasone; Cyclosporine A; Intrathecate Methotrexate, Hydrocortisone (patient with persistent active CNS disease)

·        Kill the over stimulated Antigen Presenting Cells: Etoposide (VP-16)

·        Treat the triggering agent: Antibiotic drugs, Antiviral drugs

·        Supportive Therapy: Prophylactic Cortimoxazole, Oral anti-mycoctic, Gasoprotection.

HLH is an uncommon but likely underdiagnosed disease. The mortality is uniformly high, and a timely diagnosis is imperative. Infections are common triggers in both genetic and acquired HLH. If not treated properly both the type may or may not lead to terminal multiple organ failure.

The disease had shown gender equivalence and estimation of universal generality of one in a count of 50,000. The genetic form is most likely to be present in the paediatric population and with some exceptional in adult population.

Angelin Jaimon Augustine , II Pharm - D