1. What is Haemophagocytic lymphohistiocytosis?

Hemophagocyticlymphohistiocytosis (HLH) is a rare but potentially fatal disease of normal but overactive cells calledhistiocytes and lymphocytes that commonly appears in the first year of life, although it has been seen in all age groups.
 

2. What are the types of HLH?

There are two types of HLH, Primary and Secondary. Primary or familial HLH is the inherited autosomal recessive form, which usually constitutes about 25 percent of the total HLH cases. The onset of primary HLH is usually the first few months to years of life. It is more commonly seen in consanguineous families. Secondary HLH develops in association with infection, malignancy, autoinflammatory or metabolic conditions. Both types have similar clinical presentations and outcomes.
 
 

3. Which are the various illnesses that can be associated with secondary HLH?

Infections, Autoimmune disorders, Malignancies and immune deficiency states.
 
 

4. Why does HLH occur?

HLH occurs in response to excess immune activation which is secondary to certain mutations or genetic alterations.
 
 

5. How does a child with HLH present?

Typically the child has high fever lasting for 7 or more days, skin rash, fails to grow well,  neurological symptoms, an enlarged liver, spleen and lymph glands, easy bruising, and tendency for infections.
 

6. How is HLH diagnosed?

The diagnosis of HLH is based on a set of criteria which depend on symptoms, clinical signs and laboratory features. The criteria are as follows:
3 OUT OF THE FOLLOWING 4:

• Fever
• Enlarged spleen
• Low blood counts
• Swelling of the liver.

 
 
AND at least one of the following 4:

• Hemophagocytosis on bone marrow, liver or lymph glands
• Increased ferritin
• Increased sIL2R α
• Absent or very decreased NK cell function

Other tests supportive of HLH diagnosis:

• High serum triglycerides
• Low serum sodium
• Low fibrinogen levels

7. How is HLH treated?

The initial therapy consists of  8 weeks of etoposide, dexamethasone, cyclosporine A, and in some cases injecting drugs into the spinal fluid (intra thecal therapy)
Continuation therapy is instituted to keep the disease inactive and lasts from week 9-40.
It consists of Etoposide,Dexamethasone and Cyclosporine A
 
 

8. How long does therapy continue?

In primary HLH, cure can be achieved only by stem cell transplantation (SCT). In secondary HLH, therapy is not continued beyond 40 weeks, usually only 8 weeks are necessary.
 

9. What is the supportive care for HLH?

Prophylactic co trimoxazole 2-3 times weekly.
An oral anti fungal drug during the initial therapy.
Antiviral therapymaybe considered in children with ongoing viral infections.
Injections of immune globulin given intravenously once every 4 weeks during the initial and continuation therapy.
 

10. How do children with HLH do long term?

Children with secondary HLH usually respond well to chemotherapy. Sometimes secondary HLH may even resolve spontaneously, or with treatment of the underlying condition.
Familial HLH is the more difficult one to treat and progresses to death rapidly if untreated. Medical treatment causes stabilization of the disease till stem cell transplant can be arranged. About two thirds of children who undergo transplantation get cured of their disease.
 
 
 
 
 

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Profile of hemophagocyticlymphohistiocytosis in children in a tertiary care hospital in India.
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Diagnosing and treating hemophagocyticlymphohistiocytosis in the tropics: systematic review from the Indian subcontinent.
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3. Postgrad Med J. 2013 Apr;89(1050):185-92. doi: 10.1136/postgradmedj-2012-130955. Epub 2012 Dec 15.A clinicopathological analysis of 26 patients with infection-associated haemophagocyticlymphohistiocytosis and the importance of bone marrow phagocytosis for the early initiation of immunomodulatory treatment.

Nair V, Das S, Sharma A, Sharma S, Sharma P, Ray S, Bhattacharya S.
 
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4. BMJ Case Rep. 2012 Sep 30;2012. pii: bcr2012006982. doi: 10.1136/bcr-2012-006982.

Haemophagocyticlymphohistiocytosis: a cause for rare but fatal outcome in tuberculosis.
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6. Rheumatol Int. 2013 May;33(5):1363-6. doi: 10.1007/s00296-011-2291-2.

Infection-associated haemophagocyticlymphohistiocytosis: a case series using steroids only protocol for management.
Giri PP, Pal P, Ghosh A, Sinha R.
 
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7. Pediatr Neurol. 2009 Sep;41(3):207-10. doi: 10.1016/j.pediatrneurol.2009.04.004.

Prolonged neurologic course of familial hemophagocyticlymphohistiocytosis.
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8. Indian J Hematol Blood Transfus. 2009 Jun;25(2):78-80. doi: 10.1007/s12288-009-0018-2. Epub 2009 Jul 5.

Familial hemophagocyticlymphohistiocytosis.
Raka S, Nayar P, Godbole R, Manchanda R.
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9. J Assoc Physicians India. 2008 Jun;56:453-7.

Hemophagocticlymphohistiocytosis--recent concept.
Bhattacharyya M, Ghosh MK.
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10. J Infect. 2008 May;56(5):381-8. doi: 10.1016/j.jinf.2008.02.013. Epub 2008 Apr 10.

Visceral leishmaniasis associated hemophagocyticlymphohistiocytosis--case report and systematic review.
Rajagopala S, Dutta U, Chandra KS, Bhatia P, Varma N, Kochhar R.
 
http://www.ncbi.nlm.nih.gov/pubmed/18405976
 
 

11. Indian J Pediatr. 2009 Jun;76(6):643-5. doi: 10.1007/s12098-009-0123-0. Epub 2009 Apr 16.Reactive haemophagocyticlymphohistiocytosis.

Pramanik S, Pal P, Das PK, Chakrabarty S, Bhattacharya A, Banerjee S.
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