HLH (Hemophagocytic Lymphohistiocytosis) At a Tertiary Care Hospital, B J Wadia Hospital for Children,In Mumbai, India
Authors: Desai Mukesh Manharlal , Palaha Harvinder Iqbal , Desai Snehal , Madkaikar Manisha , Agarwal Bharat , Shah Nitin , Swami Archana , Ghosh Kanjaksha 
Published: October 2019

Abstract
Abstract 4936
We present a retrospective analysis of HLH diagnosed at B J Wadia Hospital for Children, a tertiary care exclusive pediatric institute in Mumbai. In all, 43 cases were diagnosed as HLH as per 2009 Guidelines (Filipovich et al). There were 15 (34.9%) males and 28 (63.1%) females. The mean age was 3 yrs 4 mths with a range of 15 days to 12 yrs. The commonest presenting symptom was fever in 85% of cases. RS, GI, Renal and CNS symptoms were seen in 48.8%, 65%, 11.6% and 24% of our cases. Skin pigmentation, Petachiae, Oedma and arthritis was present in 12(27.9%); 4(9.3%), 13(30.2%), and 4(9.3%) of cases respectively. 41(95.3%) babies had Hepatomegaly while 35(81.3%) had Splenomegaly. Lymphadenopathy was seen in 13(30.2%). 12 (27.9%) had pigmentation, 13(30.2%0 had oedema while 4 (9.3%) each had petachiae and arthritis.
Mean Hb of 8.2 gm/dl and a range of 3.5 to 10 gm/dl. The Mean WBC count & ANC were 8030 (range 1300 – 29400) & 4614 (300-19400). 37(86%) had thrombocytopenia. Liver injury 27(62.7%), hyponatremia 28(65.1%) and renal failure in 6(13.95%) was seen at diagnosis. Coagulopathy was present in 38(88.4%) and serum ferritin was >500 in 36(83.7%) with a mean of 26135 ng/ml and range of 82 to 200,000 ng/ml. 24(55.8) cases had Hypertriglyceridemia with mean levels of 236. 13 patients had infections 6 UTI & 7 bacterial diarrhoea. Only 2 out of 16 children had CSF abnormality at diagnosis. BM was hypo cellular in 3 and hyper cellular in 40 and all showed hemophagocytosis. PS showed HLH in 4 cases. Cultures isolated K pneumoniae in 5, P aeruginosa in 2, S. Typhi in 1, Candida in 4, and H1N1 in 1. Kalazar was the cause of HLH in 1 and 2 patients had P vivax seen on PS. 1 child had SPTCL & HLH while another child has ALCl & HLH. The child with SPTCL had gross hemophagocytosis on skin biopsy as well as in the Bone Marrow.
Perforin was done in 30(70%) and was low in 6/30 (20%) cases, while GRA (Granule Release Assay) was done in 15(35%) and was abnormal in 4/15(26.6%). GRA was established last year only. In 29(67.4%) cases IAHS was diagnosed. The IAHS were, HIV 1, Post Chicken pox 1, Dengue 2, Viral aseptic meningitis 1, P vivax 1, Leishmaniasis 1, MTB in 1, S. typhi in 1, gram −ve sepsis in 8, candidia in 3, viral infection 9. 2 cases had MAS (Macrophage Activation Syndrome) with JRA; serum ferritin was as high as 200,000 ng/ml at diagnosis. 1 child had Griscelli Syndrome with HLH. Perforin deficiency presented at a mean age of 5 mths & all had severe fulminant presentation with brief H/o of viral infection and hepatosplenomegaly. Hepatic injury was severe and rapidly progressive, CNS affection was present in 3/6 cases and all died. 2/4 children with GRA abnormalities presented early at 15 days & 1 mth of life, 1 had a gm −ve sepsis with response to HLH protocol but relapsed & Died, the other child presented with fever, hepatosplenomegaly, pancytopenia & neuroregression and BMA confirmed HLH. Of the other 2 babies with GRA abnormalities 1 was a case of Griscelli who presented at 4 yrs 6 mths of life while the other presented at 1 6 mths yr of life as what appeared like IAHS and sucumbed to his disease. 2/4 with GRA abnormalities are alive and well. 1 child had thrombocytopenia and Malena as the sole presentation of HLH and the Bone Marrow done 4 times showed gross hemophagocytosis. 2/4 children with elevated creatinine required peritoneal dialysis.
All our cases received Dexa, CsA & Etoposide as in HLH 2004 protocol. We ensured that the 1st 2 doses of etoposide were given after which etoposide may be witheld depending on clinical situation. IT MTX was given when there was CSf abnormalities or gross CNS signs. The Mortality was 32.5% (14/43). 3 of them died during Follow up with relapse of HLH, 1 child with ALCL died of Lymphoma while child with SPTCL is alive but with systemic symptoms. 8/43 (18.6%) are lost to follow up. Majority of IAHS did well with treatment. 8 are presently on regular follow up. In IAHS reassesment of HLH status if normal at 8 weeks, treatment was discontinued. 21/43 children completed 8 weeks of treatment.

Conclusions:
HLH is not an uncommon diagnosis in tertiary care centre in India. IAHS was the commonest cause of HLH and prompt dignosis with treatment HLH 2004 protocol is necessary to control the hyperinflammation. Our Ferritin values were very high. Incidence of Perforin deficiency was 20% and 26.6% respectively. Mortality in perforin deficiency was 100%. Bacterial infection and fungal infections were also common among the IAHS.

Disclosures:
No relevant conflicts of interest to declare.