ISSN - 0973-0958

Pediatric Oncall Journal

Neonatal Hemophagocytic Lymphohistiocytosis (HLH) 12/03/2015 00:00:00

Neonatal Hemophagocytic Lymphohistiocytosis (HLH)

Purvi Mittal1, Sunil Taneja1, Yashwant Kumar Rao1, Ambrish Gupta2.
1Department of Pediatrics, GSVM Medical College, Kanpur, India,
2Department of Pharmacology, GSVM Medical College, Kanpur, India.

Dr. Purvi Mittal, Flat no. 7 Panch Ratan Apt, 7/128 Swaroop Nagar, Kanpur 208002, India.
neonate, hemophagocytic lymphohistiocytosis
A 28 days old female child presented with fever for 3 days followed by fullness of abdomen. She was born at term by non-consanguineous marriage. Elder sibling had died at 1 ½ months of age due to septicemia. On presentation, the child was dull and lethargic, had hepatosplenomegaly with few purpuric spots on the abdomen. Antibiotics were started in view of clinical suspicion of sepsis. Investigations showed hemoglobin 9.5g/L, white cell count (WBC) 5900 cells/cumm (neutrophils 19%), platelets 35,000 cells/cumm, serum bilirubin 18.6 mg/dl (direct 0.6 mg/dl), C-reactive protein (CRP) 5.51mg/L, prothrombin time (PT) > 100 sec and activated partial thromplastin time (APTT) >100 sec. Blood culture did not grow any organism. Ultrasound (USG) abdomen revealed hepatosplenomegaly with mild ascites. Babygram (x-ray of entire body) and CT scan head did not reveal any bony lesion. During the following week condition of the child deteriorated and a repeat blood count was done which showed a drop in hemoglobin to 7.5g/L, WBC decreased to 3000 cells/cumm (neutrophils 8%). Platelets dropped down to 20,000 cells/cumm, ESR was 60mm and there were atypical large mononuclear cells with moderate amount of foamy cytoplasm. Four days later a bone marrow aspiration was done which was suggestive of hypoplastic marrow with hemophagocytes. Serum ferritin was > 16500 ng/ml, triglycerides were 260 mg/dl. Serum bilirubin increased to 30.1 mg/dl (direct 16.7 mg/dl). At the time of doing flow cytometry total leucocyte count was 2,800 cells/cumm with 90% lymphocytes and there were 42% T cells (Normal range 50-72%), 6.3% B cells (Normal range 16-38%), 40% NK cells (Normal range 9-16%), 57% NK+ perforin (Normal range 80-90%). The child was started on steroids and intravenous immunoglobulin ivig (2gm/kg) on day 5 but continued to deteriorate and expired on day 7 of admission.
The lymphoproliferative disorder of hemophagocytic lymphohistiocytosis (HLH) can be divided into two categories: primary (familial) hemophagocytic lymphohistiocytosis (FHL) and secondary HLH. The incidence of FHL is 1:50,000 births, with an equal gender distribution. (1) In contrast to secondary HLH, which may affect any age and may resolve spontaneously, FHL is seen primarily in children and is fatal if untreated. (1) Most cases of FHL are diagnosed before 2 years of age, and the disease may present in the newborn period. (2-4) The diagnostic criteria for HLH include fever for 7 or more days, splenomegaly, cytopenia of two or three lineages (unassociated with a hypocellular or dysplastic marrow), hypertriglyceridemia and/or hypofibrinogenemia, and histopathological evidence of hemophagocytosis in the bone marrow, spleen, liver, or lymph nodes. (5) Hepatomegaly, jaundice, lymphadenopathy, edema, and rash are also seen. There can be central nervous system involvement with meningismus, seizures, encephalopathy, and/or spinal fluid pleocytosis. Cutaneous manifestations include erythroderma, generalized purpuric macules and papules and morbilliform eruptions. Neonates presenting with isolated thrombocytopenia or hepatic dysfunction, with other characteristic findings becoming evident subsequently, have also been reported. (4) Clinical and laboratory parameters fulfilled the criteria for the diagnosis of HLH. In view of the fact that one sibling had died of a septicaemic illness, a possibility of hereditary HLH was entertained, but since gene mutation studies could not be done it could not be proved.
Because neonatal HLH can be rapidly fatal without specific intervention, it is recommended to start a treatment when a high clinical suspicion exists and results of diagnostic studies are still pending. Stem cell transplant is the standard treatment for FHL, once remission is achieved on immuno-modulatory therapy. (6) However in our setup genetic diagnosis is not available and stem cell therapy is difficult, hence we used steroid with ivig as a favorable response with ivig has been observed. (7) Other therapies include combined use of etoposide, cyclosporine A, and corticosteroid. Intrathecal treatment is suggested for patients with central nervous system. When the HLH protocol is ineffective, anti-thymocyte globulin may be suggested. Genetic counseling and family planning is of utmost importance. Subsequent pregnancies should be closely monitored and offspring referred for genetic testing. Mutations in the perforin gene have been reported to be present in 20-40% of FHL. Perforin staining in cytotoxic cells by flow cytometry has been documented as a screening test to identify children with FHL. (6) Other tests for genetic analysis include mutations in the Munc13-4 and syntaxin 11 gene. (8)
Authors Contribution
PM, ST, YKR drafted the article. All authors critically appraised the manuscript for intellectual content.
Compliance with Ethical Standards
Funding None
Conflict of Interest None
  1. Henter JI, Arico M, Elinder G, Imashuku S, Janka G. Familial hemophagocytic lymphohistiocytosis. Primary hemophagocytic lymphohistiocytosis. Hematol Oncol Clin North Am.1998;12:417–33.  [CrossRef]
  2. Huang F, Arceci R. The histiocytosis of infancy. Semin Perinatol. 1999;23:319–31.  [CrossRef]
  3. Parizhskaya M, Reyes J, Jaffe R. Hemophagocytic syndrome presenting as acute hepatic failure in two infants: clinical overlap with neonatal hemochromatosis. Pediatr Dev Pathol.1999;2:360–6.  [CrossRef]
  4. Levendoglu-Tugal O, Ozkaynak MF, LaGamma E, Sherbany A, Sandoval C, Jayabose S. Hemophagocytic lymphohistiocytosis presenting with thrombocytopenia in the newborn. J Pediatr Hematol Oncol. 2002;24:405–9.  [CrossRef]
  5. Henter JI, Elinder G, Ost A. Diagnostic guidelines for hemophagocytic lymphohistiocytosis. The FHL Study Group of the Histiocyte Society. Semin Oncol.1991;18:29–33.  [PubMed]
  6. Henter JI, Horne A, Arico M, Egeler RM, Filipovich AH, Imashuku S, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48:124-31.  [CrossRef]
  7. Rajajee S, Ashok I, Manwani N, Rajkumar J, Gowrishankar K, Subbiah E. Profile of hemophagocytic lymphohistiocytosis; efficacy of intravenous immunoglobulin therapy.Indian J Pediatr. 2014; 81(12):1337-41.  [CrossRef]  [PubMed]
  8. Janka GE. Hemophagocytic lymphohistiocytosis. Hematology 2005; 10: 104-107.  [CrossRef]


Cite this article as:
Mittal P, Taneja S, Rao Y K, Gupta A. Neonatal Hemophagocytic Lymphohistiocytosis (HLH). Pediatr Oncall J. 2015;12: 112-113. doi: 10.7199/ped.oncall.2015.69
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License
Disclaimer: The information given by is provided by medical and paramedical & Health providers voluntarily for display & is meant only for informational purpose. The site does not guarantee the accuracy or authenticity of the information. Use of any information is solely at the user's own risk. The appearance of advertisement or product information in the various section in the website does not constitute an endorsement or approval by Pediatric Oncall of the quality or value of the said product or of claims made by its manufacturer.
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0