Hemophagocytic lymphohistiocytosis, what about hair?

Abstract

A 1-month-old boy, born to nonconsanguineous parents, without notable family health history, presented with febrile pancytopenia and splenomegaly. Clinical examination disclosed no other anomaly, notably no neurological alteration. His initial complete blood count showed normocytic anemia (hemoglobin 105 g/L), thrombocytopenia (84 × 109/L), and neutropenia (0.8 × 109/L) without lymphopenia. Upon worsening of this pancytopenia, associated with persistent fever despite antibiotics, a bone marrow aspirate revealed no blasts but the presence of histiocytes with hemophagocytosis (Image 1A). High serum triglycerides, ferritin, and lactic dehydrogenase were observed at respectively 3.3 mmol/L, 71 000 μg/L, and 788 U/L together with hypofibrinogenemia (1.1 g/L). Molecular tests for toxoplasmosis, HSV, EBV, CMV, HHV6, and parvovirus B19 were negative. Clinical examination revealed the presence of partial albinism with silver-gray hair. This feature associated to the biological anomalies, evoked a diagnosis of Griscelli or Chediak Higashi syndrome. However, bone marrow cells did not contain giant cytoplasmic granulations. Moreover, microscopic analysis of hair revealed clumps of melanin of various sizes irregularly distributed throughout the hair shaft, suggestive of Griscelli syndrome (Image 1B,C). Cerebrospinal fluid (CSF) analysis revealed hyperproteinorachia (0.73 g/L) and 20/μL leucocytes (92% lymphocytes CD4+, CD3+, DR+, CD25−) in favor of asymptomatic central nervous system hemophagocytic lymphohistiocytosis (HLH). Sequencing of the RAB27 gene in a blood sample finally revealed a homozygous missense mutation in exon 3, confirming the diagnosis of type 2 Griscelli syndrome.1 Corticosteroid therapy was initiated followed by alemtuzumab administration. The patient then underwent a haplo-identical allogeneic hematopoietic stem cell transplantation and is well 8 months later. Children with GS2 indeed present with partial albinism, associated with hemophagocytic lymphohistiocytosis. RAB27A deficiency is responsible for a defective exocytosis of cytotoxic granules from T cells and natural killer cells, which may cause secondary immune overactivation leading to HLH. In the absence of treatment, the evolution is rapidly fatal. Although poorly codified, treatment consists in suppression of the triggering factor, control of HLH with chemotherapy or immunotherapy followed by an allo-HSCT.2 The pejorative evolution of this pathology makes its early recognition essential. Thus, children presenting with HLH must systematically benefit from a search for partial albinism. The presence of silver-gray hair makes necessary microscopic examination. The authors declare that they have no conflict of interest. ME and EC performed analyses. BLC, AH and CT treated the patient. BLC, MCB and ME wrote the manuscript.