Haemophagocytic lymphohistiocytosis and silvery hair in Griscelli syndrome.

Abstract

An 11-year-old boy was seen in consultation for silvery discoloration of his hair and eyebrows (top). Examination of a hair under the microscope revealed numerous unevenly distributed large clumps of pigment in the hair shaft (bottom left), in comparison with normal hair (bottom right). He had been diagnosed with type 2 Griscelli syndrome when he developed infections and haemophagocytic lymphohistiocytosis (HLH) during the first year of life, and had been treated by haematopoietic stem cell transplantation (HSCT) from his compatible brother. Thereafter, he developed normally, but the hair anomalies persisted. Type 2 Griscelli syndrome results from a mutation in the RAB27A gene, which encodes a protein that is a is a key effector of cytotoxic granule exocytosis and is involved in immune regulation; in the case of type 2 Griscelli syndrome, these immune abnormalities lead to increased susceptibility to infections and HLH. This function is restored by HSCT. However RAB27A protein is also involved in the trafficking of melanosomes within melanocytes and this function is not corrected by HSCT. The latter explains the large clumps of pigment visible in the hair shaft, a pathognomonic finding. Hair shaft examination under the microscope can be easily performed in almost every setting and thus allows confirmation of the diagnosis. It does not, however, allow a distinction between the different types of Griscelli syndrome.