Griscelli Syndrome Associated With Hemophagocytic Lymphohistiocytosis

Griscelli syndrome (GS) is a rare autosomal recessive disorder characterized by partial albinism, hepatosplenomegaly, pancytopenia, hepatitis, immunologic abnormalities, and lymphohistiocytosis.¹ Here, we describe a case of Griscelli syndrome associated with hemophagocytic lymphohistiocytosis (HLH).

A female, aged 2 months, was transferred to our hospital with thrombocytopenia, s/p splenectomy, hyperbilirubinemia, and atypical myelodysplasia. She was born at 36 weeks gestation by C-section for abnormal fetal heart sounds. On physical exam, she had bronze, jaundiced skin with scleral icterus. Her hair was silvery-gray with a metallic sheen on the frontal scalp and brown on the temporal and occipital scalp (Figure 1). She had retention hyperkeratosis of the frontal scalp. Her liver was palpated 3 cm to 4 cm below the costal margin. Total leukocyte count was 41000 per mm³ and platelet count was 18,000 per mm³. Total bilirubin was 4.7 mg per dL, AST was 235 U per L, and ALT was 106 U per L. Ferritin was 1394 ng per mL (NL: 7-91). She was diagnosed with HLH based on the presence of fever, history of splenomegaly, cytopenias of 2 of 3 lineages in the peripheral blood, elevated ferritin, and soluble IL2 >2400 units per mL. Light microscopy showed large clumps of melanin granules along the hair shaft, consistent with Griscelli syndrome (Figure 2). The patient was started on 8 weeks of induction chemotherapy with dexamethasone, etoposide, and cyclosporine.

There have been less than 100 reported cases of Griscelli syndrome. Most patients have been diagnosed between 4 months and 7 years of age, with a mean age of about 17 months.¹ Type 1 GS patients have neurologic symptoms and mutations in MYO5A. Prognosis depends on the severity of neurologic manifestations. Type 2 GS patients have mutations in RAB27A and hemophagocytic syndrome, with abnormal T-cell and macrophage activation. This type has a grave prognosis if untreated. Type 3 GS patients have mutations in melanophilin and are characterized by partial albinism.² This type does not pose a threat to those affected.

Our patient has type 2 Griscelli syndrome, and following the 8 week induction of steroids and immunosuppressants, which can delay hyperactivation of lymphocytes and macrophages,³ she will proceed to stem cell/bone marrow transplant, which is used to treat HLH. The finding of silvery-gray hair, hepatosplenomegaly, and immune deficiency should alert clinicians to consider GS, since an early diagnosis may be life saving.

The authors have disclosed no relevant conflicts of interest.