Chédiak-Higashi syndrome: brain MRI and MR spectroscopy manifestations.

Chédiak-Higashi syndrome is a rare inherited metabolic disorder characterized by partial oculocutaneous albinism, immunodeficiency, and neurological dysfunction. We present the brain magnetic resonance imaging (MRI) and MR spectroscopy (MRS) findings obtained during the accelerated phase of the disorder in an 8-year-old. The brain MRI manifestations at recurrences 15 months and 24 months later are reported as well.

Successful use of emapalumab in refractory hemophagocytic lymphohistiocytosis in a child with Chédiak-Higashi syndrome: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis is a life-threatening disease heralded by fever, cytopenia, hepatosplenomegaly, and multisystem organ failure. Its association with genetic mutations, infections, autoimmune disorders, and malignancies is widely reported. CASE PRESENTATION: A 3-year-old male Arab Saudi patient with insignificant past medical history and parental consanguinity presented with abdominal distension of moderate severity and persistent fever despite receiving antibiotics. This was accompanied by hepatosplenomegaly and silvery hair. The clinical and biochemical profiles were suggestive of Chédiak-Higashi syndrome with hemophagocytic lymphohistiocytosis. The patient received the hemophagocytic lymphohistiocytosis-2004 chemotherapy protocol and had multiple hospital admissions mainly due to infections and febrile neutropenia. After achieving the initial remission, the patient's disease reactivated and did not respond to reinduction with the hemophagocytic lymphohistiocytosis-2004 protocol. Due to the disease reactivation and intolerance of conventional therapy, the patient commenced emapalumab. The patient was successfully salvaged and underwent an uneventful hematopoietic stem cell transplantation. CONCLUSIONS: Novel agents such as emapalumab can be helpful for the management of refractory, recurrent, or progressive disease, while avoiding the toxicities of conventional therapy. Due to a paucity of available data on emapalumab, additional data are needed to establish its role in hemophagocytic lymphohistiocytosis treatment.

Rituximab and cyclosporine therapy for accelerated phase Chediak-Higashi syndrome.

A 19-month-old male with Chediak-Higashi syndrome developed Epstein-Barr virus (EBV)-associated accelerated phase. Real-time polymerase chain reaction showed high EBV-DNA levels in plasma and peripheral blood mononuclear cells. His condition was refractory to conventional treatments for hemophagocytic lymphohistiocytosis, including corticosteroids, cyclosporine, and etoposide. In situ hybridization revealed higher proportion of EBER-1-positive cells in CD19+ cell fraction than in CD8+ cell fraction. Complete remission was achieved by combination therapy with rituximab and cyclosporine; subsequent bone marrow transplantation was successful. Combination therapy with rituximab and cyclosporine could be effective in patients with EBV-infected T and B cells.

Generalized periodontitis associated with Chédiak-Higashi syndrome.

BACKGROUND: Chédiak-Higashi syndrome (CHS) is a rare immunodeficient disorder. Patients with CHS are prone to severe periodontitis. To date, limited improvement following periodontal therapy has been reported. Thus, successful clinical outcomes in patients with CHS are of interest. METHODS: A 12-year-old girl was referred to the Department of Pediatric Dentistry, Hôtel-Dieu/Garancière Hospital, for acute gingival inflammation and periodontal destruction. After a periodontal examination, the patient was sent to the Department of Medicine, Robert Debré Hospital, for a hematologic examination and was diagnosed with CHS. She has been receiving medical and dental treatments since that time. The medical treatment consisted of continuous, long-term antibiotherapy. Supportive periodontal therapy was initiated with 4-month recall periods. We report the diagnosis process and the 9-year follow-up. RESULTS: Radiographs and a periodontal examination showed deep probing pockets and extensive alveolar bone resorption. Hematologic and immunologic investigations showed normal values. Peripheral blood smears showed giant granules in neutrophils and leukocytes characteristic of CHS. Clinical improvement was observed after the initial periodontal therapy. No periodontitis recurrence was noted over a period of 9 years. CONCLUSIONS: This case report shows that it is possible to treat periodontitis and maintain the periodontal health of a patient with a mild CHS phenotype over a long period. Patient compliance, regular dental follow-ups, and long-term systemic antibiotic treatments may be useful in stabilizing the periodontal condition of patients with CHS. Dentists must be aware that aggressive periodontitis, combined with general clinical signs, in young patients may reflect rare systemic disorders requiring biologic investigation.

A novel frameshift mutation of Chediak-Higashi syndrome and treatment in the accelerated phase.

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive immunodeficiency disease characterized by frequent infections, hypopigmentation, progressive neurologic deterioration and hemophagocytic lymphohistiocytosis (HLH), known as the accelerated phase. There is little experience in the accelerated phase of CHS treatment worldwide. Here, we present a case of a 9-month-old boy with continuous high fever, hypopigmentation of the skin, enlarged lymph nodes, hepatosplenomegaly and lung infection. He was diagnosed with CHS by gene sequencing, and had entered the accelerated phase. After 8 weeks of therapy, the boy had remission and was prepared for allogenic stem cell transplantation.

Acute myeloid leukemia with pseudo-Chèdiak-Higashi anomaly exhibits a specific immunophenotype with CD2 expression.

Acute myeloid leukemia (AML) with pseudo-Chèdiak-Higashi (PCH) anomaly is a rare morphologic entity. We characterized 5 cases by multiparameter flow cytometry and found that in all cases, the blasts aberrantly expressed CD2, a pan-T cell-associated marker, in addition to their myeloid-associated markers. In contrast, CD2 was expressed in only 25 (17.9%) of 140 cases of newly diagnosed AML without PCH anomaly. CD2 expression correlated strongly with AML with PCH anomaly (P < .01), suggesting a link between a specific immunophenotypic marker, CD2, and AML with PCH anomaly.

Chediak-Higashi syndrome: report of a case with uncommon presentation and review literature.

Chediak-Higashi syndrome (CHS) is a very rare autosomal recessive immunodeficiency disorder characterized by partial albinism, recurrent pyogenic infections, and large granules in all granule-containing cells. The author describes a Thai girl who was the first case of CHS in Thailand. She presented in the accelerated phase of CHS, which leads to repeated infections and bleeding, often resulting in fatal outcome. Pancytopenias, hepatosplenomegaly, lymphohistiocytic infiltration in bone marrow and the abnormal characteristic granules in leukocyte clinched the diagnosis.

NK cell effector functions in a Chédiak-Higashi patient undergoing cord blood transplantation: Effects of in vitro treatment with IL-2.

NK cell cytotoxicity in Chédiak-Higashi syndrome (CHS) is strongly impaired as lytic granules are not released upon NK-target cell contact, contributing to several defects typical of this severe immunodeficiency. Correction of NK cell defects in CHS should improve the outcome of hematopoietic stem-cell transplantation, proposed as therapy. We investigated NK cell functions in a CHS patient before and after cord-blood transplantation, and the ability of in vitro IL-2 treatment to restore them. Before the transplant, the strong defect in NK cell-mediated natural and antibody-dependent cytotoxicity, as well as in IFN-γ production, could be restored up to normal levels by in vitro IL-2 treatment. This cytokine also caused the appearance of smaller lysosomal granules and their orientation towards the NK-target cell contact area, thus suggesting that IL-2 had a more general capacity to restore NK cell effector functions. Moreover after the transplant, although the successful engraftment, NK cell cytotoxicity resulted still partially impaired at one year, almost normal at ten years and, anyhow, fully recovered by in vitro IL-2 treatment. Taken together, our results indicate that IL-2 had a wide capacity to restore NK cell effector functions, being able to reverse the altered cytotoxic activity, lytic granule pattern, and cytokine production observed in the CHS patient.

Chédiak-Higashi syndrome. Neurologic appearance.

A 25-year-old man was first seen with a neurologic disorder that resembled a spinocerebellar degeneration and parkinsonism. A peripheral smear revealed the characteristic peroxidase-positive panleukocytic granules associated with the Chédiak-Higashi syndrome. He did not have any associated oculocutaneous abnormalities. The Chédiak-Higashi syndrome may appear primarily with neurologic dysfunction and should be considered in a differential diagnosis of children and young adults first seen with a spinocerebellar degeneration or movement disorder.

Chédiak-Higashi syndrome: presentation of seven cases.

CONTEXT: Chédiak-Higashi Syndrome (CHS) is a rare autosomal recessive disease characterized by recurrent infections, giant cytoplasmic granules, and oculocutaneous albinism. OBJECTIVE: To describe clinical and laboratory findings from CHS patients. DESIGN: Case report. SETTING: The patients were admitted into the Allergy and Immunology Unit of the Instituto da Criança, a tertiary public care institution. CASES REPORT: Seven patients had oculocutaneous albinism, recurrent infections and giant cytoplasmic granules in the leukocytes. One patient had low IgG levels and three showed impaired bactericidal activity of neutrophils. Six patients died of infectious complications during the accelerated phase. Therapy included ascorbic acid and antibiotics. Chemotherapy was used for the accelerated phase in two patients. Bone marrow transplantation (BMT) was proposed for one patient. DISCUSSION: The authors emphasize the need for early diagnosis and therapy of CHS. BMT should be indicated before the accelerated phase of the disease has developed.

[Chédiak-Higashi disease (report on a new case) (author's transl)]. / La maladie de Chédiak-Higashi. A propos d'une nouvelle observation.

A typical case of Chédiak-Higashi disease is reported in a French four years old boy (no parents consanguinity). The clinical aspect of oculo-cutaneous and pilar hypopigmentation, associated with recurrent infections led to the diagnosis of C. H. disease which was confirmed by the presence of giant leukocytes granulations in the blood and giant melanosomes in epidermal melanocytes; these giant pigmented granules, are made of a limiting unique membrane with granular matrix and periodic filamentous structures, which correspond to stade I, II and III melanosomes. In keratinocytes, melanosomes are rare, never isolated and scattered in cytoplasm, but grouped in giant melanosomes complexes. No specific immunity deficiency is found in this patient but the chemotaxis of neutrophil polymorphonuclear leukocytes was decreased but restored by levamisole treatment. Concanavaline A Cap formation by polymorphonuclear leukocytes was abnormally increased, but returned at a normal level after cyclic GMP incubation and levamisole treatment. Unfortuntely, the patient died soon after accelerated phase had begun, in an anatomo-clinical picture of pseudo-lymphoma. A pathogenic discussion of CH disease is presented with the help of a study of 102 cases of literature.

[Prolonged remission of infectious symptoms during treatment with ascorbate in a case of Chediak-Higashi syndrome]. / Prolungata remissione della sintomatologia infettiva durante il trattamento con ascorbato in un caso di sindrome di Chediak-Higashi.

A case of Chédiak-Higashi syndrome in a 12-years old girl is presented. The Authors refer recent advances in the pathogenetic mechanism and in the treatment of this syndrome. Furthermore, they report a prolonged remission of infections during ascorbic acid therapy.

A novel frameshift mutation of Chediak-Higashi syndrome and treatment in the accelerated phase

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive immunodeficiency disease characterized by frequent infections, hypopigmentation, progressive neurologic deterioration and hemophagocytic lymphohistiocytosis (HLH), known as the accelerated phase. There is little experience in the accelerated phase of CHS treatment worldwide. Here, we present a case of a 9-month-old boy with continuous high fever, hypopigmentation of the skin, enlarged lymph nodes, hepatosplenomegaly and lung infection. He was diagnosed with CHS by gene sequencing, and had entered the accelerated phase. After 8 weeks of therapy, the boy had remission and was prepared for allogenic stem cell transplantation.