Contents
Extremely rare autosomal recessive immunodeficiency disorder leading to a decrease in phagocytosis.
- Type of primary immunodeficiency
Salient features:
CHINA
- Chediak-Higashi
- Immunodeficiency
- Neurologic manifestations
- Oculocutaneous albinism
History:
Chediak-Higashi syndrome (CHS) was first described by Beguez-Cesar in 1943 in 3 siblings bearing the main clinical features of neutropenia and abnormal granules in leukocytes. Subsequently, Steinbrinck reported another case in 1948. Chediak, a Cuban haematologist, reported another case in 1952; [3] and in 1954, Higashi, a Japanese paediatrician, described a series of cases and found maldistribution of myeloperoxidase in neutrophilic granules of affected patients.
Classification
- Classic CHS: Classic, early-onset form
- Atypical CHS: Attenuated, later-onset form
Pathophysiology
Defect in long arm of chromosome 1:
- Lysosomal trafficking regulator (LYST)
- Chediak-Higashi syndrome (CHS1) gene
Disruption of protein synthesis & storage and secretory functions of lysosomal granules
(of leukocytes, fibroblasts, dense bodies of platelets, azurophilic granules of neutrophils, and melanosomes of melanocytes)
↓
Enlarged vesicles and non-functional lysosomes
Clinical features
Clinical quartet:
Clinically it is characterized by occulocutaneous albinism, photophobia, silver-grey hypopigmented hair and recurrent pyogenic infections particularly of the skin, respiratory tract and gastrointestinal tract due to functional abnormality of neutrophils.
- Partial oculocutaneous albinism
- Immunodeficiency
- Bleeding defects
- Peripheral neuropathy
Partial oculo-cutaneous albinism (OCA):
Decrease in skin & retinal pigments.
- Silver/blonde hair with albinism
Other ophthalmologic symptoms:
- Photophobia
- Increasing red reflex
- Horizontal/rotating nystagmus
Immunodeficiency: Recurrent infections
- Organisms: Bacterial and fungal infections with staphylococcal, streptococcal, pneumococcal, and beta-hemolytic species being the most predominant
- Sites: Skin and upper respiratory tract infections
Bleeding tendency (mild): Platelet-type
- Epistaxis, mucosal or gum bleeding, and easy bruising
Neurologic manifestations (late symptom):
- Peripheral neuropathy (M/C)
- Sensory loss
- Muscle weakness
- Cerebellar ataxia
- Cognitive impairment
Accelerated phase (85%):
Hemophagocytic lymphohistiocytosis associated with multi-organ inflammation characterized by fever, hepatosplenomegaly, lymphadenopathy, neutropenia, anaemia, and sometimes thrombocytopenia. It is caused by the inappropriate stimulation of the macrophages in the bone marrow and the lymphoid organs that leads to phagocytosis of blood cells and production of a large number of pro-inflammatory cytokines.
- 90% mortality
Diagnosis
Complete blood count (CBC):
- Neutropenia
Genetic testing:
- LSYT & CSH1 genes
Peripherla blood smear (PBS):
- Characteristic giant cytoplasmic granules in granulocytes
Bone marrow biopsy (FNAC):
- Giant inclusion bodies in leukocyte precursors
- Terminal phase: Non-malignant lymphohistiocytic infiltration of multiple organs (pseudolymphoma).
Hair/skin biopsy:
- Clumped melanin granules
Differential diagnosis:
- Oculocutaneous albinism
- Hermansky Pudlak syndrome (specifically HPS-2)
- Cross syndrome
- Griscelli disease
Management
Supportive management:
- High-dose vitamin C
- G-CSF (for neutropenia)
- Antimicrobial treatment (for infection)
- Dental hygeine
- Platelet transfusion (for severe bleeding)
Definitive treatment: Allogeneic hematopoietic stem cell transplantation (HSCT)
- M/effective if performed before accelerated phase
Accelerated phase:
- Combination therapy: Etoposide, dexamethasone, and cyclosporine
Summary: