CHEDIAK-HIGASHI SYNDROME
DEFINITION:
A generalized cellular disorder which affects all
granule-containing cells resulting in recurrent infections and
ocular, neurological, and skin manifestations.
EPIDEMIOLOGY:
- incidence: ?
- age of onset:
- risk factors:
- familial - autosomal recessive
PATHOGENESIS:
- gene defect -> abnormal membrane fluidity -> uncontrolled
granule membrane fusion -> formation of giant cytoplasmic
granules in all granule-containing cells -> generalized disease:
- progressive coalescence of azurophilic and specific
granules during myelopoiesis in the bone marrow -> formation
of giant azurophil and specific granules results in:
- death of myeloid precursors in the bone marrow re-sulting
in a neutropenia
- defective chemotaxis, degranulation, and bactericidal
activity of the remaining neutrophils
- inability of neutrophils to move normally
- delayed fusion of abnormal granules with phagosomes
containing ingested microbes - inability to concentrate
hydrolytic enzymes into neutrophil lysosomes (i.e.,
cathepsins, elastase)
- reduced iC3b receptor expression
- increased susceptibility to infection
- especially gram + and - bacteria
- S. aureus and beta-hemolytic Strep. isolated most
frequently
2. Other Hematological Cells
- function poorly in antibody-dependent cell-mediated
cytolysis of tumor cells
2. Platelets
- unable to concentrate seritonin and ADP -> storage pool
deficiency of seritonin and ADP -> platelet aggregation
defect -> normal platelet concentration but prolonged
bleeding time
3. Others
- defects noted in monocytes, macrophages, and natural
killer cells
3. Melanocytes
- failure to dispense pigment -> contain giant melanosomes
-> partial albinism of hair and skin and silver-tinged hair
4. Other Cells
- Schwann cells - central and peripheral neuropathies
- Retinal cells - photophobia, nystagmus, altered red reflex
- Fibroblasts
CLINICAL FEATURES:
- increased susceptibility to recurrent infections
- skin, respiratory tract, chronic cough
- mucous membranes (gingivitis, peridontitis)
2. Ocular Manifestations
- usually the presenting complaint or finding
- extreme photophobia, rotary nystagmus, increase red reflex
3. Neurological Manifestations
- onset in adulthood
- motor, sensory, and cranial nerve neurologic defects
- ataxia, muscular weakness
- seizures
4. Skin Manifestations
- partial albinism
- hair colour varies from blond to dark brown but has a
silvery tint in bright light
5. Complications
- occurs in 85% of patients
- an EBV or other lymphotrophic viral infection may initiate
this phase characterized by a lymphoma-like picture with
fever, generalized lymphadenopathy, hepatosplenomegaly, (hepatomegaly),
pancytopenia, and sepsis (a viral infection may stimulate
lymphohistiocytic proliferation within the reticuloendothelial
system)
INVESTIGATIONS:
- 2,000-15,000 WBC's (50-70% PMN's)
- normal platelet count but prolonged bleeding time
- pancytopenia in accelerated phase
2. Neutrophil Function
- chemotaxis - decreased
- superoxide release - increased
- bacterial killing
3. Cytochemistry (Wright Stain)
4. Prenatal Diagnosis
- giant neutrophil granules present in fetal blood
MANAGEMENT:
- Paediatrics, Dermatology, Neurology, Ophthalmology, OT, PT
- management of infections and seizures
- no role for prophylactic antibiotics
- ascorbic acid may improve the clinical status and
phagocytic function
2. Accelerated Phase
- may partially arrest the lymphohistiocytic infiltration of
the reticuloendothelial system but is not effective in
arresting the progression of the disease
2. acyclovir and prednisone
- may provide temporary improvement in fever, pancytopenia,
and decrease the bleeding time
3. bone marrow transplantation
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