Chediak Higashi disease is characterized by the following except?
Ans. A. Neutrophilia. (Ref, Robbing pathology 8th/pg. 154)Befects, Phauocytzc,CellsDiseaseMolecular Defect(s)SymptomsChronic granulomatous disease (C6D)Deficiency of NADPH oxidase (any one of four component proteins), failure to generate superoxide anion, other O2 radicalsRecurrent infections with catalase-positive bacteria and fungiChediak-Higashi syndromeGranule structural defectRecurrent infection with bacteria; chemotactic and degranulation defects; absent NK activity, partial albinismLeukocyte adhesion deficiencyAbsence of CD 18--common b chain of the leukocyte integrinsRecurrent and chronic infections, failure to form pus, does not reject umbiliicai cord slumpCHEDIAK-HIGASHI SYNDROME (CHS)INTRODUCTION# autosomal recessive disease.0# affects lysosomes in leukocytes, Schwann cells, melanocytes, renal tubular cells, and thyroid cells.# Associated with partial oculocutaneous albinism, neuropathy, and recurrent infections.Q# Neutrophils from these patients respond poorly to chemotactic stimuli and exhibit impaired intracellular killing (and degranulation) and depressed T-cell and NK cell killing of microbes.# Antimicrobial prophylaxis with Trimethoprim-Sulfamethoxazole is recommended. QPATHOGENESIS# CHS is caused by mutations in LYST (lysosomal trafficking regulator) gene, located on chromosome lq42-q44.Q# Ocular albinism.# Oversized and dysmorphic lysosomes, storage granules, or related vesicular structures.# Increased susceptibility to infection: due to giant neutrophil granules.C/F:# Decreased pigmentation of hair and eyes resulting in partial albinism, photophobia, and nystagmus.# The phenotype includes neutropenia, abnormal susceptibility to infection, and malignant lymphoma.# From 85 to 90% of CHS patients develop a lymphoproliferative syndrome, the "accelerated phase" of the disorder, characterized by generalized lymphohistiocytic infiltrates, fever, jaundice, hepatosplenomegaly, lymphadenopathy, pancytopenia, and bleeding.RX:# Management of the early stage include management of infectious complications.- Prophylactic antibiotics (trimethoprim-sulfamethoxazole) should be given, and infections should be treated vigorously with appropriate antibiotic therapy.# Ascorbic acid (20 mg/kg/day) has corrected the microbicidal defect in some patients.# Bone marrow transplantation is the Rx of choice during progression to the accelerated phase.- Bone marrow transplantation is curative.Q(but has no effect on the neurologic ones).INHERITED DISORDERS OF PHAGOCYTE FUNCTION:CLINICAL MANIFESTATIONSDEFECTSDIAGNOSISChronic Granulomatous Diseases (70% X-linked, 30% Autosomal Recessive)Severe infections with catalase-positive microorganisms such as S. aureus, Burkholderia cepacia , Aspergillus spp.,Chromobacterium violaceum; often hard to culture organism; excessive inflammation with granulomas, frequent lymph node suppuration; granulomas can obstruct GI or GU tracts; gingivitis, aphthous ulcers, seborrheic dermatitis.No respiratory burst due to the lack of one of four NADPH oxidase subunits in neutrophils, monocytes, and eosinophils.QNBT or DHR test; no superoxide and H2O2 production by neutrophils;Q immunoblot for NADPH oxidase components; genetic detectionChediak-Higashi Syndrome (Autosomal Recessive)Recurrent pyogenic infections, especially with S. aureus;QReduced chemotaxis andGiant primary granules inmany patients get lymphoma-like illness; periodontalphagolysosome fusion,neutrophils and otherdisease; partial oculocutaneous albinism, nystagmus, progressive peripheral neuropathy, mental retardation in some patientsincreased respiratory burst activity, defective egress from marrow, abnormal skin window; defect in LYST.Qgranule-bearing cells (Wright's stain); genetic detectionMyeloperoxidase Deficiency (Autosomal Recessive)Clinically normal except in patients with underlying disease (eg. diabetes mellitus); then candidiasis or other fungal infections.No myeloperoxidase due to pre-and posttranslational defectsNo peroxidase in neutrophils; genetic detection.Leukocyte Adhesion DeficiencyType 1: Delayed separation of umbilical cord, sustained neutrophilia, recurrent infections of skin and mucosa, gingivitis, periodontal diseaseImpaired phagocyte adherence, aggregation, spreading, chemotaxis, phagocytosis of C3bi-coated particles; defective production of CD18 common to leukocyte integrinsReduced phagocyte surface expression of the CD18- containing integrins with monoclonal ab againstLFA-1 (CD18/CD11a), Mac-1 or CR3 (CD18/CD11b), p150,95 (CD18/CD11c); genetic detectionType 2: Mental retardation, short stature, Bombay (hh) blood phenotype, recurrent infections, neutrophilia.Impaired phagocyte rolling along endothelium.QReduced phagocyte surface expression of Sialyl-Lewisx, with monoclonal antibodies against CD15s; genetic detection.QHyper IgE-Recurrent Infection Syndrome (Autosomal Dominant) (Job's Syndrome)Eczematoid or pruritic dermatitis, "cold" skin abscesses, recurrent pneumonias with S. aureus with bronchopleural fistulae and cyst formation, mild eosinophilia, mucocutaneous candidiasis, characteristic facies, restrictive lung disease, scoliosis, delayed primary dental deciduationReduced chemotaxis in some patients, reduced suppressor T cell activity.Clinical features, involving lungs, skeleton, and immune system; serum IgE > 2000 IU/ mL
Neutrophilia
Defective degranulation
Delayed microbial killing
Giant granules
Immunity