Transcript Childhood Encephalitis 兒童時期之腦炎

Malignancy
 NHL 7.7% - mostly extranodal, all B cell type
 Others – Waldenstrom’s macroglobulinemia
– Hodgkin’s disease
– Adenocarcinoma - stomach, ovary, colon
– Sq cell Ca - vagina, skin, mouth, lung
– Ca - breast, prostate
– Melanoma
Cunningham-Rundes and Bodian
(Clin Immunol 1999; 92:34-48)
GI Diseases (n=248)
Nodular lymphoid hyperplasia
Malabsorption, no other diag.
Giardiasis
UC
Ulc. Proctitis
Crohn’s disease
Malnutrition needing TPN
Campylobacter enteritis
10
10
8
4
3
9
5
5
Cunningham-Rundes and Bodian
(Clin Immunol 1999; 92:34-48)
Granulomatous disease
20% patients
Lung, lymph nodes, skin, bone marrow, and liver
Histology: non-caseating granuloma,
indistinguishable from sarcoidosis
Asymptomatic/ dyspnea if lung
involvement/anemia or thrombocytopenia if
hypersplenism
Corticosteroid : effectively in some but increased
risk of infection
Splenectomy
Laboratory Abnormalities
 IgG, mostly with  IgA and IgM
Lymphopenia 20%
B cell numbers - mostly normal
 CD4/CD8 ratios,  in CD4+CD45+ T cells
Low or absent isohemagglutinin titers and
specific Ab levels
T cell in vitro proliferation : subnormal in 50% to
mitogen, antigens
Differential diagnosis
Primary immunodeficiency syndrome
X-linked agammaglobulinemia
Transient hypogammaglobulinemia of infancy
Infectious agents
CMV, EBV, HIV
Malignancy
Lymphoma, multiple myeloma, CLL
Protein-losing states
Nephrotic syndrome, Protein-losing enteropathy
Drugs
Cyclophosphamide, phenytoin, Gold, Penicillamine
XLA
Mutation of gene
Btk
CVID
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--
--
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Family Hx
X-linked
Onset
Late 1st year Any age
Recovery
-
THI
-
1st year
2-4 y/o
Lymph node
small
hyperplasia
B cell umber
absence
near normal
normal
T cell
normal
subtle
normal
IgG ↓
IgA ↓
IgM ↓
IgG ↓
IgA ↓
IgM ↓
IgG ↓
IgA ↓
IgM  or normal
Ig
--
Treatment
Early and aggressive antibiotic therapy,
Replacement with IVIG: 400 mg/kg/month
Ongoing therapy for autoimmune and
inflammatory disorders & surveillance for
malignancy
IVIG
Trough levels > 350 mg/dL without infection
Levels > 500 mg/dL if severe infection persists
Back or abdominal pain, nausea, vomiting, chills,
fever, and myalgia -> nonanaphylactic
binding of infused Abs to microbial Ag
True anaphylactic reactions : rare
flushing, facial swelling, dyspnea, hypotension
anti-IgA antibodies (IgE isotype)
IVIG
Receive very low IgA product is completely IgA
deficient
Risk of infection :
HIV : no risk
HCV : more severe course in CVID patients
Treatment IL-2
Clin Immunol 2001;100(2) :181-90
15 patients received PEG-IL-2 12-18 mo / 29 control
 T cell proliferative response to mitogen
 T cell proliferative response to antigen (candida
and tetanus)
 Antibody response to immunization with
neoantigen bacteriophage fX 174
 Days of bronchitis, diarrhea and joint pain
Treatment
Retinoic acid
Decreased vitamin A level in CVID patients
Associated with chronic bacterial infection and
splenomegaly
Supplementation :  IL-10 ,  TNF-a
in vivo:  IgA ,  mitiogen response to PHA
Eur J Clin Invest 2000;30(3) :252-9
Cimetidine ?
IL-10 ?
Mortality and Survival
248 patients; median follow-up 7 yrs (0-25)
57 died from 1-32 yrs after diagnosis, ages 590 yrs (median age 43) - 27%
Causes -Lymphoma, cor pulmonale, hepatitis,
malnutrition, other malignancies, vasculitis,
etc.
Poor prognostic signs: % of peripheral B cells,
initial IgG level
For each %  in B cell numbers, risk of death
on follow-up  by a factor of 0.92
Cunningham-Rundes and Bodian
(Clin Immunol 1999; 92:34-48)