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 10

Malabsorption, no other diag. 10

Giardiasis 8

UC 4

Ulc. Proctitis 3

Crohn’s disease 9

Malnutrition needing TPN 5

Campylobacter enteritis 5

Cunningham-Rundes and Bodian (Clin Immunol 1999; 92:34-48)

Granulomatous disease20% patients Lung, lymph nodes, skin, bone marrow, and liverHistology: 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 IgMLymphopenia 20%B cell numbers - mostly normal CD4/CD8 ratios, in CD4+CD45+ T cellsLow or absent isohemagglutinin titers and

specific Ab levels T cell in vitro proliferation : subnormal in 50% to

mitogen, antigens

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

Differential diagnosis

XLA CVID THI

Mutation of gene Btk -- --

Family Hx X-linked -- --

Onset Late 1st year Any age 1st year

Recovery - - 2-4 y/o

Lymph node small hyperplasia --

B cell umber absence near normal normal

T cell normal subtle normal

Ig IgG ↓

IgA ↓

IgM ↓

IgG ↓

IgA ↓

IgM ↓

IgG ↓

IgA ↓

IgM or normal

Treatment

Early and aggressive antibiotic therapy, Replacement with IVIG: 400 mg/kg/monthOngoing therapy for autoimmune and

inflammatory disorders & surveillance for malignancy

IVIG

Trough levels > 350 mg/dL without infectionLevels > 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, hypotensionanti-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

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 X 174 Days of bronchitis, diarrhea and joint pain

Clin Immunol 2001;100(2) :181-90

Treatment

Retinoic acidDecreased vitamin A level in CVID patients

Associated with chronic bacterial infection and splenomegalySupplementation : IL-10 , TNF-in vivo: IgA , mitiogen response to PHA

Cimetidine ? IL-10 ?

Eur J Clin Invest 2000;30(3) :252-9

Mortality and Survival248 patients; median follow-up 7 yrs (0-25)57 died from 1-32 yrs after diagnosis, ages 5-

90 yrs (median age 43) - 27%Causes -Lymphoma, cor pulmonale, hepatitis,

malnutrition, other malignancies, vasculitis, etc.Poor prognostic signs: % of peripheral B cells,

initial IgG levelFor 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)