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THINK BEYOND THE BUGS
Immune Deficiency Syndromes in the Appalachia
Presented by: Demetrio R. Macariola, M.D. FAAP
Disclosure Statement of Financial Interest
I, Demetrio R. Macariola ,
DO NOT have a financial interest/arrangement
or affiliation with one or more organizations
that could be perceived as a real or apparent
conflict of interest in the context of the subject
of this presentation
Disclosure Statement of
Unapproved/Investigative Use
I, Demetrio Macariola,
DO/DO NOT anticipate discussing the
unapproved/investigative use of a commercial
product/device during this activity or
presentation.
Learning Objectives
1. Describe the different immune deficiency
syndromes in our community in outpatient setting.
2. Describe the pathogens associated with each
deficiency syndrome.
Immune Deficiency Syndromes in the Appalachia
over 4 years
CVID:
20
Agammaglobulinemia:
2
Transient Hypogammaglobulinemia: 2
Chronic Granulomatous Disease:
4
Hyper IgE Syndrome:
2
HIV:
1
TOTAL:
35
“MY CHILD IS ALWAYS SICK”
4 year old boy who developed pneumococcal pneumonia and
bacteremia at 8 months later on developing E. coli UTI at 10
months and non typeable H. influenzae bacteremia at 2 years of
age. Had been having recurrent pneumonia and sinusitis that
mom thinks he cannot get over it.”. PE unremarkable.
Laboratories
Initial immunoglobulin levels: IgM: low, IgG: normal, IgE: normal
After 2 weeks: immunoglobulin levels: IgM normal, IgG: low, IgE: normal
Diptheria and Tetanus titers: non protective
CD 19 lymphocyte count: normal
Differential Diagnosis?
1. Common Variable Immunoglobulin Deficiency
2. Transient Hypogammaglobulinemia
3. Agammaglobulinemia
4. Hyper IgE Syndrome
Common Variable Immunoglobulin Deficiency
Infections usually occurs after 6 months
Can affect both genders
Non protective diphteria and tetanus titers
Treatment: Immunoglobulins
“Something not right is going on”
2 month old boy previously healthy developed
right leg weakness after getting oral polio vaccine.
His dad is concern that “ something not right is going on”.
PE: right lower extremity weakness.
Laboratories
Initial : IgM, IgG, IgA non detectable
Repeat: immunoglobulin levels non detectable
CD 19 lymphocyte count : zero
Differential Diagnosis
1. Agammaglobulinemia
2. Transient hypogammaglobulinemia
3. Hyper IgE syndrome
4. Chronic granulomatous disease
Agammaglobulinemia
May be autosomal recessive or X-linked
All immunoglobulins and CD 19 lymphocytes are
non detectable.
“We belong to a family with immunoglobulin
deficiencies”
9 month old girl who had 2 episodes of otitis media
within 3 months. No other infections. PE in
unremarkable. Two family members with CVID.
Laboratories
IgA normal, low IgM IgG
Diphteria and tetanus titers: normal
CD 19 lymphocytes: normal
Differential Diagnosis
1. Agammaglobulinemia
2. Transient hypogammaglobulinemia
3. Hyper IgE syndrome
4. Chronic granulomatous disease
Transient Hypogammaglobulinemia of Infancy (THI)
Low immunoglobulin levels that resolves between 2-3 years old.
Normal diphteria and tetanus titers
Normal CD 19 lymphocyte counts
“Rashes, asthma & infections not going away”
15-year-male presented with recurrent pneumonia and sinusitis.
Pneumatocele was observed in the chest Xray. Had several
episodes of sinusitis and pneumonia in the past. Had been
having moderate to severe asthma. PE findings pertinent for
eczema and crackles.
Laboratories
IgG, IgM levels: normal
IgE level: 3000 mg/dl
Blood culture: S. aureus
Differential Diagnosis
1. Agammaglobulinemia
2. Transient hypogammaglobulinemia
3. Hyper IgE syndrome
4. Chronic granulomatous disease
Hyper IgE Syndrome
Also known as Job syndrome
Eczema, asthma, recurrent sinusitis, lymphadenitis
Markedly elevated IgE level
Elevated eosinophils
“Unusual germ from a facial wound”
3 year girl who developed cervical adenitis that did
not improved with amoxicillin-clavulanate. The cervical
adenitis recurred and was treated with trimethoprimsulfamethoxazole with improvement.
Laboratories:
Wound culture: Burkholderia cepacia
Immunoglobulin levels: normal
Neutrophil oxidative burst test: positive
Differential Diagnosis
1. Agammaglobulinemia
2. Transient hypogammaglobulinemia
3. Hyper IgE syndrome
4. Chronic granulomatous disease
Chronic Granulomatous Disease
Can be autosomal recessive or x-linked
Rx: Trimethoprim-sulfamethoxazole, itraconazole
Gamma interferon
“My niece always have these skin bumps”
11 year old girl who lives with her aunt had been
having repeated skin infections for 2 years. Had
been on multiple antibiotics. Pertinent PE findings generalized
impetigo and oral thrush.
Laboratories:
Immunoglobulin levels: Elevated IgM, IgE, IgA and IgG
CD4 count: low
CBC: lymphopenia
Differential Diagnosis
1. CVID
2. Hyper IgE syndrome
3. Hyper IgM syndrome
4. HIV
IMMUNOGLOBULIN DEFICIENCY SYNDROMES
IN OUR AREA
1. Hypogammaglobulinemia- X-linked, autosomal recessive
2. Common Variable Immunoglobulin Deficiency
3. Transient Hypogammaglobulinemia of Infancy
4. Hyper IgE Syndrome/Job syndrome
Pathogens Commonly Affecting Patients with
CVID and Agammaglobulinemia
1.Encapsulated bacteria: Pneumococcus, E.coli, H. influenzae,
Salmonella, Mycoplasma
2. Viruses: enteroviruses, hepatitis C, CMV, VZV
3. Parasite: Giardia
Pathogens Commonly Affecting Patients with
CGD
Bacteria: S. aureus, Serratia marcescens, B. cepacia, Nocardia.
Fungi: Aspergillus
Pathogens Commonly Affecting Patients with
Hyper IgE
S. aureus
Chest xray
Lobar Pneumonia
Pneumatocele
Pathogens & Associated Conditions
E. coli sepsis: Galactosemia
Recurrent Neisseria infection: Terminal Complement Deficiency
Deep Candida Infection: Myeloperoxidase Deficiency
Disseminated Maycobacterial Infection: T lymphocyte Deficiency
P. jerovecii infection: T lymphocyte deficiency
Encapsulated bacterial infection: Splenic Dysfuntion
10 warning signs of Immune Deficiency

Eight or more new ear infections within one year.

Two or more serious sinus infections within 1 year.

Two or more months on antibiotics with little effect.

Two or more pneumonias within 1 year.

Failure of an infant to gain weight or grow normally.
10 warning signs of Immune Deficiency

Recurrent, deep skin or organ abscesses.

Persistent thrush in mouth or elsewhere on skin, after 1 year.

Need for intravenous antibiotics to clear infections.

Two or more deep-seated infections such as sepsis, meningitis or cellulitis.

A family history of primary immune deficiency.
Review Question
A 4-year-old boy was diagnosed to have chronic
granulomatous disease which of the following may be
used as prophylactic antibiotic treatment?
A. ampicillin
B. cephalexin
C. trimethoprim-sulfamethoxazole
D. ceftriaxone
E. ertapenem
Review Question
On a 6-year-old boy with recurrent meningococcal
infection which of the following immune deficiency
syndrome will you suspect?
A. common variable immunoglobulin deficiency
B. complement deficiency
C. galactosemia
D. Job syndrome
E. Bruton’s agammaglobulinemia
References:
1. 2012 4th edition Principles and Practice of Pediatric Infectious
Diseases- Long, Pickering & Probe
2. 2012 edition AAP Red Book- Pickering
3. 2009 edition Principles and Practice of Infectious Diseases
4. Immune Deficiency Foundation Websitehttp://primaryimmune.org/
Special Thanks
1. To Ms. Danielle Crumly- ID clinic nurse
2. Colleagues
3. Residents and medical students who had rotated with
pediatric ID.
4. Nurses at Niswonger Children Hospital
5. Nurses at ETSU Infusion Center