Immune Deficiency Syndromes in the Appalachia

Presented by: Demetrio R. Macariola, M.D. FAAP

THINK BEYOND THE BUGS

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.

1. Describe the different immune deficiency syndromes in our community in outpatient

setting.2. Describe the pathogens associated with

each deficiency syndrome.

Learning Objectives

Immune Deficiency Syndromes in the Appalachia over 4 yearsCVID: 20Agammaglobulinemia: 2Transient Hypogammaglobulinemia: 2Chronic Granulomatous Disease: 4Hyper IgE Syndrome: 2HIV: 1TOTAL: 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.

LaboratoriesInitial 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 Deficiency2. Transient Hypogammaglobulinemia 3. Agammaglobulinemia4. Hyper IgE Syndrome

Common Variable Immunoglobulin DeficiencyInfections usually occurs after 6 monthsCan affect both gendersNon protective diphteria and tetanus titersTreatment: 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.

LaboratoriesInitial : IgM, IgG, IgA non detectableRepeat: immunoglobulin levels non detectableCD 19 lymphocyte count : zero

Differential Diagnosis1. Agammaglobulinemia2. Transient hypogammaglobulinemia3. Hyper IgE syndrome4. Chronic granulomatous disease

AgammaglobulinemiaMay be autosomal recessive or X-linkedAll 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.

LaboratoriesIgA normal, low IgM IgG

Diphteria and tetanus titers: normal

CD 19 lymphocytes: normal

Differential Diagnosis1. Agammaglobulinemia2. Transient hypogammaglobulinemia3. Hyper IgE syndrome4. Chronic granulomatous disease

Transient Hypogammaglobulinemia of Infancy (THI)Low immunoglobulin levels that resolves between

2-3 years old.Normal diphteria and tetanus titersNormal 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.

LaboratoriesIgG, IgM levels: normal

IgE level: 3000 mg/dl

Blood culture: S. aureus

Differential Diagnosis1. Agammaglobulinemia2. Transient hypogammaglobulinemia3. Hyper IgE syndrome4. Chronic granulomatous disease

Hyper IgE SyndromeAlso known as Job syndromeEczema, asthma, recurrent sinusitis, lymphadenitisMarkedly elevated IgE levelElevated eosinophils

“Unusual germ from a facial wound”3 year girl who developed cervical adenitis that didnot improved with amoxicillin-clavulanate. The

cervicaladenitis recurred and was treated with

trimethoprim-sulfamethoxazole with improvement.

Laboratories:Wound culture: Burkholderia cepaciaImmunoglobulin levels: normalNeutrophil oxidative burst test: positive

Differential Diagnosis1. Agammaglobulinemia2. Transient hypogammaglobulinemia3. Hyper IgE syndrome4. Chronic granulomatous disease

Chronic Granulomatous DiseaseCan 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

IgGCD4 count: lowCBC: lymphopenia

Differential Diagnosis1. CVID2. Hyper IgE syndrome3. Hyper IgM syndrome4. HIV

IMMUNOGLOBULIN DEFICIENCY SYNDROMES IN OUR AREA

1. Hypogammaglobulinemia- X-linked, autosomal recessive2. Common Variable Immunoglobulin Deficiency3. Transient Hypogammaglobulinemia of Infancy4. 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 xrayLobar Pneumonia Pneumatocele

Pathogens & Associated ConditionsE. coli sepsis: GalactosemiaRecurrent Neisseria infection: Terminal

Complement DeficiencyDeep Candida Infection: Myeloperoxidase

DeficiencyDisseminated Maycobacterial Infection: T

lymphocyte DeficiencyP. jerovecii infection: T lymphocyte deficiencyEncapsulated 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 QuestionA 4-year-old boy was diagnosed to have chronicgranulomatous disease which of the following may be used as prophylactic antibiotic treatment?A. ampicillinB. cephalexinC. trimethoprim-sulfamethoxazoleD. ceftriaxoneE. ertapenem

Review QuestionOn a 6-year-old boy with recurrent meningococcalinfection which of the following immune deficiency syndrome will you suspect?A. common variable immunoglobulin deficiencyB. complement deficiencyC. galactosemiaD. Job syndromeE. Bruton’s agammaglobulinemia

References:1. 2012 4th edition Principles and Practice of

Pediatric Infectious Diseases- Long, Pickering & Probe

2. 2012 edition AAP Red Book- Pickering3. 2009 edition Principles and Practice of Infectious

Diseases4. Immune Deficiency Foundation Website-

http://primaryimmune.org/

Special Thanks1. To Ms. Danielle Crumly- ID clinic nurse2. Colleagues3. Residents and medical students who had

rotated with pediatric ID.4. Nurses at Niswonger Children Hospital5. Nurses at ETSU Infusion Center