Case Discussion:

Primary Immunodeficiencies
Case to Discuss

01 A baby boy with BCG-itis and oral thrush

02 A boy with recurrent pneumonia

03 A boy with severe mastoiditis and neutropenic sibling

 Case 1

3-month-old baby boy

Persistent oral thrush and BCG-itis

History of Illness

Term baby born by eSC. BCG-site was swollen and

BW: 3400 grams. became an abscess.
No illness at perinatal period. Neither hepatosplenomegaly or
BCG given at 20 days old. lymphadenopathy found.

Birth 2 weeks old 3 months old

Developed oral thrush.

Persists even though topical
antifungals have been given.

No history of previous hospitalization

Nutrition: exclusive breastfeeding
Still thriving well
Family Pedigree
 Physical Examination
Alert, normal vital sign

Normocephaly

No bulging fontanelle

Oral thrush

Abscess at BCG-site

No lymphadenopathy or
hepatosplenomegaly
Good nutritional status
What kind of laboratory
investigations will you ask for?

a. Complete blood count, HIV antibody

b. Complete blood count, CD4, CD8
c. Complete blood count, PCR HIV
d. Complete blood count, HIV antibody, lymphocyte subset, level
of Ig G, A, M, E
Laboratory Examination
Laboratory Patient’s value Brother’s value Normal range
Hemoglobin (g/dL) 7.5Lymphopenia 9.4 11.5-14.5
Hematocrit (%) 22.2Low T & NK cells
33 33-43
Leukocyte (/mL) 6,550 13,600
Normal B cells 4,000-12,000
Thrombocyte (/mL) 381,000Normal IgG;465,000
low level of IgM150,000-400,000
and IgA
Absolute lymphocyte count (/mL) 2,307 1,904 >3,000
CD3+CD45+T cells (cells/%) 243 (6) 2,500-5,500 (53-84)
CD4+ T cells (cells/%) 39 (1) 4 (0) 1,600-4,000 (35-64)
CD8+ T cells (cells/%) 135 (3) 2 (0) 560-1,700 (12-28)
CD19+ B cells (cells/%) 3532 (88) 12-2,100 (14-76)
CD16+CD56+ NK cells (cells/%) 26 (1)
IgG (mg/dL) 411 409 206-601
IgA (mg/dL) < 26.2 <2.2 28-47
IgM (mg/dL) < 16.8 <18.1 17-105
PCR HIV Not detected Not detected
What is the most suitable diagnosis?

a. X-linked agammaglobulinemia
b. Hyper IgM syndrome
c. Severe combined immunodeficiency
d. Common variable immunodeficiency
Diagnosis
Opportunistic Infection
in infancy 1. > 4 new ear infections within 1 year
2. > 2 serious sinus infections within 1 year
3. > 2months of oral antibiotic treatment with little effect
4. > 2 episodes of pneumonia within 1 year
5. Failure of an infant to gain weight or grow normally
Family history 6. Recurrent, deep skin or organ abscesses
7. Persistent thrush in mouth or fungal infection on skin
8. Need for intravenous antibiotics to clear infections
9. > 2 deep-seated infections, including septicemia
10. A family history of PID
Underlying
immunodeficiency?
 Diagnosis
A baby boy with BCG–itis and fungal infection
Pick up the sign
Similar family history

SCID T-B+NK-
Lymphopenia, low T & NK cells, normal B cells
Recognize the pattern BCG-itis
Low IgM & IgA, normal IgG
Oral candidiasis

Follow diagnostic protocol

Molecular Defect in SCID

This patient: mutation in IL2RG

gene
How do you treat this patient?

a. Treat current infection and give antimicrobial prophylaxis

b. Give IVIg replacement therapy
c. Planned for HSCT
d. All of the above
Management
Antimicrobial prophylaxis IVIG replacement therapy while waiting for
Cotrimoxazole(4 mg/kg/dose; qd) HSCT
Itraconazole (5 mg/kg/dose; bid) IVIG 400-600 mg/kg/dose every 28 days
Acyclovir (600 mg/m2/dose; qid)
Planned for HSCT
Anti TB drugs
Rifampicin (15mg/kg/dose; qd)
Isoniazid (10mg/kg/dose; qd)
Pyrazinamide (20 mg/kg/dose; qd)
Follow Up
Follow Up

• Good functional humoral immunity

(assessed by pneumococcal post
vaccination antibody)
• Inactivated vaccinations started 12
months post transplant.
• Active vaccination (MMR and varicella)
started 24 months post transplant.
Case 2

11-year-old boy

Recurrent sinopulmonary tract infection

History of Illness
Diagnose as pulmonary TB, underwent
ATB for 18 months without significant
Multiple superficial skin infection since
improvement
infancy
Still had fever and difficulty to gain
Growth start to faltering since 2 y.o.
weight

Infancy 2 years old 4 years old

He had history of chronic recurrent

cough, fever and looks thinner than
the other child
History of Illness
Had recurrent sinusitis, otitis media, and
chronic diarrhea Referred to CMH
Mostly had no improvement with oral Evaluation for underlying condition
antibiotic therapy

6 years old 8 years old 11 years old

Underwent sinus and mastoid surgery

due to recurrent sinusitis and otitis
media
Family Pedigree
Physical Examination

Alert, tachypnea, tachycardia, fever

Anthropometric status: BW/Height : 25/34 (74%) àundernourished
Pale, stomatitis, otorrhea AS
Lungs: rhonchi on both side
Heart and abdomen: within normal limit
Extremities: macula hyperpigmentation spread in all extremity
 Laboratory Examination
Results Results Normal reference

Hemoglobin (g/dL) 9.5 IgM (mg/dL) 0 52-242

Hematocryte (%) 32.2 IgG (mg/dL) 87 608-1,572
Leukocyte (/µL) 23,100 IgA (mg/dL) 0 45-236

Thrombocyte (/µL) 627,000 Total IgE (mg/dL) 3.8

CD3+ (%; /µL) 95; 2179 56-84;
Diff count 0/1/0/85/12/2 1,000-2,200
ESR (/mm) 55 CD4+ (%; /µL) 3; 920 31-52; 530-1,300
HIV antibody non-reactive CD8+ (%; /µL) 50; 1,134 18-35; 330-920
CD16+ (%; /µL) 3; 64 0-60; 0-390
CD19+ (%; /µL) 0; 1
How do you interpret the lab results?

a. Hypogammaglobulinemia with normal B Cell

b. Hypogammaglobulinemia with low B Cell
c. Hypogammaglobulinemia with normal T Cell
d. Hypogammaglobulinemia with low T Cell
What is the most suitable diagnosis?

a. X-linked agammaglobulinemia
b. Hyper IgM syndrome
c. Severe combined immunodeficiency
d. Common variable immunodeficiency
 Diagnosis
A boy with recurrent bacterial infection (skin, respiratory
Pick up the sign
symptoms, diarrhea) since infancy

X-linked Agammaglobulinemia
Hypogammaglobulinemia
Recognize the pattern
Absent/ low B cell

Follow diagnostic protocol

 Primary B Cell Immunodeficiencies

This patient: mutation in BTK

gene

Fischer et al. Nat Immunol. 2004;5:23-30.

Management

IVIG replacement therapy

IVIG 400-600 mg/kg/dose every 28 days
IVIG Replacement Therapy
in Predominantly Antibody Deficiencies

Effect of IVIG dose (mg/kg per 28 days) Effect of trough IgG level (mg/dL) on pneumonia
on trough IgG level (mg/dL) incidence per patient-year

Orange et al. Clin Immunol. 2010;137:21-30.

Case 3

4-year-old boy

Severe infection in left mastoid area

History of Illness
Left fascial & oculomotor nerve palsy
Recurrent upper respiratory tract
infection & otitis media Blood & tissue culture à
Pseudomonas aeruginosa
3-4 episodes per year

18 months old 3 years 10 months old 4 years old

Subcutaneous infection in left mastoid

area
High fever, otorrhea
No history of previous TB infection
No history of vaccine adverse reaction
Mastoid CT scan: mastoiditis with
bilateral cholesteatoma à
mastoidectomy & debridement à
wound dehiscence
Family Pedigree

At 3 y.o. diagnosed as cyclic neutropenia

normal level of IgG & IgM
Regularly on G-CSF injection
Died at 8 y.o. due to severe pneumonia
Physical Examination

Alert, normal vital sign

Necrotic ulcer with

edematous and
erythematous margin in left
mastoid area, ear lobe and
canal

Facial asymmetry on the

left side
 Laboratory Examination
April 13th May 7th April 21th May 10th Normal
reference
Hemoglobin (g/dL) 8.8 11.3
IgM (mg/dL) 423.3 339 43-196
Hematocryte (%) 28.2 34.7 IgG (mg/dL) 27 262 463-1,236
Leukocyte (/µL) 4,200 3,970 IgA (mg/dL) <26 <26 25-154
Thrombocyte (/µL) 735,000 510,000 Total IgE (mg/dL) 0.2 1.2
Diff count 0.2/0.2/9.4/ 0.5/1/4.5/ CD3+ (%; /µL) 52; 1355 65; 1622 56-75;
1,400-3,700
40.8/49 66.5/27.5
CD4+ (%; /µL) 29; 767 38; 962 28-47;
ANC (/µL) 420 178 490-1,300

ESR (/mm) 53 58 CD8+ (%; /µL) 10; 266 22; 556 16-30;
440-1,200
CD16+ (%; /µL) 10; 249 2; 54 2-76;
20-1,400
CD19+ (%; /µL) 33; 869 29; 717
How do you interpret the lab results?

a. Neutropenia
b. Elevated IgM
c. Low IgG, IgA, IgE
d. All of the above
What is the most suitable diagnosis?

a. X-linked agammaglobulinemia
b. Hyper IgM syndrome
c. Severe combined immunodeficiency
d. Common variable immunodeficiency
 Diagnosis
A boy with recurrent upper respiratory tract infection &
Pick up the sign otitis media
Severe mastoiditis

X-linked HIGM
Neutropenia,
Recognize the pattern
Low IgG, IgA, and IgE with elevated IgM

Follow diagnostic protocol

 Molecular Defect in HIGM

This patient: mutation in CD40L gene

Fischer et al. Nat Immunol. 2004;5:23-30.

How do you treat this patient?

a. Treat current infection and give antimicrobial prophylaxis

b. Give IVIg replacement therapy
c. Planned for HSCT
d. Option A and B
e. Option A, B, and C
Management
Antimicrobial prophylaxis IVIG replacement therapy IVIG 400-600
Cotrimoxazole(4 mg/kg/dose; qd) mg/kg/dose every 28 days
Itraconazole (5 mg/kg/dose; bid)

Infection control G-CSF (5 mcg/kgBW) when neutropenia

Mastoidectomy continued by debridement occurred
Antibiotics administration which
susceptible with sensitivity test
Summary
Be aware of PID
SPURR infection (severe, persistent, unusual, recurrent, running in family)
Family history
Severe adverse reaction to vaccine

Diagnosis
Pick-up the sign, recognize the pattern, and follow diagnostic protocol
Genetic test: not always needed

Treatment
Depends on the disease itself
Thank You