TIS

Immunodeficiency
Approach to Primary
Immunodeficiency
 Q. When do you suspect PID?
• 1 or more systemic bacterial infections (sepsis, meningitis);
• 2 or more serious respiratory or documented bacterial infections within 1 year
(cellulitis, abscesses, draining otitis media, pneumonia, lymphadenitis)
• serious infections occurring at unusual sites (liver, brain abscess)
• infections with unusual pathogens (Pneumocystis jiroveci, Aspergillus, Serratia
marcescens, Nocardia, Burkholderia cepacia)
• infections with common childhood pathogens but of unusual severity
• +ve family history for PID
• +ve family history for early infant death
• FTT with or without chronic diarrhea
• Live vaccine acquired diseases
Main types of PID?
• Predominant B cell
• Predominant T cell
• Combined B and T cell
• Granulocyte defect
• Complement Defect
What clues can a CBC give in PID?
• CBC clues:
- persistently raised TLC in absence of any signs of infection: LAD
- if absolute lymphocyte count is normal unlikely that there is a T cell
defect.
- Normal plt count and size: Wiskott Aldrich unlikely
Case #1
Q. 4 year old boy presents in clinic with c/o ear discharge since 4
weeks. How will you proceed?
Evaluation

History
• Discharge features, pain, any meds for ear : took 2 courses of antibiotics over the past 4 weeks.
infection.
: h/o similar discharge required tympanostomy at 2
• Any previous h/o discharge? yrs of age
• Fever? : 101F, 2/day, with cough and rhinorrhea on and off
since 4 weeks
• Cough?
: poor appetite, poor activity
• Systemic review
: no admissions but repeated courses of antibiotics
• Past admissions
for ear discharge
• Birth Hx
: SVD at term, unremarkable immediate post natal
• Immunization course, cord separated at 10 days uneventfully
• Family hx: consanguineous/sib death? : Non consanguineous and no sib death
Differential Diagnosis
• Mastoiditis
• Cerebral Abscess/Meningitis
• Primary immunodeficiency
• Primary Ciliary Dyskinesia
Evaluation

Examination Examination
• Appearance • Febrile, Tachycardic
• Vitals • Pale, thin looking
• Anthropometry • Weight 3rd to 10th percentile, Ht 50th percentile
• General physical • HEENT: scant tonsillar tissue, no erythema, no
exudate, LN small and difficult to palpate
• HEENT
• CNS: no signs of meningeal irritation, GCS 15/15
• CNS
• Chest: decreased breath sound right lower lung
• Chest
field and crepts
Rest of the examination: unremarkable
Evaluation

Labs:
CBC, BLCS • CBC: Hb 9, TLC 26 (90% N), Plt 300.
CXR • CXR: right lung field white out
CRP/ESR • O-ve blood group with absent
Ig Levels hemagglutinins
Flow cytometry • Ig levels: IgA, IgM, IgG low
Genetic study • Flow: Absent CD19+

Diagnosis: X-linked agammaglobulinemia

 Predominant B cell defect (humoral immunodeficiency)
• First screening test: IgA – if normal you’ve ruled out the most common B cell defect i.e IgA
deficiency. Even other forms of B cell defects since IgA in these conditions would also be
low.
• If Ig level is low don’t forget to rule loss of protein before you jump to IVIG i.e nephrotic,
protein losing enteropathy.
• In that case measure titers to SPECFIC antigens to establish whether synthesis is adequate
or not.
• Be wary of recent transfusions: you cant comment on levels for these patients since blood
products contain antibodies.
• Isohemagglutinins will be absent (remember absence of these will be normal for AB blood
group individuals)
• Once you establish low Ig, next step is flow to enumerate the B cells followed by Genetic
studies.
• XLA has absence of B cells (CD19, CD20) unlike CVID, IgA deficiency, hyper IgM syndrome.
Treatment of B-cell defects

• Judicious use of antibiotic to treat documented infections & regular

administration of IVIG/Subcutaneous IG.
• IVIG at a dose of 400mg/kg/month. ↑ dose for severe infections.
• CVID patients and IgA deficiency patients can have IgE against IgA present in IVIG
which can lead severe anaphylactic reactions. Ideally the CVID patients should be
screened for anti-IgA IgE antibodies and given the IVIG preparation free of IgA.
Case #2
3 month old, boy, with c/o diarrhea since 2 weeks. How will you
proceed?
History:
• Diarrhea questions Watery to mucoid, no blood, 10 episodes/day, no
vomiting
• Fever
No fever
• Feeding history
Exclusive DBF since birth
• Systemic review
Has Oral thrush, no ear discharge, no cough, no history
• Prev history of cyanosis, no change in urinary complaints, has a
• Birth Hx diaper rash.
• Immunisation Since birth on and off diarrhea, admitted twice because
of diarrhea and 1 episode of pneumonia needing IV
• Family Hx. antibiotics.
Unbooked, SVD at term, BW 3.0kg
Consanguineous parents, 1 sib death boy at 6 months of
age – multiple admissions due to chest infection
Differential Diagnosis
• Cystic Fibrosis
• HIV
• Primary immunodeficiency
• Shwachman-Diamond Syndrome
Examination
• General look • Irritable, hypertelorism, antimongoloid slant,
• Vitals small mandible, low set ears
• Tachycardic, tachypneic
• Anthropometry
• General physical • Wt 2.8kg, Length 50cm

• Systemic • Ant fontanelle flat, oral thrush, no ear

discharge
• Chest b/l conducting sounds, CVS
unremarkable
• Abd non distended, non tender
• Genitalia: Diaper rash
Labs
• CBC • Hb 10, TLC 6.5 with Absolute Lymphocyte
• BLCS count of 1000, Plts 286
• Na: 128, K: 2.6, Hc03 10
• Electrolytes, BUN/Cr
• CXR • CXR: absent thymic shadow
Further tests?

• HIV PCR • Negative

• Ca • Calcium: 9.2mg/dl
• Flow cytometry • T-, B+, NK-
• Immunoglobulins • Low
• Echo • Normal

Diagnosis: SCID
Genetic studies to evaluate subtype, likely X-linked recessive.
Severe Combined Immunodeficiency
• Mutation in 1 of 13 known genes that encode components of immune system
• All lack thymus.
• Present within 1st few months of life with diarrhea, pneumonia, otitis media,
sepsis and cutaneous infections, FTT and wasting.
• Most common SCID in US is X-linked Severe combined immunodeficiency
followed by autosomal recessive Adenosine Deaminase deficiency.
Treatment
• True pediatric emergency i.e. need definitive treatment before the infections set in.
• Treatment is immune reconstitution via stem cell transplant or gene therapy.
• If diagnosis is made at birth or within 1st 3.5 months of life >92% cases can be treated
successfully with HLA identical or Tcell depleted haploidentical parental HSCT.
• No need for preablation or posttransplant GVHD prophylaxis.
• ADA deficient SCID has option of enzyme replacement therapy – provides protective
immunity but overtime there is lymphocyte decline. Should be given ONLY if stem cell
transplant is not possible b/c enzyme therapy will confer graft rejection capability.
Spot Diagnosis
Measles
• Rubeola- paramyxovirus
• Incubation 8-12 days
• Fever, lethargy, Cough, coryza, conjunctivitis with clear discharge and photophobia
• Koplik spots
• Rash begins on the face and spreads to trunk and extremities
• Measle IgM develops 24 to 48 hours after rash.
Hand-Foot-Mouth Disease
• Enteroviruses
• coxsackieviruses A and B
• echoviruses
• Vesicular lesions, may be petechial
• Associated with aseptic meningitis, myocarditis
Erythema Infectiosum
• Fifth disease
• Parvovirus B-19
• Pre-school and young school-age children
• Prodrome: mild malaise
• Rash: “slapped cheek”, circumoral pallor, peripheral mild macular distribution
 Thank you
Feedback/Questions: sheri.pariha@aku.edu