Learning Objectives Define the recurrent infections and differentiate the patient with a primary immunodeficiency (PID) from the "normal person“. Recognize infectious signs and symptoms, and opportunistic infections of primary immunodeficiency that warrant screening and referral to a specialist. Understand noninfectious signs and symptoms that should raise concern for primary immunodeficiency. Determine appropriate testing for patients for whom immunodeficiency is suspected. Discuss the management of patients with primary immunodeficiency. Appreciate secondary causes of immunodeficiency

1. Clinical Presentation
Recurrent Infections
Dr. Muhammad Barkaat Hussain
PhD

2. Learning Objectives
• Define the recurrent infections and differentiate the patient with a
primary immunodeficiency (PID) from the "normal person“.
• Recognize infectious signs and symptoms, and opportunistic
infections of primary immunodeficiency that warrant
screening and referral to a specialist.
• Understand noninfectious signs and symptoms that should
raise concern for primary immunodeficiency.
• Determine appropriate testing for patients for whom
immunodeficiency is suspected.
• Discuss the management of patients with primary
immunodeficiency.
• Appreciate secondary causes of immunodeficiency.

3. Prolonged severe recurrent purulent
ear and sinus discharge
• A 12-month-old male
child presents to the
paediatrician with
prolonged severe
recurrent purulent ear
and sinus discharge
and purulent cough
expectorate.

4. Sinus discharge
• Frontal and maxillary
sinuses were more
affected

5. Purulent cough expectorate

6. Past Medical History
• Off and on ear, sinus and pulmonary
infection

7. Family History
• There is family history of similar condition
in his older brother who is currently
receiving regular monthly treatment to
avoid recurrence of such infections.

8. On examination
• Examination revealed bilateral otitis
media, frontal and maxillary sinusitis
and right sided pneumonia
• Lab tests?

9. Lab. Investigation
• Investigations detected low levels of IgG,
IgA and IgM

10. Diagnosis
• B-cell immunodeficiency
• Follow up

11. Global Burden of Infectious Diseases
• Infectious diseases are a leading cause of death worldwide
• One death in three of the ~54 million deaths worldwide is
from an infectious cause
• Most of these deaths are in developing areas of the world
and children are more affected
• Many of the these deaths are due to preventable causes
• Pneumonia and Diarrhea – account for 40% of these death
• Tuberculosis
• Measles
• Malaria

12. • What are risk factors for infections?

13. Risk factors for infections
• Living in unhygienic conditions
• Unavailability of safe drinking water
• Improper sewerage system
• Unhygienic food
• Unlawful sexual practices
• Malnutrition or unbalanced diet
• Defective immune system

14. • What type of people who are at high risk for
infections ?

15. People at high risk
• Elderly
• Immunosuppressed or
immunocompromised
• Chronic disease states

16. Clinical Scenario
• Salman was born at full
term after a normal
pregnancy
• His parents were unrelated
• He was not given Bacille
Calmette–Guérin (BCG)
at birth
• He was well until 2
months, when he
developed pneumonia and
needed antibiotics

17. Cont-----
• Routine immunizations were postponed until he
had recovered, but he then developed ‘antibiotic-
related’ diarrhoea, which did not settle after the
antibiotics were stopped.
• After 3 months a further chest infection occurred,
his weight fell from the 25th centile to below the
third
• He was admitted for investigation for failure to
thrive or grow

18. Finding on examination
• On examination, he was a thin, undernourished infant on
the 25th centile for length. There were no rashes or
lymphadenopathy, but his liver was palpable just below the
right costal margin.
• He had slight tachycardia and tachypnoea
• Based on history and clinical findings what investigation
you would recommend to make diagnosis

19. Investigations?

20. Investigation Revealed
• Chest X-ray showed a
silent atypical pneumonia
• Bronchoscopy for
microbiological tests
revealed Pneumocystis
jiroveci on staining of the
fluid
• A marked deficiency of T
cells with normal numbers
of B cells but no
immunoglobulin
production was also
observed

21. Diagnosis
• Severe combined immunodeficiency (SCID)
• He was treated with high dose co-trimoxazole for the Pneumocystis
and referred promptly to a specialist unit for human stem cell
transplantation, where he was put in isolation and given
immunoglobulin therapy to prevent further infections.
• The diagnosis was investigated further by mutation analysis, starting
with the commonest form of this type of SCID, X-linked common γ
chain cytokine receptor deficiency, which was positive.

22. SCIDs:
Severe Combined Immunodeficiencies
• Typically the most severe types of immunodeficiencies.
• Lethal within 6-12 months if not treated.
SCID is often called "bubble boy disease"
SCID became widely known during the
1970's and 80's, when the world learned of
David Vetter, a boy with X-linked SCID,
who lived for 12 years in a plastic, germ-
free bubble

23. DAVID VETTER the bubble boy
• https://www.youtube.com/watch?v=B84GJ
OsioSA

24. Prevalence in Saudi Arabia
• Severe combined immunodeficiency (SCID) is estimated
at 1 in 2,906 Saudi live births, which is higher than the
incidence reported from the US (frequency of 1/58,000
children).
• Around 70–80% Primary immune deficiency (PID)
remain undiagnosed.
• PID affects at least 10 million people worldwide

25. Diagnostic facilities in Saudi Arabia
• An advanced clinical diagnostic immunology service at
King Faisal Specialist Hospital and Research Centre
(KFSHRC) had been established in the last 30 years that
allowed access to diagnose most of the known PIDs.
• Extensive genetic testing that includes Sanger sequencing,
Targeted next-generation sequencing PID gene panel, and
whole exome sequencing is offered to affected patients.

26. Secondary (acquired) Immunodeficiency
Infections
T lymphocyte deficiency (HIV)
Medications
Immunosuppressive drugs, (Corticosteroids, cyclosporin, tacrolimus, purine
analogues-azathioprine, alkylating agents etc), anti-TNF-alfa monoclonal
antibody, cytotoxic anti cancer drugs
Organ transplant
Chronic Diseases
(liver, kidney, diabetes Mellitus etc)
• iver

27. Causes of recurrent infections
Anatomic lesion
Congenital or acquired, and disorders affecting the function of specific organs are
important causes of recurrent infections in adults
Secondary cause of immunosuppression
Secondary immune disorders due to other medical conditions or
treatments for these conditions are a much more common cause of
recurrent infections than primary immunodeficiencies
Congenital (primary) immunodeficiencies
Most congenital (primary) immunodeficiencies do not present in adulthood, However, the
number of recognized immunodeficiencies has expanded dramatically in recent decades, and
primary immunodeficiency is probably not as rare as previously thought. In addition, there
are increasing reports of milder phenotypes of disorders that were previously recognized
only in the most severe forms (eg, DiGeorge syndrome).

28. What happens if immune deficiency diseases
are not treated?

29. Why immune deficiency diseases are
important ?
• Recurrent and opportunistic infections
• Autoimmune diseases
• Malignancies
• If not diagnosed and treated early can lead to
permanent organ damage and loss of life
• Now 90% of PID can be treated effectively

30. Timing of Presentation for primary
immune deficiency diseases
• Presentation may occur soon after birth or may be delayed,
depending on the immune defect.
• Typically, T lymphocyte and combined defects are severe and
patients present before 6 months of age.
• Patients with antibody deficiencies generally present after 6 months
of age when passive maternal antibodies have declined, or often
much later in life.
• Patients with complement and phagocytic defects frequently have a
delayed presentation

31. • What are the clinical features that would make
you suspect primary immunodeficiency ?

32. List the clinical features that would make you
suspect primary immunodeficiency
• Suspect PID in any individual with SPUR
• Severe
• Persistent
• Unusual and
• Recurrent infections

33. • Does type of micro-organisms give any clue
regarding degree and cause of
immunodeficiency?

34. Type of opportunistic infections gives clues to the
degree and cause of immunodeficiency
• Catalase + Staph aureus, E coli, Klebsiella,
Serratia, Burkholderia , nocardia (Neutrophil)-
Unusually severe infections by common
pathogens
• Mycobacterium (T-cell)
• Extracellular encapsulated bacteria-(antibody or
complement)
• Chronic mucocutaneous candidiasis (T-cell)
• Invasive fungal infection-severe immune
deficiency (T-cell)
• N. Meningitis, N. gonorrhoeae (complement)-may
be accompanied by autoimmune disorders.

35. • What are causes of secondary immune
deficiency disorder?

36. Classification of ID
Primary
(Congenital)
Genetic Mutation
Monogenic (Single gene)
Polygenic (Multiple genes)
Secondary
(Acquired)
Malnutrition
Viral and Bacterial
Infections
(AIDS)
Immunosuppressive
Therapy
(Corticosteroids)
Excessive Proteins Loss
(Burns, nephrotic
syndrome)

37. Summary
• Primary disorders of immune function should be considered in children
who have recurrent and/or complicated bacterial infections, recurrent
soft tissue or organ abscesses, two or more episodes of bacterial sepsis
or meningitis; persistent oral candidiasis; infection with opportunistic,
unusual, or "signature" organisms; failure to thrive; or a family history of
immunodeficiency or unexplained early deaths.
• A careful history, physical examination, and screening evaluation can
identify the disorder easily.
• B cell and combined B and T cell abnormalities account for nearly three-
fourths of the primary immunodeficiencies and should be considered
initially. Isolated T cell, phagocytic, and complement defects are rare.

38. Additional source of leaning
• Pages, 44-48 Study Guide