PID

Question 1

What is Chronic Granulomatous Disease (CGD) characterized by?

Answer 1

Recurrent infections usually with low-grade pathogens, abscesses, and suppurative granulomas

CGD is marked by normal humoral and cellular immunity.

Question 2

What is the typical onset age for Chronic Granulomatous Disease?

Answer 2

First 2 years of life

CGD is generally chronic.

Question 3

What is the common outcome of untreated Chronic Granulomatous Disease?

Answer 3

Death from overwhelming infection

Early diagnosis and treatment can change this outcome.

Question 4

What is the pathophysiology of Chronic Granulomatous Disease?

Answer 4

Inability of phagocytic cells to kill ingested bacteria

CGD neutrophils do not undergo the respiratory burst characteristic of phagocytic cells.

Question 5

What are common clinical features of Chronic Granulomatous Disease?

Answer 5

Purulent inflammation due to catalase-positive, low-grade pyogenic bacteria

Recurrent catalase-positive bacterial or fungal infections should raise suspicion.

Question 6

What percentage of patients with CGD are X-linked recessive?

Answer 6

76%

The rest are autosomal recessive forms.

Question 7

What is the mean age at diagnosis for the X-linked form of CGD?

Answer 7

3 years

The autosomal-recessive form has a mean age of 7.8 years.

Question 8

What are the two patterns of infection in CGD populations?

Answer 8

1. Inability of phagocytic cells to effect microbicidal activity
2. Involvement of the mononuclear phagocyte system

These lead to various types of infections including pneumonitis and deep-seated infections.

Question 9

What are common sites of infection in Chronic Granulomatous Disease?

Answer 9

Pneumonitis, infectious dermatitis, perianal abscesses

Deep-seated infections may include purulent lymphadenitis, hepatomegaly, and splenomegaly.

Question 10

What is a characteristic clinical feature of lymphadenitis in CGD?

Answer 10

Chronic, suppurative, and granulomatous

Often requires surgical drainage.

Question 11

What are common pulmonary complications in CGD?

Answer 11

Pneumonia, chronic granulomatous infiltrations, pulmonary fibrosis

Aspergillus accounts for most infections (>80%).

Question 12

What imaging findings are associated with pulmonary disease in CGD?

Answer 12

Extensive infiltration of lung parenchyma, prominent hilar adenopathy

Descriptions include bronchopneumonia and pleural effusion.

Question 13

What laboratory findings are common in CGD?

Answer 13

Leukocytosis with neutrophilia, elevated ESR and CRP, anemia of chronic inflammation

Normal immune function is typically present.

Question 14

What is the essential functional finding in CGD?

Answer 14

Deficiency of microbicidal activity against catalase-positive bacteria

Neutrophils and monocytes display diminished or absent respiratory burst.

Question 15

What is a reliable screening test for CGD?

Answer 15

Nitroblue tetrazolium (NBT) test

Phagocytes from patients with CGD do not reduce NBT.

Question 16

What is the key to managing Chronic Granulomatous Disease?

Answer 16

Early diagnosis and prophylactic antimicrobial therapy

Rapid treatment of infections is also crucial.

Question 17

What prophylactic treatment is recommended for CGD?

Answer 17

Cotrimoxazole (daily)

Reduces the incidence of severe bacterial infections by 70%.

Question 18

What are common infections seen in Common Variable Immunodeficiency Disorders?

Answer 18

Recurrent bacterial infections, sinusitis, pneumonia

Chronic pulmonary disease is also common.

Question 19

What characterizes the immunological profile in Common Variable Immunodeficiency?

Answer 19

Decreased production of IgG, low levels of IgA and/or IgM

Weak or absent antibody response to immunizations.

Question 20

What are common autoimmune diseases associated with Common Variable Immunodeficiency?

Answer 20

Autoimmune hemolytic anemia, thrombocytopenic purpura

Other conditions include rheumatoid arthritis and inflammatory bowel disease.

Question 21

What is a common pulmonary complication in patients with Common Variable Immunodeficiency?

Answer 21

Chronic lung disease including bronchiectasis

Can be seen in children under 3 years of age.

Question 22

What are characteristic laboratory findings in Common Variable Immunodeficiency?

Answer 22

Decreased levels of IgG, decreased IgM and/or IgA

Testing vaccine response is important for diagnosis.

Question 23

What is the treatment strategy for infections in Common Variable Immunodeficiency?

Answer 23

Prompt administration of antimicrobial therapy

Treatment may be required for an extended period.

Question 24

What is the first-line treatment for autoimmune cytopenias in CVID?

Answer 24

Glucocorticoids

Higher doses of IVIG may also be considered.

Question 25

What do recognition receptors recognize?

Answer 25

Molecular patterns of microbes with less specificity ## Footnote They are essential to the innate immune response.

Question 26

Where are recognition receptors expressed?

Answer 26

On innate immune cells: neutrophils, macrophages, dendritic cells, and NK and NKT-cells ## Footnote These cells play a crucial role in the immune defense.

Question 27

What does complement activation facilitate?

Answer 27

Elimination of microbes by phagocytes ## Footnote It also links innate and adaptive immune responses.

Question 28

What percentage of patients with PID are affected by primary B-cell immunodeficiencies?

Answer 28

65% ## Footnote These are the most common type of immunodeficiency.

Question 29

List the milder forms of B-cell immunodeficiencies.

Answer 29

* Transient hypogammaglobulinemia of infancy (6.8%) * Selective IgA deficiency (18.7%) * IgG subclass deficiency (12%) * Specific antibody deficiency (1.2%) ## Footnote These milder forms are often less severe than the more profound deficiencies.

Question 30

What are the more severe forms of B-cell immunodeficiencies?

Answer 30

* CVID (37.5%) * Agammaglobulinemia (10.7%) ## Footnote These conditions lead to significant immune system challenges.

Question 31

When do children with XLA typically present with severe infections?

Answer 31

After 3–6 months of life ## Footnote This is due to profound or absent antibody deficiency.

Question 32

What is typically seen on a chest x-ray in infants with XLA?

Answer 32

Normal thymic shadow ## Footnote This differs from infants with SCID.

Question 33

What is included in the workup for B-cell immunodeficiencies?

Answer 33

* CBC * Lymphocyte phenotyping * Measurement of serum immunoglobulins * Specific antibody concentrations ## Footnote These tests help assess immune function.

Question 34

What confirms the diagnosis of XLA?

Answer 34

Lack of BTK protein expression in monocytes by flow cytometry and gene sequencing ## Footnote BTK mutations are critical in XLA.

Question 35

What is the mainstay treatment for B-cell immunodeficiencies?

Answer 35

* IV or subcutaneous immunoglobulin G substitution * Antibiotic prophylaxis and therapy * Prevention of bronchiectasis and other pulmonary complications ## Footnote These treatments help manage infections and maintain immune function.

Question 36

What is SCID?

Answer 36

Severe Combined Immunodeficiency ## Footnote It is a medical emergency during infancy.

Question 37

What are some milder forms of SCID?

Answer 37

* X-linked hyper-IgM syndrome (CD40-ligand deficiency) * DiGeorge syndrome * Ataxia telangiectasia (AT) * Hyper-IgE syndromes ## Footnote These conditions can present with similar but less severe symptoms.

Question 38

What should raise concern for a combined immunodeficiency?

Answer 38

Unexplained infections with opportunistic pathogens ## Footnote These infections indicate a potential failure in immune response.

Question 39

What are the clinical presentations of severe combined immunodeficiencies?

Answer 39

* Lymphopenia * Hypogammaglobulinemia * Recurrent infections by bacteria, viruses, fungi, and opportunistic pathogens ## Footnote The absence of a functional immune response leads to these symptoms.

Question 40

What diagnostic findings are typical for SCID?

Answer 40

* Absent thymic shadow on CXR * Genetic mutations in IL-2RG * Absent or significantly reduced TRECs ## Footnote These findings are crucial for diagnosis.

Question 41

What is the treatment for SCID?

Answer 41

* Prevention of infections * Immunoglobulin G replacement * HSCT * Enzyme replacement therapy (ADA deficiency) ## Footnote Early intervention is vital for survival.

Question 42

What is ataxia telangiectasia?

Answer 42

An autosomal recessive neurodegenerative disease with associated combined immunodeficiency ## Footnote It is caused by mutations in the ATM gene.

Question 43

What are the pulmonary manifestations of ataxia telangiectasia?

Answer 43

* Recurrent upper and lower respiratory infections * Complications like bronchiectasis and ILD ## Footnote These complications can severely impact quality of life.

Question 44

What is a common presentation of hyper-IgE syndromes?

Answer 44

Elevated serum IgE, eosinophilia, eczema, and sinopulmonary infections ## Footnote These symptoms can lead to significant health issues.

Question 45

What genetic mutations are associated with hyper-IgE syndromes?

Answer 45

* Mutations in STAT3 * Mutations in DOCK8 * Mutations in Tyk2 * Mutations in PGM3 ## Footnote These genes are involved in immune signaling and response.

Question 46

What are the diagnostic workup components for hyper-IgE syndromes?

Answer 46

* CBC with differential * Lymphocyte phenotyping * Serum immunoglobulins * Specific antibody concentrations ## Footnote These tests help identify the underlying immunodeficiency.

Question 47

What is the primary treatment for autosomal dominant hyper-IgE syndrome?

Answer 47

Supportive therapy and targeted antimicrobial therapy ## Footnote This includes antibiotic prophylaxis and immunoglobulin G replacement when necessary.