[03.27] Approach to Patient with Suspected Immunodeficiency Disorders V2.1.pdf

Differentiate between self and non-self

What is the most important function of the immune system?

Antigens that are toxic or malignant

What needs to be recognized by the immune system?

Self-antigens and foreign antigens that are harmless

What needs to be ignored by the immune system?

Intracellular (viruses, some bacteria, and parasites) and Extracellular (most bacteria, fungi, and parasites)

What are the two types of pathogens the immune system protects against?

Malignant cells

What is an example of an altered or modified self cell that the immune system eliminates?

Major Histocompatibility Complex (MHC) class I

How are malignant cells presented as abnormal for neutralization?

Altered state of our immune system

What is Immunodeficiency?

Recurrent infections

What is the general theme or main clinical manifestation of immunodeficiency?

Inborn Errors of Immunity (IEI)

What is the current term for Primary Immunodeficiency (PID)?

Born with it (genetic problem/mutation)

What is the defining characteristic of Primary Immunodeficiency (PID)/Inborn Errors of Immunity (IEI)?

Early on, as a child, or first few years of life

When is the typical presentation of Primary Immunodeficiency (PID)?

Acquired over time

How is Secondary Immunodeficiency (SID) characterized?

A consequence of another disease, secondary to environmental factors, or an adverse consequence of medical intervention

What are three possible causes of Secondary Immunodeficiency (SID)?

Burns, major surgeries, emotional stress, lack of sleep

What are four examples of acute states that can cause Secondary Immunodeficiency (SID)?

More common

In terms of epidemiology and incidence, how does Secondary Immunodeficiency (SID) compare to Primary Immunodeficiency (PID)?

Toxoplasmosis, Others (Syphilis, Hepatitis B), Rubella, Cytomegalovirus (CMV), and Herpes simplex

What does the TORCH mnemonic refer to, which can cause secondary immunodeficiency in children while they are in the womb?

Infection, Drugs (e.g., cytotoxic agents, steroids), Protein-losing states, Lymphoreticular malignancies

What are four factors from which an immune defect observed in secondary immunodeficiency clearly results?

Uncontrolled blood sugar (diabetes)

If a patient with diabetes has immunodeficiency, what is the first cause a clinician should think about, rather than PID?

Clinical picture of immunodeficiency

What follows the component of the immune system involved (what is lost, deficient, or abnormal)?

Bone marrow precursor stem cells, Blood cells (Lymphocytes, Neutrophils, Monocytes), Soluble molecules (Antibodies, Cytokines, Complement components)

What are the components of the immune system whose absence or malfunction can cause immunodeficiency?

Clinical presentation and Bugs/pathogens involved

What two factors must a clinician look at when assessing a patient for immunodeficiency?

Medical History and Physical Features

What two steps should always precede Laboratory Testing in diagnosing immunodeficiency?

Unusual, chronic, recurrent infections

What is one clinical feature that should raise suspicion of immunodeficiency?

Brain, liver, or lungs

What are three examples of unusual sites where serious infections may occur in an immunodeficient patient?

Opportunistic infections (e.g., Fungal infections)

What type of infection with unusual pathogens is suspicious for immunodeficiency?

Infections with common pathogens but with unusual severity

What characteristic of common pathogens should raise suspicion of immunodeficiency?

8-10 infections in a year

What is the average number of viral/respiratory tract infections a preschool child going to daycare may have?

If they need drugs or antibiotics to get better

What question should be asked to determine if a child's recurrent infections are concerning for immunodeficiency?

Inborn errors of immunity (IEI)

What foundation contributed to educating people about IEI (formerly PID)?

Four or more

What is the minimum number of new ear infections within one year in a child that is a warning sign of PID?

Two or more

What is the minimum number of new ear infections within one year in an adult that is a warning sign of PID?

Two or more

What is the minimum number of serious sinus infections within one year in a child that is a warning sign of PID?

Two or more

What is the minimum number of sinus infections within one year, in the absence of allergy, in an adult that is a warning sign of PID?

Two or more months on antibiotics with little effect

What warning sign of PID in children relates to antibiotic usage?

Recurrent need for intravenous antibiotics to clear infections

What warning sign of PID in adults relates to antibiotic usage?

One

What is the minimum number of pneumonias per year for more than one year that is a warning sign of PID in children?

Two or more

What is the minimum number of pneumonias within one year that is a warning sign of PID in adults?

Chronic diarrhea with weight loss

What warning sign of PID is specific to adults?

Failure of an infant to gain weight or grow normally

What growth-related warning sign of PID is specific to children?

Recurrent viral infections (e.g., colds, herpes, warts, condyloma)

What warning sign of PID in children is often the biggest clue?

Recurrent, deep skin, or organ abscesses (e.g., liver or lungs)

What deep abscess warning sign is shared by both children and adults?

Persistent thrush in mouth or fungal infection on skin

What fungal infection warning sign in children is concerning, but less so than in adults?

Persistent thrush or fungal infection on skin or elsewhere

What fungal infection warning sign in adults is often never normal?

Thrush

What fungal infection is hardly seen in an adult and is never normal?

Two or more deep-seated infections including septicemia and meningitis

What severe infection warning sign is specific to adults?

Infection with normally harmless tuberculosis-like bacteria

What unusual bacterial infection warning sign is specific to adults?

Extrapulmonary TB or TB of the bones

What manifestation of TB in the Philippines, despite compliance with treatment, is more unusual and concerning for immunodeficiency?

A family history of primary immunodeficiency

What is one of the most important questions to ask when assessing for PID?

Two or more

What number of warning signs in children increases the risk of immunodeficiency?

Complications (e.g., Otitis media $\rightarrow$ mastoiditis; Respiratory infections $\rightarrow$ bronchiectasis)

What often results from chronic respiratory infections in immunodeficient patients?

Pneumonia, meningitis, sepsis

What are three examples of severe bacterial infections in immunodeficient patients?

Pneumocystis, Candida, Aspergillus, Pseudomonas

What are four examples of opportunistic organisms whose infections are possible in immunodeficiency?

Failure to thrive with or without chronic diarrhea

What chronic condition in children is a red flag for immunodeficiency, but must not be mistaken for merely malnutrition?

Malnutrition

What is the most common reason for immunodeficiency worldwide?

Secondary (acquired) immunodeficiencies

What type of immunodeficiency is most commonly caused by malnutrition?

HIV and rubella

What are two examples of maternal illnesses during pregnancy that should be asked about in the patient's history?

IgA deficiency

What specific disease increases the risk of developing adverse reactions to blood transfusions?

Anti-IgA antibodies

What do IgA deficient patients have that reacts to IgA antibodies in transfused blood?

Severe T-cell deficiency (whether combined or single T-cell deficiency)

What condition is a contraindication for live vaccines?

Live vaccine (e.g., live polio)

What may cause a severely T-cell deficient patient to actually contract the disease?

BCG vaccine

What vaccine in the Philippines may cause adverse reactions like granulomas or abscesses in patients with T-cell deficiency?

Relative lack of maturity of secondary lymphoid organs, Innate immunity and immune system affected, Absence of maternal IgG transfer

What are three factors making premature infants more vulnerable to infections?

32 weeks AOG

Before what gestational age does maternal IgG transfer not occur?

Maternal IgG

What protects humoral immunodeficient children for the first few months, delaying the onset of illness?

Diabetes and Renal failure

What are two diseases that can cause secondary immunodeficiencies in adults?

Hypoproteinemia or Hypoalbuminemia

What is the state in renal disease that leads to loss of protein, meaning the immune system cannot make antibodies?

Infectious disease (HIV), Malnutrition, Environmental stress, Age extremes, Surgery and trauma, Immunosuppressive drugs, Genetic and metabolic diseases

What are seven extrinsic factors leading to defects of immune function?

Spleen

What secondary lymphoid organ, if damaged or removed, can lead to insufficient immunoglobulins?

Down’s syndrome

What genetic disease can lead to an immunodeficient state due to anatomic or metabolic problems?

Respiratory anatomy (Eustachian tube less angled), small jaw

What are two anatomic problems that can cause immunodeficiency in patients with Down’s syndrome?

Single most important part of history

What is Family History when assessing risk for primary immunodeficiency?

X-linked or autosomal-recessive inherited traits

What inheritance pattern do many primary immunodeficiencies follow?

Early infant deaths, Recurrent or chronic infection, Lymphoreticular malignancies, Autoimmune disorders

What four conditions should be asked about in the Family History?

Sickle cell disease

What hemoglobinopathy, more common in African-Americans, can cause immunodeficiency due to sickling and clotting?

Chronically ill, exhibit irritability, loss of subcutaneous fat, and pallor

What is the general appearance of patients with immunodeficiency?

Growth

What is an important parameter to plot on growth charts for children?

Small or absent tonsillar, adenoidal, or peripheral lymph node tissues

What physical features of lymphoid tissue may point to immunodeficiency in children who normally have hypertrophic tonsils?

Chronic infectious stimulation and infiltration by other cells

What can cause lymphadenopathy and hepatosplenomegaly in immunodeficiency disorders?

Wiskott-Aldrich syndrome

What B- or T-cell deficiency is associated with Eczema?

Severe combined immunodeficiency diseases

What immunodeficiency is associated with Severe dermatitis?

Lymphocyte adhesion defects and Hyper-IgE syndrome

What two conditions are associated with recurrent skin infections and abscesses?

T-cell defects, Combined immunodeficiencies, and Mucocutaneous candidiasis

What three conditions are associated with oral/nail candidiasis?

Cartilage hair hypoplasia and Chédiak-Higashi syndrome

What two conditions are associated with sparse/hypopigmented hair?

Ataxia telangiectasia

What condition is associated with Ocular telangiectasia?

Chédiak-Higashi syndrome

What condition is associated with Oculo-cutaneous albinism?

Hyper-IgM syndrome

What condition is associated with Oral ulcers?

Neutrophil defects

What immune defect is associated with periodontitis, stomatitis, gingivitis, and dental decay?

Chronic respiratory disease

What condition commonly causes Clubbing (a sign of chronic hypoxia)?

Hypothyroidism

What endocrine condition is associated with DiGeorge Syndrome?

X-linked Agammaglobulinemia

What endocrine condition is associated with Growth hormone deficiency?

Wiskott-Aldrich Syndrome

What hematologic condition is associated with Small platelets?

Hyper-IgM Syndrome

What hematologic condition is associated with Neutropenia?

SCID, ADA deficiency

What two conditions are associated with Bony dysplasia?

T-cells

What component of the immune system, if predominantly affected, usually means B-cells and adaptive responses also have problems (combined defect)?

Recurrent viral and fungal infections

What type of infections are characteristic of T-cell predominant defects?

B-cells

What is the most common possible problem area in immunodeficiency?

Recurrent sinopulmonary infections, Chronic gut or gastrointestinal symptoms, Malabsorption syndromes, Bacterial infections (Pneumococcal, Staphylococcal), rarely viral

What are five characteristic features of B-cell predominant defects (humoral immunodeficiency)?

Abscesses and sterile pus, Staphylococcus infections, No neutrophils in the periphery

What three characteristics are associated with Granulocyte (phagocyte/neutrophil) defects?

Recurrent Neisserial infections

What type of infection is characteristic of Complement defects (e.g., with MAC problems)?

Graft-versus-host disease

What condition is a special consideration that suggests a potential T-cell problem, similar to a vaccine?