Allergy / Immunology Flashcards

1
Q

Type 1 - Acute Response

  • Mast cell degranulation (releasing histamine). ____ is responsible for most of the acute symptoms. Reaction is ____ mediated.
  • Occurs within ___ hour after exposure - usually within minutes.
  • Ex: Insect stings, most drug and some food allergies, seasonal/environment allergies, some cases of asthma

Type 1 - Late-Phase Response
- Occurs ____ hours after the immediate reaction. Lasts hours to days. Usually has an eosinophilic inflammatory infiltrate.

A

Type 1 - Acute Response

  • Mast cell degranulation (releasing histamine). Histamine is responsible for most of the acute symptoms. Reaction is IgE mediated.
  • Occurs within 1 hour after exposure - usually within minutes.
  • Ex: Insect stings, most drug and some food allergies, seasonal/environment allergies, some cases of asthma

Type 1 - Late-Phase Response
- Occurs 3-12 hours after the immediate reaction. Lasts hours to days. Usually has an eosinophilic inflammatory infiltrate.

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2
Q

TYPE 2 - Cytotoxic Hypersensitivity
- Path: ____ antibody binds to a cell receptor or fixed-tissue antigen. These are autoantibodies. Meditated by antibodies other than IgE. The antibodies target body tissue instead of foreign stimuli.

  • In general, reactions are chronic.
  • Classic examples: ____ disease (IgA in lungs and kidneys), ___, ___ disease, ___ pemphigoid, ___, hemolytic disease of the newborn
A

TYPE 2 - Cytotoxic Hypersensitivity
- Path: IgG or IgM antibody binds to a cell receptor or fixed-tissue antigen. These are autoantibodies. Meditated by antibodies other than IgE. The antibodies target body tissue instead of foreign stimuli.

  • In general, reactions are chronic.
  • Classic examples: Goodpasture disease (IgA in lungs and kidneys), AIHA, Graves disease, bullous pemphigoid, ITP, hemolytic disease of the newborn
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3
Q

TYPE 3: Immune Complex Hypersensitivity
- A hypersensitivity reaction occurs when an antibody (usually IgG) reacts with a target antigen to form ____s, which precipitate and activate complement with small vessel inflammation and necrosis.

  • Typically systemic illnesses
  • Examples: ___, ___, ___, ___
A

TYPE 3: Immune Complex Hypersensitivity
- A hypersensitivity reaction occurs when an antibody (usually IgG) reacts with a target antigen to form ICs, which precipitate and activate complement with small vessel inflammation and necrosis.

  • Typically systemic illnesses
  • Examples: Rheumatoid arthritis, SLE, glomerulonephritides, serum sickness
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4
Q

TYPE 4: Cell-Mediated Delayed-Type Hypersensitivity

  • Path: _____ dependent.
    • Reaction peaks in 24-72 hours.
    • NOT antibody or complement mediated. It is a _____ response
  • Ex: ____, some types of contact dermatitis, delayed-type hypersensitivity component of asthma, ___ dermatitis
A

TYPE 4: Cell-Mediated Delayed-Type Hypersensitivity

  • Path: T-cell dependent.
    • Reaction peaks in 24-72 hours.
    • NOT antibody or complement mediated. It is a DELAYED response
  • Ex: Tuberculin sensitivity (PPD test for Tb), some types of contact dermatitis, delayed-type hypersensitivity component of asthma
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5
Q

Contrast-mediated reactions

  • Are caused by ___ release from basophils and mast cells. The true cause of this hypersensitivity is unknown, but it is known that unlike true type 1 hypersensitivity reactions, ___ is NOT involved.
  • RFs: Previous allergic-like/anaphylactoid reaction, atopy, using beta blockers
    • There is no evidence that sensitivity to __ or __ predisposes to radiocontrast media reactions.
A

Contrast-mediated reactions

  • Are caused by histamine release from basophils and mast cells. The true cause of this hypersensitivity is unknown, but it is known that unlike true type 1 hypersensitivity reactions, IgE is NOT involved.
  • RFs: Previous allergic-like/anaphylactoid reaction, atopy, using beta blockers
    • There is no evidence that sensitivity to seafood or iodine predisposes to radiocontrast media reactions.
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6
Q

ANAPHYLAXIS

  • Path: Type 1 IgE mediated allergic reaction
  • Note that ASA-induced anaphylaxis is a separate syndrome from ASA-induced urticaria; both of these are separate from ASA-induced asthma, which is often associated with rhinosinusitis and polyps (Samter triad)
  • Pt:
    • Symptoms develop within 1 hour of exposure. Usually begins within 5-10 mins after antigen exposure but can be delayed up to 2 hours.
    • Involves TWO organ systems
      • Urticaria (rash), pruritus, angioedema, flushing
        • Urticaria and angioedema are the most common manifestations of anaphylaxis, followed by flushing and respiratory tract symptoms in approx 50% of those affected.
      • Cough, wheezing, stridor, dyspnea
      • GI: nausea, emesis, diarrhea
      • Hypotension is a late finding
A

ANAPHYLAXIS

  • Path: Type 1 IgE mediated allergic reaction
  • Note that ASA-induced anaphylaxis is a separate syndrome from ASA-induced urticaria; both of these are separate from ASA-induced asthma, which is often associated with rhinosinusitis and polyps (Samter triad)
  • Pt:
    • Symptoms develop within 1 hour of exposure. Usually begins within 5-10 mins after antigen exposure but can be delayed up to 2 hours.
    • Involves TWO organ systems
      • Urticaria (rash), pruritus, angioedema, flushing
        • Urticaria and angioedema are the most common manifestations of anaphylaxis, followed by flushing and respiratory tract symptoms in approx 50% of those affected.
      • Cough, wheezing, stridor, dyspnea
      • GI: nausea, emesis, diarrhea
      • Hypotension is a late finding
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7
Q
  • Dx: Clinical, meet any 1 of 3 diagnostic criteria by the World Allergy Organization
      1. Acute onset (within mins-several hours) of signs/symptoms involving the skin, mucosal tissue, or both (eg generalized urticaria, itching or flushing of skin, swollen lips/tongue/uvula) AND at least 1 of the following
        - Respiratory compromise (eg dyspnea, wheeze/bronchospasm, stridor, hypoxia)
        - Decreased BP or associated symptoms of end-organ dysfunction (eg fainting, dizziness, incontinence)
      1. > 2 of the following occurring acutely after exposure to a likely allergen
        - Involvement of the skin and/or mucosal tissue
        • 80-90% of anaphylactic reactions have some cutaneous manifestations (commonly urticaria and/or angioedema)
          - Respiratory compromise
          - Decreased BP or associated symptoms of end-organ dysfunction
          - Persistent GI symptoms (eg crampy abdominal pain, nausea, vomiting, diarrhea)
      1. Decreased BP following exposure to a known allergen (low age-specific SBP OR a decrease in SBP by 30% or more in infants/children)
A
  • Dx: Clinical, meet any 1 of 3 diagnostic criteria by the World Allergy Organization
      1. Acute onset (within mins-several hours) of signs/symptoms involving the skin, mucosal tissue, or both (eg generalized urticaria, itching or flushing of skin, swollen lips/tongue/uvula) AND at least 1 of the following
        - Respiratory compromise (eg dyspnea, wheeze/bronchospasm, stridor, hypoxia)
        - Decreased BP or associated symptoms of end-organ dysfunction (eg fainting, dizziness, incontinence)
      1. > 2 of the following occurring acutely after exposure to a likely allergen
        - Involvement of the skin and/or mucosal tissue
        • 80-90% of anaphylactic reactions have some cutaneous manifestations (commonly urticaria and/or angioedema)
          - Respiratory compromise
          - Decreased BP or associated symptoms of end-organ dysfunction
          - Persistent GI symptoms (eg crampy abdominal pain, nausea, vomiting, diarrhea)
      1. Decreased BP following exposure to a known allergen (low age-specific SBP OR a decrease in SBP by 30% or more in infants/children)
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8
Q
  • Tx:
    • *IM Epinephrine 0.__mg/kg (max 0.5mg) 1:___ for immediate response.
      • Epipen: for less than ___kg, pediatric version ____mg (Epipen Jr). For >___kg, use adult version ___mg.
      • The effects of epinephrine are blunted in pts on beta-blockers, so they are relatively contraindicated in pts at risk of anaphylactic reaction. Suspect beta-blockade if response to epinephrine is poor.
    • Pts with evidence of hypotension or shock are immediately given a bolus of normal saline IV. In addition, given epinephrine 0.01mg/kg (max 0.5mg) IM every 15-20 mins as needed.
    • Oral benadryl
      • H1/H2 blockers, usually diphenhydramine and cimetidine, for response in 30-40 mins. Help relieve hives but not the airway swelling or shock.
  • Prevention (3 As)
    • Avoidance of the allergen
    • Antihistamines (occasionally steroids)
      • Patients with hx of anaphylactoid reactions to contrast should receive ___ AND ___ prior to the next administration of IV contrast.
    • Allergen-specific immunotherapy. Takes up to 1 year to show an effect, with maximal effect in 3 years
A
  • Tx:
    • *IM Epinephrine 0.01mg/kg (max 0.5mg) 1:1000 for immediate response.
      • Epipen: for <30kg, use pediatric version 0.15mg (Epipen Jr). For >30kg, use adult version 0.3mg.
      • The effects of epinephrine are blunted in pts on beta-blockers, so they are relatively contraindicated in pts at risk of anaphylactic reaction. Suspect beta-blockade if response to epinephrine is poor.
    • Pts with evidence of hypotension or shock are immediately given a bolus of normal saline IV. In addition, given epinephrine 0.01mg/kg (max 0.5mg) IM every 15-20 mins as needed.
    • Oral benadryl
      • H1/H2 blockers, usually diphenhydramine and cimetidine, for response in 30-40 mins. Help relieve hives but not the airway swelling or shock.
  • Prevention (3 As)
    • Avoidance of the allergen
    • Antihistamines (occasionally steroids)
      • Patients with hx of anaphylactoid reactions to contrast should receive diphenhydramine AND corticosteroids prior to the next administration of IV contrast.
    • Allergen-specific immunotherapy. Takes up to 1 year to show an effect, with maximal effect in 3 years
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9
Q

ANGIOEDEMA

  • Pt: Subcutaneous swelling, particularly of the lips, mouth, face, and throat
  • For isolated angioedema without urticaria, consider ACE inhibitor-induced angioedema or hereditary angioedema.
A

ANGIOEDEMA

  • Pt: Subcutaneous swelling, particularly of the lips, mouth, face, and throat
  • For isolated angioedema without urticaria, consider ACE inhibitor-induced angioedema or hereditary angioedema.
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10
Q

URTICARIA

  • Pt:
    • Wheel, erythema, but no hypotension. TRUE urticaria due to allergy will resolve within 24 hours. Urticaria due to viral infection (most common reason for urticaria in pediatrics) may last longer like a week
A

URTICARIA

  • Pt:
    • Wheel, erythema, but no hypotension. TRUE urticaria due to allergy will resolve within 24 hours. Urticaria due to viral infection (most common reason for urticaria in pediatrics) may last longer like a week
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11
Q

Acute Urticaria
- Superficial, raised, blanching, transient, pruritic skin lesions that have been present for less than ___ weeks, usually lasting for 24-48 hours.

A

Acute Urticaria
- Superficial, raised, blanching, transient, pruritic skin lesions that have been present for <6 weeks, usually lasting for 24-48 hours.

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12
Q

Chronic Urticaria
- Urticaria lasting >___ weeks

  • Causes:
    • Majority (~80%) of chronic urticarial cases in the past were considered idiopathic.
      • With the identification of the important role of autoimmunity, ~60% of these previously idiopathic chronic urticaria pts are now considered to have _______ etiologies.
        • These pts also have high rates of autoimmune diseases, such as autoimmune hypothyroidism, hyperthyroidism (Graves), SLE, JIA, and RA.
    • Physical urticarias (urticaria to cold, heat, pressure, vibration, sunlight, and water (aquagenic)
      • Acquired cold urticaria
      • Familial cold urticaria
      • Cholinergic urticaria
      • Immediate pressure urticaria
      • Delayed pressure urticaria
    • One unique situation of a delayed food reaction that can cause hives 3-6 hours after a meal consisting of mammalian meat. This is when a pt is sensitized to ______ (“alpha-gal”), which is a carbohydrate allergen. Alpha-Gal has been identified as an allergen that is linked to tick bites.
      • Dx: ______
  • Associated disorders:
    • Autoimmune disorders: celiac disease, Sjogren, SLE, RA, DM1
    • Thyroid disorders: Hypo and hyperthyroidism, check _____!
    • Malignancy
  • Dx:
    • Exclude drugs and systemic signs/diseases.
  • Work-up: Do NOT send any routine labs (eg CBC, BMP, ESR, C3, C4, ANA) in the initial workup unless guided by hx and physical. Serum tests for allergen-specific IgE antibodies are appropriate if hx suggests a probable trigger.
    • Lab tests are unlikely to reveal abnormalities
A

Chronic Urticaria
- Urticaria lasting >6 weeks

  • Causes:
    • Majority (~80%) of chronic urticarial cases in the past were considered idiopathic.
      • With the identification of the important role of autoimmunity, ~60% of these previously idiopathic chronic urticaria pts are now considered to have autoimmune etiologies.
        • These pts also have high rates of autoimmune diseases, such as autoimmune hypothyroidism, hyperthyroidism (Graves), SLE, JIA, and RA.
    • Physical urticarias (urticaria to cold, heat, pressure, vibration, sunlight, and water (aquagenic)
      • Acquired cold urticaria
      • Familial cold urticaria
      • Cholinergic urticaria
      • Immediate pressure urticaria
      • Delayed pressure urticaria
    • One unique situation of a delayed food reaction that can cause hives 3-6 hours after a meal consisting of mammalian meat. This is when a pt is sensitized to galactose-alpha-1,3-galactose (“alpha-gal”), which is a carbohydrate allergen. Alpha-Gal has been identified as an allergen that is linked to tick bites.
      • Dx: IgE to galactose-alpha-1,3-galactose
  • Associated disorders:
    • Autoimmune disorders: celiac disease, Sjogren, SLE, RA, DM1
    • Thyroid disorders: Hypo and hyperthyroidism, check TSH!
    • Malignancy
  • Dx:
    • Exclude drugs and systemic signs/diseases.
  • Work-up: Do NOT send any routine labs (eg CBC, BMP, ESR, C3, C4, ANA) in the initial workup unless guided by hx and physical. Serum tests for allergen-specific IgE antibodies are appropriate if hx suggests a probable trigger.
    • Lab tests are unlikely to reveal abnormalities
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13
Q

Chronic Urticaria

  • Tx:
    • Reassurance
    • Most do well with only _______ and avoiding known triggers
      • Sedating H1 blockers are the most effective treatment for common transient urticaria
        • 1st generation: Benadryl ((1mg/kg, max 25mg), short acting) and hydroxyzine are commonly used
        • 2nd generation: Antihistamines that block the H1 receptor and are less sedating compared to diphenhydramine include fexofenadine, loratadine, desloratadine, cetirizine, and levocetirizine.
      • Antihistamines that block H2 receptor include cimetidine, ranitidine, and famotidine.
    • Another set of medications that can be used include leukotriene pathway modifiers such as montelukast and zafirlukast.
    • A short course of corticosteroids is generally NOT recommended as 1st line therapy.
  • Tx:
    • Step 1: 2nd generation H1 antihistamines (Cetirizine/Zyrtec, Loratadine/Claritin, Fexofenadine/Allegra)
    • Step 2: One or more of the following
      • Increasing dose of 2nd generation H1 antihistamine to up to 4x standard dose
      • Add 2nd generation antihistamine
      • Adding H2 antagonist (famotidine, ranitidine, cimetidine)
      • Adding leukotriene-receptor antagonist (Montelukast)
      • Adding 1st generation H1 antihistamine at bedtime (diphenhydramine/Benadryl)
    • Step 3: Increase dose of 1st generation H1 antihistamine
    • Step 4 (Refractory disease):
      • Omalizumab (antiE antibody) injections subq every 4 weeks
      • Cyclosporine or tacrolimus
  • Prognosis
    • Self-limited and episodic disease in majority of patients.
A

Chronic Urticaria

  • Tx:
    • Reassurance
    • Most do well with only antihistamines and avoiding known triggers
      • Sedating H1 blockers are the most effective treatment for common transient urticaria
        • 1st generation: Benadryl ((1mg/kg, max 25mg), short acting) and hydroxyzine are commonly used
        • 2nd generation: Antihistamines that block the H1 receptor and are less sedating compared to diphenhydramine include fexofenadine, loratadine, desloratadine, cetirizine, and levocetirizine.
      • Antihistamines that block H2 receptor include cimetidine, ranitidine, and famotidine.
    • Another set of medications that can be used include leukotriene pathway modifiers such as montelukast and zafirlukast.
    • A short course of corticosteroids is generally NOT recommended as 1st line therapy.
  • Tx:
    • Step 1: 2nd generation H1 antihistamines (Cetirizine/Zyrtec, Loratadine/Claritin, Fexofenadine/Allegra)
    • Step 2: One or more of the following
      • Increasing dose of 2nd generation H1 antihistamine to up to 4x standard dose
      • Add 2nd generation antihistamine
      • Adding H2 antagonist (famotidine, ranitidine, cimetidine)
      • Adding leukotriene-receptor antagonist (Montelukast)
      • Adding 1st generation H1 antihistamine at bedtime (diphenhydramine/Benadryl)
    • Step 3: Increase dose of 1st generation H1 antihistamine
    • Step 4 (Refractory disease):
      • Omalizumab (antiE antibody) injections subq every 4 weeks
      • Cyclosporine or tacrolimus
  • Prognosis
    • Self-limited and episodic disease in majority of patients.
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14
Q

Urticarial Vasculitis
- Pt: Painful, long-lasting wheals 48-72 hours in a fixed location (characteristic) (in contrast to chronic urticaria, which resolves in minutes to hours or migrates continually)

- Can resemble chronic urticaria. However, pts report hives lasting >\_\_h in a \_\_\_\_ location (in contrast to chronic urticaria, which resolves in mins-hours or migrate continually). Other red flags include residual \_\_\_\_\_, hyperpigmentation, or purpura.  - Can be associated with an underlying autoimmune disease, most commonly SLE. Therefore, pts should be appropriately evaluated. - Abnormal lab findings include elevated ER, positive ANA, and hypocomplementemia. - Dx: \_\_\_\_\_
A

Urticarial Vasculitis
- Pt: Painful, long-lasting wheals 48-72 hours in a fixed location (characteristic) (in contrast to chronic urticaria, which resolves in minutes to hours or migrates continually)

- Can resemble chronic urticaria. However, pts report hives lasting >24 h in a fixed location (in contrast to chronic urticaria, which resolves in mins-hours or migrate continually). Other red flags include residual ecchymosis, hyperpigmentation, or purpura.  - Can be associated with an underlying autoimmune disease, most commonly SLE. Therefore, pts should be appropriately evaluated. - Abnormal lab findings include elevated ER, positive ANA, and hypocomplementemia. - Dx: Skin biopsy
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15
Q

ALLERGIC RHINITIS

  • RFs: Female gender, a serum total IgE >100 IU/mL before the age of 6, particulate air pollution and maternal smoking.
  • Protective factors against the development of rhinitis: Number of siblings at home, use of day care, increased grass pollen counts, living on a farm, Mediterranean diet
  • Pt:
    • The “_____” occurs with frequent rubbing of the nose and can progress to a transverse nasal crease.
    • ____ lines are folds below the eyes due to edema; they frequently accompany allergic shiners.
    • The nasal mucosa is usually swollen and pale.
      • Pale turbinates is likely due to allergies. Red turbinates is likely due to viral infection.
    • “____” of the posterior oropharynx is due to chronic post-nasal discharge.
  • Tx:
    • Avoidance of triggers.
      • Dust mites are a common source of perennial AR.
        • Impermeable, zippered covers on mattresses, box springs, and pillows considerably reduce the amount of dust mite allergen in the bedroom by trapping the allergen in its main reservoirs! If coupled with laundering of all bed linens at least every other week, dust mite allergen recovery from bed surfaces is reduced by as much as 90%.
        • Effects methods of reducing dust mite exposure: Removing upholstered furniture, heavy draperies, encasing bedding in airtight allergen-impermeable covers, washing bedding weekly in water at temps >130F, removing wall-to-wall carpeting, replacing curtains with blinds, and controlling humidity.
        • Dust mites require a relative humidity >50% to be most viable, so suggest measures to reduce in-home humidity. Regular use of humidifiers and evaporative coolers promote dust mite survival, as dust mites do not survive in humidity <50%.
    • ______ are 1st line and are the most effective agent for nasal allergies
    • Other options are 2nd generation antihistamines (cetirizine, singulair).
      • 1st generation histamine blockers (diphenhydramine, chlorpheniramine, and hydroxyzine) have the major side effect of sedation.
      • 2nd generation antihistamines (eg cetirizine, fexofenadine, loratadine) do not cross the blood-brain barrier as much and are more specifically aimed at the H1 receptor and not the other receptors.
    • Allergen-specific immunotherapy, or desensitization, is generally the last resort in therapy.
      • The most common side effect from allergy immunotherapy is the development of a large local reaction, but this is NOT a contraindication to therapy.
      • Contraindications:
        • Poorly controlled ________ (majority of deaths occur in these patients)
          • Pts with poorly controlled asthma should not receive AIT bc AIT can potentially induce a severe asthma exacerbation.
        • _______ disease
        • _____ and _____. Beta-blockers decrease response to epinephrine that may be needed to combat adverse reactions and ACE-i can accentuate angioedema.
        • Malignancy, autoimmune disease, immunodeficiency syndrome (concern that therapy may worsen underlying disease)
        • It is NEVER attempted in patients with hx of reactions involving significant skin desquamation, such as________, bc even small doses of the drug may induce irreversible and potentially fatal recurrent desquamative reactions. _____ and diffuse erythroderma with desquamation are other types of reactions for which desensitization should not be attempted. Desensitization is also not indicated for serum sickness reaction, nephritis, hepatitis, and other severe non IgE-mediated reactions.
A

ALLERGIC RHINITIS

  • RFs: Female gender, a serum total IgE >100 IU/mL before the age of 6, particulate air pollution and maternal smoking.
  • Protective factors against the development of rhinitis: Number of siblings at home, use of day care, increased grass pollen counts, living on a farm, Mediterranean diet
  • Pt:
    • The “nasal salute” occurs with frequent rubbing of the nose and can progress to a transverse nasal crease.
    • Dennie-Morgan lines are folds below the eyes due to edema; they frequently accompany allergic shiners.
    • The nasal mucosa is usually swollen and pale.
      • Pale turbinates is likely due to allergies. Red turbinates is likely due to viral infection.
    • “Cobblestoning” of the posterior oropharynx is due to chronic post-nasal discharge.
  • Tx:
    • Avoidance of triggers.
      • Dust mites are a common source of perennial AR.
        • Impermeable, zippered covers on mattresses, box springs, and pillows considerably reduce the amount of dust mite allergen in the bedroom by trapping the allergen in its main reservoirs! If coupled with laundering of all bed linens at least every other week, dust mite allergen recovery from bed surfaces is reduced by as much as 90%.
        • Effects methods of reducing dust mite exposure: Removing upholstered furniture, heavy draperies, encasing bedding in airtight allergen-impermeable covers, washing bedding weekly in water at temps >130F, removing wall-to-wall carpeting, replacing curtains with blinds, and controlling humidity.
        • Dust mites require a relative humidity >50% to be most viable, so suggest measures to reduce in-home humidity. Regular use of humidifiers and evaporative coolers promote dust mite survival, as dust mites do not survive in humidity <50%.
    • Intranasal corticosteroids (Flonase) are 1st line and are the most effective agent for nasal allergies
    • Other options are 2nd generation antihistamines (cetirizine, singulair).
      • 1st generation histamine blockers (diphenhydramine, chlorpheniramine, and hydroxyzine) have the major side effect of sedation.
      • 2nd generation antihistamines (eg cetirizine, fexofenadine, loratadine) do not cross the blood-brain barrier as much and are more specifically aimed at the H1 receptor and not the other receptors.
    • Allergen-specific immunotherapy, or desensitization, is generally the last resort in therapy.
      • The most common side effect from allergy immunotherapy is the development of a large local reaction, but this is NOT a contraindication to therapy.
      • Contraindications:
        • Poorly controlled asthma (majority of deaths occur in these patients)
          • Pts with poorly controlled asthma should not receive AIT bc AIT can potentially induce a severe asthma exacerbation.
        • Cardiac disease
        • ACE-inhibitors and Beta-blockers. Beta-blockers decrease response to epinephrine that may be needed to combat adverse reactions and ACE-i can accentuate angioedema.
        • Malignancy, autoimmune disease, immunodeficiency syndrome (concern that therapy may worsen underlying disease)
        • It is NEVER attempted in patients with hx of reactions involving significant skin desquamation, such as Steven-Johnson syndrome or TEN, bc even small doses of the drug may induce irreversible and potentially fatal recurrent desquamative reactions. Erythema multiforme and diffuse erythroderma with desquamation are other types of reactions for which desensitization should not be attempted. Desensitization is also not indicated for serum sickness reaction, nephritis, hepatitis, and other severe non IgE-mediated reactions.
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16
Q

FOOD ALLERGIES (IGE-MEDIATED)

  • Common triggers: WEMPS:
    • W___
    • E___
    • M___
    • P___
    • S____
  • While allergies to milk, egg, wheat, and soy often resolve during childhood (85% of children) (the ones commonly outgrown by 5yo are the only ones with <5 letters), allergies to ___, ___, and ____ are more likely to persist (only 20% of children outgrow).
  • Tx:
    • Pts with severe food allergy must be prescribed an epinephrine autoinjector and trained in how to use it.
    • Avoid triggers and eliminate offending food from child’s diet.
    • Allergy-specific Immunotherapy (AIT) approaches that introduce the allergen in small doses to desensitize the immune system to that allergen have emerged in recent years and are offered in specialty settings for select pts.
  • In the absence of a recent reaction, many allergists recommend annual retesting for milk, egg, wheat, and soy allergies, and less frequent retesting for allergies more likely to persist.
A

FOOD ALLERGIES (IGE-MEDIATED)

  • Common triggers: WEMPS:
    • Wheat
    • Eggs
    • Milk and soy
    • Peanuts and treenuts
    • Seafood (crustacean shellfish and fish)
  • While allergies to milk, egg, wheat, and soy often resolve during childhood (85% of children) (the ones commonly outgrown by 5yo are the only ones with <5 letters), allergies to peanuts, tree nuts, and shellfish are more likely to persist (only 20% of children outgrow).
  • Tx:
    • Pts with severe food allergy must be prescribed an epinephrine autoinjector and trained in how to use it.
    • Avoid triggers and eliminate offending food from child’s diet.
    • Allergy-specific Immunotherapy (AIT) approaches that introduce the allergen in small doses to desensitize the immune system to that allergen have emerged in recent years and are offered in specialty settings for select pts.
  • In the absence of a recent reaction, many allergists recommend annual retesting for milk, egg, wheat, and soy allergies, and less frequent retesting for allergies more likely to persist.
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17
Q

Prevention of food allergies

  • Feeding _____ formula during first 4 months of life may help prevent development of both atopic and cow milk protein allergy.
  • Delaying introduction of solid foods or highly allergenic foods does not decrease the risk of developing food allergies.
A

Prevention of food allergies

  • Feeding hydrolyzed formula during first 4 months of life may help prevent development of both atopic and cow milk protein allergy.
  • Delaying introduction of solid foods or highly allergenic foods does not decrease the risk of developing food allergies.
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18
Q

Guidelines for prevention of peanut allergies

  • Infant criteria
    • Severe eczema, egg allergy, or both
      • Rec: Strongly consider evaluation by sIgE measurement and/or skin prick test
    • Mild-moderate eczema
      • Rec: Introduce peanut-containing foods around 6mo
    • No eczema or any food allergy
      • Rec: Introduce peanut-containing foods at appropriate age in accordance with family preferences and culture practice
A

Guidelines for prevention of peanut allergies

  • Infant criteria
    • Severe eczema, egg allergy, or both
      • Rec: Strongly consider evaluation by sIgE measurement and/or skin prick test
    • Mild-moderate eczema
      • Rec: Introduce peanut-containing foods around 6mo
    • No eczema or any food allergy
      • Rec: Introduce peanut-containing foods at appropriate age in accordance with family preferences and culture practice
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19
Q

Cow’s milk allergy (CMA)

  • Path: ___ Mediated
  • Tx: ___ formula
  • Ppx: ____ during the first 4-6mo after birth reduces the risk for cow milk protein allergy.
A

Cow’s milk allergy (CMA)

  • Path: IgE Mediated
  • Tx: Soy formula
  • Ppx: Exclusive breastfeeding during the first 4-6mo after birth reduces the risk for cow milk protein allergy.
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20
Q

Latex Allergy
- Development of latex allergy in children mainly occurs in those with a condition that gives them an increased exposure to latex-containing products (eg ____, congenital ____ problems).

  • The main RFs for development of latex allergy in children with spina bifida are the number of surgeries, total serum IgE, presence of a VP shunt, and a personal hx of atopy.
    • Greatest RF for all children (not just spina bifida) is multiple surgeries at an early age.
  • Interestingly, several fruits and vegs cross-react with latex. While these pts can show a high IgE level to multiple fruits, vegs, and nuts, the main ones that show clinical relevance are: PKB PACT (PeeKaBoo PACT)
    • __, __, __
    • __, __, __, __
A

Latex Allergy
- Development of latex allergy in children mainly occurs in those with a condition that gives them an increased exposure to latex-containing products (eg spina bifida, congenital urologic problems).

  • The main RFs for development of latex allergy in children with spina bifida are the number of surgeries, total serum IgE, presence of a VP shunt, and a personal hx of atopy.
    • Greatest RF for all children (not just spina bifida) is multiple surgeries at an early age.
  • Interestingly, several fruits and vegs cross-react with latex. While these pts can show a high IgE level to multiple fruits, vegs, and nuts, the main ones that show clinical relevance are: PKB PACT (PeeKaBoo PACT)
    • Papaya, Kiwi, Banana (fruits)
    • Potato, Avocado, Chestnut, Tomato (nuts and vegs)
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21
Q

Allergy to penicillin

  • Only 2% (1-3%) of individuals with a penicillin allergy are expected to react to cephalosporins
  • Desensitization is a procedure using gradually increasing doses of penicillin to induce a _____ state of drug tolerance.
A

Allergy to penicillin

  • Only 2% (1-3%) of individuals with a penicillin allergy are expected to react to cephalosporins
  • Desensitization is a procedure using gradually increasing doses of penicillin to induce a TEMPORARY state of drug tolerance.
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22
Q

ALLERGY TESTING

  • All patients with reactions to penicillin antibiotics should receive skin allergy testing to confirm this allergy.
  • 2 main forms of allergy testing: Positive results on both allergy skin testing and a serum allergy test only suggest sensitivity to a potential allergen, but a negative test is strong evidence against allergy to that substance.
  • Pts must be off antihistamines for a minimum of ___ hours (4 half-lives of the medications) before skin testing bc these often blunt the response and give a false-negative reaction. Short-term steroids do not block skin testing for immediate hypersensitivity but do interfere with delayed hypersensitivity!
    • Most medications should be stopped approx 5-7 days before performing test.
    • Medications such as H1 blockers, H2 blockers (ranitidine), ___s, ____ antidepressants, and ________ should be avoided prior to performing test.
      • TCAs have antihistaminergic properties, so these medications should be avoided as they can suppress allergy skin test results.
      • ______ are a relative contraindication to allergy skin testing.
  • Radioallergosorbent test (RAST): Serum allergen-specific IgE (sIgE) levels, which quantify IgE levels to specific foods.
    • RAST is generally considered 2nd line by most allergists bc it is less sensitive compared to skin testing, and it measures IgE levels rather than directly measuring histamine release caused by IgE receptors signaling on mast cells. IgE levels alone do a poor job of predicting whether the pt has an actual allergy.
    • Circumstances where RAST may be preferred
      • Skin testing is inconvenient or difficult to perform
      • Some patients cannot undergo skin testing bc of skin disease that would obscure wheal and flare results (eg extensive ____) or bc they cannot stop taking medications that suppress the skin test response
      • Children less than ___yo
A

ALLERGY TESTING

  • All patients with reactions to penicillin antibiotics should receive skin allergy testing to confirm this allergy.
  • 2 main forms of allergy testing: Positive results on both allergy skin testing and a serum allergy test only suggest sensitivity to a potential allergen, but a negative test is strong evidence against allergy to that substance.
  • Pts must be off antihistamines for a minimum of 72 hours (4 half-lives of the medications) before skin testing bc these often blunt the response and give a false-negative reaction. Short-term steroids do not block skin testing for immediate hypersensitivity but do interfere with delayed hypersensitivity!
    • Most medications should be stopped approx 5-7 days before performing test.
    • Medications such as H1 blockers, H2 blockers (ranitidine), TCAs, atypical antidepressants, and benzodiazepines should be avoided prior to performing test.
      • TCAs have antihistaminergic properties, so these medications should be avoided as they can suppress allergy skin test results.
      • Beta blockers are a relative contraindication to allergy skin testing.
  • Radioallergosorbent test (RAST): Serum allergen-specific IgE (sIgE) levels, which quantify IgE levels to specific foods.
    • RAST is generally considered 2nd line by most allergists bc it is less sensitive compared to skin testing, and it measures IgE levels rather than directly measuring histamine release caused by IgE receptors signaling on mast cells. IgE levels alone do a poor job of predicting whether the pt has an actual allergy.
    • Circumstances where RAST may be preferred
      • Skin testing is inconvenient or difficult to perform
      • Some patients cannot undergo skin testing bc of skin disease that would obscure wheal and flare results (eg extensive atopic dermatitis) or bc they cannot stop taking medications that suppress the skin test response
      • Children <2yo
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23
Q

Food Protein-Induced Proctocolitis FPIAP / Cow Milk Protein Allergy / Allergic Colitis
- Path: ____ mediated type __ hypersensitivity reaction to very large milk protein, cause inflammatory response in distal colon

  • Typically presents in the first few months after birth, with a mean age at onset of 2mo.
  • Trigger: Milk and protein are the most common. Possible cross-reactivity with soy, egg, corn
  • Pt:
    • Enterocolitis with abdominal distension, diarrhea, ____ in infancy between 2-8 weeks of age.
  • Tx:
    • Eliminate exposure to culprit food
    • For formula-fed infant, use ____ formula with protein partially broken down, such as Similac Alimentum. In some cases, an ___ formula will be needed.
    • For breastfeeding infant, remove ___, all ___, and ___ in mother’s diet (for 2-4 weeks first as challenge). With complete elimination, bleeding typically clears within 1-2 weeks.
      • With elimination of cow’s milk and dairy products from the maternal diet, infant’s symptoms should resolve within 3-4 days. If pts have persistent symptoms (ie persistent mucus and blood in stool), the next recommendation is to eliminate all soy, followed by each of the following: eggs, nuts, wheat, corn, strawberries, citrus, and chocolate.
  • Prognosis: Generally spontaneously resolves before ___mo (50% by 6 months and 80-90% by 2 years). Planned reintroduction (around 9 mo)
A

Food Protein-Induced Proctocolitis FPIAP / Cow Milk Protein Allergy / Allergic Colitis
- Path: Non-IgE mediated type 4 hypersensitivity reaction to very large milk protein, cause inflammatory response in distal colon

  • Typically presents in the first few months after birth, with a mean age at onset of 2mo.
  • Trigger: Milk and protein are the most common. Possible cross-reactivity with soy, egg, corn
  • Pt:
    • Enterocolitis with abdominal distension, diarrhea, bloody bowel movement/rectal bleeding in infancy between 2-8 weeks of age.
  • Tx:
    • Eliminate exposure to culprit food
    • For formula-fed infant, use extensively hydrolyzed formula with protein partially broken down, such as Similac Alimentum. In some cases, an amino acid-based formula will be needed.
    • For breastfeeding infant, remove cow’s milk, all dairy (butter, cream), and soy (and eggs) in mother’s diet (for 2-4 weeks first as challenge). With complete elimination, bleeding typically clears within 1-2 weeks.
      • With elimination of cow’s milk and dairy products from the maternal diet, infant’s symptoms should resolve within 3-4 days. If pts have persistent symptoms (ie persistent mucus and blood in stool), the next recommendation is to eliminate all soy, followed by each of the following: eggs, nuts, wheat, corn, strawberries, citrus, and chocolate.
  • Prognosis: Generally spontaneously resolves before 12mo (50% by 6 months and 80-90% by 2 years). Planned reintroduction (around 9 mo)
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24
Q

Food protein-induced enterocolitis syndrome (FPIES)
- Path: ____ mediated responses to food involving the small intestine and stomach

  • Common triggers: cow’s milk, soy formulas, solid foods (rice, oat, grains, egg, vegs, poultry, fish)
  • Pt: Typically occurs in infants between 1 week and 3 months of age.
    • Profuse, protracted/repetitive vomiting, often with diarrhea (watery or bloody), abdominal distension, leading to dehydration and lethargy in the acute setting (often requiring rehydration), or weight loss and failure to thrive in a chronic form.
  • Tx:
    • May be medical emergency and requires _____
    • Long-term management requires ____
A

Food protein-induced enterocolitis syndrome (FPIES)
- Path: Non-IgE mediated responses to food involving the small intestine and stomach

  • Common triggers: cow’s milk, soy formulas, solid foods (rice, oat, grains, egg, vegs, poultry, fish)
  • Pt: Typically occurs in infants between 1 week and 3 months of age.
    • Profuse, protracted/repetitive vomiting, often with diarrhea (watery or bloody), abdominal distension, leading to dehydration and lethargy in the acute setting (often requiring rehydration), or weight loss and failure to thrive in a chronic form.
  • Tx:
    • May be medical emergency and requires IV fluid resuscitation.
    • Long-term management requires dietary elimination and avoidance of causative food.
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25
Q

Red flags for primary immunodeficiency. Suspect with any 2 of the following within a year:

  • > =4 ear infections
  • > =2 serious sinus infections
  • Need for >=2 months on antibiotics
  • Failure to thrive
  • Recurrent, deep skin or organ abscesses
  • Persistent thrush in mouth or fungal infection on skin
  • Need for IV antibiotics to clear infection
  • Repeated invasive infections (eg >2 pneumonias, septicemia, meningitis)
  • Family hx of PI
A

Red flags for primary immunodeficiency. Suspect with any 2 of the following within a year:

  • > =4 ear infections
  • > =2 serious sinus infections
  • Need for >=2 months on antibiotics
  • Failure to thrive
  • Recurrent, deep skin or organ abscesses
  • Persistent thrush in mouth or fungal infection on skin
  • Need for IV antibiotics to clear infection
  • Repeated invasive infections (eg >2 pneumonias, septicemia, meningitis)
  • Family hx of PI
26
Q

B-cell deficiency: Recurrent ____ infections (after maternal antibodies are depleted).

  • Bacteria: ___, ___, ___
  • Viruses: ____
  • Protozoa: ___
A

B-cell deficiency: Recurrent sinopulmonary infections (after maternal antibodies are depleted).

  • Bacteria: Encapsulated (eg Strep pneumoniae, Haemophilus influenzae), S aureus, Pseudomonas
  • Viruses: Enterovirus
  • Protozoa: Giardia
27
Q

T-cell deficiency: Opportunistic infections.

  • Bacteria (mostly intracellular): Salmonella, syphilis
  • Mycobacteria: Tuberculosis, Mycobacterium avium complex
  • Viruses: CMV, HSV, varicella-zoster virus, EBV, hepatitis, HPV, molluscum contagiosum
  • Fungi: Candida, Aspergillus, coccidioidomycosis, Cryptococcus, histoplasmosis
  • Protozoa: Pneumocystis, toxoplasmosis, cryptosporidiosis, isosporiasis, microsporidiosis
A

T-cell deficiency: Opportunistic infections.

  • Bacteria (mostly intracellular): Salmonella, syphilis
  • Mycobacteria: Tuberculosis, Mycobacterium avium complex
  • Viruses: CMV, HSV, varicella-zoster virus, EBV, hepatitis, HPV, molluscum contagiosum
  • Fungi: Candida, Aspergillus, coccidioidomycosis, Cryptococcus, histoplasmosis
  • Protozoa: Pneumocystis, toxoplasmosis, cryptosporidiosis, isosporiasis, microsporidiosis
28
Q

Combined B- and T-cell deficiency: All above infections

A

Combined B- and T-cell deficiency: All above infections

29
Q

Phagocytic disorder: Skin and organ abscesses

- Bacteria: S aureus

A

Phagocytic disorder: Skin and organ abscesses

- Bacteria: S aureus

30
Q

Complement deficiency: Overwhelming sepsis

  • Encapsulated organisms
  • Bacteria: Neisseria meningitidis, H influenzae
A

Complement deficiency: Overwhelming sepsis

  • Encapsulated organisms
  • Bacteria: Neisseria meningitidis, H influenzae
31
Q

Test for immunodeficiencies

  • B cell
    • Quantitative:____
    • Qualitative: _____
      • In terms of antibody function, measuring antibody titers to ____ antigens is a useful initial test.
    • Tertiary tests: Neoantigen studies, mitogens
  • T cell
    • Quantitative: ____
    • Qualitative: ____
    • Tertiary tests: Specific enzyme measurement, mitogens
  • Phagocytic
    • Quantitative: CBC with differential
    • Qualitative: Neutrophil oxidation (eg NBT, DHR)
    • Tertiary tests: Surface glycoproteins
  • Complement
    • Quantitative: C3, C4
    • Qualitative: ____
    • Tertiary tests: Individual complement (eg C5, C6)
A

Test for immunodeficiencies

  • B cell
    • Quantitative: Quantitative immunoglobulins
    • Qualitative: Response to vaccines
      • In terms of antibody function, measuring antibody titers to polysaccharide antigens is a useful initial test.
    • Tertiary tests: Neoantigen studies, mitogens
  • T cell
    • Quantitative: Flow cytometry
    • Qualitative: Delayed type hypersensitivity (eg Candida, mumps)
    • Tertiary tests: Specific enzyme measurement, mitogens
  • Phagocytic
    • Quantitative: CBC with differential
    • Qualitative: Neutrophil oxidation (eg NBT, DHR)
    • Tertiary tests: Surface glycoproteins
  • Complement
    • Quantitative: C3, C4
    • Qualitative: CH50
    • Tertiary tests: Individual complement (eg C5, C6)
32
Q

B-cell deficiencies

  • X-linked agammaglobulinemia
  • Common variable immunodeficiency
  • Specific antibody deficiency
  • Selective IgA deficiency
  • Hyper-IgM syndrome
  • X-linked lymphoproliferative disease (Duncan syndrome)
  • Transient hypogammaglobulinemia of infancy

Total quantitative immunoglobulin levels should be measured in the initial lab workup.

A

B-cell deficiencies

  • X-linked agammaglobulinemia
  • Common variable immunodeficiency
  • Specific antibody deficiency
  • Selective IgA deficiency
  • Hyper-IgM syndrome
  • X-linked lymphoproliferative disease (Duncan syndrome)
  • Transient hypogammaglobulinemia of infancy

Total quantitative immunoglobulin levels should be measured in the initial lab workup.

33
Q

X-Linked (Bruton) Agammaglobulinemia (XLA)

  • Path:
    • Underlying defect affects the (B-cell protein tyrosine kinase) BTK gene (at Xq22) that encodes for ______ protein, which is necessary for B-cell development.
    • Complete lack of mature immunoglobulin-carrying ____ in the peripheral circulation.
    • In contrast, B-cell precursors are normal in the bone marrow, but their development is arrested at a pre-B-cell stage.
  • Pt: Recurrent bacterial infections (of the respiratory tract) in association with absent-to-low immunoglobulins of all classes.
    • The absence of normal B cells also precludes the formation of normal lymphoid and tonsillar tissues (small tonsils).
      • Infections beginning at ____ mo of life after all the placentally transferred maternal antibodies IgG has been consumed.
    • Encapsulated bacterial infections of the respiratory tract are common and include pneumonia, otitis media, and sinusitis.
    • These children generally handle viral infections well, with the exception of hepatitis and enterovirus infections.
    • Persistent and recurrent giardiasis is common.
    • These children also have a predisposition to enterovirus infections and are at high risk if given the live polio vaccine (an enterovirus).
  • Dx:
    • _______ are the only characteristic physical finding, as these tissues are rich in B cells.
    • CBC is normal.
    • Complete lack of mature B cells. B lymphocytes are absent from the blood and from lymph tissue.
    • Severe deficiency of all the immunoglobulin classes.
  • Tx: Regular ____ infusions or subcutaneous immunoglobulin (SQIG) to prevent recurrent infections.
  • These patients should NOT receive ____ (oral polio, live attenuated flu, BCG, oral typhoid, and yellow fever) due to risk of infection.
A

X-Linked (Bruton) Agammaglobulinemia (XLA)

  • Path:
    • Underlying defect affects the (B-cell protein tyrosine kinase) BTK gene (at Xq22) that encodes for Bruton tyrosine kinase protein, which is necessary for B-cell development.
    • Complete lack of mature immunoglobulin-carrying B-cells (CD19 + cells) in the peripheral circulation.
    • In contrast, B-cell precursors are normal in the bone marrow, but their development is arrested at a pre-B-cell stage.
  • Pt: Recurrent bacterial infections (of the respiratory tract) in association with absent-to-low immunoglobulins of all classes.
    • The absence of normal B cells also precludes the formation of normal lymphoid and tonsillar tissues (small tonsils).
      • Infections beginning at 6-12 mo of life after all the placentally transferred maternal antibodies IgG has been consumed.
    • Encapsulated bacterial infections of the respiratory tract are common and include pneumonia, otitis media, and sinusitis.
    • These children generally handle viral infections well, with the exception of hepatitis and enterovirus infections.
    • Persistent and recurrent giardiasis is common.
    • These children also have a predisposition to enterovirus infections and are at high risk if given the live polio vaccine (an enterovirus).
  • Dx:
    • Small or absent lymph nodes and tonsils are the only characteristic physical finding, as these tissues are rich in B cells.
    • CBC is normal.
    • Complete lack of mature B cells. B lymphocytes are absent from the blood and from lymph tissue.
    • Severe deficiency of all the immunoglobulin classes.
  • Tx: Regular IVIG infusions or subcutaneous immunoglobulin (SQIG) to prevent recurrent infections.
  • These patients should NOT receive live vaccines (oral polio, live attenuated flu, BCG, oral typhoid, and yellow fever) due to risk of infection.
34
Q

Combined Variable Immunodeficiency (CVID)

  • Mild form of XLA
  • Path: Inability of B cells to differentiate
  • Pt: Can present at any age. Most often seen in the 2nd and 3rd decades (mean age of onset is 26.3yo) and is very rare before 6yo.
    • Recurrent infections (usually sinopulmonary infections with encapsulated bacteria).
    • A spruelike illness is very common.
    • A sarcoid-like disease with _____ of the spleen, liver, lungs, and skin is common and can present as hepatosplenomegaly.
    • A number of _____ conditions are seen in CVID, including ITP, pernicious anemia, hemolytic anemia, malabsorption, and pancytopenia.
  • Dx:
    • CBC normal.
    • _____ number of B cells (on flow cytometry) but ____ of immunoglobulins (B cells are dysfunctional).
    • QIG shows decrease of in ⅔ classes of Ig (___, ___, or ___)
      • IgG levels are typically <300mg/dL, and IgA and IgM levels are <50mg/dL
    • Poor immunoglobulin function as demonstrated by IgG titers to vaccines (diphtheria/tetanus for protein and pneumococcal for polysaccharide).
    • Cannot make diagnosis for <5yo
  • Tx: ____ Immune globulin Ig replacement.
A

Combined Variable Immunodeficiency (CVID)

  • Mild form of XLA
  • Path: Inability of B cells to differentiate
  • Pt: Can present at any age. Most often seen in the 2nd and 3rd decades (mean age of onset is 26.3yo) and is very rare before 6yo.
    • Recurrent infections (usually sinopulmonary infections with encapsulated bacteria).
    • A spruelike illness is very common.
    • A sarcoid-like disease with noncaseating granulomas of the spleen, liver, lungs, and skin is common and can present as hepatosplenomegaly.
    • A number of autoimmune conditions are seen in CVID, including ITP, pernicious anemia, hemolytic anemia, malabsorption, and pancytopenia.
  • Dx:
    • CBC normal.
    • Normal number of B cells (on flow cytometry) but paucity of immunoglobulins (B cells are dysfunctional).
    • QIG shows decrease of in ⅔ classes of Ig (IgG, IgA, or IgM)
      • IgG levels are typically <300mg/dL, and IgA and IgM levels are <50mg/dL
    • Poor immunoglobulin function as demonstrated by IgG titers to vaccines (diphtheria/tetanus for protein and pneumococcal for polysaccharide).
    • Cannot make diagnosis for <5yo
  • Tx: IVIG/SQIG Immune globulin Ig replacement.
35
Q

Specific Antibody Deficiency

  • Like XLA and CVID, pts with specific antibody deficiency have recurrent sinopulmonary infections with encapsulated organisms.
  • Tx: IVIG/SQIG and specific therapy for infectious complications.
A

Specific Antibody Deficiency

  • Like XLA and CVID, pts with specific antibody deficiency have recurrent sinopulmonary infections with encapsulated organisms.
  • Tx: IVIG/SQIG and specific therapy for infectious complications.
36
Q

Selective IgA Deficiency

  • Most common primary immune disorder
  • Pt:
    • Most pts are asymptomatic
    • About ⅓ have recurrent sinopulmonary infections and/or recurrent giardiasis.
    • Associated with autoimmune diseases such as celiac disease and Hashimoto’s.
    • Some are at increased risk of developing ______ reactions after receiving blood products.
  • Dx: QIg shows decreased IgA less than ___ mg/dL
    • CBC is normal.
  • Tx: For pts with recurrent infection, tx with ____.
    • _____ is contraindicated bc pts can develop allergic reactions.
    • There is an increased risk of _____ with blood transfusions in these pts; therefore, washed RBCs are required for transfusions.
A

Selective IgA Deficiency

  • Most common primary immune disorder
  • Pt:
    • Most pts are asymptomatic
    • About ⅓ have recurrent sinopulmonary infections and/or recurrent giardiasis.
    • Associated with autoimmune diseases such as celiac disease and Hashimoto’s.
    • Some are at increased risk of developing anaphylactic reactions after receiving blood products.
  • Dx: QIg shows decreased IgA <7mg/dL
    • CBC is normal.
  • Tx: For pts with recurrent infection, tx with prophylactic antibiotics.
    • IVIG/SQIG is contraindicated bc pts can develop allergic reactions.
    • There is an increased risk of anaphylaxis with blood transfusions in these pts; therefore, washed RBCs are required for transfusions.
37
Q

Hyper-IgM Syndrome
- X-linked and AR forms (X-linked is more common)

  • Path:
    • Absence of _____ is the hallmark
    • Inability of IgM to switch to IgG or IgA, resulting in low levels of IgG and IgA
  • Pt:
    • These children are at higher risk of bacterial infections like those found in hypogammaglobulinemia, including recurrent sinopulmonary infections with encapsulated bacteria, giardiasis, and bacterial and viral meningitis.
    • In addition, the X-linked type increases susceptibility to ____
  • On exam, it is typical to find enlarged lymph nodes and hepatosplenomegaly.
  • Dx: QIg shows decreased IgG, IgA, and IgE but normal/high IgM
    • ____ demonstrating lack of CD40L
  • Tx: Therapy aimed at correcting the hypogammaglobulinemia by giving ___ and prophylactic antibiotics for PCP.
    • ____ can be curative and is the most appropriate tx for X-linked disease.
A

Hyper-IgM Syndrome
- X-linked and AR forms (X-linked is more common)

  • Path:
    • Absence of CD40 ligand is the hallmark
    • Inability of IgM to switch to IgG or IgA, resulting in low levels of IgG and IgA
  • Pt:
    • These children are at higher risk of bacterial infections like those found in hypogammaglobulinemia, including recurrent sinopulmonary infections with encapsulated bacteria, giardiasis, and bacterial and viral meningitis.
    • In addition, the X-linked type increases susceptibility to Pneumocystis jiroveci pneumonia (PCP)
  • On exam, it is typical to find enlarged lymph nodes and hepatosplenomegaly.
  • Dx: QIg shows decreased IgG, IgA, and IgE but normal/high IgM
    • Flow cytometry demonstrating lack of CD40L
  • Tx: Therapy aimed at correcting the hypogammaglobulinemia by giving IVIG/SQIG and prophylactic antibiotics for PCP.
    • Bone marrow transplant can be curative and is the most appropriate tx for X-linked disease.
38
Q

X-Linked Lymphoproliferative Disease (Duncan Syndrome)

  • Pt: Causes severe or fatal infections with _____
    • A common malignancy is extranodal Burkitt-type lymphoma.
  • Tx: During the acute EBV attack and polyclonal expansion, steroids, immunosuppressants, or cytotoxic agents may be useful to stem the response. Currently, the only cure is _______.
A

X-Linked Lymphoproliferative Disease (Duncan Syndrome)

  • Pt: Causes severe or fatal infections with Epstein-Barr virus (EBV).
    • A common malignancy is extranodal Burkitt-type lymphoma.
  • Tx: During the acute EBV attack and polyclonal expansion, steroids, immunosuppressants, or cytotoxic agents may be useful to stem the response. Currently, the only cure is allogeneic stem cell transplantation.
39
Q

Transient Hypogammaglobulinemia of Infancy

  • Abnormal prolongation of the physiological hypogammaglobulinemia that occurs naturally 4-6 mo of age.
  • Diagnosis _____!
  • Usually, these children have normal IgG levels by ___ yo.
A

Transient Hypogammaglobulinemia of Infancy

  • Abnormal prolongation of the physiological hypogammaglobulinemia that occurs naturally 4-6 mo of age.
  • Diagnosis of exclusion!
  • Usually, these children have normal IgG levels by 3-4 yo.
40
Q

22q11. 2 Deletion Syndrome (Velocardiofacial syndrome, DiGeorge syndrome)
- Path: Developmental defect of 3rd and 4th pharyngeal pouch. Thymus absence or disorder causes deficient T cell development
- In complete DiGeorge’s, T cells are absent and B cells are present, but the B cells cannot produce specific antibodies due to the lack of T-cell help. These infants can have immunodeficiency as extreme as SCID.

  • CATCH 22
    • C_____: Conotruncal defects: ___ > ToF > interrupted aortic arch > truncus arteriosus
    • A______ - Micrognathia (small chin), shortened philtrum, dorsal rotated ears/squared off/overfolded ear helices, bulbous nasal tip with nasal dimple, hypoplastic alae nasae. HTN
    • T_____ - no thymic shadow, immune deficiency
    • C____, velopharyngeal insufficiency
    • H____
    • Deletion on chromosome 22
  • Dx: Suspect with pt with low ____ cells and characteristic clinical findings. Confirm by ____
  • Tx:
    • Calcium replacement and correction of cardiac defects.
    • TMP-SMX ppx against PCP.
    • Thymic transplants can correct severe defects, but this tx is reserved for those with complete DiGeorge syndrome.
    • Hematopoietic cell transplantation from an HLA-identical donor without T-cell depletion is a reasonable alternative.
    • IVIG is useful if antibody production is poor
A

22q11. 2 Deletion Syndrome (Velocardiofacial syndrome, DiGeorge syndrome)
- Path: Developmental defect of 3rd and 4th pharyngeal pouch. Thymus absence or disorder causes deficient T cell development
- In complete DiGeorge’s, T cells are absent and B cells are present, but the B cells cannot produce specific antibodies due to the lack of T-cell help. These infants can have immunodeficiency as extreme as SCID.

  • CATCH 22
    • Cardiac: Conotruncal defects: VSD > ToF > interrupted aortic arch > truncus arteriosus
    • Abnormal facies - Micrognathia (small chin), shortened philtrum, dorsal rotated ears/squared off/overfolded ear helices, bulbous nasal tip with nasal dimple, hypoplastic alae nasae. HTN
    • Thymic aplasia - no thymic shadow, immune deficiency
    • Cleft lip/palate, velopharyngeal insufficiency
    • Hypocalcemia/hypoparathyroidism
    • Deletion on chromosome 22
  • Dx: Suspect with pt with low CD3+ T cells and characteristic clinical findings. Confirm by fluorescence in situ hybridization (FISH)
  • Tx:
    • Calcium replacement and correction of cardiac defects.
    • TMP-SMX ppx against PCP.
    • Thymic transplants can correct severe defects, but this tx is reserved for those with complete DiGeorge syndrome.
    • Hematopoietic cell transplantation from an HLA-identical donor without T-cell depletion is a reasonable alternative.
    • IVIG is useful if antibody production is poor
41
Q

Nezelof Syndrome

- __inheritance? form of ____ that leads to varying degrees of T-cell dysfunction

A

Nezelof Syndrome

- AR form of thymic hypoplasia that leads to varying degrees of T-cell dysfunction

42
Q

SCID (Severe Combined Immunodeficiency)
- SCID is a collection of known diseases that result in ineffective T and B cells

  • Path: Defects in T cell maturation, resulting in lack of circulating T cells. B cells may be present but are dysfunctional
  • Classification
    • 50% X-linked SCID: ____ defect.
    • 25-30% ____ deficiency
    • 15-20% of cases are due to failure of purine salvage pathways.
      • ___ deficiency is the most common
  • Pt:
    • Overwhelming sepsis
    • Chronic lung infections
    • Eczematous-like skin lesions
    • Diarrhea
    • FTT
  • Labs/imaging
    • CBC shows decreased ___.
      • Infants with SCID are almost universally lymphopenic for their age
    • Serum immunoglobulin levels: QIg shows no __, no __, no ___
    • CXR may show ___; however presence of thymic shadow does not rule out SCID since thymus is present in rarer forms of SCID.
  • Dx
    • Criteria
      - less than __ yo
      - Either absolute CD3 T cell less than ___ OR absolute CD3 T cell > 300 w absent naive CD3/CD45RA T cells (has more memory than naive)
      • Genetic testing, ADA activity
    • These patients will have low ___
      • PCR for TRECs is a viable screening test for the presence of T cells in the newborn.
      • Other patients with low TREC (T cell receptor excision circles), a biomarker of naive T cells: SCID most common > DiGeorge > Trisomy 21
      • An absence of TRECs may suggest SCID
    • Definitive test: ____ to quantify lymphocyte subsets
  • Management
    • Diagnosis is a medical emergency! Prompt recognition and early tx with ____ is essential for survival.
    • Avoid live vaccines
    • Cannot do urine catheterization
A

SCID (Severe Combined Immunodeficiency)
- SCID is a collection of known diseases that result in ineffective T and B cells

  • Path: Defects in T cell maturation, resulting in lack of circulating T cells. B cells may be present but are dysfunctional
  • Classification
    • 50% X-linked SCID: IL-2 receptor gamma (IL-2Rg) defect.
    • 25-30% recombination-activating gene (RAG) deficiency
    • 15-20% of cases are due to failure of purine salvage pathways.
      • Adenosine deaminase deficiency is the most common
  • Pt:
    • Overwhelming sepsis
    • Chronic lung infections
    • Eczematous-like skin lesions
    • Diarrhea
    • FTT
  • Labs/imaging
    • CBC shows decreased WBC.
      • Infants with SCID are almost universally lymphopenic for their age
    • Serum immunoglobulin levels: QIg shows no IgM, no IgG, no IgA
    • CXR may show lack of a thymic shadow; however presence of thymic shadow does not rule out SCID since thymus is present in rarer forms of SCID.
  • Dx
    • Criteria
      • <2 yo
      • Either absolute CD3 T cell <300 OR absolute CD3 T cell > 300 w absent naive CD3/CD45RA T cells (has more memory than naive)
      • Genetic testing, ADA activity
    • These patients will have low TREC
      • PCR for TRECs is a viable screening test for the presence of T cells in the newborn.
      • Other patients with low TREC (T cell receptor excision circles), a biomarker of naive T cells: SCID most common > DiGeorge > Trisomy 21
      • An absence of TRECs may suggest SCID
    • Definitive test: flow cytometry to quantify lymphocyte subsets
  • Management
    • Diagnosis is a medical emergency! Prompt recognition and early tx with BMT is essential for survival.
    • Avoid live vaccines
    • Cannot do urine catheterization
43
Q

X-Linked SCID

  • Most common form of SCID and accounts for nearly 50% of SCID cases
  • Only boys are affected.
  • Path: Total failure of T-cell and NK-cell development (T- and NK-).
    • B cells produced by the child are present (B+), but they also do not function normally.
  • Boys with absent T-cell function are presumed to have X-linked SCID. Diagnosis is confirmed by molecular analysis of the gene for gamma-c.
  • Tx: BMT restores normal T-cell development and function, but B-cell function is usually not restored. Thus, these pts still require IVIG for antibody replacement.
A

X-Linked SCID

  • Most common form of SCID and accounts for nearly 50% of SCID cases
  • Only boys are affected.
  • Path: Total failure of T-cell and NK-cell development (T- and NK-).
    • B cells produced by the child are present (B+), but they also do not function normally.
  • Boys with absent T-cell function are presumed to have X-linked SCID. Diagnosis is confirmed by molecular analysis of the gene for gamma-c.
  • Tx: BMT restores normal T-cell development and function, but B-cell function is usually not restored. Thus, these pts still require IVIG for antibody replacement.
44
Q

SCID due to Purine Salvage Pathway Disorders

  • 2 purine salvage pathway disorders manifest as SCID:
    • 1) ADA (adenosine deaminase) deficiency
      • Affects T cells, B cells, and NK cells (T-, B-, and NK-).
      • Pt: Spectrum of disease, with milder forms not diagnosed until adulthood, but most pts present within months of birth with recurrent infections, profound lymphopenia, and hypogammaglobulinemia.
      • Dx: Low ADA levels in RBC and high deoxyadenosine and dATP in blood and urine.
      • Tx:
        • Bone marrow transplant is curative, but modified adenosine deaminase is available and effective treatment for children awaiting a suitable donor.
    • 2) PNP (purine nucleoside phosphorylase) deficiency (rare)
A

SCID due to Purine Salvage Pathway Disorders

  • 2 purine salvage pathway disorders manifest as SCID:
    • 1) ADA (adenosine deaminase) deficiency
      • Affects T cells, B cells, and NK cells (T-, B-, and NK-).
      • Pt: Spectrum of disease, with milder forms not diagnosed until adulthood, but most pts present within months of birth with recurrent infections, profound lymphopenia, and hypogammaglobulinemia.
      • Dx: Low ADA levels in RBC and high deoxyadenosine and dATP in blood and urine.
      • Tx:
        • Bone marrow transplant is curative, but modified adenosine deaminase is available and effective treatment for children awaiting a suitable donor.
    • 2) PNP (purine nucleoside phosphorylase) deficiency (rare)
45
Q

Recombination-Activating Gene (RAG) Deficiency

  • AR disorder. Most severe form of SCID.
  • T and B cells are absent, but the NK cells and nonlymphoid hematopoietic cell lines are normal (T-, B-, NK+).
  • Tx: BMT is both the tx and the cure.
A

Recombination-Activating Gene (RAG) Deficiency

  • AR disorder. Most severe form of SCID.
  • T and B cells are absent, but the NK cells and nonlymphoid hematopoietic cell lines are normal (T-, B-, NK+).
  • Tx: BMT is both the tx and the cure.
46
Q

Reticular Dysgenesis

  • Very rare form of SCID.
  • T-, B-, NK- SCID
  • Tx: BMT is curative; those without it die in infancy
A

Reticular Dysgenesis

  • Very rare form of SCID.
  • T-, B-, NK- SCID
  • Tx: BMT is curative; those without it die in infancy
47
Q

Omenn Syndrome

  • Variant of _____.
  • Path: Partial inactivation of either the RAG1 or RAG2 gene.
  • Pt: Severe erythroderma, diarrhea, hepatosplenomegaly, and FTT.
  • Hypogammaglobulinemia, elevated IgE, and marked eosinophilia
A

Omenn Syndrome

  • Variant of RAG deficiency.
  • Path: Partial inactivation of either the RAG1 or RAG2 gene.
  • Pt: Severe erythroderma, diarrhea, hepatosplenomegaly, and FTT.
  • Hypogammaglobulinemia, elevated IgE, and marked eosinophilia
48
Q

Wiskott-Aldrich syndrome

  • Iheritance?? Affects boys
  • Pt:
    • Triad: 1) ____ 2) ____ 3) ____ (EXIT: Eczema, X-linked, Immunodeficiency, Thrombocytopenia)
    • Boys can present in the first few days of life with abnormal bleeding.
      • Classic clinical scenario describes a ______
    • Increased risk of B-cell lymphoma and leukemia
  • Dx:
    • CBC has decreased WBC and decreased platelets.
      • ____ platelets are diagnostic for WAS. (In contrast, ITP causes thrombocytopenia with ___ platelets).
    • On the human side, ___ is decreased and ___ and ___ are elevated.
  • Tx: ___ from an HLA-matched donor.
    • ___ is effective in improving the platelet course if BMT cannot be done
    • ____ replacement is needed for poor antibody response.
A

Wiskott-Aldrich syndrome

  • X-linked. Affects boys
  • Pt:
    • Triad: 1) Eczema 2) Low platelets / thrombocytopenia (with small platelets) 3) Susceptibility to encapsulated bacteria and opportunistic infections (EXIT: Eczema, X-linked, Immunodeficiency, Thrombocytopenia)
    • Boys can present in the first few days of life with abnormal bleeding.
      • Classic clinical scenario describes a boy with prolonged bleeding from his circumcision site.
    • Increased risk of B-cell lymphoma and leukemia
  • Dx:
    • CBC has decreased WBC and decreased platelets.
      • Small platelets (microthrombocytes) are diagnostic for WAS. (In contrast, ITP causes thrombocytopenia with large platelets (macrothrombocytes)).
    • On the human side, IgM is decreased and IgA and IgE are elevated.
  • Tx: BMT from an HLA-matched donor.
    • Splenectomy is effective in improving the platelet course if BMT cannot be done
    • IVIG replacement is needed for poor antibody response.
49
Q

Ataxia-Telangiectasia

  • ___inherited? disorder.
  • Path:
    • 90% due to Mutation in ____ gene on chromosome 11q22-23.
  • Pt:
    • 2 main characteristics
      • 1) ___
      • 2) ___
    • Frequent infections with encapsulated organisms.
    • Endocrine abnormalities, esp diabetes mellitus
    • There is a high risk of malignancy, esp of lymphocytic leukemias or lymphomas.
  • Labs: Serum levels of____ and ___ are elevated.
    • Elevated levels are a highly sensitive marker for this disease
  • Dx:
    • In a child >5yo: Ataxia + telangiectasia + elevated alpha1-fetoprotein
    • In a child <5yo: Telangiectasias may not yet be present, so the diagnosis is still considered without this classic finding.
  • B cells are usually normal in number, but IgA and IgE levels are low.
    • IgA deficiency is found in ~70%.
    • IgG deficiency is found in ~50%, mainly due to a selective decrease in IgG2 and IgG4 subclasses.
    • IgM and IgD are normal.
    • Serum ___ and serum ___ levels are severely diminished to absent. IgE and IgM levels can be diminished or normal
  • Tx: Prophylactic antimicrobial therapy, platelet transfusion for severe bleeding episodes. IVIG for severe antibody deficiency. ____ is the only curative tx.
A

Ataxia-Telangiectasia

  • AR disorder.
  • Path:
    • 90% due to Mutation in ATM gene on chromosome 11q22-23.
  • Pt:
    • 2 main characteristics
      • 1) Cerebellar ataxia
      • 2) Oculocutaneous telangiectasia
    • Frequent infections with encapsulated organisms.
    • Endocrine abnormalities, esp diabetes mellitus
    • There is a high risk of malignancy, esp of lymphocytic leukemias or lymphomas.
  • Labs: Serum levels of alpha1-fetoprotein and CEA are elevated.
    • Elevated alpha-1-fetoprotein (AFP) levels are a highly sensitive marker for this disease
  • Dx:
    • In a child >5yo: Ataxia + telangiectasia + elevated alpha1-fetoprotein
    • In a child <5yo: Telangiectasias may not yet be present, so the diagnosis is still considered without this classic finding.
  • B cells are usually normal in number, but IgA and IgE levels are low.
    • IgA deficiency is found in ~70%.
    • IgG deficiency is found in ~50%, mainly due to a selective decrease in IgG2 and IgG4 subclasses.
    • IgM and IgD are normal.
    • Serum IgG2 and serum IgA levels are severely diminished to absent. IgE and IgM levels can be diminished or normal
  • Tx: Prophylactic antimicrobial therapy, platelet transfusion for severe bleeding episodes. IVIG for severe antibody deficiency. BMT is the only curative tx.
50
Q

Bloom Syndrome

  • ___inheritance? Chromosomal instability disorder
  • Path: Deficiency of ____
  • Pt:
    • Small stature, telangiectasia, CNS abnormalities, and immunodeficiency.
    • High association with leukemias.
A

Bloom Syndrome

  • AR Chromosomal instability disorder
  • Path: Deficiency of DNA ligase I
  • Pt:
    • Small stature, telangiectasia, CNS abnormalities, and immunodeficiency.
    • High association with leukemias.
51
Q

Nijmegen Breakage Syndrome

  • Rare ___inheritance? disease
  • Path: Mutation in the Nijmegen breakage syndrome 1 gene (NBS1), which makes nibrin
    • Combined cellular and humoral immunodeficiency
  • Pt:
    • Bird-like face, microcephaly, and average or near-average IQ.
    • High incidence of lymphoid cancers.
A

Nijmegen Breakage Syndrome

  • Rare AR disease
  • Path: Mutation in the Nijmegen breakage syndrome 1 gene (NBS1), which makes nibrin
    • Combined cellular and humoral immunodeficiency
  • Pt:
    • Bird-like face, microcephaly, and average or near-average IQ.
    • High incidence of lymphoid cancers.
52
Q

Leukocyte Adhesion Deficiency Type 1 (LAD1)
- ____inheritance? disorder

  • Path: _____ deficiency, an adhesion molecule needed for leukocytes to leave the circulation and enter tissues to fight infection.
    • Defect is a mutation in the gene that encodes CD18 located on chromosome 21, and results in lack of formation of adhesion molecules. Children have neutrophilia, but the neutrophils do not accumulate at the site of infection.
  • Pt:
    • Delayed ______
      • Usually umbilical cord separates and sloughs off at an average of 14 days (but may take up to 45 days). Is considered delayed after ____ weeks.
      • Delayed separation of the umbilical cord and omphalitis are frequently the 1st signs of this disorder.
    • Baseline persistent ____ (with neutrophilia)
    • Recurrent necrotizing infections at places where the body interfaces with the environment (ie skin, mucosa, gut, lungs).
    • There is impaired wound healing, and when skin lesions heal, they leave characteristic cigarette paper scarring.
  • Dx: _____ to check for absence of CD18 on leukocytes.
  • Tx:
    • Antibiotics for milder cases
    • _____ is TOC.
A

Leukocyte Adhesion Deficiency Type 1 (LAD1)
- AR disorder

  • Path: CD18 deficiency, an adhesion molecule needed for leukocytes to leave the circulation and enter tissues to fight infection.
    • Defect is a mutation in the gene that encodes CD18 located on chromosome 21, and results in lack of formation of adhesion molecules. Children have neutrophilia, but the neutrophils do not accumulate at the site of infection.
  • Pt:
    • Delayed separation of cord
      • Usually umbilical cord separates and sloughs off at an average of 14 days (but may take up to 45 days). Is considered delayed after 4 weeks.
      • Delayed separation of the umbilical cord and omphalitis are frequently the 1st signs of this disorder.
    • Baseline persistent leukocytosis (with neutrophilia)
    • Recurrent necrotizing infections at places where the body interfaces with the environment (ie skin, mucosa, gut, lungs).
    • There is impaired wound healing, and when skin lesions heal, they leave characteristic cigarette paper scarring.
  • Dx: Flow cytometry to check for absence of CD18 on leukocytes.
  • Tx:
    • Antibiotics for milder cases
    • BMT is TOC.
53
Q

Job Syndrome (Hyper IgE syndrome)

  • Path:
    • Failure to produce ______, leading to inability of neutrophils to respond to chemotactic stimuli. Defective chemotaxis
  • Pt: Coarse facies, retained primary teeth, recurrent abscesses, and eczema/skin disorders.
    • Eczema
    • Scoliosis, hyperextensibility, fractures
    • Recurrent infections with S aureus, H influenzae, and S pneumoniae classically described as “____” abscesses.
    • Pts also have postinfection pulmonary cysts (pneumatoceles)
    • The characteristic appearance (described as coarse or lion-like) is an asymmetric face, broad nose, prominent forehead, triangular jaw, 2 rows of teeth (retained primary teeth) due to delayed dental exfoliation.
  • Pts have elevated ____ (2,000-100,000 IU initially but this decreases to normal levels as they get older) and _____. Despite the name hyper-IgE syndrome, elevated IgE is not needed to make the diagnosis, and high IgE levels can be found in other conditions (such as parasitic infections and atopic dermatitis).
  • Tx:
    • Antibiotics are used for skin infections. Use of TMP/SMX for prophylaxis is indicated.
    • Some recommend tx with cyclosporine A, recombinant interferon gamma, or IVIG.
A

Job Syndrome (Hyper IgE syndrome)

  • Path:
    • Failure to produce interferon gamma, leading to inability of neutrophils to respond to chemotactic stimuli. Defective chemotaxis
  • Pt: Coarse facies, retained primary teeth, recurrent abscesses, and eczema/skin disorders.
    • Eczema
    • Scoliosis, hyperextensibility, fractures
    • Recurrent infections with S aureus, H influenzae, and S pneumoniae classically described as “cold” abscesses.
    • Pts also have postinfection pulmonary cysts (pneumatoceles)
    • The characteristic appearance (described as coarse or lion-like) is an asymmetric face, broad nose, prominent forehead, triangular jaw, 2 rows of teeth (retained primary teeth) due to delayed dental exfoliation.
  • Pts have elevated IgE (2,000-100,000 IU initially but this decreases to normal levels as they get older) and eosinophilia. Despite the name hyper-IgE syndrome, elevated IgE is not needed to make the diagnosis, and high IgE levels can be found in other conditions (such as parasitic infections and atopic dermatitis).
  • Tx:
    • Antibiotics are used for skin infections. Use of TMP/SMX for prophylaxis is indicated.
    • Some recommend tx with cyclosporine A, recombinant interferon gamma, or IVIG.
54
Q

Chediak-Higashi Syndrome
- _____inheritance? disease

  • Path: Defect in the ____ gene responsible for vesicle trafficking regulatory proteins and causes altered lysosomes and granules within the cells.
  • Pt:
    • Partial oculocutaneous albinism (with silvery sheen to hair and skin), mild intellectual disabilities, and progressive peripheral neuropathy.
    • Frequent bacterial infections / recurrent pyogenic infections.
    • Infection with EBV frequently induces an accelerated phase
  • Dx: _____ in neutrophils and eosinophils on the peripheral smear are pathognomonic
  • Tx:
    • Tx options for the accelerated phase include steroids and either VP16 or vincristine or a BMT.
    • _____ corrects the immunologic and hematologic manifestations but not the neurologic ones.
A

Chediak-Higashi Syndrome
- AR disease

  • Path: Defect in the LYST gene responsible for vesicle trafficking regulatory proteins and causes altered lysosomes and granules within the cells.
  • Pt:
    • Partial oculocutaneous albinism (with silvery sheen to hair and skin), mild intellectual disabilities, and progressive peripheral neuropathy.
    • Frequent bacterial infections / recurrent pyogenic infections.
    • Infection with EBV frequently induces an accelerated phase
  • Dx: Giant granules in neutrophils and eosinophils on the peripheral smear are pathognomonic
  • Tx:
    • Tx options for the accelerated phase include steroids and either VP16 or vincristine or a BMT.
    • BMT corrects the immunologic and hematologic manifestations but not the neurologic ones.
55
Q

Chronic Granulomatous Disease (CGD)

  • Path: Disorder of neutrophil function in which there is a defect in the respiratory burst, which under normal circumstances, results in the killing of bacteria.
    • Defect of neutrophil/macrophage function where failure to produce oxygen radicals to kill phagocytosed microorganisms. Can eat but can’t kill _____ organisms.
    • Defect in ______ enzyme complex- inability to form hydrogen peroxide and impaired intracellular killing decreases superoxide production
  • Pt: Chronic recurrent organ (lung, liver, and lymph nodes) and skin abscesses (most common Staph aureus)
    • SPACE: Staph aureus/Serratia/Salmonella, Pseudo, Aspergillus, Candida, Enterobact
    • BLACKNESS (same mnemnic for CF pts): Burkholderia cepacia, Aspergillus (most common), Nocardia, Staph aureus (2nd most common), Serratia, Salmonella
    • (Strep pyogenes, a catalase-negative organism, is rarely implicated in pulmonary infections for pts with chronic granulomatous disease.)
  • CBC has normal number of neutrophils/ANC as CGD is a result of deficit of neutrophil function rather than production.
  • Dx:
    • Previously NBT (nitro blue tetrazolium): In CGD pt, the _____ dye does not turn dark blue.
    • _____ oxidation (flow cytometry-based test) that measures superoxide production. Test for phagocyte (neutrophil) oxidative burst by flow cytometry.
  • Tx:
    • Early use of prophylactic TMP/SMX, itraconazole, and interferon-gamma to decrease the number of serious infections.
    • _____ can be curative
A

Chronic Granulomatous Disease (CGD)

  • Path: Disorder of neutrophil function in which there is a defect in the respiratory burst, which under normal circumstances, results in the killing of bacteria.
    • Defect of neutrophil/macrophage function where failure to produce oxygen radicals to kill phagocytosed microorganisms. Can eat but can’t kill catalase + organisms.
    • Defect in NADPH oxidase enzyme complex- inability to form hydrogen peroxide and impaired intracellular killing decreases superoxide production
  • Pt: Chronic recurrent organ (lung, liver, and lymph nodes) and skin abscesses (most common Staph aureus)
    • SPACE: Staph aureus/Serratia/Salmonella, Pseudo, Aspergillus, Candida, Enterobact
    • BLACKNESS (same mnemnic for CF pts): Burkholderia cepacia, Aspergillus (most common), Nocardia, Staph aureus (2nd most common), Serratia, Salmonella
    • (Strep pyogenes, a catalase-negative organism, is rarely implicated in pulmonary infections for pts with chronic granulomatous disease.)
  • CBC has normal number of neutrophils/ANC as CGD is a result of deficit of neutrophil function rather than production.
  • Dx:
    • Previously made by NBT (nitro blue tetrazolium): In CGD pt, the yellow dye does not turn dark blue.
    • Dihydrorhodamine (DHR) oxidation (flow cytometry-based test) that measures superoxide production. Test for phagocyte (neutrophil) oxidative burst by flow cytometry.
  • Tx:
    • Early use of prophylactic TMP/SMX, itraconazole, and interferon-gamma to decrease the number of serious infections.
    • Bone marrow transplant can be curative
56
Q

COMPLEMENT DISORDERS
Evaluation
- Patients with defects in the complement system usually present with recurrent infections by encapsulated organisms (H influenzae and N meningitidis).

  • _____ (total hemolytic complement assay) is the 1st screening test to look for complement deficiency! It measures the total complement hemolytic activity of the classical pathway.
    • A normal test shows that all factors (C1-C9) are present.
    • If the CH50 is low or absent, check for individual complement factors (C1-C9).
A

COMPLEMENT DISORDERS
Evaluation
- Patients with defects in the complement system usually present with recurrent infections by encapsulated organisms (H influenzae and N meningitidis).

  • CH50 (total hemolytic complement assay) is the 1st screening test to look for complement deficiency! It measures the total complement hemolytic activity of the classical pathway.
    • A normal test shows that all factors (C1-C9) are present.
    • If the CH50 is low or absent, check for individual complement factors (C1-C9).
57
Q

C1, C2, and C4 deficiencies

- Recurrent sinopulmonary infections (and ear infections when young) with encapsulated bacteria.

A

C1, C2, and C4 deficiencies

- Recurrent sinopulmonary infections (and ear infections when young) with encapsulated bacteria.

58
Q
C3 deficiency (complete absence)
- Pt: Severe pyogenic infections with encapsulated bacteria
A
C3 deficiency (complete absence)
- Pt: Severe pyogenic infections with encapsulated bacteria
59
Q

C5-C9 MAC (membrane attack complex) deficiency

- If you have a pt with invasive pneumococcal or meningococcal disease, check for a complement deficiency.

A

C5-C9 MAC (membrane attack complex) deficiency

- If you have a pt with invasive pneumococcal or meningococcal disease, check for a complement deficiency.

60
Q
Hereditary Angioedema (C1 esterase deficiency)
- \_\_\_\_inheritance? disorder
  • Path: Defect in _____ enzyme function with secondarily decreased C4 levels.
    • Type I: Decreased C1-INH (85% of cases)
    • Type II: Nonfunctioning C1-INH (15% of cases, normal levels but dysfunctional)
  • Pt:
    • Recurrent episodes of localized angioedema of distensible tissues (lips, eyelids, GI tract, genitalia, and upper airway)
      • The swelling that occurs is nonpruritic and usually resolves within 5 days.
      • Unlike angioedema and urticaria caused by IgE-mediated hypersensitivity reactions, HAE does not cause _______
  • Consider HAE in a pt with sudden onset of ______ and _____.
  • Dx:
    • Screen by checking for LOW ___ levels.
    • If C4 levels are low, diagnose by a decreased C1-INH functional assay. Either low levels of C1-INH or dysfunctional C1-INH
      • If C1-INH level is low, then it is Type 1 HAE.
      • If C1-INH level is normal, it is nonfunctioning C1-INH enzyme, and it is Type 2 HAE.
  • Tx:
    • Purified ____, which replaces the missing enzyme, is the TOC for acute attacks
    • ____ can be used when C1-INH is unavailable.
A
Hereditary Angioedema (C1 esterase deficiency)
- AD disorder
  • Path: Defect in C1 inhibitor enzyme (C1-INH) function with secondarily decreased C4 levels.
    • Type I: Decreased C1-INH (85% of cases)
    • Type II: Nonfunctioning C1-INH (15% of cases, normal levels but dysfunctional)
  • Pt:
    • Recurrent episodes of localized angioedema of distensible tissues (lips, eyelids, GI tract, genitalia, and upper airway)
      • The swelling that occurs is nonpruritic and usually resolves within 5 days.
      • Unlike angioedema and urticaria caused by IgE-mediated hypersensitivity reactions, HAE does not cause urticaria or pruritus.
  • Consider HAE in a pt with sudden onset of abdominal pain and extremity swelling.
  • Dx:
    • Screen by checking for LOW C4 levels.
    • If C4 levels are low, diagnose by a decreased C1-INH functional assay. Either low levels of C1-INH or dysfunctional C1-INH
      • If C1-INH level is low, then it is Type 1 HAE.
      • If C1-INH level is normal, it is nonfunctioning C1-INH enzyme, and it is Type 2 HAE.
  • Tx:
    • Purified C1-INH, which replaces the missing enzyme, is the TOC for acute attacks
    • FFP can be used when C1-INH is unavailable.