Allergy/Immunology Flashcards
Secondary Causes of PID
Meds (steroids, chemo, anti epileptics) Infections (HIV, TB etc), Structural (CF, indwelling catheter, impaired membrane integrity), Malignancy, Other (DM, renal insufficiency, protein losing enteropathy, malnutrition, asplenia)
T cell Defect age of onset
2-6 months
T cell typical bacteria
Gram + and -ve bacteria
Mycobacteria
T cell typical fungi
Candida, PJP
T cell defect sites of infection
sinopulmonary, GI, septicemia
T cell typical viruses
CMV, EBV, parainfluenza, adenovirus
Associated features of T cell defects
Omenn Syndrome, Disease post BCG or VZV vaccine
B cell typical age of onset
> 6 months after maternal immunoglobulin is gone. Up until adulthood
B cell typical bacteria
Encapsulated (streptococcus and haemophilus)
B cell Typical Viruses
Enterovirus
B cell Typical fungi/parasites
Giardia, cryptosporidium
B cell sites of infection
otitis media, sinusitis, pneumonia, arthritis, meningoencephalitis
SINOPULMONARY
B cell associated features
Autoimmunity, lymphoma
Phagocytic age of onset
Early onset
Phagocytic typical bacteria
staph, pseudomonas, serratia
Phagocytic typical viruses
none really
Phagocytic typical fungi/parasites
candida, aspergillus
Phagocytic Sites of Infection
Deep abscesses (liver, lungs), gingivitis, osteomyelitis, skin
Phagocytic Associated Features
Delayed cord separation, poor wound healing
Complement age of onset
Any
Complement typical bacteria
Pneumococcus and meningococcus
Complement Sites of infection
Septicemia, meningitis
Complement associated features
autoimmunity (can get a lupus like picture
Humoral Assessment: Number
Quantitative Ig levels, albumin for secondary loss Lymphocyte subsets (evaluates B cell numbers, CD 19 cells)- flow cytometry
Humoral Assessment: Function
Specific antibodies to vaccines the patient was exposed to
Isohemagglutinins (IgM antibody to blood group A and /or B)
Cellular Assessment: Number
Total Lymphocyte counts
Lymphocyte subsets to evaluate T cell numbers (CD4 and CD8). Flow cytometry
Cellular Assessment: Function
lymphocyte proliferation in response to mitogens and antigens
TRECs
T cell receipt Beta repertoire
Phagocytic Assessment: Number
Neutrophil Counts
Phagocytic Assessment: Function
NBT or NOBI (for CGD)
Measurement of adhesion markers: CD 11 and CD 18 (LAD)
Complement Assessment: Number
C1 esterase inhibitor (good for hereditary angioedema)
Specific complement levels
Complement Assessment: Function
Total Hemolytic Complement (CH50) Alternate Pathway (AH50) C1 Esterase inhibitor function (for hereditary angioedema)
X Linked Agammaglobulinemia: pathophysiology
Mutation in Bruton Tyrosine Kinase
No B Lymphocytes in Blood: No lymph tissue, no immunoglobulin production
No lymph nodes or tonsils
XLA Age of onset
6-24 months (when maternal IgG disappears)
XLA Types of recurrent infections
otitis media, pneumonia, sinusitis, diarrhea, arthritis, meningitis, sepsis, skin infections
ENCAPSULATED BACTERIA (strep, haemophilus)
Enteroviral meningoencephalitis
XLA Diagnosis
Absent B cells (<2% of lymphocytes)
Absent IgG, IgA, IgM
Absent antibodies to vaccines
Genetic confirmation of BTK mutation
Management of XLA
Antibiotics for active infections
IVIg for life
Follow PFTs and CT: at risk for bronchiectasis
CVID Age of Onset
1st decade of life, 3rd decade of life
CVID Clinical features
Recurrent Infections, Autoimmunity, Malignacy
Presence of lymph tissue normal or enlarged
CVID Infections
Recurrent sinopulmonary infections (encapsulated bacteria)- bronchiectasis and fibrosis in lungs GI Infections (Giardia and campylobacter) Atypical Bacteria (Mycoplasma, Ureaplasma joint infections)
CVID types of AI/Inflammatory processes occur in what % of patients
20-25% patients Cytopenias GI (IBD, pan gastritis, small bowel nodule lymphoid hyperplasia), Arthritis Granulomas (lung, liver, spleen, skin) Thyroiditis
Is CVID at risk of malignancy?
Yes Increased lymphoreticular and gastric malignancies 15% in aldutgood Non Hodgkin's lymphoma Gastric Carcinomas
CVID Lab
Decreased Serum IgG (normal or reduced IgA0
Normal or low numbers of B cells
Decreased/absent antibodies to vaccines
Low Isohemagglutinins
Management of CVID
Antibiotics to treat infections
IgG replacement for life ( DOES NOT DECREASE AI OR MALIGNANCY)
PFTs and Chest CTs
SCID Pathophysiology
Defective Tcell and B cell function
Mutation in common gamma chain of IL-2 receptor on X chromosome (X LINKED)
SCID age of onset
2-6 months
die in infancy without treatment
SCID Clinical Features
Persistent, recurrent, sever, opportunistic infections
Bacterial, fungal, viral, sinopulmonary, oral thrush, chronic diarrhea
FTT
Absent Lymph Nodes and Tonsils
Absent thymus
Diagnosis of SCID
Lymphopenia
Severely reduced T cell Numbers
B and NK cell numbers can be low, normal, or elevated
Low or absent T cell function (in vitro lymphocyte proliferation in response to mitogens and antigens(
Absent antibodies to vaccines
Management of SCID
IVIg
PJP Prophylaxis
Blood products should be CMV -ve and irradiated
No breast feeding if mother is CMV +ve
Avoid Live vaccines
Strict isolation
New immune system ASAP: HSCT. Gene therapy for some cases (ADA deficiency)
Wiskott Aldrich Syndrome Triad
Thrombocytopenia, Eczema, Recurrent Pyogenic Infections (encapsulated organisms)
Can also have autoimmunity
Increased risk of malignancy as well
Diagnosis of WAS
Thrombocytopenia (small too), lymphopenia Variable IgG High IgA Low IgM High IgE Poor antibody responses to some vaccines Decreased T cell function
Management of WAS
IVIg
PJP prophylaxis
HSCT
Monitor for AI and malignancy
Ataxia Telangiectasia mode of inheritance
AR
Ataxia Telangiectasia clinical features
Ataxia (starts as a toddler)
Progressive Neurodegeneration
Telangiectasia (face, conjunctiva, ear lobes)
Immune deficiency (only in 2/3, not as severe)
25% develop malignancy especially LYMPHOMA
Abnormal DNA repair…should avoid Xray and CT
Ataxia Telangiectasia type of malignancy
LYMPHOMA
Ataxia Telangiectasia Diagnostic Labs
Increased Alpha Fetoprotein Decreased T cell numbers Low or normal IgG Absent IgA Sometimes elevated IgM Decreased T cell function Can have poor antibody response to some vaccines
Ataxia Telangiectasia Management
Supportive (HSCT doesn't fix neuro problems) Avoid Ionizing radiation IVIg for those with humoral deficiencies Genetic counselling (ATM increased risk of breast cancer)
DiGeorge Syndrome clinical features
CATCH-22 Cardiac Defects (interrupted aortic arch) Abnormal Facial Features Thymic Hypoplasia Cleft Palate and midline abnormalities Hypocalcemia 22q11 deletion
Also FTT, DD, Psychiatric issues
DiGeorge Syndrome Lab Features
Mildly reduced CD4 and CD8
Hypocalcemia
Normal or mildly reduced T cell function
May (rare) have poor response to vaccines
DiGeorge Syndrome Management
Usually only have mild T cell deficiency which improves with age.
Some have complete DiGeorge- severe T cell deficiency
Blood products should be CMV -ve and irradiated
Should not have live vaccines until immune competence is demonstrated
Screen parents too
Chronic Granulomatous Disease Genetics
Phagocytic Defect
Defect in NADPH oxidase
65% are X linked (others are AR)
CGD organisms
Susceptible to catalase positive pathogens S. Aureus Aspergillus Nocardia Serratia Marcesscens Burkholderia Cepacia Salmonella
CGD Clinical Features
Recurrent bacterial and fungal infections (suppurative adenines, pneumonia, abscess, osteo, sepsis)
Abscesses and granulomas (in organs)
Inflammation (IBD)
CGD Lab features
Normal or increased neutrophil numbers
Abnormal NOBI or NBT
CGD Management
Antibiotics for infection
Antibacterial and Antifungal prophylaxis (septa and itraconazole)
Anti-inflammatory treatments if needed
HSCT
Hyper IgE Syndrome (Job Syndrome) Clinical features
AD mutation STAT3
Recurrent Abscesses in the skin, lungs (cold boils)
Mucocutneous Candidiasis
Eczema
Facial Features (deep set eyes, prominent forehead, broad nasal bridge, bulbous nose, coarse skin)
Delayed shedding of teeth
Bone fractures, scoliosis, joint hyperlaxity
Lab features HyperIGE
VERY high IgE >20 000
Eosinophilia
Normal IgG, IgA, IgM
Function: poor antibody response to vaccines
Management of Hyper IgE
Treat Infections
Anti Staph prophylaxis (septra)
Leukocyte Adhesion Defects Pathophysiology
AR
Deficiency in adhesion molecules (abnormal neutrophil migration and penetration into tissue)
LAD Clinical features
Delayed Separation of umbilical cord (>4 weeks)
Staph infections in 1st year of life (dental, gingivitis, intestinal)
NO PUS FORMATION
LAD Lab Findings
Neutrophilia
Absent surface adhesion molecules CD11 and CD 18
LAD Management
Antibiotic treatment and prophylaxis
HSCT
Complement Deficiencies Characteristics
Severe, recurrent or invasive infections with encapsulated bacteria
Defects in C1-C4: Rheumatic Diseases
Defects in C5-C9: Disseminated Neisseria Infections, meningitis
Management of Complement Deficiencies
Antibiotic Prophylaxis
Immunizations (meningococcal and pneumococcal)
Lab Features of Complement Deficiencies
C3 C4 usually normal
Other complement levels more useful
Abnormal CH 50 (function)
AH 50 (alternate pathway function)
PJP prophylaxis is needed in what type of immune deficiency
Cell mediated (T cell)
Does Transient hypogammaglobulinemia need treatment?
No! Usually self resolves
Hyper IgM type of immunodeficiency
Combined Immunodeficiency
Hyper IgM Clinical features
Infections (bacterial in 1st year of life, opportunistic as well)
Autoimmunity
Liver Disease (sclerosis cholangitis, chronic hepatitis)
Malignancy (lymphoma)
Lab Features of Hyper IgM
High IgM Low IgG Low IgA Normal T and B cells 50% have neutropenia Poor antibody response to vaccines
Hyper IgM management
Immunoglobulin replacement therapy
PJP prophylaxis
HSCT (for immune deficiency and to prevent malignancy)
Cartilage Hair Hypoplasia
Short limbed dwarfism combined immune deficiency Short pudgy hands, hyper extensible joints, sparse hair Hirschsprung disease Immune: SCID to near normal Increased frequency of malignancy
Management: immunoglobulin replacement to HSCT
IRAK 4 Deficiency
recurrent, sever, invasive infections
Normal B and T, phagocyte and complement function
Chronic Mucocutaneous Candidiasis features
Persistent candida infection in the skin, nails and mucous membranes
Endocrine Autoimmunity
APCED
Hereditary Angioedema
Recurrent episodes of swelling to face, extremities and internal organs
No urticaria, pain, heat or itch
Deficiency in C1 esterase inhibitor (AD). Low C4 levels
Hereditary Angioedema Management
Concentrates of C1 inhibitor infusions during attacks
Androgens for prophylaxis as well
ALPS
Autoimmune cytopenias
Lymphoproliferation
Increased malignancy
Management with immune suppression
Lab findings of ALPS
Anemia, Neutropenia, and/or thrombocytopenia
Elevated IgG
Elevated % of T cells not expressing CD4 or CD 8
Elevated B12 levels
Normal antibody responses to vaccines
Normal T cell function
IPEX
Immune Dysregulation
Polyendocrinopathy (IDDM)
Enteropathy
X linked
Epinephrine should be given via what route for anaphylaxis
IM
Dose of epinephrine for anaphylaxis
0.01mg/kg IM max dose 0.5mg
How often can you repeat epi for anaphylaxis
every 5-15 minutes
Why don’t we give SC epi for anaphylaxis
Local vasoconstriction may inhibit absorption
When do we give IV epi for anaphylaxis
After 3 doses of IM epi
Persistent hypotension despite fluid resuscitation
In patients who are on Beta Blockers and are not responding to epi in anaphylaxis…what can you give them?
Glucagon
Has inotropic and chronotropic effects…not mediated through beta receptors
IV bolus
Second line agents in anaphylaxis (5)
Salbutamol Nebulized Epinephrine H1 Antagonist (antihistamines) H2 Antagonists (ranitidine) Corticosteroids
When do most biphasic reactions occur?
Within first 4-6 hours
5-20% of patients with anphylaxis
What increases your risk of a biphasic reaction?
Delayed epinephrine
More than one dose of epi
Severe symptoms at presentation
Anaphylaxis teaching
Epi pen
Anaphylaxis Action Plan
Medical Identification Device
Consider 3 day course of antihistamines and corticosteroids
Avoidance of trigger if obvious from history
Referral to Allergist
Most common causes of anaphylaxis
Food, venom, medication
Skin prick testing advantages
Fast
More sensitive than serum specific IgE
High negative predictive value
Cost Effective
SPT disadvantages
False Positives
Affected by use of antihistamines and steroids
Risk of systemic reaction
Can not perform if skin site affected
Serum Specific IgE testing pros (RAST)
Not affected by antihistamines, steroids, montelukast
No risk of systemic reaction
Can be performed if skin disease
Serum Specific IgE testing cons (RAST)
False positives if elevated total IgE
Less sensitive compared to SPT
More expensive
Management of Food Allergy
Avoid trigger OIT Epi auto injector Anaphylaxis Action Plan Medical Identification Device
Who is at high risk of a food allergy?
Having a first degree relative with an allergic condition (asthma, eczema, allergies)
How to prevent food allergy in children
No dietary restrictions during pregnancy or breastfeeding
Exclusively breastfed for 6 months
Hydrolyzed formula if infant not breastfed
Don’t delay introduction of allergenic foods
Regular ingestion of newly introduced foods
Who gets food protein proctitis
Exclusively breastfed infants ages 2-8 weeks
Cow’s milk protein, eggs, soy, corn
Clinical features of food protein proctitis
Blood tinged stools
Otherwise healthy
Management and diagnosis of food protein proctitis
Skin testing and IgE not helpful
Eliminate food from moms diet or extensively hydrolyzed formula
By 9 months 95% will tolerate food
Food protein induced enterocolitis syndrome (FPIES) onset
1-4 weeks after introduction of food
FPIES trigger foods
CMPA Soy grains rice meat poultry egg potato legumes
FPIES S/Sx
Repetitive vomiting 1-3 hours after ingesting food
hypotension
relieved by 3 years usually
FPIES diagnosis
Skin testing and serum IgE not helpful
Eliminate offending agent
Venom Allergy 3 types of reactions
Local reaction (erythema, swelling, pruritus. immediate onset, resolves in a day) Large Local Reactions (localized erythema, swelling >15cm. Develops 12-48 hours after sting and resolves in 5-10 days) Systemic Reaction (anaphylaxis, generalized cutaneous symptoms beyond the site of the sting)
Management of venom allergy
If local reaction: testing not indicated
Anaphylaxis: Epi pen, all require testing, Immunotherapy
Generalized cutaneous reactions (<16 no testing. >16 yo testing if high risk)
What is the cross reactivity between penicillins and cephalosporins?
2%
Urticaria/Angioedema onset
Minutes to Days after exposure
Resolves 1-2 days after stopping medication
Treat with antihistamines
Exanthemous Eruption onset
Days to 2 weeks after drug exposure
Diffuse fine macule and papule
Resolves 5-14 days after stopping medication
Fixed Drug Eruption features
Hyperpigmented plaques Same site wth re exposure Discontinue the medication Topical steroids and antihistamines Steroids if really severe
Erythema Multiforme Features
Target Lesions Mucosal membrane involvement Stop meds Topical steroids, antihistamines Steroids for severe cases
SJS/TEN features
1-3 weeks after drug exposure
Fever, sore throat
Blistering lesions and skin detachment (<10% SJS, >30% TEN)
Mucus membrane
Discontinue med and supportive treatment
Systemic corticosteroids and IVIG controversial
Drug rash with eosinophilia features
Onset 1-8 weeks after drug exposure
Rash, Eosinophilia, hepatic dysfunction, fever, facial angioedema, LAD
stop meds
steroids if bad
Serum Sickness
1-3 weeks after drug exposure Rash, arthralgia, renal disease, fever LOW COMPLEMENT Stop med, NSAIDs, analgesia Steroids or plasmapheresis for severe cases
Serum Sickness- LIKE
1-3 weeks after drug exposure No renal disease NORMAL COMPLEMENT Stop med, NSAIDs, analgesia Steroids for severe cases
Can you have flu vaccine if allergic to eggs?
Yes
Egg allergic patients…can they receive all vaccines?
MMR: receive as a single dose
Inactivated Influenza Vaccine: single dose normal monitoring
Live Attenuated Influenza Vaccine: single dose normal monitoring
Yellow fever: NEEDS SKIN TESTING BEFORE!
Chronic Urticaria Treatment
2nd gen antihistamine
second line: increase dose 4 fold
third line: add montelukast or cyclosporin or omalizumab
short course of steroids
Hereditary Angioedema Inheritance
AD
Hereditary Angioedema Pathphys
C1 esterase inhibitor deficiency/dysfunction
Allergic Rhinitis Treatment
Allergen Avoidance Second gen antihistamine Intranasal corticosteroids LTRA Immunotherapy
