Endo/Allergy/Immuno Flashcards
What are the characteristics of familial short stature?
Normal growth velocity
BA=CA
Predicted adult ht appropriate for mid=parental height
What are the characteristics constitutional delay of growth and maturation?
Normal growth velocity
BA delayed 2-4 ages
What is the significance of BA and CA being > 3 year apart?
always pathologic
What are the characteristics of GH deficiency?
Congenital or acquired
Isolated or mutiple pituitary hormone deificenices
Poor growth velocity
Delayed bone age
Low response on GH stim tests
Low IGF-1
What are the stages of female pubertal development?
- Breast
- Hair
- Growth
- Menarche
What are the stages of male pubertal development?
- Testicular volume
- Penile length
- Hair
- Growth
What is premature thelarche?
Isolated breast development
6-24 months
Does not exeed SMR 3
No change in growth percentile
What is premature adrenarche?
Pubic hair and axillary hair, body odor, acne but no thelarche
Ealy secretion of DHEA
NO change in growth %
Bone age=CA
What is the definition of precious puberty?
Pubertal signs prior to 8 in girls and 9 in boys
What are the red flags for precious puberty?
Rapid progression
BA progressed beyond 2 years
Predicted adult ht
What is a clue to differentiate central vs. peripheral precious puberty?
If it occurs out of the normal sequence likely peripheral
Clue to peripheral PP in girls?
Estrogen dependent effects predominate
Clue to peripheral PP in boys?
Testes are inappropriately small
What is the definition of delayed puberty?
Absence of secondary sex characteristics after 13 in girls and 14 in boys
What are the clues to primary gonadal failure?
Elevated LH and FSH with low testosterone and estrogen
What are the clues to permanent of functional pituitary or hypothalamic dysregulation?
Low LH and FSH with low testosterone/estrogen
What are the characteristics of Turner Syndrome?
45XO
Mean adult height 144 cm
GH improved height
Gonadal failure 96%, infertility 99%
What are the characteristics of Klinefelter syndrome?
47XXY
1in 600 males
Puberty often begins at appropriate age with penile enlargement and pubic hair then stalls
SMALL FIRM TESTES, gynecomastia, infertility
Increased learning and behavioral difficulties
What are the characteristics of ketotic hypoglycemia?
Common form of childhood hypoglycemia
18M-5Y
Typically during periods of intercurrent illness, limited food intake
Associated with ketonuria and ketonemia
What is the starting dose of insulin in DMT1?
0.5Units/kg/day
What is the sick day management for DMT1?
Give 10-20% of TDD as rapid insulin by SC or pump
What is the insulin sensitivity factor?
Amount BG will drop for every unit of rapid insulin given
100/TDD
Eg. TDD=40 therefore ISF=2.5 (1 unit will drop BG by 2.5)
Give enough rapid insulin to lower BG to a target of 6-8 mmol
What is most likely for a child with ambigious gentalia with bilaterall masses in the folds?
Almost always testis therefore a unvirulized male
What defines clitriomegaly?
> 1 cm
What defines micropenis?
What is the approach to DSD?
- Is it a virilized 46XX or undervirilized 46 XY or mosaicism?
- Are the gonads palpable?
- Karyotype
- Ultrasounds
- Exclude lifethreatening CAH
What is the DDX for a virilized female?
- CAH
- Virilizing maternal disease
- Maternal androgen use
- Mixed gonadal dysgenesis
Basic labs: 17 OHP lytes, glucose, ACTH, renin, tesosterone, LH, FSH
What is the DDX for an undervirilized male?
- Reduced testosterone production
- Abnormal testicular development
- Testosterone biosynthetic defect
- 5 alpha reductase deficiency
- Androgen receptor disorder
Labs: Testosterone, dihydrotestosterone, LH, FSH, Mullerian inhibiting substance, lytes, glucose
What percentage of pediatric thryoid nodules are malignant?
20%
Who is at risk for Ricketts?
Exclusively breastfed Moms with Vit D deficiency Not exposed to enough sunlight Darker skin Northern communitities
Peaks incidence of DMT1?
2
4-6
10-14
What is the pathogenesis of DMT1?
Destruction of the beta cells of the pancreas
80% must be destroyed to affect glycemic control
How do you diagnose DMT1?
Random >11.1
Fasting >7
What are the acute complications of DMT1?
DKA- If ketones give 10-20% of TDD until no ketones
Hypoglycemia-
What are the long term complications of DMT1?
ASsociated autoimmune disorders Growth Retinopathy- 10Y then Q3-5Y Nephropathy-10Y with DM>5Y annual urine microalbumin Neuroapthy Macrovascular
What are the biochemical criteria for DKA?
Glucose >11
PH
What is the initial ketone formed in DKA?
Acteoacetic acid
Does strip testing accurately access severity of ketosis?
NO because Bhydroxybuttrate doesn’t react
What happens to Na in DKA?
Increased plasma osmolality
H2O moved out of cells therefore diluted
Osmotic diuresis therefore more free water loss
What happens to K in DKA?
Osmotic diuresis and ketoacid load cause increased K excretion
However movement out of the cells because of low pH
Increased serum K but decreased total bodyK
Starting dose for insulin in DKA?
0.05-0.1 units/kg/hour
How long should the insulin infusion continue?
AG normal pH > 7.3 HCO3 >15 Glucose >11 Tolerating PO intake
What are the possible complications of DKA?
- Cerebral edema
- DVT
- Aspiration
- Arrhythmia
- Increased amylase and lipase
What are the risk factors for DMT2?
Obesity
Family history
Racial background
Puberty and conditions of insulin resistance
How do you screen for DMT2?
Fasting blood glucose at 10 year or puberty
Repeated Q2Y
Where are catecholamines produced?
Adrenal inner medulla
Where are steroid hormones produced?
Adrenal outer cortical tissue:
- Zona glomerulosa: Mineralocorticoids
- Zona fasciculate: glucocorticoids
- Zona reticularis: sex hormones
What is aldosterone?
Regulated by RAS and K elvels
Maintenance of intravascular volume through conserving sodium and eliminating K/H
What is required for differentiation of sex organs?
Sex determining region on Y chromosome
Early gonads are bipotential until 6-8 weeks
What is required to be male?
Testosterone from Leydig cells- directs formation of internal male urogential tract from WOlffian ducts
Anti-Mullerian hormone from Sertoli cells- suppresses development of Mullerian ducts
What is the role of DHT?
More potent testosterone
In the presence of DHT, will develop into male structures
DHT made from test by 5 alpha reductase
What should be offered to parents who are known carriers or have a child with CAH?
Dexamethasone before 7-8 weeks to suppress fetal HPA before virilization
70% of female with have normal gentalia at birth
DO an CVS 10-12 weeks or Amino at 14-18 weeks to determine if male or female. If male, d/c dex
What are the symptoms of cushing syndrome?
- Moon facies
- Buffalo hump
- Truncal obesity
- Striae
- HTN
- Hyperglycemia
- Masculinization
- growth failure
- Amenorhhea
- Osteoporosis
What are the adverse effects of steroids?
Growth suppresion Myopathy AVN Osteopenia Immunosuppresion Peptic ulceration HTN Hyperlipidemia Cataracts Pseudotumor cerebri
Why is congenital hypothryoidism so bad?
T4 is critical to the myelinization of the CNS
What are symptoms of congential hypothyroidism?
Large posterior fontanelle Lethargy Hypotonia Hoarse cry Feeding problems Constipation Macroglossia Umbilical hernia Dry skin Hypothermia Prolonged jaundice
What is the difference between primary and secondary adrenal insufficiency?
Primary: Adrenal gland abN
Secondary: hypothalamic or pituitary dysfunction
What is the DDX of a primary adrenal insufficiency?
Inherited: CAH, CAhypoplasia Autoimmune: APS Infectious: TB, Meingococcemia Trauma Adrenal hypoplasia Oatrogenic
What are the most common causes of secondary adrenal insufficiency?
Prolonged steroid use Tumor CNS trauma irradiation Infection Surgery
How can you tell primary vs secondary adrenal insufficiency?
Primary: ACTH elevated, hyperpigmented, hypoNA, hyperK
Secondary: ACTH low, no hyperpig, Isolated hypoNA HISTORY OF A CNS INSULT
What is the most common form of CAH?
21- Hydroxylase deficiency
What are the causes of hypercalcemia?
High 5-Is Hyperparathyroidism Idiopathic: Williams Infantile: SubQ fat necrosis Infection:TB Infiltration: Malignancy, Sarcoid Ingestion Skeletal disorders
Two PE exam for calcium?
Chvostek sign: tapping on the parotid gland results in muscle spasm with movement of the upperlip (CH=cheek)
Trousseau: spasm with blood pressure cuff
What are the main causes of hypocalcemia?
Nutritional -Vita D Renal insufficiency Nephrotic syndrome Hypoparathyroidism PseudohypoPTH
What are the risk factors for cerebral edema in DKA?
1. Younger age Newly diagnosed More profound acidosis Attenuated rise in serum sodium Greater hypocapnia Increased BUN Bicarbonate therpay for acidosis Administrationof insulin in the first hour of therapy High volumes of fluid given during the first 4 hours
How long does the honeymoon period last in T1DM?
2-4 weeks
What are clues to T cell disorders?
2-6M Gram+/-/Mycobacteria CMV, EBV, Parainflu Candidia, PCP Sinopulmonary, FTT, Diarrhea Omenn syndrome, Disease post BCG, VZV vaccine
What are clues to B cell disorders?
>6M (After MOms IGG is gone) Encapsulated organized Enterovirus Giardia, cryptosporidium Sinopulmonary, GI, Arthritis, Meningoencephalitis Autoimmunw, lymphoma
What are clues to phagiocytic disorders?
Early onset Staph, pseudonom, serratia Candidia, aspergillus Abscesses, mouth ulcers, Osteomye Delayed cord separation, poor wound healing
What are clues to complement disorders
Any age
Pneumococcal, Meningococcal
Speticemia, meningitis
Autoimmune
What are the 10 warning signs of PID?
Four or more new ear infections in 1 year
2 or mroe serious sinus infections within 1 year
2 or moremonths on antibiotics with little effect
Two or more pneumonias within 1 year
Failure of an infant to gain weight or grow normally
Recurrent deep skin or organ abscesses
Persisten thursh in the mouth or fungal infections on the skin
Need for IV antibiotics to clear infection
Two or more deep seated infections including sepsis
A family history of PID
What are the clues on history to PID?
Autoimmunity: cytopenia, colitis, arthritis
FFT
Eczema
Delayed cord separation
Reactions to live viral vaccines
FHx: consanguinity, infantile deaths, Affected maternal uncles (Xlinked)
How do you assess the humoral/B cell
Number: Immunoglobulins, lymphocyte subsets (flow CD 19)
Vaccine response, Isohemagglutinin to blood groups
How do you assess the cellular/T cell
Number: Lymphocyte subsets (CD 4/8)
Function: Lymphocyte proliferation, Adenosine deaminase and purine nceloside phosphorylase levels, TRECS
How do you assess phagocytic
Number: neutrophil counts
Function: NBT or NOBI
CD11 CD18 measurement of adhension markers
Complement assessment
Number: C1 esterase inhibitor levels, specific complement levels
Function: Total hemolutic complement CH50, C1 esterase inhibitor function
What are the most common group of PID?
Humoral/B cell
What are the common B cell disorders?
- X linked agammaglobulinemia
- Common variable immune deficiency
- Transient hypogammaglobulinemia of infancy
What are the characteristics of XLA?
-Caused by mutations in Bruton Tyosine Kinase
Absent B cell s in peripheral blood
No B cells= no lymphatic tissue (Tonsils and LN)
No immunoglobulin production
Males, 6-24 months
Recurrent infections: sinopulmonary, otitis media, GI, arthritits, meningitis, sepsis
Encaulsated bacteria
No IGA,G,M
No vaccine responses
What is the management of XLA?
Antibiotics for infecitons IVIG for lfie: monthly IV or weekly SC PFTs and chest CT: bronchiectasis Genetic confirmation of BTK mutuation Genetic counselling
What are the characteristics of CVID?
Recurrent infecitons, autoimmunity, malignancy
Will have lymphatic tissue
Recurrrent bacterial and sinopulmonary infections
Can have bronchiectasis
Mycoplasma, enteroviruses, Giardiasis
Autoimmunity in 20-25%
Increased incidence of LYMPHOMA AND ALL CA
Decreased IgG, vaccine response
What is the management of CVID?
Antibiotic treatment of infecitons
IVIG for life
Monitor for autoimmunity and malignancy
What are the characteristics of SCID?
Present at 2-6M, Die by 1 year if not treated
Mutation in gamma chain of IL2 receptor, X linked
MEDICAL EMERGENCY
Persistent, recurrent, severe infections
FTT
NO lymph nodes
What is the CXR finding of SCID?
NO THYMUS
What are the lab features of SCID?
Lymphopenia
Severely reduced T cell numbers
Absent response to vaccines
What is the management of SCID?
Aggressive antimicrobial therapy IVIG PCP PPX CMV negative irradiated products Strict protective isolation BMT
What is the triad of Wiskott-Aldrich?
- Thrombocytopenia
- Eczema
- Recurrent pyogenic infections
X linked
Watery/bloody diarrhea in first months
Encapsulated organisms
What are the lab findings of Wiskott-Aldrich?
- Small, low numbers of plts
- Low IgM, high IgA,Ige
- Poor antibody responses to vaccines
- Decreased T cell functions
What is the management of Wiskott-Aldrich?
IVIG
Antibiotic PPX
BMT
What are the features of ataxia-telangiectasia?
AR, ATM Gene
Ataxia: Cerebellar, around 18 months, wheelchair bound by teenage
Telangiectasia: face, conjunctiva, ear lobes, 2-4 years
Progressive neurodegeneration
Recurrent sinopulmonary infections and bronchiectasis
What are the lab features of AT?
INcrease alpha FP
Decreased T cell
Absent IgA
Decreased T cell function
What is the management of AT?
Confirmation by gene sequencing
Abnormal DNA repair: increased sensitivity to irradiation, try not to XR, CT
15% develop malignancy: lymphoma
Supportive, NO BMT
What are the features of DiGeorge?
CATCH 22 Cardiac defects: Ao arch Abnormal facial features (hooded eyelids, hypertelorism, low set ears, notched pinnae, micorgnathia, short philtrum, high arched palate) Thymic hypoplasia Cleft palate and midline abN Hypocalcemia 22q11 deletion FTT, DD, Psychiatric issues
What are the features of chronic granulomatous disease?
Defect in NADPH oxidase: required for effective phaogocytic killing of certain pathogens
65% Xlinked, AR
Susceptible to catalase positive pathogens: S aureus, aspergillus, nodcardia, serratia, burkholderia, salmonella
Recurrent bacterial and fungal infections
Abscesses and granulomas
What is the workup and management of CGD?
Abnormal Nuetrophil oxidative burst index or Nitroblue tetrazolium test
Aggresive antibiotics treatment for current infections
PPX: bacteria and fungal
Anti inflam
BMT
What are the characteristics of Hyper IgE syndrome?
Autosomal dominant in STAT3
Recurrent abscesses in skin, joints, lungs COLD BOILS
Eczema, Coarse facial features
Delayed shedding of teeth
Bone fractures, scoliosis, joint hyperlaxity
Rx infections, anti staph PPX
What are the characteristics of leukocyte adhesion defects?
Deficiency in adhesion molecules: abnormal neutrophilmigration and penetration, remain inblood
Delayed separation of umbilical cord
Staph infections: dental, gingivitis, intestinal
Neutrophilia, absent surface adhesion molescules: CD11, CD18
What are the characteristics of complement deficiencies?
Autosomal recessive
Defects in early: C1,C2,C4: rheumatic diseases, lupus, infection
Defects in late: C5-9: invasive Nerissa and pneumoncoccal infections
Antibiotic ppx and immunizations
What are the four components of management of PIDs?
Antibiotics
Vaccinations
IVIG
BMT
What are the characteristics of Transient HypoIG of infancy?
Physiological nadir at 6 months
Slow to increase, up to 6-12 years
No need to treat
What are examples of type I allergic reactions?
Anaphylaxis
Food allergy
Allergic rhinitis
What are examples of type II allergic reactions?
Autoimmune cytopenias
Goodpasteurs
What are examples of type III allergic reactions?
SLE
Serum sickness
Glomerulonephritits
ACID 1 Allergic (IgE) 2 Cytotoxic (hemolytic reaction) 3 Immune Complex (SLE, serum sickness) 4 Delayed (contact dermatitis)
What are examples of type IV allergic reactions?
Contact dermatitis
Psoarsis
What is the breakdown of system involvement in anaphylaxis?
Cutaneous 80-90%
Respiratory 60-70%
GI 50-60%
Cardio 10-30%
In a patient with anaphylaxis who are receiving beta blockers, what other therapy can you use?
Glucagon
Inotropic and chronotropic effects that are not mediated through beta receptors
Why is a period of observation recommended in anaphylaxis?
4-6 hours
Why? Biphasic reaction
Recurrence of symptoms after initial resolution
Risk: delayed epinephrine, more than dose of epi, severe symptoms
What is the discharge management of anaphylaxis?
- Epinephrine autoinjector
- Anaphylaxis action plan
- Consider 3 day course of antihistamines and steroids
- Medical ID bracelet
- Referral to an allergist
- Avoidance of trigger if obvious
What are the epipen doses?
> 25kg: Epipen 30 mg
10-25: 15 mg
<10 kg: epipen jr or ampule of epi
What percentage of anaphylaxis has an identifiable trigger?
1/3
What is skin prick testing?
Pros cons
Solutions containing proteins placed on skin, pricking allowing introduction into skin. Localized hive if sensitized
Pro: Result in 15 min, more sensitive compared than seurm specific IgE, high negative predictive value, cost effective
Cons: False +, affected by antihist and steriods, risk low of systemic reaction, not if atopic disease
What are the serum specific IgE testing?
Eg: Rast and ImmunoCAP
-Allergen of interest bound to solid phase matrix
Patients seurm added
If IgE present against, will bind to allergen
Fluorescence is measured (anti IgG labelled and will attach to IGE)
What are the pros and cons of RAST (serum specific IgE) testing?
Pro: Not affected by antihistamines, steroids, montelukast, no risk of systemic reaction, can be performed if patient has skin disease
Cons: False + if total IgE is elevated, less sensitive than SPT, more expensive than SPT
What is the gold standard for diagnosis of food allergy?
Oral food challenge
Gradual feeding of suspected food with careful supervision
What is the management of a food allergy?
Avoidance of responsible food
EpiPen
Anaphylasix action plan
Medical ID bracelet
How do you prevent food allergies?
No dietary restrictions during pregnancy or breastfeeding
Exclusive breastfeeding for the first 6 months
Hydrolyzed formula if not breastfed
DO NOT delay the introduction of any specific solid food including allergenic foods beyond 6 months
Regular ingestion of newly introduced food
What are the characteristics of food protein induced procitits?
Exclusively BF infants 2-8 weeks
Transfer of food protein ingested by mother through milk
Cows milk protein, egg, soy, corn
What is food protein induced enterocolitis syndrome?
1-4 weeks after introduction of food
Cows milk, soy, grain, rice, meat, egg, potato, legums
Repetitive vomting 1-3 hours after ingestion
Skin testing and RAST not helpful
Eliminate offending food
What are the three type of venom reactions?
- Local reactions
- large local reactions
- Systemic reactions
What is immunotherapy for allergies?
Administration of gradually increasing quantities of allergens until a dose is reached that is effective in inducing immunologic tolerance to allergens
What is immunotherapy used for?
Venom allergy
Allergic rhinitis
Allergic asthma
Atopic dermatitis with aeroallergen sensitization
What are the most likely drugs to cause anaphylaxis?
Antibiotics
Anticonvulsants
NSAIDS
Radiocontrast media
What is pencillin allergy mediated by?
IgE against a major determinant
What is DRESS?
Drug rash with eosinophilia and systemic symptoms
1-8 week onset
Rash, fever, LN, facial angioedema, hepatic dysfunction, eosinophilia
Drugs: sulfonamides, minocycline, allopurinol, anticonvulsants
Systemic steriods in some
What is serum sickness?
Onset 1-3 weeks
Rash, fever, arthritis, renal disease
Low complement
Type III
What are the signs of allergic rhinitis?
Allergic shiners Dennnie Morgan lines Allergic salute Horizontal crease Allergic facies Enlarged pale nasal tubinates Cobblestoning in the psoterior oropharnyx
Pathophysio of type I hypersensitivity reactions?
Immediate
IGe production against antigens with binding mast cells and release of inflammatory mediators
What is the pathophys of type II reactions?
Antibody mediated
Antibodies against soluble antigens may form complexes which deposit in the vessels of tissues
Pathophysio of type I hypersensitivity reactions?
Immediate
IGe production against antigens with binding mast cells and release of inflammatory mediators
What is the pathophys of type II reactions?
Antibody mediated
Antibodies other than igE directed against cell of tissue antigens causing damage
What is the pathophys of type III reactions?
Immune complex mediated
Antibodies against soluble antigens may form complexes which deposit in the blood vessels
What is the pathophys of type IV reactions?
T cell mediated
Reactions of T cell against self antigens
What is the pathophys of allergic disease?
IgE response
Potential allergens cause rapid expain of T helper type 2 cells that secrete cytokines
IgE crosslink, breakdown of mast cells and basophils
Leads to release of inflammatory mediators: proteases, prostaglandins, histamine and bradykinin
What is the significance of major and minor determinants in testing for penicillin allergies?
Penicillin metabolized into major and minor determinants.
Skin testing with minor determinants is important in screening for anaphylaxis.
Major determinants: accelerated and late reactions by IgE
Minor determinants: anaphylaxis.
What are the three types of hymenoptera stings?
Bees: barbed stingers, die single sting. sting only when provoked
Wasps: Do not have barbed stingers, sting multiple times. Aggressive and sting without provocation
Ants: envenomate by anchoring their madibles into the skin and pivoting. Bite aggressively if nests disturbed
How common is allergic rhinitis?
40%
What is the mechanism of allergic rhinitis?
Hypersensitivity reaction to specific allergens occuring in sensitized patients mediated by IgE.
What is the first line therapy for allergic rhinitis?
Intranasal steroids > 2 years old
What is angioedema?
Transient swelling of the dermis or subQ tissue
May occur with anaphylaxis or episodes of urticaria.
What is hereditary angioedema?
Type 1 80%
Presents with recurrent swelling episodes, recurrent attackes of abdo pain and episodes of airway obstruction
Low C1esterase inhibitor activity results in anbility to stop the completement cascase
What are the two most recognized mechanisms for anaphylaxis
- Cross-linking of high affinity IgE receptors of the surgace mast cell sand basophils after binding IgE
- Non IgE mediated direct activation of mast cells
What are the three ways to diagnose anaphylaxis?
- Acute onset inless involving skin, mucosal or both with either resp compromise or hypotension
- 2+ occuring rapidly after exposure to likely alelrgen: skin, rsp, hypoBP, Gi
- Reduced BP after exposure to known allergen for that patient
What is the most common cause of anaphylaxis?
Food 90%
Milk, egg, soy, wheat, peanut, fish
What are the routes of immunotherapy?
SC: AR, allergic asthma, wasps
SL: aeroallergens
What are the second line agents for anaphylaxis?
H1 anatagonists: cetirizine (less sedating)
H2 anatagonists
Steroids
Ventolin
What is the most common chronic relapsing skin dsiease in childhood?
Atopic dermatitis
What are the hallmark features of atopic dermatitis?
Severely dry skin
Itchy: scratching leads to inflammation
Lichnification in flexural folds
How do you diagnose atopic dermatitis>
Eczematous dermatitis
Chronic and relapsing course
Pruritis
What are the treatment possibilities for atopic dermatitis?
Cutaneous hydration: lukewarm baths then emollient Topical steriods Topical calcineurin inhibits (tacrolimus) Antihistamines Systemic steriods Cyclosporine Phototherapy Avoidance of irritants and food triggers
What is serum sickness?
Systemic immune-complex mediated hypersensitivity vasculitis
Type III hypersensitvity from Ab-Ag complexes
How is measuring isohemagglutinins helpful for PID wu?
One of the most useful tests for B cell function
Determines the presence and titer of isohemagglutinins
Measures mostly IgM, may be absent in the first 2 years of life and are absent if patient is blood type AB
How is a candida skin test helpful for PID wu?
If test is positive (induration >10mm at 48 hour) all T cell defects are excluded
What are the types of immunity?
Innate: early line of defense, mediated by cells that are always present
Adaptive: stimulated by microbes, fine specificity for substances and responds more effectively against each successive exposure to a microbe