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Yamini AI Board Review 1B

Yamini Ai Board Review 1B

by ytigger@hotmail.com, Sep. 2014

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	Treatment of ABPA	long–term steroids, (daily prednisone x 14 days, then 3–6 month taper) 16 weeks itraconazole or voriconazole
	Diagnostic Criteria for ABPA in asthmatics	Asthma: + SPT to Aspergillus fumigatus IgE>1000 (417 IU/mL) Incr IgG and IgE to A fumigatus Central bronchiectasis peripheral eos (>1000)
	Diagnostic criteria for ABPA in CF	clinical deterioration not due to other causes total serum IgE>1200 ng/mL (500 IU/mL) + SPT to Aspergillus fumigatus Incr IgG and IgE to A fumigatus fixed chest film abnl (infiltrates, mucusplug)
	Types of fungal sinusitis	acute/fulminant (invasive) chronic/indolent (invasive) fungus ball allergic fungal sinusitis (most common)
	Causative fungi for allergic fungal sinusitis	Bipolaris Curvularia Alternaria Rhizopus Dreschslera Helminthosporum Fusarium Aspergillus
	CT findings for allergic fungal sinusitis	hyperattenuation heterogenous opacification calcification
	Lab findings for allergic fungal sinusitis	Gross: allergic mucin (thick, viscous, tan/brown colored) Histo: branching noninvasive fungal hyphae, eos in sheets, CHarcot leyden crustals Lab: Incr IgE, fungal IgG, positive fungal SPT
	Treatment for allergic fungal sinusitis	Endoscopic sinus surgery nasal saline irrigations oral steroids (usu just before surgery) Topical nasal steroids Immunotherapy–controversial – antifungals don't help
	Allergic fungal sinusitis sx (acute and chronic	Acute; F, nasal congestion, acute facial pain, headache, diplopia, anosmia acute Chronic: vision changes/loss, proptosis, sinus tenderness to palpation, malaise, fatigue
	Allergic fungal sinusitis diagnositc criteria	Type I hypersensitivity to fungi (SPT or IgE) Nasal polyposis Positive fungal stain of sinus contents Histo: eo rich mucin and fungal elements with no invasion of resp mucosa
	Lung disease by TH1 v. TH2	Th1: CD8: HP, COPD CD4: granulomatous (TB, sarcoid, berylliosis) TH2: asthma, ABPA, pulm eosinophilia, HIV, Graves
	Hypersensitivity pneumonitis by type (symptoms for Acute)	explosive reps sx non productive cough fever takes 4–6 hours spontaneous recovery HRCT: normal/fleeting ground glass opacities
	Hypersensitivity pneumonitis by type (symptoms for Subacute)	Progressive Slow onset productive cough no systemic sx HRCT: diffuse micronodules, air trapping, mild fibrosis
	Hypersensitivity pneumonitis by type (symptoms for Chronic)	No explosive sx no fever Fibrotic lung Anorexia/weight loss Permanent damage likely HRCT: groudn glass opacities, emphysema, honeycoming, parenchymal micronodules
	Hypersensitivity pneumonitis diagnostic criteria	Presence of typical sx evidence of exposure (history and + IgG0 + radiograph or HRCT BAL lymphocytosis >20% (low CD4/8 ratio<1) Sx on reexposure Can also see bibasilar dry rales, decr DLCO, decr PaO2 with exercise
	Hypersensitivity Pneumonitis: Faenia rectivirgula	Farmer's lung (moldy hay/compost)
	Hypersensitivity Pneumonitis: Micropolyspora faeni	Farmer's lung (moldy hay/compost)
	Hypersensitivity Pneumonitis: Thermoactinomyses vulgaris	Bagassosis (modly sugar cane)
	Hypersensitivity Pneumonitis: thermoactinomyces sacchari	ventilation penumonitis (humidfier and A/c)
	Hypersensitivity Pneumonitis: Naegleria gruberi	ventilation pneumonitis (humidifier and A/C)
	Hypersensitivity Pneumonitis: Acanthamoeba	Ventilation pneumonitis (humidifier, and A/C0
	Hypersensitivity Pneumonitis: Bacillus cerus	Humidifier's lung (cool mist humidifier)
	Hypersensitivity Pneumonitis: Kelbsiella oxytoca	Cool mist humidifier
	Hypersensitivity Pneumonitis: Mycobacterium avium intracellulare	hot tub lung
	Hypersensitivity Pneumonitis: aspergillus	Malt worker's lung (malt, tobacco and soy)
	Hypersensitivity Pneumonitis: penicillium casei	Cheese worker's lung (moldy cheese)
	Hypersensitivity Pneumonitis: penicillium roqueforti	Cheese worker's lung (modly cheese)
	Hypersensitivity Pneumonitis: Pseudomonas	Machine operator's lung
	Hypersensitivity Pneumonitis: Acinetobacter	Machine operator's lung
	Hypersensitivity Pneumonitis: Mycobacter	Machine operator's lung
	Hypersensitivity Pneumonitis: Avian proteins	Bird fancier's lung
	Hypersensitivity Pneumonitis: aspergillus	Bird fancier's lung
	Hypersensitivity Pneumonitis: Bacillus subtilis	Detergent worker's lung
	Hypersensitivity Pneumonitis: Alternaria	Woodworker's lung
	Hypersensitivity Pneumonitis: STachybotrys	winegrowe's lung
	Hypersensitivity Pneumonitis: aureobasidium	air–conditioner lung
	Hypersensitivity Pneumonitis: trichosporum cutaneum	Summer–type HP (Japan0
	Hypersensitivity Pneumonitis: Pzizia	El nino lung
	Hypersensitivity Pneumonitis: Candida albicans	Saxophonist's lung
	Hypersensitivity Pneumonitis: epicoccum nigricans	basement shower lung
	Hypersensitivity Pneumonitis: sitophilus	Wheat weevil lung
	Hypersensitivity Pneumonitis: toluene/ toleuene diisocyanate	chemical worker's lung
	Hypersensitivity Pneumonitis: phthalic acid	epoxy resin worker's lung
	Hypersensitivity Pneumonitis: trimellitic anhydride	plastic worker's lung
	Lab findings in Hypersensitivity pneumonitisi (BAL, lung bx, PFT)	BAL: incr CD8, lymph.20%, incr neut, eos, >1% mast, incr IgG/A/M, incr hyaluronic acid Bx: noncaseating granulomas, mononuclear cell ifniltrates of alveolar walls, foamy histiocytes, giant cells, peribronchiolar fibrosis PFT, 4–6 hrs exposure ––> decr FEV1, FVC, DLCO
	Diff'l Dx for hypersensitivity pneumonitis	Organic Dust toxic syndrome Fire–eater's lung Humidifier fever Silo unloader's disease byssinosis histiocytosis usual interstitial pneumonia occasional interstitial lung disease
	What is organic dust toxic syndrome aka sx epi	aka pulmonary mycotoxicosis noninfectious febrile illness in workers after dust exposure (contaminated by bact/fung spores) 30–50 times more common than HP young, usually in summer complete recovery
	What is fire–eater's lung	choking, cough, resp sx from aspiration of flammable petrochemicals used in fire eating fever and pleuritic chest pain
	Humidifier fever	toxic alveolitis, recirculated water with ednotoxin chest tightness 4–8 hrs after exposure
	Silo unloader's disease is due to _____	acute exposure to NO2 ––> asphyxia
	Byssinosis due to	inhalation of cotton, flax, hemp bronchoconstriction on first day, improves with time
	Occasional interstitial lung disease is usually due to	flock or nylon lifeguarding at pool (endotoxin may be cause)
	Drugs that cause Hypersensitivity pneumonitis	A Boy Came From a Good Home to Make Nice Purple Sweets Amiodarone, Beta blockers, Chlorambucil/clozapine/cyclosporine Fluoxetine, Gold Heroin/HMG Co–A reductase inhibitors Methotrexate, minocycline Nitrofurantoin Procarbazine Sulfsalazine
	Hypersensitivity pneumonitisi	Avoidance of offending agent Glucocorticoids if severe
	Usual Interstitial pneumonitis aka sx imaging Tx	aka idiopathic pulmonary fibrosis most common SOB, nonproductive cough X–ray: diffuse interstitial infiltrates CT: honeycombing PFT: restrictive, low DLCO Tx: steroids, txpt
	Acute interstitial pneumonitis aka features	aka Hamman–Rich syndrome – diffuse alveolar damage, fever, severe SOB over 1 day, flu–like sx, rapid resp decomp
	Nonspecific interstitial pneumonia	uncommon ILD (dx of exclusion) good prognosis
	COPD staging	GOLD criteria mild = FEV1>80% (gold1) mod = 50–80 (gold 2) severe 30–50 (gold 3) <30, <50% normal with chronic resp failure (gold4)
	Airway inflmmation in COPD due to	neutrophisl and macrophages (release matrix degrading enzymes) Nicotine (inhibits tissue inhibitors of matrix metalloproteinases (TIMPs)) Sputum eosinophils (marker of viral exac)
	Centrilobular v panlobular emphysema	upper v lower lobes cigarette smoke v. alpha1 antitrypsin deficiency
	COPD treatment	short/long acting anticholinergics LABA (in isolation) ICS only for moderate/severe COPD
	Allergenic proteins for main allergens	milk – casein/whey egg – ovalbumin, ovomucoid peanut – vicilin, conglutin, glycinin fish – parvalbumin shellfish – tropomysin
	oral allergy syndrome: betv1 (birch) –>	apple, peach Mald1
	What is Heiner's syndrome?	Food hypersensitivity of unknown immuen mech recurrent pneumonia, pulm infiltrates, hemosiderosis, Fe def anemia, FTT Dx: hx, peripheral eos, milk precipitins, lung bx, elimination diet
	Dermatitis herpetiformis is associated with ____ disease	Celiac. pts are gluten sensitive
	Examples of nonimmunologic anaphylaxis	Vancomycin Opiates Radiocontrast media Cold urticaria (causes mast cell /basophil mediator release in absence of IgE)
	Biphasic reaction – timing –frequency – recommended observation time	– usu several hours, as late as 72 h – 20% of episodes – 8 hrs is sufficient (24 has been advocated, we do 4)
	Drugs that interfere with correcting the hypotension associated with anaphylaxis	– Beta–blockers (blunt epi effect, interfere c normal compensatory tachycardia) – ACEIs (blocks ATI –> ATII, blocks enzyme that destroys kinins) – ARBs (no data) – Tricyclic (exaggerate response to epi by blocking reuptake) – MAOIs (prevent degradation of epi)
	Anaphylaxis in mastocytosis versus other forms	Total/mature >20 = mastocytosis Total/mature <10 = other cause
	Lab findings in anaphylaxis	histamine: rise by 5 min, elevated only 30–60m urinary histamine: elevated 24h serum tryptase: 15–180 min (peaks 60–90 min) Platelet activating factor
	Pretreatment for radiocontrast, cold, fluorescein related anaphylaxis	– 50 mg prednisone 13, 7, 1h before procedure – 50 mg benadryl 1h before – use low osmolar contrast – decreases risk of reaction to <1%
	Role of H1 in anaphylaxis	– coronary artery constriction – bronchoconstriction – systemic vasodilation – incr capillary permeability – tachycardia – pruritis – rhinorrhea
	Role of H2 in anaphylaxis	– coronary artery vasodilation – incr force of contractions – incr capillary permeability – increase mucus secretion
	Role of H3 in anaphylaxis	Autonomic receptor downregulator
	Perioperative anaphylaxis usually due to...	neuromuscular blocking agents hypotonic induction agents (barbiturates) antibiotics opioids latex colloids
	Natural Rubber latex – number of proteins – Health care workers react to ____ – more common allergens in those with sensitized patients with spina bifida	– 13 protein allergens – Hev b 5, 6, 7 (acidic protein; hevein/prohevin; patatin–like) – Hev b 1 (rubber elongation factor) Hev b3 (prenyltransferse)
	Natural Rubber latex – key food associated antigens	– Hevb2 (beta–1/3 glucosidase) ––> bell pepper, olive – HevB5 (acidic protein) ––> kiwi, potato, sugar beet – Hev B 6 (hevein, prohevein) ––> avocado, banana, chestnut, sweet pepper – Hevb7 (patatin like protein) ––> potato/tomato – Hevb13 (latex esterase) ––> potato
	Constarch powder in latex jobs ________	absorbs allergens and sesnitizes by inhalation
	Dipped rubbed products	cause most reactions b/c heat vulcanized at lower temperatures with more intact proteins
	Exercise induced anaphylaxis: Food dependent exercised induced anaphylaxis – timing of events – associated foods – two subtypes – management	– sx after physical activity – food min/hrs prior to exercise ––> anaphylaxis – crustaceans, cephalopods, celery, grapes, chicken, wheat, buckwheat, tomato, dairy, mushrooms – some react after any food (rare) some after specific food. – avoid exercise 4–6 h after food, epi
	Family apidai – types of insects	Honey bee (apis mellifera) Killer bee (African–European Hybrid bees) Bumblebee (Bombus spp)
	Bees (which type) – female stings – aggressive – sting when provoked – sting in large numbers – loud/slow attack – beeswax nest with numerous combs –subterranean/concealed nest	– Honeybee – Killer Bee – Honeybee, Bumblebee (nests) – Killer bee – Bumblebee – Honeybee – Bumblebee
	Family vespidae – which insects	Subfamily Vespinae – vespula (yellow jacket) – Dolichovespula arenia (yellow hornet) – Dolichovespula maculata (white–faced hornet) Subfamily Polistinae – Posistes (paper wasp)
	Which vespid – multiliayer paper nests of masticated wood – nes of single layer of combs – dangling legs in flight – aggressive – sting repeatedly – picnic/trashcan – sting for no reason	– yellow jacket and hornets – wasp – wasp – yellow jacket – all of them – yellow jacket – yellow jacket
	Which vespid? – aerial nesting – nests in concealed locations (underground, decaying logs) – sensitivity to vibrations – responsible for most human stings	– yellow hornets – yellow jackets – hornets – yellow jackets
	Family formicidae – features – location –nests	Solenopsis invicta (imported fire ant) – anchor by mandibles and pivot to give multiple stings and sterile pustule – southeastern US – large subterranean nests
	Rates of reactions – rates of death	3% adult, 1% children 30–50 fatal stings/year – half with no prior history
	Testing for venom IT	– intradermal (0.001–0.01 mcg/mL in 10 fold increments) – conc >1 mcg/ml venom ––> irritant effects – SPT if severe anaphylaxis hx – if negative skin test, in vitro before saying not necessary – sting challenge (gold standard for efficacy of VIT)
	Skin test sensitivity in venom testing does/does not correlate with degree of sting reaction	does not
	If severe hypothension after hymenoptera sting, do this test...	Baseline serum tryptase level
	Management (testing, venom IT) based on rxn: – No reaction – Large local – urticaria/angioedema – anaphylaxis	– (1–3% risk systemic reaction) – (5–10% risk), no SPT/IgE, no VIT – SPT/IgE. If positive ––> child 10% risk, no VIT. If adult 20% risk , VIT. – SPT/IgE. If positive ––> child 40% risk adult 60% risk ––> VIT. If neg ––> repeat testing
	Safety of VIT and Efficacy	– 50% have large local reactions – 5–15% have systemic sx during buildup – <5% require epi – 75–95% efficacy
	Dosing for venom IT	Single: main 100 mcg venom, up to 200 if IT fails Mixed: 300 mcg maint Imported fire ant = whole body extract – maint dose of 0.5 ml of 1:10 to 1:200 wt/vol extract monthly
	Types of biting insects that cause allergies	Kissing Bug (triatoma) – nocturnal painless bite Mosquito (culicidae) – anaphylaxis rare Horsefly/Deerfly (tabanidae) – large blood sucking flies with painful bite Asian Lady Beetle (Harmonia axyridis) – sensitized individuals sometimes have rhinitis, urticaria, asthma sx with bites
	Gell–Coombs classification of drug reactions	Type I: anaphylaxis Type II: Antibody dependent cytotoxic reactions Type III: immune complex reactions Type IV: Cell mediated or delayed hypersensitivity reactions
	Sub classification of type IV reactions (cytokines, cells, clinical manifestations)	IVa: Th1 cytokines, IFNg; monocytes; eczema IVb: Th2 cytokines, IL–4//5; eosinophils; maculopapular/bullous IVc: CTL (perforin, granzyme); CD4/CD8; maculopapular/bullous to pustular c incr CD8 T IVd: T cell and IL–8; PMNs; pustular
	HLA–DR3 associated with increased reactions to ____	insulin, gold, penicillamine
	HLA–B5701 associated with reactions to	abacavir
	PCN testing to...	Major determinants = benzylpencilloyl polylysine (Prepen) Minor determinants = PCN G, pnicilloate, penilloate Ampicillin/amoxicillin (3–25 mg/ml)
	% of PCN allergy due to major determinant	80%
	NPV and PPV of PCN drug testing	NPV 97% to rule out anaphylaxis PPV is 60%
	Aztreoname cross reacts with _____	ceftazidime
	Amoxicillin while EBV –––>?	80% have a rash
	__% of pts have a delayed maculopapular rash with amp/amox which _______ IgE mediated	10% is not
	PCN cross reactivity	moderate with carabpenems (impipenem, meropenem) if positive skin testing rare with PCN (2%)
	Which generation cephalosporin causes more allergic reactions	first and second generation
	Typical sulfa reaction – mechanism – common in this disease – type I reactions are due to ____ – cross reactivity	Delayed maculopapular rash – T cell mediated – common in HIv (40–70%) – N4 sulfonamidoyl hapten = major determinant. rare – little cross reactivity between sulfonamid abx and sulfonamide nonabx (furosemide)
	Pseudoallergic reactions – mechanism – examples – risk factors – how to prevent	Anaphylactoid reactions – non IgE mediated. Basophil/mast activation – radiocontrast dye, ASA, NSAIDS, opiates – women, asthma/atopy, cardiovascular hx, prior hx of reaction – decrese risk by using lower ionic contrast media and premed with steroids/antihistamines (doesn't work with true anaphylaxis)
	Blistering drug reactions – difference between SJS and TEN – steroids? – High risk triggers – mechanism of action – treatment	– SJS = <10% epidermal detachment (often confluent purpuric macules, systemic sx, fever, organ involvement – eye/liver/kidney/lung). TEN = >30% involvement – steroids helpful in SJS, contraindicated in TEN – PCN, sulfonamides, anticonvulsants, NSAIDs, allopurinol – Fas/FasL mediated apoptosis of epidermal cells + CTL activation and perforin release –supportive. IVIG can help by Fas–blocking abs
	Vancomycin and Red–man syndrome – sx – mechanism – treatment – can also cause ____ (other triggers: ____)	– flushing, erythema, pruritis – direct activation of mast cells – decrease infusion rate, premed with antihistamines, stop concurrent narcotics – linear IgA bullous dermatitis (tense blisters). Can occur with captopril, furosemide, lithium, bactrim
	ACEI Reactions – common sx – frequency – mechanism – frequent in ___ race – resolution	– cough (20%) – angioedema: usually in first week, but 30% present months/yrs later – due to ACEIs interfering with bradykinin degradation so antihistamines don't help – more common in African Americans – can have intermittent episodes when switched to another antihypertensive
	DRESS – common causes – sx – timing/course – treatment	Drug Rash with Eosinophilia and Systemic symptoms – anticonvulsants, sulfonamides, allopurinol, minocycline – fever, lymphadenopathy, hepatitis, facial edema – occurs wks after tx, develops over days and may continue despite stopping drug x weeks – Steroids, if no response, IVIG
	Fixed drug eruption – what is it – common cuases	– purple–blue macule at same location upon each exposure to a drug (can take any derm manifestation) – bactrim, phenolphthalein
	Local anesthetics (lidocaine, other –caines) are most often associated with ____ reactions and positive skin prick tests do/do not predict actual allergy.	Vagal do not
	Perioperative agents and drug reactions – due to ____ – use of skin testing	– usually quaternanry ammonium muscle relaxants (sux). Also latex, abx, barbs, propofol. – skin testing helpful if positive, but predictive value unknown if negative
	Insulin allergy – frequency of insulin antibodies – increased risk with HLA–____ – Allergenicity of preparations = treatment	– 50% –DR3 – bovine> porcine> human – most continue insulin treatment. antihistamines or splitting helps. Occ protamine allergy if NPH insulin (switch to nonprotamine). insulin desens is possible (though anaphylaxis rare)
	Cytokine release syndrome – associated with – sx –	– biologics. Rituximab (anticd20) and muromonab (antiCD3), sirolimus (rapamycin) – fever, rash, wheeze, capillary leak syndrome, meningoencephalopathy, GI sx, abnormal LFTs, uric acid, LDH, IL–6, TNFa –
	Sx associated with interferon therapy	flu sx, urticaria, dermatitis, vasculitis, ITP, autoimmunity, depression
	Common reaction with these drugs TNF inhibitors Etanercept Epoetin Alteplase and tPA anti–TNF drugs (infiliximab, etanercept) Cetuximab	– serum sickness – injection site / local reactions – pure red cell aplasia – anaphylactoid reactions – disseminated mycobacterial infxn or TB (annual PPD) – alpha–gal
	Common causes for drug induced cytopenias – anemia – thrombocytopenia	– quinidine, methyldopa, PCN – quinidine, propylthiouracil, gold, sulfonamides, vancomycin, heparin
	Pulm drug hypersensitivity – sx – triggers	– cough, migratory infiltrates, peripheral eosinophilia, pumonary fibrosis – bleomycin, methotrexate, nitrofurantoin (also pleural effusion or interstitial penumonitis/fibrosis), NSAIDS (eosinophilic pneumonia)
	Serum sickness – triggers – sx – occurs in antigen/antibody excess – tx	PCN, sulfonamides, phenytoin – fever, erythema multiforme or urticaria, arthralgias, lymphadenopathy – antigen excess – stop the med, steroids, antihistamines (NO DESENSITIZATION)
	Drug Induced cutaneous lupus – associated with ___ abs – rash appearance – common triggers – differs from drug–induced lupus (systemic) which has ___ abs and caused by ____ drugs	anti–Ro (SSA) photodistributed erythema/scalyannular plaques weeks after starting drug HCTZ, CCBs, ACEIs, antifungals – antihistone, procainamide, hydralazine, phenytoin, isoniazid
	Chemtheropeutics and the reaction type: Platins (cisplatin/carboplatin/ oxiplaten) Taxanes (pacilitaxel, docetaxel) asparaginase	– anaphylaxis (desens works) – anaphylactoid (treat/prevent with steroids/antiH) – either (but some only react to asparginase from E coli)
	contraindications to drug desensitzation	– blistering skin reactions (TEN/SJS) – immune complex mediated reactions (serum sickness) – DRESS – hepatitis –hemolytic anemia – nephritis
	Chronic urticaria lasts ___ weeks	6
	Cold urticaria syndromes that have a negative ice cube test	Cold induced cholinergic urticaria Systemic cold urticaria Cold dependent dermatographism
	cholinergic urticaria – aka – trigger – apperance – tests – can present similar to ___	– generalized heat urticaria – elevation of body temp (heat/exercise, stress, spicyfoods) – small punctate wheals – intradermal methacholine, exercise challenge, hot water bath – exercised induced anaphylaxis b/c can p/w hypoTN. EIA don't react to passive heating
	Aquagenic urticaria – trigger – test	– wheals from contact with water, indpdt of temp, salinity important – 35 degree water compress x 30 min to upper body
	Delayed pressure urticaria – trigger – test	–trigger sx 30 min to 12 h after pressure – sling with 10–15 lb weight x 15 min and pt watches for response x 4–24 h
	Urticaria treatment – first line –second line – third line	1: antihistamine 2: 2nd gen antihistamine, H2 blockers, doxepin, singulair, steroids if refractory??? 3: cyclosporine, tacrolimus, methotrexate, sulfsalazine, dapsone, hydroxychloroquine, omalizumab, colchicine, IVIG
	Hypocomplementemic Urticarial Vasculitis syndrome – sx – lab	urticaria + hypocomlemetemia with arthralgias/arthritis, obstructive lung disease, glomerulonephritis, uveitis, angioedema, recurrent abd pain – low C3, C4, C1q, antiC1q abs, ESR
	Urticarial vasculitis – sx –labs –histo	– lesions are less pruritic and more painful/burning. Last > 24h with residual purpura/hyperpigmentation – ESR, arthralgias, myalgias, fever, leukocytosis – histopath leukocytoclassi and vessel wall damage
	Patch testing timing	Place pathces on day 1, read and remove on day 3, read again on day 5
	Patch test scoring:	extreme rxn: confluent vesicles/bullae, ulcer strong: microvesicles/erythema in 50%+ weak: erythema and edema that is palpable doubtful – erythema irritant reaction: mild glazed appearnace, mod: follicular/pustular, extreme: ulcerative
	Allergic v irritant contact dermatitis	Allergic – more pruritic, crescendo phenomenon, slower to develop Irritant – more stinging, reaction almost immediate with decrescendo patch testing
	Photocontact dermatitis – photoallergic: triggers requiring prior sensitizaiton – phototoxic: triggers not requiring prior	requires light and the exposure – PABA, chlorhexidine, thiourea, NSAIDS, thiazide diuretics, dapsone, sulfonylureas – psoralens, furocoumarins, tar, lime, celery, parsnip, tetracyclines, amiodarone, diuretics, quinine, NSAIDs
	Contact urticaria – types – examples	IgE dependent ( all the usual suspects) v. IgE indpdt (fragrances, arthropods, jellyfish, coral)
	Ten most common contact allergens	nickel sulfate neomycin myroxylon pereirae (balsam of Peru) fragrance mix thimerosal sodium gold thiosulfate quaternium–15 formaldehyde bacitracin cobalt chloride
	Potassium dichromate comes from	stainless steel, chrom plating, tanned leather
	Chromates come from	textile, leather tanners, wet cement
	Cobal dichloride comes from	dental implants, artificial joints, engines/rockets
	Nickel containing material tests	Dimethylglyoxime test (pink = positive)
	Poison ivy/oak sumar caused by – corss reactivity	urushiol, an oleoresin from sap – cross reactivity with mango peels
	Most common cause of hand eczema in flower workers	Alstroemeria (peruvian lily)
	Common causes for contact derm	ambrosia (giant/dwarf ragweed) compositae (chrysanthemums, daisies) liliaceae (tulip, hyacinth, asparagus, garlic) Amarylidaceae (daffodil, narcissus) Primrose (primula) umbeliliferae (carrots, celery, parsnips) urticaceae (nettles) rutaceae (orage, lemon, grapefruit)
	Balsam of Peru cross reactivity	wide but most common is cinnamon and vanillin
	Preservative agents commonly triggering contact dermatitis that are formaldehyde releasers	diazolinidinyl urea imidazolindinyl urea quaternium–15 DMDM hydantoin Bromonitropropane
	Preservative agents commonly triggering contact dermatitis that are not formaldehyde releasers	parabens methylisothiazolinone phenoxyethanol PCMX and or PCMC benzlkonium chloride thimerosol
	hair products that cause contact dermatitis	cocamidopropul betaine paraphenylene diamine glycerol thioglycolate
	Nails and contact dermatitis	ethylacrylate foramadlehyde based nail resins
	Exceipient chemicals that cause allergic contact dermatitis	antioxidants, edta butylen glycol, polyethylene glycol, propylene triethanolamine ethylenediamine vegetable gums chlorocresol, thimerosal benzylalkonium chloride cetrimide lonalin chloramine–T butyl alcohol
	Chemical free sunblocks have	titanium dioxide and zinc oxide (rare sensitizers)
	Test photoallergic contact dermatits with	photo patch testing (patch + UVA (320–400 nm UV light)
	Topical corticosteroids and allergic contact dermatitis – common causes – common screening agents – when to read patch results	– Gr A (hydrocortisone), Gr B (triamcinolone), Gr C (betamethasone), Gr D(hydrocortisone 17 butyrate) – budesonide and tixocortol pivalate 1% – 7 days after application d/t immunosuppression of steroid usually pts only react to 1–2 classes
	Common resins causing allergic contact dermatitis	epoxy (uncured) colophony (from pine trees, in makeup, meds) ethylenediamine dihydrochloride ( in creams, nystatin, aminophylline) paraphenylendiamine (henna) topical abx (bacitracin, neomycin)
	Allergic contact cheilits – affects ___ – triggers	– lips – dental devices, lipstickes, lip balms, nail polish, cigarette paper, essential oils
	Surgical implant dermatitis – diagnostic cirteria	– dermatitis (local/general) after implant surgery – dermatitis persitent and resistant to therapy – positive patch test to metallic component or implant or acryllic glues – resolution of dermatitis after removal of implant
	Systemic contact dermatitis	generalized rash from systemic administration of drug to which previously had allergic contact dermatitis aka baboon syndrome b/c indurated erythema in groin area (seen in steroids or benadryl)
	This type of vaccine is protective after 1 dose	live attenuated
	IVIG/Ig interfere with this type of vaccine	live atennuated
	Examples of live vaccines	LMNOP and RSV Live vaccines include MMR Nasal flu Oral Polio Rotavirus Smallpox, Shingles Varicella
	Whole cell inactivated vaccines	Polio (IPV) Hepatitis A Rabies
	Fractional inactivated vaccines	Subunit: Hep B, trivalent influenza virus vaccine, pertussis, HPV Toxoid: tetanus, diptheria
	Polysaccharide inactivated vaccines	Pneumococcal (23–valent, pneumovax) Meningococcal (Menomune)
	Contraindications for live attenuated flu vaccine	immunocompromised pts hx of GBS history of recurrent wheeze or severe asthma
	Conjugated inactivated vaccines	Prevnar (13 serotype) Meningococcal: Menactra) – immunogenicity improved with conjugation of polysaccharide to protein and is T cell dpdt.
	Separation of vaccines	– not needed for inactivated vaccines – 28 days for live vaccines (if not given on same day)
	Waiting period btwn administration of passive Ab (IVIG and RBC) and live vaccine	tetanus Ig 3 months IVIG wait 8 months packed RBCs wait 6 months – if given too soon, repeat dose – if live vaccine given, wait >2wks to give product – not a problem with monoclonal antibodies
	Vaccines containing egg	Influenza Yellow Fever
	Common triggers for IgE mediated reactions to vaccines	Gelatin (MMR, VZV, rabies, yellowfever) Egg (yellow fever, flu – but probably fine) Latex – vials in rubber stoppers Yeast – Hep B vaccine – Japanese encephalitis virus vaccine causes delayed urticaria/angioedema
	Unique reactions to vaccines MMR Tetanus Pertussis Varicella Yellow Fever Smallpox	Unique side effects from vaccines – transient rash, thrombocytopenia, late fever – brachial neuritis, arthus reaction – febrile seizures, cyring, hypotonic event – chickenpox like rash – encephalitis – myopericarditis, eczema vaccinatum
	Contraindications to vaccines	– severe allergic reaction to prior dose – encephalopathy <7 days after pertussis containing vaccine – history of GBS (flu, meningococcal) – pregnancy and immunosuppression
	Etiology of peds v. adult bronchiolitis	Peds: RSV, rhino, paraflu, HMPV, influenza Adult: inhalational injury, mycoplasma, drug, hypersensitivity pneumonitis, connective tissue disease
	Independent risk factor for the development of frequent wheezing	RSV infection
	SWelling from HAE lasts ____	2–4 days
	% of new mutations in HAE (no family hx)	15%
	HAE specific therapies for acute attacks	C1 INH concentrate (Berinert 20 U/kg IV) kallikrein inhibitor (ecallantide = Kalbitor 30 SQ) bradykinin receptor antagonist (Icatibant = Firazyr 30 SQ q6 h, max 3 doses/24h)
	Long term HAE therapy	Attenuated androgens (danazol, stanozolol) Plasma derived C1 INH (Cinryze, 1000 u IV q3–4d)
	Common AEs with attenuated androgen therapy	hepatotoxicity dysplipidemia masculinization headaches
	Short term prophylaxis for HAE – when to use – what meds	– before oral/gen surg procedures – androgens (high dose, 3–5 d prior), C1 esterase inhibitor (1–2 h prior)
	OB/GYN considerations in HAE – contraception – pregnancy – Delivery	– avoid estrogens. Progestin ok – androgens contraind, C1 inh tx preferred – plasma derived c1inh tx advised before c/s, forceps, vacuum
	Warning signs for PIDs	>=4 new otitis in 1 year >= 2 serious sinusitis in 1 year >= 2 mo on abx with little effect >= 2 pneumonias in 1 year failure of infant to gain weight / grow recurrent deep skin or organ abscesses persistent thrush in mouth or skin fungal need for IV abx to clear infxns >= 2 deep seated infxn (including septicemia FMHx of PID
	Which HAE medication has a black box warning for anaphylaxi	Kalbitor (ecallantide)
	Common organisms associated with antibody deficiency	Viruses: enterovirus (XLA) Bacteria: S pneumo, H flu, Moraxella, Pseudomonas Protozoa: Giardia – no mycobac, fungi
	Common organisms associated with combined immunodeficiencies	Viruses: all, esp CMV, RSV, EBV Bacteria: Salmonella, Listeria, enteric Mycobacteria: nonTB (incl BCG) Fungi: Candida, Aspergillus, Cryptococcus, Histoplasma capsulatum Protozoa: Pneumocystis jiroveci, Toxplasma, Cryptosporidium parvum
	Common organisms associated with phagocyte defects	BActeria: S aureus, burkholderia cepacia, nocardia, Serratia Mycobacteria: NonTB (incl BCG) Fungi: candida, aspergillus – no viruses, protozoa
	Common organisms associated with complement deficiency	Neisseria meningitidis – no viruses, mycobac, fungi, protozoa
	Initial workup for PID: Quantitative assessment	Humoral: flow (cd 19/20), Igs Cellular: CBC/D, HIV, flow (CD3/4/8/16/56) Phagocytic: ANC, flow (CD11, 18, 15a) Complement: C3/4
	Initial workup for PID qualitative or functional assessment	Humoral: hemagglutinin titers, dep/tet/polysaccharide titers Cell: DTH response, Nk assay, mitogen/antigen stim, cytokine production, cytotoic assays Phagocytic: NBT, Antineutrophil antibodies Comlement: CH50, AH50
	SCID Gene defect based on lymphocyte phenotype: T– B+ NK–	IL–2RG JAK3 PNP (can have +/– NK)
	SCID Gene defect based on lymphocyte phenotype: T– B+ NK+	IL–7RA IL–2RA CD45 CD3 (delta, episilon, zeta) PNP (can have +/– NK)
	SCId Gene defect based on lymphocyte phenotype: T– B– NK+	RAG 1/2 Artemis Cemunnos Ligase IV Nijmegen breakage syndrome (NBS1)
	SCID Gene defect based on lymphocyte phenotype: T– B– NK–	ADA deficiency
	Gene defect based on lymphocyte phenotype: CD8+ lymphopenia	MHC class I deficiency (TAP 1/2, tapasin) ZAP 70 deficiency
	Gene defect based on lymphocyte phenotype: CD4+ lymphopenia	bare lymphocyte syndrome (MHC Class II deficiency) LCK deficiency HIV infection
	SCID – common gamma chain is involved in these receptor signaling	IL–2, IL–4, IL–7, IL–9, IL–15, IL–21
	IL–7Ra and CD45 and CD3 are specific for only ____ cell development so phenotype is ____	T cell B+ Nk+
	Jak3 is a signaling protein of ____ so it has the same phenotype	Common gamma chain (IL–2Rg)
	RAG 1/2 are involved in ____ therefore phenotype is _____	only VDR rearrangement of T and B cell receptor formation Nk+
	Omenn's syndrome – sx – genes	Sx: erythroderma, incr lymphoid tissues, alopecia, recurrent infections, eosinophilia, high IgE Genes: RAG 1/2, IL–7RA, ADA, ARtemis, RNA component of RNASe mitochondrial RNA
	ADA deficiency – distinct clinical features	– skeletal abnormalities – rachitic rosary rib cage – abnormal iliac bone – deafness
	PNP deficiency – distinct clinical features	lymphoreticular disease autoimmune disease
	Reticular dysgenesis – distinct clinical features – gene abnormality	– severe neutropenia, sensorineural deafness, SCID features – Adenylate kinase 2 (AK2)
	X linked SCID	common gamma chain (IL2Rg)
	Radiosensitive SCID	ARtemis Cernunnos Ligase IV Nijmegen breakage syndrome
	Artemis SCId – distinct clinical features	diarrhea, cadidiasis affects athebascan–speaking navajo/apache
	Cemunnos – distinct clinical features	devtal delay, growht failure, bird like facies, microcephaly
	LIgase IV – distinct clinical features	– developmental delay, FTT, bird like facies, microcephaly, photosensitivity, pancytopenia, malignancy
	Nijmegen breakage sydrome – clinical features	micocephaly, recurrent infections, bird like facies, devtal delay, lymphoma, short stature, clinodactyly, syndactyly, radiosensitive
	Nijmegen breakage sydrome –lab features	– class switch recombination defect (decr CD4/8, decr prolif, can have hypogam, elevated igM, defect in specific ab response, absence of HAssel's corpuscles on thymic bx)
	Ataxia Telangiectasia – clinical findings	– progressive neuronal loss (starts ~2) – Oculomotor apraxia, dysarthria, choreoathetosis – telangiectasia – sterility – leukemia/lymphoma risk – recurrent sinopulmonary infections
	Ataxia Telangiectasia – lab findings	– lymphopenia of naive T cells (CD45 RA) – poor mitogen response – class switch defect: can have hypogam and poor fxnal AB – IgA deficiency (80%) – elevated AFP and decreased CSA – Mutation in the ATM gene
	Function of ATM	ataxia–telangiectasia mutated – PI3 kinase responsible for DNA ds break repair – mutations lead to radiosensitivity
	Ataxia Telangiectasia	– treatment – prophylactic antibiotics – IVIG – chemotherapy – avoid radiation from imaging
	Chronic Mucocutaneous Candidiasis (CMC) Autoimune polyglandular syndrome (APS–1) Autoimmune polyendocrinopathy – candidiasis – ectodermal dystrophy (APECED) – clinical features	– recurrent noninvasive thrush – candidal dermatitis – dystrophic nails, enamel hypoplasia – endocrinopathies (hypoparathyroid (most common), hypoadrenalism, DM) – pernicious anemia – vitiligo, alopecia – hepatitis
	Chronic Mucocutaneous Candidiasis (CMC) Autoimune polyglandular syndrome (APS–1) Autoimmune polyendocrinopathy – candidiasis – ectodermal dystrophy (APECED) –lab features – mutation	– decr mitogen prolif and antigen prolif – some IgA deficiency – autosomal recessive, AIRE gene
	Chronic Mucocutaneous Candidiasis (CMC) Autoimune polyglandular syndrome (APS–1) Autoimmune polyendocrinopathy – candidiasis – ectodermal dystrophy (APECED) –treatment	– antifungal – autoimmune disease
	CD40/CD40L deficiency – aka – gene mutations inheritance – clinical features	HyperIgM1 = CD40L def; Hyper IgM3 = CD40 def – CD40L (CD154, TNFS5) = X linked – CD40 = aut rec – opportunistic infection, fungal, bacterial, viral – autoimmune hemolytic anemia, neutropenia
	CD40/CD40L deficiency – lab findings	Class switch defect: decr IgG/A/E variable high/normal IgM neutropenia absent germinal centers
	CD40/CD40L deficiency – treatment	IVIG PCP prophylaxis GCSF transplant (CD40L def)
	DiGeorge syndrome – clinical features	– cellular immune deficiency ( infxn, no thymus) – hypocalcemia/parathyroid def (tetany/seizures) – congenital heart disease (TOF, interrupted AA) – low set post rotated ears, short filtrum, micrognathia – devtal delay – B cell lymphoma – autoimmune disease
	DiGeorge syndrome – lab features	– complete: naive T <50/mm3 with no mit prolif – partial: decr naive T cell, usually normal mit proilf – can have low Ig if severe T cell defect – kidney agenesis (on ultrasound) – autoimmune antibodies, TUPLE1 (FISH) – low copy repeat and TBX1
	Digeorge syndrome – mutation – mnemonic	22 q 11.2 deletion (90%) 10p13–14 del (renal/gu defects) CATCH 22:Cardiac defects abnormal facies thymic hypoplasia cleft palate chromosome 22
	Digeorge syndrome – treatment	– thymus txpt – IVIG – abx prophylaxis – live vaccines if normal prolif – surgery for congenital defects – neuropsychiatric therapy
	NEMO deficiency (null mutation) – aka – clinical features	X linked inconginentia pigmenti males: lethal females: scarring, alopecia, hypodontia
	NEMO deficiency (hypomorphic mutation) – aka – clinical features	X linked anyhdrotic ectodermal dysplasia with immunodeficiency Male: – decr sweat, hyperthermia, hypotrichosis, hypodontia, conical incisors, nail abnormality – severe bact infxn, OIs incl mycobacteria Female: usu normal
	NEMO deficiency – lab findings	hypogam and poor polysaccharide resonse (defect in CD40 activation pathway) TLR defect (NFkB is central in TLR activation) decr Nk cytotoxicity normal T cell count and function
	Nemo deficiency – treatment	– IVIG, interferon gamma – HSCT under investigation
	LZ–NEMO deficiency – clinical features – distinct lab features – therapy	Clin: normal ectoderm, MAI infxn, disseminated BCG Lab: impaired production of IL–12 and IFNg in response to CD40L Tx: treat mycobacteria. Antimycobacterial prophylaxis in some pts
	Hyper IgE syndrome (STAT–3) – clinical features	Triad: (1) Recurrent skin and lung infections (absceses, mucocut candidiasis, eosinophilic pustular folliculitis) (2) Severe Eczema (3) Elevated IgE – Facies: coarse, prominent mandible, hypertelorism, broad nose, skeletal abnl, retained teeth, scoliosis – hyperextensible, aortic aneurysms
	Hyper IgE syndrome (STAT–3) – lab features – inheritance – treatment	– IgE>2000, eosinophilia, normal IgM, Th17 levels decr – aut dom – prophylactic abx, IVIG
	Chracteristic infections in Hyper IgE syndrome	– S aureus – S pneumo – H flu – Candida secondary infection – pseudomonas – aspergillus
	Hyper IgE syndrome (DOCK8) – clinical features – lab features – inheritance	– viral skin infxn (HPV, HSV, VZV, molluscum) – mucocut candidiasis – eczema and allergies –risks of malignancies – pneumonias but no pneumatoceles – lab: log IgM, more eos, lymphopenia – aut rec
	Hyper IgE syndrome – how Tyk2 mutation differs from Dock8 – role of Tyk2	– similar but also has disseminated BCG and vasculitis – Tyk2 involves in IL–12 signaling to make IFNg
	IPEX – stands for – clinical findings	Immune dysregulation, polyendocrinopathy, enteropathy and x linked inheritance – severe infections – early onset type 1 DM, thyroid dz, autoimmune cytopenia – diarrhea and fTT – coronary artery disease – skin lesions: erythroderma, exoliative dermatitis, eczema, psoriasis like
	IPEX – mutation – lab values	Foxp3 (not found in all cases, X linked rec) Lab: – Scope: villous atrophy with lymphocytic infiltrates in small bowel – autoimmune abs – cytopenia, eosinophilia – high IgE, normal IgG, IgM – normal B/T number/fxn, except no T regs
	IPEX – therapy	– IVIG – treat autoimmune/endocrine – HSCT – parenteral nutrition
	X–linked lymphoproliferative disease (XLP–1) – clinical features	– fulminant EBV mononucleosis – dysgammaglobulinemia, CID with severe infxn – lymphoma: B cell/ Burkitt's, splenomegaly
	X–linked lymphoproliferative disease (xLP–1) – lab findings – mutation	HLH on BM biopsy (from failure to eliminated EBV infected B cells) low igG, high IgM low CD4, high CD8, impaired T cell function decr NK cell number and function no NKT cells anemia – mutation in SH2D1a gene for SAP
	X–linked lymphoproliferative disease (xLP–1) – treatment	IVIG HSCT chemotherapy for lymphoma
	X–linked lymphoproliferative disease (xLP–2) – mutation – how it differs from XLP1	– mutation in XIAP – colitis – preisposition to hemophagocytic lymphohistiocytosis – incr suscetibility to apoptotic stimuli
	Wiskott Aldrich syndrome – clinical features	Triad: (1) Thrombocytopenia + bleeding diathesis (2) Eczema (3 recurrent infections (pyogenic) – risk for autoimmunity and malignancy (eBV lymphoma)
	Wiskott Aldrich syndrome – lab findings – gene mutation, inheritance – treatment	– Incr IgE/A, decr IgM, normal IgG but impaired fxnal abs – impaired T cell prolif – decr plt size/function – mutation in WASp (X linked) – HSCT, treat infections, IVIG, splenectomy
	Consider antibody deficiencys if patient has ____	recurrent sinopulmonary infections enteroviral infections (XLA) giardiasis autoimmune phenomenon
	Transient hypogammaglobulinemia of infancy – clinical features – lab findings – therapy	– sinopulm/GI infxn, thrush, mild–mod meningitis, may be asx – IgG < 2SD persisting older than 6 mo. Usually normal ab responses – no Tx. Occ proph abx rarely IVIG, resolved by 2–4y
	Selective IgA deficiency – mutation – clinical features – lab findings – therapy	– unkown, some CVID + sIgAD have TACI – Most asx. Some sinopulm, gi infxn, autoimmune, atopic dz, rare transfusion reactions if they have anti–IgA ab – IgA <7 mg/dL (if >4y old) – proph abx and IVIG if specific ab defect, watch for progression to CVID
	Possibly triggers of secondary IgA deficiency	Antiepileptics Sulphasalazine ecaptopril thryroxin
	Diseases that can have selective IgA def	Ataxia telangiectasia IgG2 subclass def CMC
	Specific antibody deficiency – clinical findings – lab findings – treatment	– sinopulm infxn allergic rhinitis – normal Igs, poor polysaccharide response despite pneumovax – prophylactic abx and IVIG, watch for progression to CVID
	X linked agammaglobulinemia – mutation – clinical findings	– BTK – sinopulm/GI infxn, atypical bac, enteroviral encephalitis, septic arthritis, lymphoreticular/colorectal malignancies, bronchiectasis
	X linked agammaglobulinemia – lab findings – treatment	– histo: small/absent lymphoid tissue, no germinal centers – low IgG (<200), A, M – <2% CD19+ B cells – maturational arrest at the pre–B cell stage – can't use serological assays to diagnose infenction (HIV ELISA)
	X linked agammaglobulinemia – treatment	– IVIG – abx prophylactically – live immunizations contraindicated
	Autosomal recessive agammaglobulinemia – mutation, inheritance – clinical findings – lab findings – therapy	– surrugate light chain (V preB lambda5), mu IgM heavy chain, Iga, Igb, BLNK – sx same as XLA but can be more severe/earlier onset – low IgG/A/M, low CD19 B cells – tx same as XLA
	CVID – inheritance/mutation – clinical features	– mostly unknown, ICOS, tACI, BAFF–R, CD19, cD20 – sinopulm/GI infxn, meningitis – bronchiectasisi, BOOP – autoimmune dz, – gi/liver dz granulomatous dz nonhodgkin's lymphoma, gastic carcinoma
	CVID – lab findings treatment	IgG (<450), low A/M, impaired fxnal abs variable T cell counts/function – IVIG, treatment, Abx, no live vaccine, pulm hygeine if bronchiectasisi
	Good's syndrome – what is it	– CVID + thymoma
	Reduced switched memory B cells in CVID associated with _____	non infectious complications like hematologic autoimmunity
	Hyper IgM (type 2 and 4) – clinical features	– sinopulm and gi infxn – lymphoid hyperplasia and adenopathy CVID like but with increased autoimmune disease
	Hyper IgM type 2 – mutation and inheritance	AID deficiency (activation induced cytidine deaminase) autosomal recessive
	Hyper IgM type 4 ( mutation and inheritance)	UNG (uracil DNA glycosylase) autosomal recessive
	Hyper IgM type 2 and 4 – lab findings	– defect in class switch recombination and somatic hypermutation – no T cell defect – low IGG (<400), A, E, and normall/high IgM – normal T cell function – incr lymph nodes and giant germainl centers
	Hyper IgM type 2/4 – treatment	IVIg Abx no live vaccines
	What are the differences between HIGM 1/3 and HIGM 2/4?	T cell defects in 1/3 with absent LN and germinal centers 2/4 are Ab deficiencies with less severe infxn and lymphoid hyperplasia/adenopathy
	Phagocytic defects evaluation CBC NBT MPO Chemotaxis CD18 CD15a	– LAD 1/2/3, cyclic neutropenia, SCN, AIN, SDS – CGD – MPO deficiency – SDS, chediak–higashi, LAD, Rac2 mutation – LAD1 – LAD2
	WHIM syndrome – stands for – clinical features – treatment	Warts, hypogammaglobulinemia, infections and myelokathexis – sinopulmonary infxn – papilloma virus infxn – warts with risk of malignant transformation Tx: GSCF, IVIG, wart rx, CXCR4 inhibitor in trial
	WHIM syndrome – lab findings	neutropenia (ANC 100–500) from retention of mature granulocytes in bone marrow = myelokathexis ALC 1500 , occ decr mitogen responses IgG low, low CD19 and cD27 (B cells & switched memory b cells)
	WHIM syndrome – molecular defect	activating mutation in CXCR4 (important for bone marrow homing and trafficking of progenitor cells)
	sEvere congenital neutropenia (SCN) – clinical findings – treatment	– early onset severe bacterial infections: omphalitis, URTI/LRTI, oral ulcer, skin/liver absscess, cellulitis, meningitis – rx: GcSF, HSCT, monitor for myelodysplasia/AML
	severe congenital neutropenia – laboratory findings – molecular defect	– ANC < 200 – BM: maturation arrest of netrophil precursors at promyelocyte stage – aut rec (HAX1 (Kost mann syndrome) – aut dom Elastase (ELA–2), GCI1, GSCF–R – X linked WASP
	Types of phagocytic cell disorders – Defects in bone marrow production/release	WHIM severe congenital neutropenia cyclic netropenia
	Cyclic neutropenia – clinical features – treatment	– oral ulcers, fever, skin infection, abscesses – prophylactic ABx, GSCSF
	Cyclic neutropienia – lab findings – molecular defect	– decr neutrophiles, plts, monos, reticulocytes for 3–6 d in 21 day cycle – need to get CBC 2–3 /wekk x 6 weeks to diagnose –auto dom: ELA–2
	Types of phagocytic cell disorders – Defects in adhesion and chemotaxis	– LAD1 – LAD2 – LAD3
	Types of phagocytic cell disorders – Defects in leukocyte granula formation – Defects in oxidative killing	– Chediak Higashi – CGD
	LAD1 – clinical features – treatment	– recurrent pygoenic infections (impaired pus formation) – delayed wound healing (delay cord separation) – necrotic skin infections – gigivoperiodontitis – omphalitis Rx: abx rx and rpophylaxis, GCSF, HSCT
	LAD1 – lab findings – molecular defect	– leukocytosis – decr cd18 on neut (<2% sev, 2–30% mild/mod, 40–60% carrier) – defect ITGB2 ––>defect in CD18 (common chain of b2 integrin family ––> defect in adhesion – CD18 binds LFA1, Mac1 P150,95 (CD 11a, b, c)
	LAD2 – clinical features – treatment	– less evere skin/lung infxn – no delayed cord separation – impaired but not absent pus formation – devtal delay, microcephaly , short stature Rx: abx proph, fucose supplementation
	LAD2 – lab findings – treatment	– leukocytosis, absence of CD15a – bombay blood phenotype (hh) – abnormal sequenc of GDP fucose transporter – mutation in FUCT1 ––> no fucosylation ––> no Sialyl–Lewis (CD15) ––> defect in rolling
	LAD3 – clinical features – lab findings – mutation	– same as LAD1 + bleeding diathesis – leukocytosis, normal cD18, abnl RAP1 gtpase fxn – caldag–ge1 mutation ––> failure of cytokine activation of integrins
	Chediak– Higashi – clinical features	oculocutaneous albinism hypopigmented skin/iris/hair recurrent infections bleeding tendency neurologic defects lymphoma like syndrome risk of HLH
	CHediak Higashi –lab findings – mutations	– enlarged primary granules in neut/eos – neutropenia, decr chemotais – absent Nk cytotoxicity – evenly distributed larger melanin granules on hair shaft – CHS or LYST mutation
	CGD – clinical features – common organisms	– ifxn with cat positive organisms – granuloma formation (GI/GU obstruction) – poor wound healing – autoimmune dz – BAct: S aureus, burkholderia, serratia, nocardia, – Fungi: aspergillus fumigatus/nidulans
	CGD – lab findings – mutation	abnormal NBT/DHR mutations in NADPH oxidase system XL: gp91 phox AR: p22, p47, p67
	CGD – treatment	bactrim and itraconazole prophylaxis IFN gamma systemic corticosteroids for granuloma formation HSCT
	IRAK4/MyD88 deficiency – clinical presentation –treatment	– severe early/onset recurretn pyogenic bacterial infections (pneumococcus, staph) – menigitis – septicemia – liver abscess – low/absent fever or inflammatory responses – TX: IVIG, proph/rx abx (bactrim and PENV)
	IRAK4/ MyD 88 deficiency – lab findings	– normal ig levels – impaired polysaccharide titers – normal B/T cell numbers – dx based on decreased TLR stimulation assay (except TLR 3) b/c defect in TLR signaling to activation of NFkb and AP–1
	IFN gamma/ IL–12/ IL–23 axis – descrie the axis – results in	TH1 cels/DC/Nk make IFN g ––> induces IL–12 from DC and macs ––> incr IFNG production. INvolves STAT 1 and 4 Mendelian susceptabilty to mycobacterial disease (MSMD)
	Nk cell deficiency associated with	HLH – primary (XLP, familial, chediak higashi, WAS) – secondary (reactive hemophagocytic syndrome) NEMO LAD1 IFN12/IFNg axis HIV infxn Malignancy
	Classical NK cell deficiency – clinical features – lab findings – gene defect	– recurrent infections with herpes, papilloma virus and mycobacteria – – decr CD16 flow, decr NK fxn – GATA2/ MCM4 mutation
	Functional Nk cell deiciency – clinical features – lab findings – gene defect	– recurrent herpes einfections – normald CD16 but decr NK function – FCRG3A (CD16 mutation = low affinity IgG receptor))
	Complement deficiencies – inheritance	All autodomal dominant except properdin = X linked
	Distinguishing complement deficiency versus complement consu,ption	Deficiency has normal complement split products while consumption has high complement split products
	Complement deficiency: early (C1q/c1s C2/C4) – clinical features – infectious organisms – lab findings – gene defect	– sinopulmonary infxn, autoimmune dz – S pneumo, H flu (encapsulated org) – low CH50 – none
	Complement deficiency: C3 – clinical features – infectious organisms – lab findings – gene defect	– sever infxn (like ab def), glomeruloneprhtisi – encapsulated organisms (neisseria) – low CH50, aH50, C3. Also C3 NE and Anti–C3 autoab – defect in C3
	Complement deficiency: MBL – clinical features – infectious organisms – lab findings – gene defect	– many asx. Autoimmme, n resp ifxn – NEisseria – decr MBL – defect in MASP2
	Complement deficiency: late component – clinical features – infectious organisms – lab findings	– menigitis arthristis, sepsis, – c5–7 associated with autoimmunity – Nesseria (menigitidis, gonorrhea) – decr CH50, specific ocmlement, AH50
	Complement deficiency: Altternative pathway – clinical features – infectious organisms – lab findings	– factor b/ d/ properdin – infections – neisseria – low AH50
	Mutations in IFNgR, p40 subunit, IL12 b1, NEMO, STAT1 are susceptible to _____ organisms	atypical mycobacteria, salmonella
	HIV 1 v 2	HIV 1: more common, virulent/infective HIV2: confined to West Afria
	HIV Viral structure	– two identical ssRNA – enzymes (RT, integrase, protease) packaged in a core of nucleocapsid p24 and outer membrate p17 – host derived lipid bilayer with gp120 and gp41
	Factor H deficiency is associated with _____ diseases	Atypical Hemolytic uremic syndrome HELLP Secondary C3 deficiency Macular degeneration
	DAF and CD59 deficiency are associated with ___ diseases	Paroxysmal Nocturnal hemoglobunuria (PNH)
	Viral entry requires____	Gp120 binds CD4 and CCR5 or CXCR4 co receptor binding ––> conformational change in gp41 ––> entry of viral genome into cytoplasm
	HIV coreceptor tropism – host cells and HIV strain and stage of infection	CCR5: – monocytes/macs – M tropic or R5 strain – acute infection CXCR4 – T cells – T tropic or X4 strain – advanced disease
	HiV in fects ____ cells which migrate to regional ympohid tissues in ___ days and an increase in viral replication within __ days after exposure	CD4+ T cells, macs, DCs 3–5 days 14 days
	Best adaptive immune response to HIV is from _____. Antibodies are detectable within ___ after infection. Neutralizing ABs against gp120 develop ___ after infection and are/are not effetive.	CTLs few weeks 2–3 months are not effective
	Most immunogenic HIV moelcules are ____. Virus atttaches to DCs by ____ binding ____.	gp120, gp40 DC–SIGN
	HIV is associated with hyper/hypo gammaglobuliemia due to ___	hyper polylconal activation of B cels
	Phases of HIV	Acute HIV syndrome (spike in viral load and most of CD4 reduction) Clinical latency AIDS
	Acute HIV syndrome – clinical features	– flu like sx x several weeks – fever, HA, pharyngtisi rash, LAD, arthralgia, N/V/D
	AIDS – clinical features	CD<200 cells/mm3 AIDS defining conditions
	What is the singificance of the cCR5delta 32 mutation	homozygous – resistant to HIV infection Heterozygous – nonprogressors (slow disease)
	ELISA for HIV – sens/spec – false postive/negative profile–	high sens, mod spec, good screen, requires confirm False pos: autoimmune diz, multiple pregnancy, multiple blood transfusions, following immuization False neg: window period (up to 6 mo)
	Rapid HIV – sens/spec – sample collection and timing	high sens, mod spec can detect HIV in blood/oral fluid <20 min turanround
	Western blot for HIV – sens/spec – psoitive test = which bands – negative test followup	high sens, high spec, but expensive positive = 2/3 major bands (anti p24, gp41, gp160/120) neg ––> repeat WB in 4 weeks or WB for HIV2. if still neg ––> virologic testing
	HIV DNA by PCR – sens/spec – detects what? – useful in __	mod sens, high spec – detects HIV1 DNA in PBMC good for acute viral syndrome if antibody test is negative or for exposed infants
	HIV RNA PCR – sens/spec – useful for __	mod sens, high spec gives quantified viral load so good for therapeutic response and indication for treatment
	HIV p24 antigen – useful for	– neonates or makre of disease progression, but mostly replaced by PCR assays – fourth generation HIV test (another screening that can detect infection sooner than eLISA)
	Management of HIV exposed infants – testing – treatment	– HIV 1 DNA PCR at birth, 2 w, 2 m, 4–6 m – ELISA 12–18 mo to definitely exclude – umbilical cord samples have high false positive – PCP prophylaxis at 4–6 wk if infant infected until at least 1 year old
	Indications for HAART	all symptomatic people asymptomatic if (CD4<350 definitely, 350–500 probably, >500 maybe). HIV RNA can influence decision to start
	Initial HAART therapy	nnRTI, PI or II + 2 NRTIs
	HAART therapy: fusion inhibitors – phase of inhibition / action – examples	– viral binding/fusion/entry – Maraviroc (binds CCR5) – Enfuvirtide (binds gp41)
	HAART therapy: Integrase inhiibitors – phase of inhibition / action – examples	– viral DNA integration – Raltegravir
	HAART therapy: Nucleotide/nucleoside reverse transcriptase inhibitors – phase of inhibition / action – examples	– reverse transcriptase (incoporates into viral dna to terminate the strand) – Zidovudine, didanosine, abacavir, tenofovir
	HAART therapy: nonnucleoside reverse transcriptase inhibitors – phase of inhibition / action – examples	– reverse transcriptase (binds RT and blocks it) – efavirenz, nevirapine, delavirdine, etravirine
	HAART therapy: protease inhibitors – phase of inhibition / action – examples	– viral assembly, blocks protease – ritonavir, indinavir, nelfinavir, lopinavir, atazanavir
	IRIS – what is it – associated OIs – sx – risk factors – treatment	– decline in clinical status (4–8 wk after HAART), reactivation of immune response to OIs when CD4 count rapidly increases – OIs: TB, PJP, CMV, herpes, MAC – new/worse sx, fever, malaise, local rxn – risk: first HAART, CD4<50, recent OI tx – Supportive, NSAIDS/steroids
	Antibiotic prophylaxis: PJP – indication – medications	– CD4<200 OR CD4% <14, thrush, AIDS illness, FUO – Bactrim, dapsone +/– pyrimethamine, atovquone
	Antibiotic prophylaxis: Toxoplasma gondii – indication – medications	– CD4<100 AND positive Toxoplasma IgG – Bactrim, dapsone + pyrimethamine _ leucovorin, Atovaquone +/– pyrimethamine
	Antibiotic prophylaxis: Histoplasm capsulatum – indication – medications	– CD4<150 AND endemic area for histoplasmosis – endemic areas = Ohio/MI river valley, Central/S america, Asia, Africa – ITraconazole
	Antibiotic prophylaxis: Coccidioides – indication – medications	– CD4<250 AND in endemic area AND positive IgM/G serologies – endemic area = sonoran deser in arizona, entral valley in CA, New mexico, w Texas, Nevada, Utah – Fluconazole, itraconazole
	Antibiotic prophylaxis: MAC – indication – medications	– CD4<50 – Azithro, clarithro, rigabutin
	Sjogren's syndrome – clinical features – autoantibody – treatment	– xeropthalmia, xerostomia, sica sx, arthritis, interstitial nephritis, RTA, pulm involvement – ANA, SS–A, SS–B, RF – Symptomatic (muscarinic agonists, csa drops, artificial tears), immunosuppressives
	Progressive systemic sclerosis or diffuse systemic sclerosis – clinical features – autoantibody – treatment	– fibrosis of skin, vasculopathy, hypertensive renal dz, interstitial lung dz, CREST sx – ANA, SCL–70, anti endothelial ab, anticentromere (good prognosis) – ACEI for renal, immunosuppressive therapy
	Progressive sstemic sclreosis and limited (CREST) – clinical features – autoantibody – treatment	– calcinosis, raynaud's, esophageal motility, sclerodactyly, telangiectasia, pulm arterial hypertension – anticentromere ab – CCB (for Raynaud's), PPI, metoclopromide, oral anticoagulation for pAH, endothelin receptor antagonist, postanoids, epoprostenol
	Polymyositis – clinical features – autoantibody – treatment	– idiopathic myositis, proximal weakness, incr CPK, aldolase – ANA, Anti–Jo1, anti SRP and anti–PL7 (antithreonyl–tRNA synthetase) – steroids immunosuppressives (azathioprine, MTX)
	dermatomyositis – clinical features – autoantibody – treatment	– idiopathic myositis, prox muscle weakness, incr CPK/aldolase and DERM features (gottron's, heliotrope rash, mechanic hands), and malignancy association – ANA, anti–JO1, antiPL–7, anti Mi2Ab (helicase) – steroids, immnosuppressives (azathioprine, mtx)
	Rheumatoid arthritis – clinical features	– f:m 3:1 4th/5th decade – weakness fatigue prodrome – symmetric joints (MCP/MTP, PIP), joint effusions, restricted motion ––> joint deformities – rheumatoid nodules over bony prominences, splenomegaly, pericarditis, vasculitis, eye dz, renal amyloidosis
	Rheumatoid Arthritis – diagnostic criteria	RA score >=6: Joints involved: 1 large (0), 2–10 large (1), 1–3 small (2), 4–10 small (3), >10 with 1 small (5) Serology: low pos RF or CCP (2), high pos RF or CCP (3) Sx duration: <6 wks 0, >=6 weeks 1 Acute phase reactants: abnormal crp and esr (1)
	Rheumatoid arthrtis – immunologic features	80% have incr RF (binds IgG Fc) Incr ESR/CRP anti cyclic citrullinated peptide (anti CCP aka ACPA) as sensitive as RF but more specific
	Rheumatoid arthritis – treatment	– NSAIDS, – steroids – intrasynovial joint injections – dMARDs – TNFa blocker, alpha–IL6R (tocilizumab), CTLA4ig (abatecept), anti cd20 mab (rituximab)
	JIA – basic features – subtypes	arthritis in <16 years old – pauciarticular (most common) – polyarticular (1/3) – juveile spondylarthropathy – systemic onset Still's disease
	Pauciarticular JIA – m:F, age – arthritis pattern – extraarticular pattern – labs – prognosis	– 1:5, usu 18–36 mo – mono or oligo articular, large – minmal (highest uveitis risk 20%) – neg RF, ANA+ – variable
	Polyarticular JIA – m:F, age – arthritis pattern – extraarticular pattern – labs – prognosis	1:4, usu 18–36 mo symmetrical poly articular (>=5) some uveitis risk 15% RF+, half ANa+ variable (RF = more disability)
	Juvenile Spondyloarthropathy JIA – m:F – arthritis pattern – extraarticular pattern – labs – prognosis	4:1, late childhoo/teen axial, sacroililtis, oligo/polyathritis ethesopathy, 20% uveitis, aortic insufficiency 90% HLAB27. neg RF chronic
	Systemic onset aka STill's JIA – m:F – arthritis pattern – extraarticular pattern – labs – prognosis	1:1, no peak polyarticular fever, rash, LAD, myopericarditis, Kobner's phenomenon (salmon rash that triggered by touching skin) incr Ig (RF/ANA useuless), incr LFT/ESR/CRP/ferritin chronic arthritis 1/2, remission 1/4, severe 20%
	SLE – diagnostic criteria	4 of below (DOPAMINE RASH) discoid rash, oral ulcers, photosensitivity, arthritis, malar rash, immune (anti DNA, anti Sm, anticardiolipin, lupus anticoag), Neurologic (sz, psychosis), renal (proteinuria >0.5 or 3+), ANA, Serositis, Heme (hem anemia, leukopenia<4000, lymphopenia <1500, plt<100k).
	Immunologic markers in SLE	ANA (very sens, lower spc) anti dsDNA (very spec less sens, active dz and lupus nephritis) anti smith (very spec, less sens, ILD) Anti Ro (SS–A), also in Sjogren's, subacute cut lpus, neonatal lupus Anti histone drug induced lupus
	Sjogren's Syndrome – types – symptoms	primary (isolated autoimmune) secondary (comlication of RA, SLE, PM, scleroderma) – xerostomia, xeropthalmia, parotid swelling, dry skin, purpura, urticaria, arthralgia, sinus infxn, obstructive airway, interstitial pneumonitis, dysphagia, CNS involvement – assoc w/ primary biliary cirrhosis, HIV, hepC
	Sjogren's ysndrome – immunologic markers	– RO/ SS–A, La/SS–B – anti Ro (majority, anti La (40%) in primary SS – ANA +, RF+ 60–80%
	Polymyositis/Dermatomyositis/Inclusion body myositis – symptoms	heliotrope rash, rash on face, shawl sign, V shape, knees elbows Gottron's papules photosensitivity Nail cracking, thickening, periungual telangiectasia Mechanic's hands 9fissured, hyperpig, scaly, (assoc c incr risk of interstitial lung dz)
	Inclusion body myositis – how it differs from poly/dermatomyositis	– more males than F – CD8 T cell mediated (PM cell med, DM is Ab med/complement) – prox muscle weakenss that has distal spread, dysphagia – biopsy basophilic rimmed vacuoles and filamentous inclusions – possible viral association – older the age at sx onset, more rapid progression
	HLA that protect fetus from maternal immune rjeection	HLA G and F are expressed on the extra villous trophoblast
	HLA gene is on chromosome	6
	TRansplant organs that do not require immunosuppression	cornea, bone, joint
	HLA matching – full versus extended match	full = 6/6 A, B, DRB1 10/10 adds C and DQ
	Best scid outcomes in which lymphocyte phenotype after transplant	T– B+ NK=
	Examles of myeloablative regimens	– total body irradiation – busulfan – etoposide – cytarabine – cyclophosphaimde – cytosine arabinoside – anti– CD45, antiCD66 anti CD20
	Examples of nonmyeloablative regimen	– fludarabine – cyclophosphamide – ATG – low dose total body irradiation – anti cd52 ab
	Examples of reduced intensity conditioning	low dose busulfan low dose melphalan
	Effects of myeloabalative v.nonmyeloablative v. reduced intensity	Myeloablative – destroys host hematopoeitic cells Nonmyelo – minimal cytopenia with significant lymphopenia Reduced – cytopenia
	Important cytokines in GVH reaction	IL–10, TNF a, IFNg
	Acute v. Chronic GVH – timing – cells – prophylaxis – treatment	– 100 days – CD45RO T cell and neutrophil V CD4T – Mtx, CSA, tacro steroids atg and T cell depletion v. t cell depletion – steroids, csa, tacro, atg, MMF, v. steroids, csa, thalidomide, ursodeoxycholic acid
	Acute v Chronic GVH	– macpap rash, diarrhea, abd pain, bloody diarrhea, ileus, cholestatic hyperbili, fever – dyspig, alopecia, sclerosis, nail dystorphy, ulcers, sicca syndrome, fascciitis, myositis, contractures, weight loss, gi web/strictures, jaundice transaminitis, restr/obstr lung defects, BO, pericarditis, cytopenias
	Sinusoidal Obstruction Syndrome – aka – associated with – diagnostic criteria	aka hepatic sinusoidal veno occlusive disease – conditioning therapy and drug tox (radiation, busulfan, csa, mtx, sirolimus) – Seattle (2 of 3 within 20 d of SCT: bili>2, hepatomeg/RUQ pain, >2% weight gain) – Baltimore (Bili>2 + 2 of 3: tender hepatomeg, >5% weight gain, ascites)
	Definitions of engraftment – neutrophil – platelet	3 days ANC >0.5 x 10^9 or 1 day of 1 x 10^9 plt >20 x 10^9
	Methods of T cell depletion for SCT	– soy bean lectin and E rosetting – E rosetting and CD34+ selection – monoclonal abs (CD3, CD2, CD6, CD25, CD52)
	Graves – pathophys – clinical features – genetic assoc	– Abs to TSH receptor. Mostly Th2 cells (also T and B) – Hyperthyroidism (palp, tremor, heat intol, sweat, anxiety, emotional lability, wt loss), goiter, exopthalmos, pretibial myxedema – HLA–DR3, CTLA4 alleles
	Hashimoto's Thyroiditis – pathophys – clinical features – genetic	– Abs to PTO, thyroglobuline, TSH receptor. Lymph infiltration, Ig and complement fix, Hurthle (epith cells with eos–philic cytoplasm) – atrophic thyroid or goiter. autoimmune thyroiditis. hypothyroid (fatigue, weak, cold intol, wt gain, constipation, dry skin, depr, growth failure) – HLA DR3, CTLA4
	APS1 differs from APS2	– APS 1 doesn't involve DM or pituitary – APS 2 is more common – APS 2 has no parathyroid or thyroid involvment – APS 1 usual develops in first 20 years, APS2 is 20–40 years.
	ALPS – stands for – clinical sx – genetics – treatment	– autoimmune lymphoproliferative syndrome – LAD/splenomeg, DN T cells, apoptosis, incr IL–10, B12, IL–18, autoimmune cytopenias with hypergam, + fam hx – Type I (fas), Type Ib (FASL), Type IIa (caspas10) – immunosuppressives. BMT curative
	Autoantibody if Addison's disease develops and associated diseases	Ab to adrenal cortex enzyme 21 hydroxylase – APS 1, APS2 (HLAb8, DR3) OR Autoab to cyp21A2 (makes cortisol) – primary adrenal failure (HLA DRB0404, DQ8, MICA 5.1)
	Diabetes Mellitus associated with autoabs to ____ – genetic HLA association	– anti–GAD65, insulin, tyrosine phosphatase, zinc T8 transporter – Genetics DR3, DQ2 and DR4, Dq8
	Lymphocytic hypophysis – what is it – associated abs	inflammation of pituitary gland ––> fatigue, HA, visual field deficits – anti–CTLA4 ab (ipilimumab)
	POEMS syndrome	polyneuropathy organomegally endocrinopathies M protein skin (hyper pigmentation, hypertrichosis)
	Nephrotic syndrome – symptoms	> 3.5 g/ day proteinuria edema hyperlipidemia hypoalbuminemia increased infections from low IgG secondary protein losses
	Nephrotic syndrome – diseases	Minimal change membranous nephropathy focal segmental glomerulosclerosis
	Nephritic syndrome – symptoms	hematuria edema hypertension
	Nephritic syndrome – diseases	Post strep GN igA nephropathy Henoch schonlein purpura Membranoproliferative glomerulonephritis Rapidly progressive GN
	Minimal Change Nephrotic syndrome – most common in – histo findings – treatment	– chidlren – nothing on light or IF. Bx = foot process effacement – prednisone
	Membranous Nephropathy – most common in – associated with diseases – histo findings – treatment	– adults – Hep B, Malaria, syphilis, cancer, drugs, SLE, toxin – GBM thick with granular staining of IgG and C3 – controversial
	FSGS – associated with diseases – histo findings – treatment	– HIV, infxn, HTN, VUR, obesity, sickle, heroin – glomerular collapse – prednisone, ACEIs
	Postinfectious glomerulnonephritis – associated antigens – lab findings – treatment	– NAPir (Nephritis associated plasmin receptor). SPEB (STrep pyogenic exotoxin B) – low C3 with immune comlexes, cryoglobulins, RF, incr IgG. Dx based on prior strep infxn or positive ASO or anti–Dnase B –abx, supportive therapy
	Most common glomeruloneprhritsi in the world	IgA nephropathy
	IgA nephropathy – biopsy findings – treatment	IgA staining of mesangium on IF. Elevated IgA complexes in serum ACE/ARB for bp. prednisone if proteinuria. Occ statins
	HSP –symptoms – biopsy findings	– purpura, abdominal pain, arthralgias, hematuria (usu males, kids) –IgA staining of mesangium on IF. Elevated IgA complexes in serum – treatment if renal dz with IVIG
	MPGN – causes of secondary MPGN – treatment	– essential mixed cryoglobulinemia (most common, assoc with HepC) – – steroids if primary, and antiplt agents. Scondary ––> IFN alpha and ribarivirin (unless low clearance)
	RPGN – biopy findings – most common cause of RPGN in adults – most common in children	crescentic GN with focal necrotizing lesions in glomeruli – pacuimmune GN – immune complex mediated GN
	Anti GMB disease – can be limited to ___ or associated with ____ – biopsy findings – diagnosis	RPGN or Goodpasture's – crescents over >50% glomeruli with staining of IgG linear along GBM – abs a/ alpha 3 chain of type IV collagen, and often + pANCA and cANCA
	Pauci IMmune Crescentic GN – secondary to _______ and associated with ____ meds – biopsy	vasculitis, WEgner's, Microscopic polyangiitis, churg STrauss Propylthiouracil, hydralazine, penicillamine, minocycline crescent shaped GN with focal lesions. 80% have + ANCA
	What key immunologic process causes MPGN	IgM immune complexes deposit on glomerular proteins, activate complement or via igM binding directly to glomerular proteins
	Primary cause of Immune complex mediated RPGN and sx	Hemolytic uremic syndrome – MAHA thrombocytopenia renal failure
	Autoantibodies to desmogleins 1 and 3 are in the _____ and cause ____	desmosome pemphigus
	BP antigens 180 and 230 are in the ______ and autoantidobides cause ______	hemidesmosome/lamina lucida pemphigoid and linear IgA bullous dermatosis
	Type VII collagen autoantibodies cause ____	epidermolysis bullosa acquisita
	Ocular Cictricial pemphigoid – wht is it – signs sx – dx – treatent	– sight threatening chronic inflammation, scarring of conjunctiva ssoc w/ systemic pemphigoid – conjunctival redness, mucus discharge, eyelid/eyelash in turning, breakdown of corneal/conj epith – biopsy – dapsone. severe dz steroids/cytotoxic therapy
	Peripheral Ulcerative Keratitis – two types – signs/sx – treatment	– (1) mild, both genders any age. (2) necrotizing (mooren's ulcer) vision threatening, adults unilat, bilat in AfAm men – pain, photophobia, redness tearing. For necr ––> corneal distruction – mild topical abx/steroids. For necr ––> immunosuppression, surgery
	Episcleritis – clinical features – treatment – optho emergency	– superficial benign inflammation, usu women, 40s, conj redness for months/days, minimal pain – cool compresses, tears, topical NSAIDS/steroids – no
	Scleritis – clinical features –tx – optho emergency	– sight threatening inflammation of sclera, usu women, 40s, 40% associ with RA. Ant eye redness, tearing, photophobia, pain c mvmt, decr vision – NSAIDS, steroids, mtx, immunosuppressants – YEs
	Uveitis – clinical features in the three types	Ant: in front of lens, sudden pain, red, photophob, vision change, miosis. Tx :top steroid Int: middle eye. bilateral blurry vision, floaters. Tx: periocular steroid Post: retina/choroid/vessels. Pain, redness, photphobia, vision loss. Tx: oral steroid/immunosup
	Autoimmune gastritis – aka –most common cause of _______ – pathogenesis – associated with HLA ____ – dx – tx	Pernicious anemia Vitamin B12 deficiency auto abs to parietal cell and intrinsif factor (target H/K atpases) ––> lymph infiltration––> parietal cell atrophy ––> b12 malabsorptio HLA b8, DR3 low b12 and anemia/neuro sx. Schilling test b12 replacement
	Celiac – sensitivity to ____ – associated with HLA___ – sx – biopsy	–gliadin (wheat, barley, rye +/– oat) – HLA DQ2 – diarrhea, flatulence, abd cramp, bloat, wt loss, fatigue, nutrional deficiency, anemia, osteoporosis – small bowel villous atrophy, resolves on gluten free diet.
	Celiac – diagnosis – IF – associated with ___	– TTG IgA auto abs (but check IgA levelas well). IgA antigliadin abs have high sens but low spec. If IgA def ––> IGG anti ttg test – granular IgA and complement at dermal/epidermal junction – dermatitis herpetiformis
	Typical EoE foods	milk, egg, wheat, soy
	Autoimmune Hepatitis – Type I auto abs – Type II auto abs	type I (classic, most common) – ANA, ss/dsDNA, saccharomyces cerevesiae, pANCA, smooth muscle, actin, soluble liver/pancreas ag type II – antiliver kidney micrsomes 1 (ALKM–1), liver cytosol antigen (ALC1 or LC1), rare ANA, +/– liver/pancreas ag, cyp2d6
	Autoimmune Hepatitis – assoc with HLA ____ – sx – lab – tx	– DR3 early dz, DR4 late onset dz – fatigue, jaundice, dark urine, abd pain, anorexia, amenorrhea, delayed menarche, HSM, spider nevi, cushingoid – AST/ALT elevation. Hypergammaglobulinemia (from auto abs) – tx steroids, immunosuppresives
	Primary Biliary Cirrhosis – associated with HLA____ – immune pathophys – autoabs	– A0201, DR8 – autoimmune attack on bile duct cells usu cd4/8 + T cells – antimitochondrial antibody
	Primary Sclerosing Cholangitis – associated with ___ disease – associated with HLA__ – autoantibodies	– ulcerative colitis – HLA B8, DR3, DRw52 – anti smooth muscle antibodies
	Inflammatory Bowel disease – typical genetic defect associated with Chron's – labs for UC and Crohn's	– NOD2/CARD15 (crohn's and Blau's) and ATG16L1 (Crohn's) – UC: ANCA+ and ASCA neg. – Crohn's: ANCAneg and ASCA pos
	Common IBD extraintestinal complications	– uveitis and episcleritis – arthritis – liver sclerosing cholangitis
	IBD treatment	Anti TNF a antibodies (infliximab and adalimumab)
	Multiple sclerosis – pathogenesis – treatment – HLA associations	– immune meditaed destruction of CNS myelin sheath by T cells. (Incr IL–12, IL–18, IFNg) – steroids, IFNb, glatiramer, natalizumab (anti–VLA4 mab), fingoimod (sphingosine1PR) – HLA–DR2
	Stiff Person syndrome – auto antibodies – pathogenesis – tx	– anti GAD (glutamic acid decarboxylase) and anti–amphyiphysin – excessive firing or the motor unit – diazepam, IVIG,
	GBS/AIDP/AMAN/ASMAN – auto antibodies	anti GM1, GD1a, GD1b, GT1a, GaINAc–GD1a
	Miller fisher syndrome auto antibodies	anti gq1b
	CIDP auto antibodies	anti ganglioside (LM1, GM1)
	Myasthenia gravis autoabs	antu AChR
	Lambert Eaton syndrome auto antibodies	Anti– VGCC
	Hyper eosinophilic syndromes – eos threshhold – cause of morbidity and mortality	– >1500/mm3 – cardiac disease
	hyper eosinophilic syndromes – subtypes	Myeloproliferative Lymphocytic Familial
	Differential for hypereosinophilic syndromes	primary EGID eosinophilic pneumonia churg– strauss syndrome systemic mastocytosis IBD adrenal insufficiency atheroembolic disease and HIV PID (ome's, HIES)
	Myeloproliferative HES variants –	FIP1L1/PDGFRA– associated HES (+ for that mutation, increased serum tryptase, most responsive to imatinib) myeloproliferative with negative FIP1L1 mutation chronic eosinophilic leukemia
	Lymphocytic HES	clonal expansion of lymphocyte populations with aberrant phenotypes and skin manifestations (angioedema, urticaria, papules, modules) – no response to imatinib
	Increased risk of ALL with these diseases	Down's Wiskott Aldrich
	Increased risk fo AMl with these diseases	BLoom's syndrome Down's congenital neutropenia Fanconi anemia
	Increased risk o CML with these_____	over expression of proto oncogen CLS2 13q deletions
	Hodgkin's lymphoma – main cell type – associated with ____ infections	Reed STernberg cell HIV/EBV
	XLP associated with this lymphoma	Ileocecal B cell lymphoma
	Burkitts' lymphoma – associated infection – associated gene defect	EBV c–myc gen translocation at 8q24
	Splenic marginal zone B cell lyphoma – associated infection – associated gene defect	HEp C deletion 7q21–32
	MALToma – associated infection – associated gene defect	– H pylori infection – trisomy 3 or t (11, 18)
	Indications for SPEP	Unexplained anemia, back pain, weakness, fatigue Osteopenia, osteolytic lesions, spontaneous fractures Renal insufficiency with bland urine sediment Heavy proteinuria in pt >40y Hyper Ca, hypergam, Ig deficiency Bence Jones proteinuria Unexplained peripheral neuropathy recurrent infections Elevated ESR or serum viscosity
	SPEP peaks (what fall under each type) A–1 globulin A–2 globulin B1 B2 Between B and gamma Gamma	–Alpha 1 antitrypsin, thyroid binding glubulin, –transcortin –Haptoglobin, ceruloplasmin –transferrin –Beta lipoprotine, igGAM, complement –CRP, fibriniogen –Immunoglobulins
	MGUS SPEP indings and diagnostic criteria	< 3 g/DL of monoclonal paraprotein spike (gamma) <10% BM involvement no myeloma related tissue impairment
	Symptoms of multiple myeloma	Calcium increase renal failure anemia bone lesions (>3 g/dL mnoclonal parparotein spike, >10% clonal plasma cells on BM bx, myeloma impairment)
	Waldenstrom's Macroglobulinemia – what is it – asssociated with these diseases – diagnosis	– malignant prolif of B cells ––> incr igM ––> pallor, organomegaly, hyperviscosity, abnl coag, neuropathy – HIV, Hep, autoabs, rickettsiosis – SPEP with M component with beta to gamma mobility
	Solitary Plasmacytoma – dx	monoclonal paraprotein spike on SPEP lytic lesion on radiograph
	POEMS – clinical features – diagnosis	– 1+ of following: osteosclerotic myeloma!!, Castleman's disease !!, organomegaly, endocrinopathy (excl DM, thyroid), edema, skin changes, papilledema – monoclonal parprotein spike on SPEP, with labmda chain on biopsy staining
	Castleman's disease – clinical features	giant cell lymph node hyperplasia angiofollicular lymph node hyperplasia
	Heavy chain disease – pathogenesis – most commonly reported – associated with autoimmune disease – rarest	– secretion of incomplete Ig heavy chains b/c inability of heavy chain to form disulfide bonds with light chain – alpha (severe diarrhea, wt loss from plasma cells) – gamma ( lymphoma like and 1/3 with RA, Sjogren's lupus, AHA) – mu (HSM, LAD, pallor)
	Which viral infection is associated with cryoglobulinemia and what types?	Hepatitis C virus (types II and III)
	Cryoglobulinemia – what is it – types	single/mixed Ig that undergo reversible precipitation at low temps – Type I: monoclonal Ig (M>G/A/light) – Type II: monoclonal RF (usu M with Fcs of IgG) – Type III: polyclonal RF
	Cryoglobulinemia – presentation by type	Type I: hyperviscosity & thrombosis: acrocyanosis, retinal hemorrhage, Raynaud's, livedo reticularis, purpura, art thrombosis) Type II/ III: joint involvement, fatigue, myalgias, renal immune complex disease, cutaenous vasculitis, neuropathy
	Cryoglobulinemia – diagnosis	serum cryoglobulins (warm tubes without anticoags) I precipitates in first 24 h III requires 7 days to precipitate
	Type I cryoglobulinemia is associated with ____	plasma cell dyscrasias multiple myeloma
	Granulomatous diseases: Th1 dominated	TB sarcoid Berylliosis Hypersensitivity pneumonitis Wegener's granulomatosis Tuberculoid leprosy
	Granulomatous diseases: Th2 dominated	Churg–STrauss syndrome Lepromatous leprosy
	Granulomatous disease – lab findings	ACE (lacks disease specificity) high vitamin D levels (1, 25(OH)2D3) osteopopntin TNFalpha
	What is Lofgren's syndrome	Triad: hilar adenopathy, acute polyarthritis, erythema nodosum
	What is the key difference between sarcoid and hpyersensitivity pneumonitis in terms of T cell counts on BAL?	CD4/8 elevated in sarcoid, decreased in HP
	Sarcoidosis – PFT findings – types of granulomas – BAL findings – treatment	– restrictive ( but occasionally mixed) – perilymphatic noncaseating granulomas with CD4/8 T cells – elevated CD4 to 8 ratio – steroids, inflixiamb if refractory
	Berylliosis – clinically similar to ___ – treatment	sarcoidosis removal from exposure to beryllium steroids
	WEgener's granulomatosis – aka – clinical features – diagnosis – treatment	– granulomatosis with polyangiitis – affects small–medium blood vessels, granulomas in resp tract. Most have sinus, lung, kidney involvement (also skin/eye) – CANCA with PR3 specificity (occ pANCA) – prednisone + cyclophosphamide/rituximab. Aziothioprinee/MMF once controlled. mild dz ––> pred + MTX
	Histiocytosis X – aka – most common sx – dx	eosinophilic granuloma of the lugn nonproductive cough lung biopsy, high res CT, cysts/nodules containing histiocytosis X cells of Langerhans origin with + CD1 and HLA–DR
	Clinical manifestations of amyloidosis	renal: protenuria, nephrotic syndrome cardiac: cardiomyopathy hepatic: HSM neuro: peripheral nuropathy, stroke MS: macroglossia Heme: bleeding diathesis pulm: tracheobronchial infiltrates, pleural effusions, parenchymal nodules skin: waxy thickening, easy bruise, subcu nodules/plaques
	Primary amyloidosis – deposits – associated with – dx –tx	most common form – Ig light chains – mutliple myeloma, Wasldenstrom's macro or non Hodgkin's lyhpoma – Ig in serum or monoclonal ight chains in urine – melphalan, prednisone, SCT
	Secondary amyloidosis – associated with – dx – tx	RA, IBD, periodic fever syndromes (FMF< FCAS< MWS) Congo red deposits in tissue/fat pad biopsy resolve chronic inflammatory state (colchicine in FMF)
	Muckle Wells syndrome – main features	sensorineural deaness recurrent hives intermittent fevers can have secondary amyloidosis with nephropathy trigger is cold temp mutation in NLRP3
	Familial MEditerranean Fever – main features	common in Turkish/ Ashkenazi Jews intermittent fevers serositis ––> abdominal pain/ pleuritis/ arthritis AA deposition (kidney, spleen liver, gut) tx with colchicine
	Mastocytosis: type s of cutaneous`	Urticaria Pigmentosa (discrete yellow–brown maculopapular/nodular with Darier) Diffuse cutaneous mastocytosis (diffuse yellow brown thick skin, no lesions, usu <3 y) Mastocytoma of skin (solitary, self limted) Telangiectasia macularis eruptiva perstans (macular telangiectasias with incr mast cells at capillaries, usu adults)
	Systemic mastocytosis – classification	Indolent systemic masto (most common, good prog) – sub: smoldering (>30% bm MCs, tryptase>200), isolated Bm masto (BM but no skin sx) Systemic masto c associated heme nonmast cell lineage (SMAHNMD) Aggressive systemic masto (hepatic fibrosis, portal HTN, malabsorption, cytopenia) Mast cell leukemia (rare, >10% immature Mc in peripheral) Mast cell sarcoma (tibia/skull) Extracutaneous mastocytoma
	Pathogenesis of mastocytosis	Activating mutations in ckit (KIT D816V0 ––> incr mast cells from constitutive activation of KIT tyr kinase signaling stem cell factor is ligand for cKIT (CD117) and is required for mast cell survival
	Medications that can trigger mastocytosis	Alcohol, AmphoB dextran, dextromethorphan IV VANc, quinine, polymyxin B alpha blocker, B blocker, opiods, Sux, atracurium, benzo/procaine ASA, NSAIDS
	Diagnostic criteria for cutaneous masto	at least one: focal dense mast cell infiltrates (>15 MC/cluster) Diffuse mast cell infiltrates (>20 MC/hp) on skin bx cKIT D816V mut
	Mast cells are stained by ____	CD117 (c kit) CD2 and or CD25
	Mastocytosis symptoms	Cutaneous: UP, flushing pruritis GI: Abd pain, N/V/D, peptic ulcer dz MS: Ms/bone pain, osteopenia/porosis, fracture CV: anphylaxis Neuropsych: decr attention, memory impairment, irritability
	Diagnosis of systemic mastocytosis	(1 major + 1 minor) OR 3 minor Major: BX c mast cell clusters (>15MC) Minor: Bx c >25% MCs spindle/atyp shape C kit D816V mutation expression of CD2/CD25 on cD117+ MCs Total serum tryptase >20
	Mast cell activation syndrome (MCAS) – what is it	pts with symptoms suggestive of mast cell activation but fail to meet WHO criteria Monoclonal MC activation syndrome (MMAS) has presence of mutation but not full WHO criteria
	Mastocytosis treatment	Trigger avoidance (EtOH, NSAIDs, narc, exercise, stinging insect) 1st/2nd gen antihistamines and H2 blockers Disodium cromoglycate (GI sx) Epi Steroids topical (UP or DCM) Imatinib (masto without ckit mutation) DEXA scan and Ca supp for osteoporosis
	Pathophys o acute Hemolytic transfusion reactions	IgM Ab: RBC Ag comlexes ––> complement mediated lysis ––> coagulation cascade ––> cytokine release ––> fever/flank pain/hemoglobinuria ––> DIC/Shock + hemoglobinuria, elevated free Hgb, DAT
	Delayed hemolytic transfusion reactions are due to ___ antigens	Rh, Kell, Kidd, Duffy + LDH, bili, DAT
	Transfusion Related Acute Lung Injury (TRALI	resp distress 1–4 hours after transfusion (donor luekocyte antibodies directed to recipient neutrophi ag or HLA)
	Warm Reactive AIHA – what is it	– polyclonal IgG against RBCs
	Cold reactie AIHA – what is it – associated with ____	– IgM binds I antigen (polysaccharide on RBCs) at temp <37 ––> complement activation – mycoplasma, mono, elderly
	Paroxysmal cold hemoglobinuria	cold reacting biphasic anti–RBC IgG ab (Donath– Landsteiner Ab) against P antigen on RBC
	Paroxysmal Nocturnal Hemoglobinuria –what is it / abs–	loss of PIG linkage proteins on rBC like CD59 and DAF
	PPrimary autoimmune neutropenia – affects ____ – clinical features – remission at ____	6–24 mo – benign – minor infections (abscesses, URIs, OM) – 2–4 years
	Neonatal allo immune thrombocytopenia – due to maternal abs against _____ – infant can develop _____ – treatment	HPA–1 inherited fetal plt antigen from father thrombocytopenia intracranial hemorrhage maternal plt transfusion
	ITP – clinical sx – treatment	– petechiaie, purpura, can develop intracranial hemorrhage – IVIG if plt <20–30
	Evan's syndrome – development of ___ and ____ with positive ___ and no known etiology – associated with ____ immunodeficiencies	ITP, AIHA DAT CVID, ALPS
	TTP clinical features – due to autoantibody to ___	fever anemia (MAHA) thrombocytopenia renal failure neuro changes Auto ab to ADAMTS13 (VWF cleaving protease)
	Heparin Induced thrombocytopenia (HIT) – mechanism – – can also happen with __ medicine or ____	IgG Fab binds comlex between heparin and platelet factor 4 ––> plt activation and consumption (less likely with LMW heparin) quinine, RBC transfusion
	Three autoantibodies seen with SLE	anti Smit Anti dsDNA anti U1 RNP
	Diagnostic criteria or ABPA in CF	acute/subacute clinical deterioration IgE>2400 ng/ml specific IgE/SPT for A fumigatus precipitating or IgG abs for A fumigatus new CXR/CT findings bronchiectasis
	Newborn screening for CT tests for	immunoreactive trypsinogen (can be falsely psoitive)
	Sweat chloride testing – lab values	elevated is >60 mEQ/L (borderline is 40–60)
	Nasal polyps with CF ahve more _____ while NP with asthma have more _____	neutrophils eosinpohils
	placental membranes expess HLAE, , G that interaction ____	LIRS (leukocyte inhibitory receptors) on Nk cells
	Pregnancy uterus has decreased ___ cells and increased ____	T and B cells NK and macrophages (prevent uterine infections)
	Sx o primary , secondary, tertiary syphilis	Primary: small painless chanchre (genitals, mouth, skin, rectum) resolves 3–6 wks Secondary: skin rash on palms/soles, condylomata lata in genitals. Constiutional sx, LAD, vision change, hair loss Tertiary: CV syphiils (aortic aneurysm, valv dz), neurosyphilis, tumors of skin/bones/liver (gumma)
	Soluble agents produced by pregnant uterus	Progesterone (blocks TNF a and changes Th1/2 blance) PGE2 (contributes to poor lypmp prolif) Th2 type cytokines (drive antibody mediated responses) Also Incr IL–10 producing T regs
	Which receptor allows transfer of maternal IgG cross the placenta and neonatal intestinal epithelium	FcRn receptor (IgG specific)
	Treatment options or pregnant women with antiphospholipid syndrome	low dose aspirin unfractionated heparin LMW heparin
	Types of antiphospholipid antibodies	anti cardiolipin anti beta2 glycoprotein I lupus anticoagulant
	Diagnosis of lyme	– not useful if asx – if symptomatic ––> ELISA/IFA to support dx, Western blot to confirm positive/indeterminate VIse (variable major protein like sequence expressed ELISA is as sens/spec as two tier testing PCR – low sens with lots of false positives
	Mechanisms to evade innate immunity used by TB	resistance to ROS (scavenging O intermediates by LAM (liparabinomannan); cyclopropanated mycolic acids in bact cell wall resist H2O2) inhiibiton of phag–lyso fusion inhibition o phag acidification (by bacilli excluding ATPase)
	Important cytokine for preventing early TB infection	IFN gamma (activates macs) (and IL–12/IL–23)
	Increased mycobacterial infections are associated with these PIDs	IL–12p40 / IL–12RB1/IL23b chain receptor def IFNgR1/2 receptor def STAT–1 def CYBB mutation Hyper IgE (tyk2 def) NEMO mut IRF8 def
	Important cytokine for granuloma formation	TNFalpha (explains why you can get reactivation of latent TB in people treated with infliximab or etanercept)
	Leprosy classifications and treatment	paucibacillary single lesion (lesions/nerves = 1) – rifampin ofloxacin minocycline x 1 paucibacillary (2–5) – 12 mo of dpasone qd and rifampin q month multibacillary (>5) – 12 mo of dapsone, rifampicin, clofazimine
	HLA links for leprosy	HLADR3 for PB HLA dq1 for MB
	Type II or Erythema Nodosum leprosum – what is it – sx	– immune complex disorder often seen during treatment of MB/BT leprosy – fever, tender nodules, neuritis, edema, arthralgias, leukocytosis, iridocyclitis, pretibial perisotitis, orchtitis, nephritis –
	Diagnosing Hep A virus infection	Serologic (IgM HAV abs at onset –4–6 mo; IgG in early convalescence to decades) Can also use RNA
	Diagnosis of HBV	RIA/EIA for serum hepatitis B surface antigen (1–10 wks ater exposure to 4–6 mo) After 6 mo – chronic infection ––> hep B surface Ab During windo period, can dx using IgM to core ag
	I chronic HBV infection need to monitor for _____	liver disease HBV DNA titers and ALt levels
	Abs/Ag in HBV carrier and vaccinated	Carrier: undetectable HbeAg, normal ALt, undetectable HBV DNA Vaccinated: Only HbsAB
	Hep C diagnosis	serologic assays for Abs HCV RNA assaysR
	outine testing for HCV recommeded i ____	illegal IV drug use Rec'd clotting factors before 1987 Received blood/tranplant before 1992 received chroni hemodialysis HIV Children born o mothers with HCV
	Hep C EVR (early virologic reponse) – defined – prognosis	– 2 log decline in HCV RNA from baseline to week 12 of treatment (if not, failure o therapy) – rapid virological response = undetectable HCV RNA by week 4 ––> predictive of sustained virologic response
	Diagnosis of syphilis	– initial non specific nontreponemal antibody test (VDRL, RPR, TRUST, all semiquantitative) – ollowed by specific treponemal test (FTA abs, MHA tp (microhemagllutination tes tfor abs to treponema), TP–PA (particle agglutination assay) TP–EIA (most favored
	Asymptomatic person with reactive nontreponemal and treponemal tests =	Latent syphilis
	Diagnosis of new infection in patient with history of syphilis	quantitative testing on RPR showing four fold or greater increase in antibody titer
	False positive non treponemal tests associated with	pregnacy IV drug use TB/ rickettsial non syphilis treponemal endocarditis HIV infection
	Allergens and their abbreviations dust mite cat dog cockroach	der p1, der f1 fel d 1 can f 1 bla g1–4, Per a 1
	Changes associated with allergen immunotherapy – Abs – receptors –basophils – cytokines	– Incr IgG1 and 4, incr then decr allergen–specific IgE, incr IgA in resp secretions – incr T regs and % CD8+ t cels – decr low afinity FceRI and FceRII (CD23) – decr basophil hypereactivity – shift from IL 4/5/13 to IFN g/TGFb/IL–10
	AIT: Conversion from Volume/volume ratio to weight/volume ration is ____ fold order f vials from least conc to maint conc	100 silver, green, blue, yellow, red
	Proteolytic enzymes in AIT – which extracts have them – which can they be mixed with	– cock roach and mold (mix with only each other and dust mite) – dustmite in 50% glycerin is safe to mix with pollen, dog, cat, cockraoch, and mold – ragweed and cat in 50% glycerin resist degradation when mixed with high protease extracts
	Weed cross reactivity	– short/giant/false/western ragweed (ambrosia)– – sage/wormwood/mugwort (artemisia) – thistle/lambs quarter/burning bush (chenopod) – pigweed / red root pigweed (amaranthus) – salt bush / wingscale (atriplex)
	Grass cross reactivity	– medow fescue / timothy / rye /Kentucky bue / orchard / red top (Festuca)
	Cross reactivity of trees	– juniper / cedar / cypress (cupressaceae) – birch /alder / hazel /hornbeam (betulaceae) – oak / beech /chestnut (fagaceae) – ash / olive / privent (oleaceae) – cottonwood / poplar / aspen (populus)
	which allergen extracts are standardized	Grass (northern grases and bermuda) ragweed cat dustmite
	AIT effective maintenance dosese are ____	5– 20 mcg per 0.5mL maint dose
	Systemic reaction rate with AIT is	1/2000 injections (greater fatal risk of on beta blocker) Fatal reaction in 1 in 2.5 million
	Probably effective maitenance dose for grass short ragweed cat dog dustmite bermuda	1000–4000 BAU 1000–4000 AU 1000–4000 BAU (1:10–1:100 w/v, 15 mcg) 500–2000 AU 300–1500 BAU
	Systemic reaction risk factors for AIT	beta blockers durng priming of pollen season during buildup during accelerated or rushed protocols first injection from new vials unstable asthma dosing error history of previous systemic reaction
	Relative contraindications to immunotherapy	pregnancy (ok to continue without increasing dose if patiet pregnant after starting) serious immunodeficiency malignancy uncontrolled asthma cardiovascular disease children < 5 years systemic mastocytosis
	histamine receptor types: H1 – receptor expression – general function – CNS function	– widespread (nerve, airway/vessel smooth muscle, epith/endoth, immune cell, hepatocytes) – Incr pruritis, vasodilation, hypoTN, tachycardia, BRONCHOCONSTR, COUGH receptor stim, decr AV node conduction time – sleep/wake, food intake, temp reg, memory
	histamine receptor types: H2 – receptor expression – general function – CNS function	– widespread (same as H1 but NOT MACS) – GASTRIC ACID secretion, vasc permeability, hypoTN, flushing, tachycardia, BRONCHODIL, AIRWAY MUCUS –neuroendocrine
	histamine receptor types: H3 – receptor expression – general function – CNS function	– histaminergeic neurons, eos, DCs, monos – pruritis, congestion. (PREVENT EXCESSIVE BRONCHOCONSTR) – decr histmaine/dopa/serotonin/norepi/Ach release
	histamine receptor types: H4 – receptor expression – general function – CNS function	– bone marrow, HSCT, eos, neut, C, TC baso, mast – incr prutitis, congestion, diff of myeloblasts – unknown
	H1 antihistamine effects – anitallergic –antiinflammatory	antiallergic: inhibit Mc/baso mediator release antiinflam: inhibit cell adhesion moelcule expr and eosinophil chemotaxis
	Histamine is metabolized by 2 major pathways	(1) histmaine N methyl trasnferase (2) diamine oxidase
	Fastest onset of the antihistamines – 1st gen – 2nd gen – topical	– epinastine (0.1 hr) – diphenhydramine = benadryl = doxepin = hydroxyzine (2h) – cetirizine = levocetirizine (1h)
	Slowest onset of the antihistamines – 1st gen – 2nd gen – topical	– chlorpheniramine (3h) – desloratadine/allegra (2h) – azelastine (0.5 h)
	Shortest halflife of the antihistamines – 1st gen – 2nd gen – topical	– benadryl – cetirizine – epinastine
	Longest halflife of the antihistamines – 1st gen – 2nd gen – topical	– chlorpheniramine – desloratidine – levocabastine
	When to dose adjust for antihistamines for hepatic/renal impairment	first gen antihistamines – for hepatic impairment 2nd gen antihistamines – for both renal and hepatic (usually)
	AEs with anithistamines	– CNS (first gen penetrate BBB) – cardiac (first gen cause prolonged QT) – H1: incr sedation/appetite, decr cog, decr CNS neurotransmission – Muscarinic: dry mouth, urinary retention, sinus tachy – alphaadrenergic: hypoTN, dizzy, reflex tachy – serotonin: incr appetite – ion channels: prolonged QT
	Second generation antihistamine that is safe in pregnancy	cetirizine and loratadine
	Longest half life among the following: loratadine cetirizine fexofenadine hydroxyzine	hydroxyzine (20h) (fexofenadine – 14h, cetirizine – 10h, loratadine 8h)
	Theophylline inhibits ____ resulting in ____ and is a ____ antagonist	phosphodiesterase cAMP adenosine antagonist
	THerapeutic range for theophylline	5–15 mg/L check level after 3 days o maximum dose
	Theophylline adverse efects – most common – most serious	– headache, nausea, vomiting, abdominal discomfort, restlessness – gastric acid secretion/reflux/diuresis – convulsions, cardiac arrhythmias, death AEs usually occur at plasma levels >20 mg/L
	Factors that decrease theophylline clearance (incr serum level)	macrolid cimetidine (not ranitidine) cipro verapamil zileuton allopurinol high carb diet CHF/ liver dz/ viral infection/ old age
	FActors that increase theophylline clearance (decrease serum level)	carabazmepine, phenobarb, phenytoin rifampin ethanol smoking tobacco/ marijuana high protein and low carb diet younger chidlre metabolize more than older
	Mechanism of beta agonists	bind GPCR and activate adenylyl cyclase ––> incr cAMP ––> activate protein kinase A ––> plation and muscle relaxation
	Types of beta agonistis	– b1: heart – b2 lung and inflammatory cells – b3: adipose tissue
	Non bronchodilator actions of beta agonists	– incr mucociliary clearance – protect epithelium a/bacteria – suppress microvascular permatbility – inhibit cholinergic tansmission
	Short acting beta 2 agonists i– ex – onset of actio – duration of action	albuterol, terbutaline pirbuterol, levalbuterol 2–4 min 4–6 hrs
	Long acting beta agonisits – example – onset of action – duration of action	formoterol, salmeterol formoterol (2–3 min), salmeterol (30) >12 h
	ultra long acting beta agonists – exmaples – onset of action – duration of action	carmoterol, indcaterol < 5 min >24 hr
	Adverse efects of beta agonists	tremor tachycardia prolonged QTc / arrhythmias hyperglycemia, hypokalemia, hypomagnesemia transient incr hypoxia
	Cardioselective beta blockers – examples – affect on bronchoconstriction	metoprolol, atenolol greater afinity for beta 1 receptors and less risk of bronchoconstriction or loss of asthma control
	Arachidonic acid pathway – ___ converts AA to _____ (3 pathways) which turn into ____ – ____ convert LTA4 to _____ (2) – ___ forms ____ (5)	(1) 15–LO, 15–HPETE, lipoxins (2) 5–LO, 5HPETE, LTA4 (3) COX1/2, PGG2, PGH2 – LTA4 hydrolase/LTB4; LTC4 synthase / LTC4/LTD4/LTE4 – PGH2 into TXA2, PGD2, PGE2, PGF2, PGI2
	Leukotriene receptors – function – receptor affinity	CysLT1R: bronchoconstriciton, mucus secretion, vascular permeability. – LTD4>LTC4>LTE4 CysLT1R: edema formation, endothelial activation (NO bronchoconstriction) – LTC4=LTD4>LTE4
	Leukotriene receptor antagonists – target – examples	cysLT1 receptor only montelukast, pranlukast, zafirlukast
	Leukotriene receptor antagonists – clinical uses	– exercise induced bronchospasm – allergic asthma/allergic rhinitis – AERD (help both early and late phase respons) – prior to aspirin desens – antiinflammatory (decr eos, decr eNO, decr bronchial hyperreactivity –
	Adverse effects of leukotriene receptor antagonists	– elevated transaminases – anaphylaxis, AE, dizzy dyspepsia, muscle weakness – suicidal thinking or behavioral changes – interacts with warfarin ––> incr PT – preg class B
	Zileuton – function – preg class – AEs – avoid if ___ – affects clearance of ____	5–LO inhibitor, good for asthma preg class C AEs: elevated LFTS! headache, dyspepsia myalgias, leukopenia avoid if liver disease or EtOH consumption decr clearance of theophylline, warfarin, propanolol
	LTB4 is a chemoattractant for ___	Neutrophils, eosinophils
	Mast cell stabilizers: mechanism	blocks IgE mediated calcium channel activation and blocks cl channels (lower intracellular ca levels)  prevents mast cell release of histamine/LTs; eo/neut activation
	Acetylcholine receptor types	Muscarinic receptors (GPCRs). (1) M1 on eos from COPD sputum (2) inhibitory receptor on parasympathetic nerves (3) primary mediator of smooth muscle contraction, most in bronchi
	Anticholinergic drugs	Atropine, Ipratropium bromide, tiotropium bromide
	Ipratropium and Titropium (blocks which receptor)	both block M2 and M3 (ipratroprium can have paradoxical bronchoconstriction)
	Allergic response (which agents affect which stage : mast cells stabilizers, anticholinergics, corticosteroids)	MC stab =both. antichol = both. steroids = late not early.
	Mechanism of corticosteroids	bind glucocorticoid receptor, heat shock proteins dissociated and steroid/receptor translocate into nucleus  gene activation and repression, interfere with NFkB, recruit histone deacetylasess, induce TF inhibitors of NFkb (FILZ, IIkkBa)
	Effects of oral steroids	decr t and B cells, decr CD4 more than 8, upregulates CXCR4, decr IgG/M, incr neut. decr eos/basos/monos, spares innate immunity
	AEs of steroids	STEROID (stunt growth, subcapsular post cataracts, steroid myopathy, Thrush, Eyes: incr IOP, cataracts, glaucoma, Endocrinediabetes, Rage(psych and incr BP), Osteopenia/porosis/obesity, Immunosuppression and Increased wt, Dysphonia, diabetes, derm)
	Medications that decrease glucocorticoid metabolism	Ketoconazole, OCPs, macrolides
	Omalizumab binds this	CH3 domain (FC portion of IgE molecule)
	Omalizumab decreases these	free serum igE and eos, expression of FceRI on effector cells, circulating IL–13 and FeNO, mediator release from mast cells and basos, B cells
	IgE binds to this portion of the FceRI	alpha chain
	AEs associated with omalizumab	local reaction at the injection site, URI, headache. Anaphylaxis (0.2% incidence) can be within 2 h or delayed
	Abatecept (orencia): target, molecular structure, indication	B7–1/B7–2 (CD80/86), CTLA4– IgG1 fusion protein, RA and JRA
	Alefacept (amevive): target, structure, indication	CD2, LFA3–IGG1 Fc fusion protein, plaque psoriasis
	Methotrexate (use, immune effect, AEs)	RA and autoimmune dz; inhibits cell replication ; teratogen, oral ulcers, nausea, diarrhea arthralgia, fatigue, LFTs, incr infxn
	Azathioprine (imuran/azasan: use, immune effect, AEs)	severe AD; inhibits purine nucleotide synthesis, myelosuppression, GIsx, hepatotoxicity, infections, skin cancer
	Mycophenolate Mofetil (CEllcept: use, immune effect, AEs)	severe AD, organ txpt; affects purine nucleotide synthesis; diarrhea, vomiting, livertox, myelosuppresiion, incr infections
	CSA and tacro function by binding which proteins	immunophilins (CSA binds cyclophilin and tacro binds FK binding protein)
	AEs of calcineurin inhibitors	nephrotox, HTN, HA, hypertrichosis, gingival hypertrophy
	Types of DNA based therapies	DNA vaccines, CpG DNA therapy(ragweed IT), oligodeoxynucleotide (antisense GATA3), siRNA (Vitravene for CMV retinitis)
	Uses for IVIG (immune, autoimmune, neuro, infectin, other)	PID; ITP/Graves opthal; CIDP/GBS, multifocal motor neuropathy; CMV pneumonitis; Kawasaki’s
	Probably beneficial uses for IVIG (immune, autoimmune, neuro, infectin, other)	Peds HIV, B cell CLL, specific ab def ; dermato/polymyositis, autoimmune uveitis; MGravis, Lambert–Eaton syndrome; neonatal sepsis, TSS, rotaviral enterocolitis; TEN SJS;
	Processing of IVIG	Isolation by modified Cohn Oncley cold ethanol fractionation for bact/prions; filtration for abs and viruses; stabilization to prevent aggregation ; viral inactivation;
	IVIG dosing and SCIG dosing	400–600 mg/kg every 3–4 weeks. 100 mg/kg/week
	IVIG not indicated for the following	selective igA def, IgG d/t protein loss, IgG subclass def, transient hypogam of infancy
	IVIG acts by the following mechanism	Fc receptor blockade (cd16 on NK, CD32 on B cll, Fc receptors on phagocytic cells)
	Common and serious IVIG reactions	headache, fever, fatigue, chills, N/V, myalgias (usu rate dpdt). Injection site reactions for SCIG. Aseptic meningitis, Anaphylaxis (esp if IgA def), acute renal failure, thrombotic events, hemolytic anemia, TRALI
	Cause of renal insufficiency when treating patients with IVIG	sucrose  hyperosmolar renal damage
	Inteferon therapy ( mechanism)	activates JAK/STAT pathways leading to antiviral/antiprolif effects
	IFN alpha AEs	fever, flu like sx, cytopenias, liver dysfxn, neuropsych sx, cerebrovascular events, hypersens, GI bleed, hyperglyc, pulm d/o, eye d/o, pancreatitis, peripheral neuropathy
	IFN alpha precautions	careful if cardiovascular dz, thyroid dysfunction, coagulation defect, or severe myelosuppression. Should have periodic eye exams
	Recombinant IFN alpha 2a indication	chronic Hep C, hairy cell leukemia, CML (pegylated for Hep B/C)
	Recombinant IFN alpha 2b indication	hairy cell leukemia, kaposi’s sarcoma, chronic hep B/C, malignant melanoma, follicular lymphoma, condylomata acuminate, (pegylated for Hep C)
	IFN alpha con–1 indication	Hep C
	IFN alpha n3 leukocyte derived	HPV genital warts
	IFN beta 1a and 1b indication	relapsing multiple sclerosis (1 b for early MS)
	Bioengineered IFN gamma 1b indication	CGD and malignant osteopetrosis
	Recombinant IL–2 indication	metastatic renal cell carcinoma and metastatic melanoma
	IFN beta and gamma precautions	caution if seizure disorder or cardiac disease (myelopsuppressio for IFN gamma, watch for autoimmune in IFN b)
	Recombinant IL–2 AEs /precautions	hypotension, diarrhea, oliguria, chills, vomiting, cytopenia, blackbox for capillary leak syndrome, coma. D/c if pts develop lethargy/somnolence. Should have normal cardiac/pulm/hpatic/CNS function at start
	Recombinant IL–11 precautions/ AES	vomiting, edema, fever, hypersen, CV abnl, pleural effusion, papilledema. Watch for anemia, incr tox after myeloablation
	Inteferon therapy ( mechanism)	activates JAK/STAT pathways leading to antiviral/antiprolif effects
	IFN alpha AEs	fever, flu like sx, cytopenias, liver dysfxn, neuropsych sx, cerebrovascular events, hypersens, GI bleed, hyperglyc, pulm d/o, eye d/o, pancreatitis, peripheral neuropathy
	IFN alpha precautions	careful if cardiovascular dz, thyroid dysfunction, coagulation defect, or severe myelosuppression. Should have periodic eye exams
	Recombinant IFN alpha 2a indication	chronic Hep C, hairy cell leukemia, CML (pegylated for Hep B/C)
	Recombinant IFN alpha 2b indication	hairy cell leukemia, kaposi’s sarcoma, chronic hep B/C, malignant melanoma, follicular lymphoma, condylomata acuminate, (pegylated for Hep C)
	IFN alpha con–1 indication	Hep C
	IFN alpha n3 leukocyte derived	HPV genital warts
	IFN beta 1a and 1b indication	relapsing multiple sclerosis (1 b for early MS)
	Bioengineered IFN gamma 1b indication	CGD and malignant osteopetrosis
	Recombinant IL–2 indication	metastatic renal cell carcinoma and metastatic melanoma
	IFN beta and gamma precautions	caution if seizure disorder or cardiac disease (myelopsuppressio for IFN gamma, watch for autoimmune in IFN b)
	Recombinant IL–2 AEs /precautions	hypotension, diarrhea, oliguria, chills, vomiting, cytopenia, blackbox for capillary leak syndrome, coma. D/c if pts develop lethargy/somnolence. Should have normal cardiac/pulm/hpatic/CNS function at start
	Recombinant IL–11 precautions/ AES	vomiting, edema, fever, hypersen, CV abnl, pleural effusion, papilledema. Watch for anemia, incr tox after myeloablation
	Recombinant Il–11 indications	chemotherapy induced thromboctyopenia
	REquirements of an aeroallergen (from Thommen's posulates)	1. buoyant 2. allergenic 3. Present in a significant concetration
	Sampling aeroallergens – type methods – two types of samplers	– sedimentation v. gravitational sampling – Durham Sampler and Settle Plates
	Pros and Cons of Durham Sampler	– microslides coated with adhesive and exposed x 24h – low cost, durable, power indepedent – biased toward larger particles, cannot determine air []
	Procs and Cons of Settle Plates	– particles are allowed to settle on agar and incibuted/examined/counted – identifies airborne organisms – biased toward larger particles, cant determine air []. good for indoor use only
	Rotorod – pros and cons	– rod sweeps through air and coated with adhesive – not effecient for small particles – not affected by wind, good for most airborne paticle and allows for calculation of []
	Burkard Spore trap –pros and cons	– known air drawn in through a sampling orifice with a tale to keep oriented – more efficient than the rotorod for particle collection < 10 micron, consistent flow speed with samples over varying time frames – more expensive and affected by wind speedA
	nderson Sieve IMpinger (Multistage Cascade Samler)	Series of sieves with air passing though – separates particles by size, good for brief collection periods and culture based sampling of airborne fungi – expensive
	Allergenco air sampler	suction sampler that collects on lab slides, usu for indoor use –
	Appearance of grass pollen and size	large (20–45 micron) round pollen grain with thickened ring and may have a cap (operculum)
	Three main allergenic southern grasses	Bermuda Bahia Johnson (also lovegrass, prarie rass, corn, sugarcane)
	Main Northern grasses	Timothy Orchard Rye Fescue Bluegrass Other(redgrass, sweet vernal, brome, velvet, canary)
	Grass cross reactivity	Bermuda, love grass, prarie grasses Bahia, Johnson, corn, sugarcanes Northern grasses
	Chenopod – cross reactivity – appearance / size – types	– chenopods and amaranths (pigweed or careless, w water hemp) – golf ball (20–35 micron) – lambsquarter, wingscale/saltbush, burning bush, russian thistle
	RAgweed (ambrosia) – appearance / size – types – pollen food asociations	– spiky golfballs, 15–25 microns – giant, short, western, false ragweed – banana, cantaloupe, watermelon season ends with first frost
	Sage and Mugwort – appearance / size – types – pollen food associations	– round with three bubbles (20–30 micron) – no other names – celery spice, peach, mustard
	Cockleburs (Xanthium) – appearance/size–	blunted spikes, similar to ragweed but larger in size and blunter spikes
	Nettle – types – apperance	stinging nettle (N America) and wall pellitory smallest pollen with 3–4 pores (round with weird polygons in the middle)
	Plantain – appearance	large 20–40 micron and periporate (6–10 pores) with a pore cap that gives donut appearance
	Dock or Sorrel – types – apperance / size	curly dock and sheep sorrel round with inclusion granules (speckled)
	Tree pollen – pollination time and exceptions	Mostly spring Fall: elm Mid winter: mountain cedar
	Ash family – examples – location – pollen appearance	ash, olive, privet, russian olive Ash (east/central N america); Olive (Western N am, europe) Square/pentagon appearance with furrows (olive/privet have three furrows)
	Birch family – examples – pollen appearance – food cross reactivity	birch, alder, hazelnut, hornbeam three pores making look like triangle or lemon APPLE, CARROT, almond, apricot, celery, cherry, coriander, fennel, hazelnut, kiwi, nectarine, parsley, parsnip, pear, pepper, plum, potato, walnut

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