AllergyImmunology Flashcards
Late-phase reaction: Occurs _ to _ hours after acute phase and initial allergen exposure; symptoms are similar to acute-phase reaction and mirror the inflammation seen in asthma and chronic allergic rhinitis
4 to 12
Differences between mechanisms of anaphylaxis and acute phase reaction
elevated serum β-tryptase in anaphylaxis non–IgE-mediated factors include C3a and C5a
Diagnosis of anaphylaxis is supported by the measurement of elevated serum _ (usually peaks in the first _ hours)
tryptase, 2 hours
Anaphyaxis: Rx
epinephrine, first oxygen, antihistamines, corticosteroids, and β-agonists (
non–IgE-triggered process that clinically resembles anaphylaxis; causes include aspirin,NSAID, radiocontrast, and, rarely, opiates
Anaphylactoid reaction (is non-IgE mediated)
Prophylaxis: anaphylactoid reaction to radiocontrast
prednisone (50 mg, administered at 13 hours, 7 hours, and 1 hour before procedure) diphenhydramine (IM or PO) 1 hour before procedure
Heriditary angioedema(HAE-C1-INH): Dx, Rx
Clinical presentation + Absence or reduced level of C1-INH plus low C4 Synthetic androgens (e.g., danazol, stanazol) Purified C1-INH Kallikrein inhibitors
How doe synthetic androgens (danazol, stanazol) work in hereditary angioedema?
Induction of C1-inhibitor synthesis
Two types of heriditary angioedema?
HAE-C1-INH, HAE-FXII
Pathogenetic mechanisms: differences between HAE-C1-INH and HAE-FXII
HAE-C1-INH: low levels of C1-esterase HAE-FXII: Activation of kallikrein-bradykinin system
Acquired angioedema suggests:
malignancy - lymphoma, leukemia Low C1q levels distinguish this from hereditary form
Mechanism of allergic contact dermatitis
T cells activated, release interferon-γ Macrophages then activated
Allergic contact dermatitis: Dx method
Patch testing
Atopic dermatitis: mechanism, rx
1/3: skin barrier defect (filaggrin mutation) Inherited: elevated IgE, eosinophilia, IgE sensitization to antigens Topical steroids, Topical FK506, antistaph abx
FK506
Tacrolimus
Tacrolimus: Indxn
- Organ transplant - Atopic dermatitis - severe refractory uveitis after BMT - MCD - vitiligo - Kimura’s disease inhibis production of IL-2 thus decreasing development of T cell populations
Systemic diseases causing urticaria
- urticarial vasculitis - mastocytosis - SLE
Urticaria:Rx other than antihistamines
doxepin
Mechanism of penicillin allergy
Acting as hapten
Can aztreonam be given to a pen-allergic patient?
- cross-reactivity with cephalosporins is 6% to 30% - carbapenems cross-react with minor determinants PCN whereas monobactams (i.e., aztreonam) can be safely administered to PCN-allergic patients
Sulfonamide mediated allergy mechanism; which patients are prone to it?
T-Cell; HIV+
Recently identified genetic mutation (platelet-derived growth factor receptor alfa [FIP1L1-PDGFRA]) in some cases
Hypereosinophilic syndrome
Why do we need to notify the blood bank that a patient has IgG A deficiency?
If prior blood transfusion, patient will develop anti-IgG A antibodies which will react with transfused blood containing IgG A. Ie: blood bank should provide IgG A free blood
Samter’s triad
asthma, aspirin sensitivity, and nasal polyps
The first case of aspirin sensitivity in a patient with asthma was described in 1902, a few years after the introduction of aspirin into clinical use. In 1968, Samter and Beers described a
asthma, aspirin sensitivity, and nasal polyps
Samter’s triad
Acute anemia in a patient on IVIG
IVIG associated hemolytic anemia
Rituximab
anti-CD20 chimeric monoclonal antibody, B cell depleter
- RA
- CLL
- GPA
- MPA
- NHL
- Post-cardiac transplant immunosupression
- AIHA
- Burkitt lymphoma, CNS lymphoma, Hodgkin: off label
- GVHDoff-label
- TTP, ITP, membranous nephropathy, lupus nephritis, pemphigus - off-labe
Infliximab
anti-TNF, RA
Cetuximab
EGFR inhibitor, metastatic colorectal cancer
Omalizumab
anti-IgE, severe asthma + urticaria
Alemtuzumab
anti-CD52
Indxn: CLL, T-cell lymphomas
B-cell lymphoma: express
CD-20
ABPA: Rx
Steroids + (? itraconazole | voriconazole)
Ivacaftor
small molecule, designed for: G551D mutation in at least one CFTR genes.
Risk of cross-reactivity between sulfonamide antibiotic and other sulfonamide containing meds
Very low
Significance: negative penicillin skin test
Highly accurate
Skin testing is highly accurate for the identification of penicillin allergy
OTOH: .. no valid reagents available for most antibiotic-specific IgE . Although the parent antibiotic compound may be used, a negative does not mean that IgE antibodies are absent.
A negative result: insufficient sensitivity or, more likely, correct drug immunogen was not used
Tryptase
Mast-cell–specific neutral protease
Indicates: systemic mast-cell activation is high for several hours after anaphylactic drug reactions.
Dx method: hypersensitivity pneumonitis
BAL, lymphocytosis with CD4:CD8 < 1
- exposure to offending antigen(s);
- compatible clinical, radiographic, or physiologic findings;
- bronchoalveolar lavage with lymphocytosis;
- positive inhalation challenge testing;
- histopathology: Poorly formed, noncaseating granulomas OR a mononuclear cell infiltrate.
Not all of these features are present in all patients.
Two models for chronic HP have a high degree of specificity. Model 1 included the following predictor variables: age, a history of down feather and/or bird exposure, the presence of diffuse craniocaudal ground-glass opacity on HRCT, and the presence of mosaic perfusion on HRCT. An “HP score” point value ≥63 (range 0 to 100) showed a specificity of 91 percent and sensitivity of 48 percent for the diagnosis of chronic HP. Model 2 included: age, history of down feather and/or bird exposure, and a moderate to high confidence in the radiographic diagnosis of HP. Using model 2, HP scores ≥57 demonstrated a specificity of 91 percent and sensitivity of 50 percent for the diagnosis of chronic HP.
Asthma: cough characteristics
Cold air, exercise, worse at night
Viral infections can lead to asthma
True
On what basis?
Rx: mild persistent asthma
inhaled glucocorticoid
Could try LTA and then switch if failure
Rx: intermittent and mild persistent asthma in adolescents and adults
Allergen identification, avoidance
- Intermittent: SABA
- Mild persistent: inhaled glucocorticoid
intermittent: short-acting inhaled beta-2-selective adrenergic agonist (Grade 1A). ) (Step 1 Rx). SABA PRN acute symptoms as well as for prevention of symptoms
●The cromoglycates can be used as alternative preventive agents (eg, prior to exercise), SABA must still be prescribed for acute bronchodilation. Problem: Withdrawal of MDI formulations from the market in most countries
Mild persistent: daily antiinflammatory medication (Grade 2A). This represents step 2 + PRN SABA
Alternative approach: LTA
Increasing evidence suggests that at least some patients with mild persistent asthma can use their anti-inflammatory therapy intermittently (that is, taken daily during periods of increased symptoms, then discontinued 1 to 2 weeks after symptoms have abated).
LABA: can they be used alone?
No
Only with glucocorticoid
Vilanterol
Ultra-long-acting beta agonists with a duration of action of up to 24 hours (eg, vilanterol and others not approved for use in asthma)
LABA controversy
Despite the beneficial effects of LABA, there has been a controversy over whether chronic use of long-acting beta agonists may be associated with rare severe asthma exacerbations and increased asthma and cardiac mortality in a small subgroup of patients.
Asthma: Mx components
- routine monitoring of symptoms and lung function
- patient education,
- control of trigger factors
- Rx comorbid conditions
- Pharmacologic therapy
Parameters for asthma severity
- Symptoms over the previous two to four weeks
- Current (PEFR or FEV1 )and FEV1/FVC values)
- Number of exacerbations requiring oral glucocorticoids in the previous year
Chronic sinusitis: Best first test
CT
Most sensitive, most specific
Recurrent sino-pulmonary infections without preceding viral infection
CVID
Asthma Classification
- Intermittent: Sx < 2 days/week, Normal FEV1 in between, FEV1 > 80%
- Persistent
- Mild: Sx > 2 d/week , FEV1 > 80
- Moderate: Sx daily, 60> FEV1 < 80,
- Severe: Sx throughout day, FEV1 < 60
Dx features
a patient over age four who demonstrates all of the following characteristics [56,81,82]:
- Significantly reduced total IgG
- Low IgA and/or IgM
- Poor response to immunization
- Absence of other immunodeficiency(ie, CVID is a diagnosis of exclusion)
Eosinophilic granulomatosis with polyangitis
Small vessel vaculitis + asthma + vasculitic rash + mononeuritis multiplex
Sensitivity of ANCA
50%
Late summer + fall
Early spring
Late spring, early summer
Late summer + fall: weed
Early spring: tree
Late spring, early summer: grass
Acute anaphylactic reaction: route of epinephrine
IM
Exertional dyspnea+abnormal inspiratory phase on flow-volume loop
VCD
Flow volume loop: significance of flat inspiratory phase
Extra-thoracic outflow obstruction
Tracheomalacia: flow volume loop
Flattening of expiratory phase
Asthma vs PVFM
PVFM is often mistaken for asthma because it is episodic, may be brought on by exertion, and the stridor may sound similar to wheezing.
Asthma: wheezing is expiratory
PVFM: Flow-volume curves may show flattening of the inspiratory loop consistent with extrathoracic airway obstruction. Between episodes, spirometry normal.
Diagnosis: flexible laryngoscopy during episode: abnormal adduction of the vocal folds, exclusion of other causes of glottic and subglottic obstruction.
Differential: PVFM
- asthma,
- angioedema,
- bilateral vocal fold palsy,
- glottic and tracheal neoplasms
- stenosis,
- laryngotracheomalacia,
- laryngospasm.
typically occurs with ..
harsh, high-pitched wheezing or vibrating sound due to turbulent airflow in the upper airways. It can occur during inspiration, expiration, or both, although it most typically occurs with inspiration.
Vocal cord motion: normal
true vocal folds abduct (open) during inspiration and partially adduct (close) during expiration.
Abduction can also be induced by sniffing and panting. Normal adduction of the true vocal folds occurs with phonation, coughing, throat clearing, swallowing, and during a Valsalva maneuver.
PVFM: Rx
- acute: reassurance + panting maneuvers (Grade 2C).
- If not effective CPAP; HeliOx
In patients with recurrent PVFM, we suggest a long-term management strategy that combines
- speech therapy
- psychological counseling, and
- avoidance of perceived laryngeal irritants (Grade 2C).
- exercise-related PVFM may : inhaled anticholinergic before exercise.
Intense pruritus + dry, scaling rash in flexural areas
Atopic dermatitis
Cetirizine
a less sedating metabolite of hydroxyzine, H1 Antagonist, Second Generation;
2-month history of fevers, headaches, purulent nasal discharge: Trigger
Think of GPA ( Wegener’s)
Look for :
50% GPA or MPA have skin lesions. The most common is leukocytoclastic angiitis, which causes purpura involving the lower extremities that may be accompanied by focal necrosis and ulceration.
Skin lesions may also include urticaria, livedo reticularis, and nodules. Occasional patients with erythema nodosum, pyoderma gangrenosum, and Sweet syndrome may also have ANCA-positive disease.
GPA: ANCA sensitivity
Upper respiratory tract only: 70%
Systemic: 90%
Joint pain, rash 7-10 days after antibiotics
Serum sickness
Asthma: best test
FEV1 response to bronchodilator
TNF-alpha inhibitors increase risk for:
Mycobacteria, Listeria, Histoplasma
Hypersensitivity reactions: features, timing
- Type 1: IgE, previous sensitization: immediately with first dose
- Type II: uncommon, antibody-mediated cell destruction, hemolytic anemia, thrombocytopenia, or neutropenia
- Type III: antigen-antibody complexes and serum sickness, vasculitis, or drug fever. Unommon and usually seen in high-dose, prolonged administration, similar to type II reactions. 1-2 weeks , since significant quantities of antibody are needed.
- Type IV: skin findings, T-cell mediated, delayed in onset by at least 48 to 72 hours and sometimes by days to weeks. Upon rechallenge, may appear within 24 hours.
urticarial rash (picture 1 and picture 2); pruritus; flushing; angioedema; wheezing; GI symptoms; and/or hypotension.
Type I
antibody-mediated cell destruction leading to hemolytic anemia, thrombocytopenia, or neutropenia,
may be asymptomatic or present with fulminant illness. - five to eight days after exposure, but may begin after much longer periods of treatment. Symptoms can start within hours if the causative drug is stopped and then restarted.
Type II
antigen-antibody complexes and usually present as serum sickness, vasculitis, or drug fever. These reactions are uncommon and usually seen in the context of high-dose, prolonged drug administration, similar to type II reactions.
- drug (including biologicals) i act as a soluble antigen. In this capacity, the drug binds drug-specific IgG, forming small immune complexes that can activate complement and precipitate.
- These immune complexes bind to Fc-IgG receptors of inflammatory cells and/or activate complement, and an inflammatory response ensues. Reexposure to similar or higher doses of the same drug can cause a more rapid and severe recurrence.
Timing — one or more weeks to develop after drug exposure, since significant quantities of antibody are needed to generate symptoms related to antigen-antibody complexes.
Type III
a localized type III hypersensitivity reaction in which antibody-antigen complexes that fix complement are deposited in the walls of small blood vessels, causing acute inflammation, infiltration of neutrophils, and localized skin necrosis.
Arthus
Drug induced lupus: timing
Weeks after exposure, stops within days of stopping drug
Cough, fever, malaise 8 hours after barn work
Farmer’s lung
hypersensitivity pneumonitis due to Thermophilus actionmycetes exposure (moldy hay)
Hypersensitivity Reactions: which one is not antibody mediated?
Type IV
Type IV drug reactions involve the activation and expansion of T cells, which requires time (normally many hours or days after antigen exposure), hence the name delayed-type hypersensitivity (DTH). In some cases, other cell types (eg, macrophages, eosinophils, or neutrophils) are also involved.
Hot tub lung
Hypersensitivity pneumonitis due to exposure to MAI
ABPA: susceptible patients?
Cystic fibrosis
Asthma
Cattle allergy
Rhinoconjuctivitis + asthma + cows
Bevacizumab, Alemtuzumab, Gemtuzumab ozogamicin
- Bevacizumab: Colon cancer, RCC, age related macular degeneration (anti-VEGF)
- Alemtuzumab: CD52 leukemias
- Gemtuzumab ozogamicin: AML
C2 deficiency
30% SLE-like illnes;
Another presentation, especially in early childhood, is recurrent pyogenic infections with encapsulated bacteria, such as Streptococcus pneumoniae, Haemophilus influenza type b, and Neisseria meningitidis
CVID: inheritance
90% sporadic, 10% familial
CVID: age of onset
20 to 40
X-linked agammaglobulinemia, SCID, CGD: age of onset
- X-linked agammaglobulinemia: defect of B-cell development, recurrent sinopulmonary infection, first 2 years
- SCID: T-cell defect that can affect B-cells, NK cells: fist 6 months.
- CGD: neutrophil function defect, catalase positive infections during first 5 years.
Recurrent epsiodes of angioedema without urticaria
DxTest:
Hereditary angioedema
C1-esterase inhibitor function
Complement levels in hereditary angioedema
C4 persistently low, C2 low during attacks
Tryptase high in:
Anaphylaxis, hereditary mastocytosis
ryptase is produced by both mast cells and basophils, although mast cells contain approximately 500-fold more than basophils. Upon activation, mast cells degranulate, releasing tryptase, along with histamine, into the extracellular environmen
AERD
aspirin-exacerbated respiratory disease
Nasal polyps: associations
chronic sinusitis, asthma, and aspirin sensitivity
Nasal polyps are abnormal gray, glistening masses filled with inflammatory material, which may form in the nasal cavity or paranasal sinuses; appearance is diagnostic.
Seen on computed tomography (CT) examination. In adults, nasal polyps are frequently associated with chronic sinusitis, asthma, and aspirin sensitivity,
in the syndrome of aspirin-exacerbated respiratory disease (AERD). Some patients have concomitant allergic rhinitis or allergic fungal sinusitis. In children, nasal polyps are most commonly associated with cystic fibrosis.
Nasal polyps: Rx
Topical glucocorticoid bid
Rinne test: positive
AC > BC
Hearing loss: elderly, high frequency dominant
Presbycussis
Presbycusis: differential
- Autoimmune hearing loss: rapid (over weeks to months).
- Meniere’s: Vertigo, tinnitus, unilateral, fluctuating, low frequency.
- Otosclerosis: genetic cause, Rinne negative, low frequency loss.
Genetic condition causing hearing loss because of fixation of stapes; Rinne negative, low frequency hearing loss.
Otoscleorsis
Bony overgrowth that involves the footplate of the stapes. As the overgrowth develops, the stapes can no longer function as a piston, but rather rocks back and forth and eventually becomes totally fixated. Conduction gradually becomes worse until a maximal conductive hearing loss of 60 dB is reached.
Differentiate inner ear cause from middle/outer ear cause of hearing loss
All outer and middle ear: conductive hearing loss;
Inner ear causes: sensorineural hearing loss.
IgG4-RD.pathogenesis
Hallmark?
lymphoplasmacytic tissue infiltration
- lymphoplasmacytic tissue infiltration of IgG4-positive cells
- May be accompanied by fibrosis, obliterative phlebitis
- majority: high IgG4.
- Presentation: subacute development of a mass in the affected organ or diffuse enlargement of an organ.
- Lymphadenopathy is common
- Symptoms of asthma or allergy may be present.
- Good initial response to glucocorticoids.
IgG4-RD.diseases
- Type 1 autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis
- Mikulicz disease (or Mikulicz syndrome) and sclerosing sialadenitis (Küttner’s tumor), inflammatory orbital pseudotumor, and chronic sclerosing dacryoadenitis
- Idiopathic retroperitoneal fibrosis
- Chronic sclerosing aortitis and periaortitis
- Riedel’s thyroiditis and a subset of Hashimoto’s thyroiditis
- IgG4-related interstitial pneumonitis and pulmonary inflammatory pseudotumors
- IgG4-related renal disease, particularly tubulointerstial nephritis
Tacrolimus.SideFx
Headache, hypertension, Tremor, AKI
Transplant.Mx
Which immunosuppresive drug: Headache, hypertension, Tremor, AKI
Tacrolimus
Elderly man started on allopurinol for gout 3 weeks ago presents with:
Diffuse generalized maculopapular rash
Lymphadenopathy
Malaise, fatigue
Peripheral eosinophilia, elevated liver enzymes
What is the diagnosis?
DRESS syndrome.
Explanation
Drug Rash with Eosinophilia and Systemic Symptoms. Patients typically develop a pleomorphic rash, peripheral eosinophilia, fever, lymphadenopathy, and multiorgan involvement (liver, kidney, cardiac, etc.). Usually occurs 2–8 weeks after exposure to the offending drug, typically with aromatic anticonvulsants, minocycline, and allopurinol. Recently, reactivation with human herpesvirus 6 has been implicated.
Dx: Clinical diagnosis. Skin biopsy may be helpful, but not diagnostic.
Tx: Stop the drug. Glucocorticosteroids and IVIG may be beneficial.
Fever
Cough (productive of scant sputum) and dyspnea
Localized rales and egophony
± Hypoxemia
CXR: Diffuse interstitial streaks
Sputum Gram stain: No organisms
Rapid antigen tests for influenza and RSV: Negative
Bronchoalveolar lavage: Organisms visible on Gomori methenamine silver stain
What is the diagnosis?
PJP
DFA is the most commonly used method for detection. Respiratory viruses are also common in this time period—consider adenovirus, as influenza and RSV tests were negative.
Dx: BAL + (DFA test or GMS stain).
Tx: TMP/SMX ± prednisone (if pO2 ≤ 70, A-a gradient ≥ 35, or resting hypoxemia on pulse ox).
oung female with PMH childhood pneumonia, pneumococcal bacteremia, and recurrent sinus infections presents with 6-month h/o:
Fevers, weight loss, arthralgias
Intermittent cola-colored urine
Papulosquamous rash on both cheeks and nose that spares nasolabial fold
Violaceous mottled rash on forearms and thighs
Bilateral MCP synovitis
↓ WBC, Hgb, and Plt
+Coombs test
U/A: RBC casts, 3+ protein
+Anti-dsDNA and +anti-Sm
systemic lupus erythematosus (SLE) associated with early complement deficiency.
Explanation
Homozygous early complement deficiency (especially C1, C2, and C4) is associated with recurrent bacterial sinopulmonary disease and development of SLE.
Usually, a case of untreated SLE without an underlying complement deficiency will not have the history of repeated pneumococcal infections.
Dx: Clinical; complement deficiency is diagnosed with the CH50 assay, which assesses the classic pathway. Homozygous deficiencies result in a very low CH50 value.
Tx: Vaccinations (can get live virus vaccines), especially meningococcal and pneumococcal conjugates + standard treatment for lupus (immunomodulation) + prophylactic antibiotics for sinopulmonary infections.
Young adult with h/o N. meningitidis bacteremia at 15 years of age presents with:
Fever and HA
Stable BP
Diffuse erythematous maculopapular rash on the extremities and thorax
Petechiae on the oral mucosa and conjunctiva
Absent Kernig and Brudzinski signs
Blood cultures: Gram-negative cocci
What is the diagnosis, and what is it associated with?
recurrent meningococcal infection associated with terminal complement deficiency.
Explanation
Suspect terminal complement deficiency when you see > 1 episode of invasive Neisseria. Deficiencies in the alternative pathway (factors D and properdin) are also associated with Neisseria but are very rare.
Dx: CH50 assay, which assesses the classic pathway; AH50 assay assesses the alternative pathway.
Tx: Vaccinations (can get live virus vaccinations), especially meningococcal and pneumococcal conjugates and vigilance for symptoms/signs of infection.
Healthy patient presents with acute:
Generalized hives
Dyspnea with wheezing after using latex gloves
↑ HR, normal BP
↓ O2 sats
↓ Air movement in the lungs and audible wheezing
What is the diagnosis?
anaphylaxis.
Explanation
Anaphylaxis is diagnosed when any 1 of the following 3 criteria is fulfilled:
1) Sudden onset with involvement of the skin/mucosal tissue and either:
Sudden respiratory symptoms, or
Hypotension
2) ≥ 2 of the following that occur suddenly after exposure to a likely allergen:
Skin/Mucosal tissue involvement
Respiratory involvement
Hypotension
GI symptoms
3) Hypotension after exposure to known allergen
Note that hypotension is not required for the diagnosis of anaphylaxis. The patient in the vignette satisfies criterion #2, as patient had skin/mucosal involvement and respiratory symptoms after exposure to latex. Other common triggers include pollen, animal dander, food (nuts, shellfish, milk, eggs, fish), insects (bees, hornets, wasps), and drugs (beta-lactams, anesthetics, muscle relaxants).
Dx: Clinical as above.
Tx: Epinephrine is 1st line therapy! Albuterol can be given for wheezing, antihistamines for hives and pruritus, normal saline for hypotension.
