Allergy and Clinical Immunology

Question 1

Ten Red Flags of Immunodeficiency

Answer 1

1. ≥ 2 new ear infections within 1 year
2. ≥ 2 new sinus infections within 1 year, in the absence of allergy
3. One pneumonia per year for more than 1 year
4. Chronic diarrhea with weight loss
5. Recurrent viral infections (colds, herpes, warts, condyloma)
6. Recurrent need for IV antibiotics to clear infections
7. Recurrent, deep abscesses of the skin or internal organs
8. Persistent thrush or fungal infection on skin or elsewhere
9. Infection with normally harmless tuberculosis-like bacteria
   10.A family history of Primary Immunodeficiency

Question 2

Primary Immunodeficiency (PID) - General Approach

Answer 2

Rule out secondary causes of immunodeficiency:
– DM, HIV infection, Cirrhosis, Nephrotic syndrome, Autoimmune disease, Malignancy,
Splenectomy/Asplenia, Immunomodulatory drugs
– Structural (obstructive tumours, urethral strictures), dermatitis, burns

Question 3

B- cell immunodeficiency

Answer 3

Repeated pyogenic infections

Inv:

Lymphocyte count,
Lymphocyte subsets,

Immunoglobulins (IgG, IgA, IgM),
vaccination titres

Question 4

T- cell immunodeficiency

Answer 4

Severe mycotic infection and
opportunistic infections

INV: Lymphocyte count, Lymphocyte subsets

Question 5

Neutrophil deficiency immunodeficiency

Answer 5

Abscess-forming infection with
low-grade pathogens

INV:
Neutrophil count,
Chronic Granulomatous
Disease (CGD) Assay

Question 6

Complement
deficiency

Answer 6

Repeated infections w/
Neisseria sp.

INV: C3, C4, CH50

Question 7

Combined Variable Immunodeficiency (CVID)

Answer 7

• Most common symptomatic PID in adults
  – Recurrent sinopulmonary infections
  – Dx: LOW IgG + LOW IgA or IgM + poor response to vaccination;
  other immunodeficiency causes ruled out (e.g. CLL)
  – Tx: IVIG or SCIG (sub-cutaneous Immunoglobulin)

Question 8

Acute Urticaria- work up and treatment

Answer 8

Common antigens/triggers = antibiotics (PCN, Sulfa), NSAIDs, insects, food
(shellfish in adults) - if there’s a trigger, there will be an obvious relationship
* Lasts < 6 weeks
* Work-up: Allergy referral for skin testing

• First line treatment: STOP medication/AVOID trigger if identified, anti-
  histamines PRN: ex. Cetirizine (Reactine)

Question 9

Red flags of urticaria

Answer 9

Red Flags of Urticaria:
Last longer than 48hr
Heal with a bruise, scar
Burning, pain

PEARL: Red Flags should raise suspicion of autoimmune/systemic disease!!!

Question 10

Chronic Spontaneous Urticaria (CSU)- diagnosis and treatment

Answer 10

• “Chronic”: >6 weeks, most days of the week, “Spontaneous”: no clear trigger
• Workup of CSU
  – CBC + diff, ESR/CRP
• Workup of other causes of chronic urticaria – as directed by clinical picture:
  – Autoimmune work-up: ANA, ds-DNA, RF
  – Serum tryptase if systemic symptoms [Mastocytosis]
  – Biopsy [urticarial vasculitis]
• Treatment of CSU
  – 1st line: Daily non-sedating antihistamine (cetirizine)
  – 2nd line: increased dose non-sedating antihistamine (4x
  – 3rd line: Omalizumab (Xolair)
  Physical Chronic Urticaria
• Trigger = Pressure (aka dermatographism), Heat, Cold

Question 11

Idiopathic Angioedema Tx

Answer 11

Angioedema + pruritus/urticaria = most likely Mast cell mediated
* Related to a Specific Trigger (food, drug, insect bite, etc.)
* Idiopathic Angioedema (can be part of CSU)
Angioedema (NO pruritus/urticaria) = Mast cell OR Bradykinin-mediated

• Differential diagnosis:
  – Related to Specific Trigger (see above)
  – Idiopathic Angioedema
• Chronic Tx: Frequent episodes : Daily antihistamine (Cetirizine)
• Rare episodes: Prednisone + antihistamine for first sign of symptoms
• Epinephrine Auto-injector

Question 12

Hereditary Angioedema (HAE) TX

Answer 12

:C1 esterase inhibitor deficiency – Types I, II, III
* PEARL: in general, a normal C4 level (in acute setting) rules OUT
HAE Types I &II
* Chronic Tx: Prophylactic C1 esterase Inhibitor (icatibant)

Question 13

Acute Treatment Angioedema

Answer 13

STOP offending agent/trigger, if possible
H1-Blocker: Diphenhydramine 25-50mg IV
H2-Blocker: Ranitidine 50mg IV
Steroids: Methylprednisolone ~60-80mg IV
*Anaphylaxis or oropharyngeal angioedema: Epi!
ACE Inhibitor Angioedema: Icatibant
Known HAE: skip above treatment, instead: C1
esterase inhibitor, Icatibant (firazyr)

Question 14

Anaphylaxis Acute TX

Answer 14

– ABCs, MOIF
– STOP drug/REMOVE trigger (if iden2fied)
– Epinephrine IM: 1:1000 (1mg/mL) – DOSE: 0.01mg/kg (max 0.5mg)
IM in anterolateral thigh, repeat q5-15min
– Epinephrine IV: 1:10,000 (0.1mg/mL) – BOLUS: 0.05-0.1 mg IV over 5
min, then INFUSE: 2-10mcg/mL
* Consider IV aXer several (i.e. 3) doses IM, profound hypotension, obese
paZents

• Adjunc2ve medica2ons:
  – H1-Blocker: Rani8dine 50mg IV q8hr PRN
  – H2-Blocker: Diphenhydramine 25-50mg IV q4-6hr PRN
  – Steroids: Methylprednisolone 125mg IV q6hr PRN
  – Glucagon – paZents on beta-blockers
  – Salbutamol – paZents with signs of bronchoconstricZon
  – Vasopressors – for persisZng hypotension
• Observe un2l symptoms improving, min. 4-6hr

Question 15

Penicillin Allergy- types

Answer 15

Approach:
– IgE-Mediated: pruritus, urticaria, angioedema, etc.
– Non-IgE-Mediated: SJS-TENS (blistering, desquamation, conjunctivitis), DRESS (eosinophilia, fever, end-organ
involvement), serum sickness (arthritis, fever)

Question 16

Management: IgE-mediated Reactions

Answer 16

– Allergy referral for Penicillin Skin Testing + Oral Challenge
* ~90% “PCN allergic” patients will test negative – can safely receive beta-lactam and cephalosporin antibiotics
* Positive skin test – AVOID penicillin, higher likelihood of reacting to 1st gen cephalosporins
– Drug Desensitization (under close observation, OK to do even in Pregnant patient (eg) with syphilis))
* If penicillin is required acutely and no time for skin testing, or skin test positive
* Note: this is a temporary induction of ‘tolerance’, and does NOT rule out allergy
* Note: this is only used in cases of IgE-mediated drug reactions (NOT if any suspicion of serum sickness, SJS-TENS,
DRESS, etc.)
– Note: Aztreonam (monobactam) – generally tolerated in penicillin allergic patients
* exception: if they have reacted to ceftazidime!