Allergy & Immunology

Drugs & Vaccines

Calcineurin Inhibitors (Cyclosporin, Tacrolimus)

• Inhibits Transcription of IL-2 → reduced T-lymphocytes activity → used for immunosuppression following Solid Organ Transplantation

• Side Effects:
• Nephrotoxicity & Hyperkalemia
• Hypertension
• Hyperglycemia
• Hyperuricemia
• Neurotoxicity (resting/intentional tremors are most common, but visual disturbances or seizures can happen)
• Cosmetic effect → Gingival Hyperplasia (with cyclosporin), Alopecia, and Hirsutism

DTaP Vaccine

• Components: Diphtheria toxoid, Tetanus toxoid, and Conjugated pertussis antigen (acellular)

• Schedule: (5 doses) → 2,4,6, 15-18 months, and 4-6 years

• Contraindications:
• Anaphylaxis ⇒ NO FUTURE DOSES
• Unstable neurological disorders (infantile spasms & uncontrolled epilepsy) OR Encephalopathy (Coma, Seizure >5mins, AMS) ⇒ DIPHTHERIA & TETANUS ONLY WITHOUT PERTUSSIS
• Seizures < 5 mins are not a contraindication

General Vaccine Talk

• Vaccines are given according to chronological age (age since birth)
• EXCEPT HBV FIRST DOSE → administered when patient weighs ≥ 2kg (usually at birth)

• Vaccines for preterm infants should NOT be delayed & are safe/proven to induce adequate response

• Mild intercurrent illnesses ARE NOT a contraindication to vaccination

Turner Syndrome

Comorbidity Screening in Turner Syndrome:

• Autoimmune diseases → Celiac (Tissue Transglutaminase antibodies) & Thyroiditis (TSH & Free T4)

• MSK → Osteoporosis (Vitamin D & DEXA)

• Renal → Horseshoe Kidney (US)

• CVS:
• Congenital Heart Disease (4-extremity BP, ECHO, ECG) {Bicuspid Aortic Valve & Aortic Coarctation}
• Aortic Dissection (TEE or MRI) {HIGH RISK IN PREGNANCY}
• Metabolic Syndrome (BP, HbA1C, LFTs, Lipid Panel)

• Vision (Ophthalmological evaluation for strabismus & myopia) & Hearing (Audiological testing for recurrent OM & CHL)

 

Tricky Presentations:

• Short Girl + hx of strabismus surgery + high-arched palate + malocclusion of teeth + short metacarpal bones → Turner Syndrome
• What will improve growth?
• Recombinant Growth Hormone (indicated when height falls <5% percentile)
• What else is given?
• Estradiol at age 11 to induce puberty & breast development & reduce risk of osteoporosis & CVS complications
• After menarche, progesterone is added to mitigate endometrial hyperplasia risk

Show X-Ray of short metacarpal bones

 

Allergic Reaction

Acute Urticaria

• Causes → Medications, Insect Bites, Infections, Rheumatological Diseases, or even idiopathic

• Pathophysiology → Mast Cell Activation causing Dermal Edema (IgE is NOT elevated in urticaria)

• Features → diffuse or localized Wheals (pruritic, erythematous plaques), each lasting <24 hours (The whole urticaria attack lasts <6 weeks)

• Management:
• If 1 isolated/sporadic attack → No additional investigations needed [ttt → 2nd gen H1-Blocker]
• If recurrent → Allergy Testing
• If systemic symptoms present OR failure of ttt OR exhibits atypical features (purpura) ⇒ Obtain Skin Biopsy & further Lab Investigations

Anaphylaxis

• Management → IM Epinephrine (may be repeated. for a total of 3 shots, in biphasic or protracted anaphylactic attack) [EPI BEFORE O2]
• If severe/refractory ⇒ IV Epinephrine
• If hypotensive ⇒ IV fluids + Trendelenburg positioning
• Adjuvants (less important)
• B2 agonist for bronchospasm
• H1/H2 blockers for hives
• Glucagon for BB reversal

Hereditary Angioedema

• Dx → LOW C4 & C1 inhibitor protein or function

• TTT
• C1 inhibitor concentrate
• Bradykinin Antagonist (Icatibant)
• Kallikrein Inhibitor (ecallantide)
Show Why

Acquired Angioedema

• Most commonly caused by ACE inhibitors (as ACE “kininase” degrades bradykinin), causing buildup of bradykinin

• Management:
1. Airway & Vasomotor instability ⇒ SC Epinephrine
1. If Fails ⇒ Emergency Tracheostomy
2. ACEi should be STOPPED

Immunodeficiencies

Common Variable Immunodeficiency

• Pathophysiology: Abnormal B-cell differentiation into plasma cells → decreased immunoglobulin production

• Features:
• Age 20-40 or even around puberty (VS XLA → in infants due to absent B-cell production)
• Recurrent Resp Infections/Sinusitis (Bacterial)
• Recurrent GI infections (Bacterial + Giardia)
• Chronic Diseases (Autoimmune - Bronchiectasis - Asthma - Fibrosis - Chronic Diarrhea - IBD like conditions)

• Dx → decreased IgG, IgA, IgM (NO RESPONSE TO VACCINES)

• Management → Immunoglobulin Replacement Therapy

X-Linked Agammaglobulinemia

• Pathophysiology: BTK gene mutation → absent B-cell production → decreased level of all immunoglobulins

• Features: Absent Lymph nodes/tonsils/adenoids + recurrent infections > 3-6 months of age + chronic enteroviral disease (usually meningitis)

• Labs: Decreased Immunoglobulins & response to vaccines
• Flow cytometry shows LOW B-cells (CD19) with Normal T-cells

• Management → Immunoglobulin Replacement Therapy

Transient Hypogammaglobulinemia of Infancy

• Prolonged (> 6 months) physiological IgG nadir

• Presentation → Asymptomatic/recurrent resp infections/Atopy

• Labs → Low IgG (Normal/Low IgA & IgM)
• NORMAL RESPONSE TO VACCINES
• NORMAL B-CELLS & T-CELLS

• Management → Follow up

Severe Combined Immunodeficiency

• Dx → Low CD19 (B-cells) and Low CD3 (T-cell)

• Management → Stem Cell Transplant

Chronic Granulomatous Disease

• UNIQE PRESENTATION:
• IBD in a child that upon biopsy shows pigment-laden histiocytes + Recurrent Infections (OM, Osteomyelitis, pneumonia) + diffuse granulomas formation

• DHR flow cytometry is preferred more than NBT testing

• Management:
• Prophylaxis ⇒ TMP-SMX, Itraconazole, INF-gamma
• Active Infection ⇒ Culture + Abx
• Definitive ttt ⇒ Hematopoietic Cell Transplant

Leukocyte Adhesion Deficiency (LAD)

• Pathophysiology: Defective CD18/Integrin → Impaired leukocyte adhesion & transmigration

• Labs → Leukocytosis with Neutrophilia (Absolute Lymphocyte count is normal)

• Presentation: Chronic infections WITHOUT pus (skin - oral ulcers - periodontitis) by staph aureus & gram negative bacilli
• Delayed Umbilical cord separation (> 3 weeks) is buzzy

Ataxia-Telangiectasia

• Characterized by presence of telangiectasias (can be ocular) + cerebellar ataxia + Immunodeficiency (variable)
• T-cell + B-cell are possible

Hyper-IgE Syndrome

• Impaired Th17 → decreased neutrophils proliferation & chemotaxis

• Features (FATED):
• Abnormal Faces
• Cold Abscess (Candida & Staph aureus)
• Retained Teeth
• IgE increased & Eosinophilia (with normal WBC count)
• Dermatitis (Eczema)

Miscellaneous

Tumor Lysis Syndrome

• Prevention (Pre-Chemo) ⇒ IV fluids + Xanthine Oxidase Inhibitors or Rasburicase

• TTT (Post-Chemo) ⇒ IV Fluids + Rasburicase

Thiazide-Induced Hyponatremia

• Hyponatremia In an elderly female with low BMI taking thiazides

• TTT → STOP thiazide & correct hyponatremia

Serum Sickness & Serum Sickness-Like Reaction

• Although future exposure may not cause recurrent symptoms, the drug should be avoided when possible.
• So, outcome is → complete resolution without sequelae

Liver Transplantation

• Major cause of morbidity & mortality → Infections

• Length of time since transplantation helps categorize likely infectious organism:
• < 1 month ⇒ Bacterial [causes high-grade fever + rapid onset hypotension/sepsis]
• 1 - 6 months ⇒ Opportunistic Pathogens
• ≥ 6 months ⇒ Higher rate of community acquired pathogens

Vitamin D Deficiency

• Causes:
• Decreased Sun Exposure (Nocturnal Occupation OR Residence in long term health-care facility)
• Heavy Skin Pigmentation & Obesity & Old Age
• Malabsorption
• CKD

• Features:
• Asymptomatic OR nonspecific msk symptoms
• Low bone density & fractures
• Osteomalacia (Bone Pain & Muscle Weakness) [MUST EXCLUDE OTHER CAUSES LIKE PMR/Thyroid Myopathy]