Immunology

Question 1

What are the mechanisms of the 4 types of hypersensitivity reactions?

Answer 1

Immediate:

Type 1: Pre-formed IgE mediated mast cell degranulation

Delayed:

Type 2: Antibody mediated cell destruction (rare, presents as cytopenias).
Type 3: Deposition of antibody-antigen complexes (serum sickness, drug reaction, vasculitides).
Type 4: T-Cell response (SJS/TEN, Dermatitis, DRESS)

Question 2

What is the interval between exposure and symptoms for each of the 4 types of hypersensitivity reactions?

Answer 2

Type 1: < 1 hour
Type 2: 1 week or more
Type 3: 1 week or more
Type 4: 48 hours or more

Question 3

How is Erythema Multiforme Major distinguished from SJS/TEN in terms of (1) exam findings, (2) etiology, (3) course, and (4) treatment.

Answer 3

1. EMM is characterized by raised target lesions, whereas the lesion of SJS/TEN are flat followed by desquamation. 2. EMM is most often related to infection (most commonly HSV), where SJS/TEN is most commonly related to drug exposure (though M. Pneumoniae is a major cause also). 3. EMM is typically self-limited, whereas SJS can progress and lead to substantial morbidity related to fluid losses, eye damage, etc. 4. Both SJS/TEN and EMM are managed symptomatically, although steroids (topical or systemic) can be used for substantial oral symptoms with EMM. Steroids are controverisal for SJS/TEN, as is IVIG.

Question 4

What are the causes of SJS/TEN?

Answer 4

Typically drugs (especially sulfa drugs and aromatic anti-epileptics), but also infection (especially M. Pneumonia–note that there may be little or no skin involvement in MIRM). About 30% of cases are idiopathic.

Question 5

What are the aromatic anti-epileptic drugs in common use (and why is this question in the immunology section?)

Answer 5

Phenytoin, carbamazepine, oxcarbazepine, lamotrigene, zonisamide, phenobarbital. These AEDs are particularly prone to provoking immune mediated reactions such as DRESS and SJS/TEN.

Question 6

What is the treatment for SJS/TEN?

Answer 6

Immediate cessation of provoking agent (if known), treatment of provoking infection (if known), and supportive care. Growing evidence supports cyclosporine, and there are reports of TNF alpha inhibitors (etanercept, infliximab) being useful too. Steroids and IVIG are options, but evidence is lacking and/or mixed.