Lec 9 Drug Induced Skin Disorders

Question 1

What are the 4 classifications of allergic reactions?

Answer 1

1. Anaphylaxis
2. Cytotoxic
3. Immune complex
4. Delayed

Question 2

1. Anaphylaxis Mechanism & Clinical Manifestation

Answer 2

i) Antigen combine with IgE antibodies bound to receptors on the surface of mast cells/basophils
ii) Bridging of IgE receptors= mast cell degranulation and release of mediators i.e. histamine
- URTICARIA

Question 3

2. Cytotoxic Mechanism & Clinical Manifestation

Answer 3

i) Antigenic determinants on cell surfaces are targets for antibodies, IgG/gM.
ii) The antibodies damage cells by activating complement, or by binding to cells through Fcg receptors, they activate cytotoxic killing e.g. K cells
- PEMPHIGUS

Question 4

3. Immune Complex Mechanism & Clinical Manifestation

Answer 4

i) Circulating immune complexes are deposited in vascular beds or on tissue surfaces.
ii) Complement is activated, neutrophils attracted and their products damage tissues

• VASCULITIS
• Drug Induced Systemic Lupus Erythematosus (DILE)

Question 5

4. Delayed Type, T cell mediated Mechanism &; Clinical Manifestation

Answer 5

Effector T lymphocytes, may be CD4+ or CD8+, producing different patterns of cytokines

Question 6

What is Maculopapular morbilliorm

Answer 6

Most common type of allergic reaction to antibiotics, especially amoxicillin, cephalosporins and gentamycin.

Also caused by phe-nothiazines, thiazides and barbituates

Question 7

What are urticaria reactions

Answer 7

Reaction occurs with penicillin, aspirin, foreign blood transfusions, indomethacin, opiates and insulin

Question 8

Sub-classification of Delayed Reaction 4a

Answer 8

4a) Th1 T-cells activate macrophages by IFNy secretion, drive the production of complement fixing antibody isotypes, and act as co-stimulators for pro-inflammatory & CD8 T cell responses

• CONTACT DERMATITIS
• TUBERCULIN REACTION

Question 9

Sub-classification of Delayed Reaction 4b

Answer 9

4b) Th2 T-cells secrete IL-4, I1-13 & IL-5 cytokines, which promote B cell production of IgE & IgG4, macrophage deactivation and mast cell & eosinophil responses

• Maculopapular rash
• Exanthemata with eosinophilia

Question 10

Sub-classification of Delayed Reaction 4c

Answer 10

4c) T-cells act as effector cells. They emigrate into the tissue and kill cells, such as hepatocytes or keratinocytes in a peforin/granzymeB and/or FasL-dependent manner

• Contact dermatitis
• Maculopapular rash
• Drug induced exantemata
• Bullous eruptions

Question 11

Sub-classification of Delayed Reaction 4d

Answer 11

CXCL8 and GM-CSF producing T-cells recruit neutrophilic leucocytes and prevent their apoptosis via GM-CSF release

-AGEP (Acute Generalized exanthematous pustulosis)

Question 12

Acute Generalized Exanthematous Pustulosis (AGEP)

Answer 12

• Can occur at any age
• Females > Males
• Always accompanied by fever an leukocytosis
• Incidence rate is 1-5 cases/million/tear
• Mortality rate 5%
• AGEP can reoccur with reintroduced drug

Question 13

Eerythema multiforme (EM), Steven Johnson syndrome (SJS) & toxic epidermal necrolysis (TEN)

Answer 13

• TEN & SJS are characterised by erythema evolving into extensive blistering that resembles a second degree burn
• Accompanied by mucosal erosions, affecting mouth, lip, conjuctiva and genitals
• EM typically affects extremities // SJS is more widespread // TEN body surface area
• EM lower morbidity// TEN higher morbifity

Question 14

Severe Cutaneous Adverse Reactions (SCARs)

Answer 14

-Medicine most commonly implicated are:
  Sulphonamide
  Antibiotic
  Anticonvulsant
  NSAIDs

EM>SJS>TEN

Question 15

What are some immediate effects of food allergy?

Answer 15

i) Gastrointestinal: vomiting, abdominal pain, diarrhoea
ii) Skin: urticaria
iii) Respiratory: rhinitis, cough, wheeze
iv) Cardiovascular: pallor, dizziness, collapse

Question 16

What are some late phase effects of food allergy?

Answer 16

• Eczema

- Allergic eosonophil gastroenteritis (Aeg)

Question 17

What is dermatitis herpetiformis?

Answer 17

• A rare but persistent immunobullous diseases with blisters in clusters most commonly on the scalp, shoulders, buttocks, elbows and knees w/ symmetry
• Characterised by extremely itchy papules and vesicles on normal or reddened skin

Question 18

What causes DH?

Answer 18

• DH & CD are due to intolerance to the giladin fraction of gluten found in wheat, rye, and barley
• Gluten triggers production of IgA antibodies and an autoimmune process that targets skin/gut
• In CD, gluten causes intestinal inflammation resulting in diarrhoea, tiredness, weight loss and abdominal discomfort

Question 19

Describe how anaphylaxis affect some organs

Answer 19

SKIN= pruritius, urticaria
RESP= shortness of breath, upper airway congestion, swelling of lips/tongue
HEART= chest pains, irregular heart beat, lbp
GASTRO= stomach cramp
SYSTEMIC= confusion, tremor, collapse