Lec 9 Drug Induced Skin Disorders Flashcards
What are the 4 classifications of allergic reactions?
- Anaphylaxis
- Cytotoxic
- Immune complex
- Delayed
- Anaphylaxis Mechanism & Clinical Manifestation
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
- Cytotoxic Mechanism & Clinical Manifestation
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
- Immune Complex Mechanism & Clinical Manifestation
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)
- Delayed Type, T cell mediated Mechanism &; Clinical Manifestation
Effector T lymphocytes, may be CD4+ or CD8+, producing different patterns of cytokines
What is Maculopapular morbilliorm
Most common type of allergic reaction to antibiotics, especially amoxicillin, cephalosporins and gentamycin.
Also caused by phe-nothiazines, thiazides and barbituates
What are urticaria reactions
Reaction occurs with penicillin, aspirin, foreign blood transfusions, indomethacin, opiates and insulin
Sub-classification of Delayed Reaction 4a
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
Sub-classification of Delayed Reaction 4b
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
Sub-classification of Delayed Reaction 4c
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
Sub-classification of Delayed Reaction 4d
CXCL8 and GM-CSF producing T-cells recruit neutrophilic leucocytes and prevent their apoptosis via GM-CSF release
-AGEP (Acute Generalized exanthematous pustulosis)
Acute Generalized Exanthematous Pustulosis (AGEP)
- 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
Eerythema multiforme (EM), Steven Johnson syndrome (SJS) & toxic epidermal necrolysis (TEN)
- 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
Severe Cutaneous Adverse Reactions (SCARs)
-Medicine most commonly implicated are: Sulphonamide Antibiotic Anticonvulsant NSAIDs
EM>SJS>TEN
What are some immediate effects of food allergy?
i) Gastrointestinal: vomiting, abdominal pain, diarrhoea
ii) Skin: urticaria
iii) Respiratory: rhinitis, cough, wheeze
iv) Cardiovascular: pallor, dizziness, collapse
What are some late phase effects of food allergy?
- Eczema
- Allergic eosonophil gastroenteritis (Aeg)
What is dermatitis herpetiformis?
- 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
What causes DH?
- 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
Describe how anaphylaxis affect some organs
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
