The document discusses drug-induced skin adverse reactions. Antibiotics, analgesics, cardiac drugs, corticosteroids and NSAIDs commonly cause such reactions. Maculopapular rash is the most common manifestation. Factors like drug properties, dose, route of administration and host factors like genetics, medical history influence reactions. Common causes of hypersensitivity discussed are penicillin, aspirin and sulfonamides. Diagnosis involves skin testing and clinical history. Management includes patient education, genetic testing, desensitization and close monitoring.

2. %DRUGS CAUSED
SKIN ADVERSE
DRUG REACTIONS

3.  Antibiotics - 38.8%
 analgesics -11%
 cardiac drugs - 9.9%
 glicocorticoids - 18.56%
 NSAIDs - 12.61%.
 Amoxicillin(25.33%) most common
 Cutaneous drug reactions (37.6%) NSAIDs
 maculopapular rash 37.73%, 17.2% fixed erythema and
urticaria 14.56%.

4.  Immunologically mediated reaction
 Unrelated to the pharmcodynamic profile of the drug
 Occur with in much smaller doses
eg:co-infection with HHV

5. TYPE OF
HYPERSENSITI-
VITY
MECHANISM CLINICAL
MANIFESTATIO-
NS
REMARKS
TYPE 1 Ig E Mediated Asthma,anaphylax
is,
Skin/prick test
TYPE 2 IgG /IgM Neutropenia,throm
bocytopenia
pemphigus
TYPE 3 Hypersensitive
vasculitis
_
TYPE 4
 Type 4a
T-Lymphocytes
Th1&Tc1 cells
Contact
dermatitis,tuberculin
Patch test(48 hour)
Type 4b Th2 cells Maculopapular rash _
Type 4c Cytotoxic T-cells Toxic
epidermalnecrosis
_
Type 4d T -cells Exanthematous _

6.  Drug Factors
 Nature of the drug
 Degree of exposure (dose, duration, frequency)
 Route of administration
 Cross-sensitization
 Host Factors
 Age and Sex
 Genetic factors (HLA type, Acetylator status)
 EBV, HIV, asthma
 Previous drug reaction
 Multiple allergy syndrome

7.  Nature of the drug
Chemical substance is clearly protein-reactive
 Degree of exposure (dose, duration, frequency)
Intermittent courses of moderate drug doses
 Route of Administration
Oral administration generally safer
 Cross-Sensitization
Structural chemical relationship /immunochemically similar
metabolites.
eg: among penicllins and cephalopsporins

8.  Age and sex
Less frequent in children and elderly patients .Common in
females than in males.
 Genetic factors (HLA type, Acetylator status)
eg: HLA B*1502 associated with carbamazepine induced
SJS/TEN in Han Chinese in Taiwan, Hong Kong, but neither
in Japanese nor Europeans
 Concurrent medical illness (EBV, HIV, asthma)
Altering metabolic pathways /Variations in the immunologic
responses to drugs. Eg:Ampicillin maculopapular rashes arise
commonly in patients EBV infection

9.  Previous drug exposure
Drug hypersensitivity in the past ,increased tendency to
develop sensitivity to new drugs
 Multiple Drug Allergy Syndrome
Patients with “multiple drug allergy syndrome” may
have a predilection to more than one non-cross-reacting
medication

10.  In this section include,
 PENCILLIN (beta-lactam antiobiotics)
 ASPIRIN (NSAIDs)
 SULFONAMIDES

11.  Penicillin belongs to a family of drugs called beta-lactam
antibiotics
 The reported history of penicillin allergy ranges from 0.7% to
10%.
 Penicillin G is the most common
 Most severe reaction being anaphylaxis
 Very high doses of penicillin can cause neurotoxicity

12. Pencillin allergy
symptoms
Hives
angioedema
Throat tightness
Wheezing
Coughing
Trouble breathing

13. A less common but more serious, sudden-onset allergic reaction to
penicillin is anaphylaxis,
 Swelling of the tongue, throat, nose and lips
 Dizziness and fainting or loss of consciousness
 Tightness in the chest and difficulty breathing

14. MECHANISM
IgE antibodies
leading mast
cell/degranulation
and causes
anaphylaxis

15. DIAGNOSIS
Test consists of
applying a minimal
amount of penicillin in
the subcutaneous
tissue. If the patient is
allergic a small allergic
reaction will appear at
the application site
after about 15 to 20
minutes.
SKIN TEST

16. ERYTHEMA
MULTIFORME
 Localized eruption of the
skin with minimal or no
mucosal involvement.
Lesions that appear within a
72-hour period and begin on
the extremities .
 Lesions remain in a fixed
location for at least 7 days
and then begin to heal .

17.  Second cause of drug-induced hypersensitivity reactions.
 Contraindicated in patients with a history of hypersensitivity
including asthma, angioedema, urticaria, or rhinitis.
 Hypersensitivity affects from 0.5% to 1.9%
 In patients with a definitive need for aspirin, desensitization
may offer.

18.  Aspirin-induced asthma (AIA) affects 10% of adults with asthma.
 After ingestion of ASA or an NSAID, an acute asthma attack
occurs within 3 hrs
 Hives
 Itchy skin
 Runny nose
 Red eyes
 Swelling of the lips, tongue or face
 Coughing, wheezing or shortness of breath
 Anaphylaxis — a rare

19.  Respiratory (serious)
 Cutaneous
 Systematic
 Type 1: aspirin-exacerbated respiratory disease
 Consists of asthma and rhinitis/nasal polyps.
 Patients between 30 and 40 years old, after respiratory tract
infection(often) ,and is more common in women.

20.  Type 2: cutaneous reactions
 Consists of urticaria and angioedema.
 Patients with chronic idiopathic urticaria ,are more sensitive to
aspirin, urticaria ( 21–30%.)
 Type 3: systemic reactions
 Occur within minutes of ingesting aspirin and consist of
hypotension, swelling, laryngeal oedema, generalized pruritis,
tachypnoea.

21. Hyper Sensitivity
Reactions via
Inhibition of the
Cyclooxygenase
Pathway

22.  Skin test with ASA-lysine have been negative.
 A clinical diagnosis, mostly on a clinical history and
assessment.
 The only definitive way to make a diagnosis is
through a provocative aspirin challenge
 Bronchial
 nasal routes
 oral

23.  Oral provocation Gold standard
 Bronchial provocation (L-lysine aspirin challenge)
 Safer
 Faster
 Less sensitive
 Nasal provocation
 Contraindicated from oral&bronchial (negative test)
 Predictive value is lower

24. ASA or NSAID-induced reactions
may be started with a dose lower
than 30 mg.
As soon as signs and symptoms of
reactions occur (20% decrease in
FEV1, rhinorrhea, ocular injection,
periorbital edema, stridor,) the
ASA challenge is stopped.

25. Morbilliform Drug
Eruption
Widespread pink-to-red flat spots or
raised bumps blanch with pressure.
Extremities the spots may appear ring-
shaped or hive-like giving a
polmorphous appearance. On the first
occasion, the skin rash usually appears
1-2 weeks after starting the drug.
However on re-exposure to the drug,
skin lesions appear within 1-3 days.

26.  0.09% of people experience a hypersensitivity reaction
 Frequency is much higher among people with HIV and AIDS.
 life-threatening reactions is less than 1/1000
 frequent T cell–mediated reactions.
 Allergic response to sulfonamide antibiotics is the arylamine group

27. Usually develop within one to three weeks after starting treatment
and resolve within one to two weeks
 fever
 painful macropapular rash
 lesions in mucous membranes,
 Cough
 sore throat or difficulty breathing
 hypotension

28.  Two regions of the sulfonamide antibiotic chemical structure are
implicated in the hypersensitivity reactions.
a) The N1 heterocyclic ring, which causes a type I reaction.
b) The N4 amino nitrogen that, in a stereospecific process, forms
reactive metabolites that cause either direct cytotoxicity or
immunologic response.
 The nonantibiotic sulfonamides lack both of these structures

30.  PATCH TEST
 INTRA DERMAL SKIN TEST

31. Patch tests
 For a skin patch test, the
allergen solution is placed
on a pad that is taped to the
skin for 24 to 72 hours
 Fairly good sensitivity
and specificity in
lamotrigine- and
carbamazepine-induced
DRESS

32. Intra dermal skin tests:
A small amount of the
allergen is injected just under
the skin
Substance does not cause a
reaction in the skin prick test
but is still suspected as an
allergen for that person
 SMX at a concentration of 80
mg/mL

33. Stevens Johnson
syndrome
Stevens-Johnson, typically
occur 7-14 days after initiation of
treatment
Begins with flu-like
symptoms, followed by a
painful red or purplish rash
that spreads and blisters.
The top layer of the affected
skin dies and sheds

34.  Educated on the generic names of the drugs they are allergic to and
other potentially cross-reacting drugs.
 Patient should be given a Medic Alert® card or bracelet
 skin test can detect penicillin.
 Genetic tests for abacavir
 Desensitisation who are sensitive to sulfonamide drugs
 Report any adverse reactions or unusual symptoms immediately.
 Careful and frequent monitoring, including symptoms and
laboratory measurements(liver function tests)