This document provides guidance on the management of drug reactions. It discusses the diagnosis and investigations of drug reactions, which can involve skin testing, drug elimination trials, and challenge tests. Skin testing methods like prick, patch and intradermal tests are outlined. The limitations and advantages of these tests are also covered. Treatment depends on reaction severity, and may involve withdrawal of suspected drugs, supportive care, corticosteroids, cyclosporine or IVIG. Prevention involves avoiding implicated drugs, pre-treatment skin testing if needed, or rapid desensitization therapy for essential drugs.

1. MANAGEMENT OF DRUG
REACTIONS
Page 1

2. DIAGNOSIS
• Drug reactions, apart from fixed drug eruption,
have non specific clinical features & it is often
impossible to identify the offending chemical with
certainty especially when a patient is receiving
many drugs simultaneously
Page 2

3. INVESTIGATIONS
• With mild asymptomatic eruptions, the history &
physical examination are often sufficient for
diagnosis
• With severe or persistent eruptions, further testing
may be required as follows:
1. Biopsy
2. Complete blood count with differential
3. Serum electrolytes
4. Antibody or immunoserology studies
5. Urinalysis, chest radiography for vasculitis
Page 3

4. Approach to a drug reaction
• The assessment of a potential drug adverse
effect includes :
1. Taking a careful history & proper clinical
examination
2. May involve a trial of:
• drug elimination
• Skin tests
• In vitro tests
• Challenge by re exposure(drug provocation
tests)
Page 4

5. Drug History
• Review the patient’s complete medication list ,
including prescription & OTC drugs
• Any previous adverse reactions to drugs/food
• Consider alternative etiologies (viral exanthems,
bacterial infections)
• Note any concurrent infections, metabolic
disorders, or immunocomprimise
• Note the interval between introduction of a drug
& onset of the eruption
Page 5

6. Drug Elimination
• Resolution of a reaction on withdrawal of a drug
is supportive incriminatory evidence but not
diagnostic
• Failure of a rash to subside on drug withdrawal
does not necessarily eliminates the possibility,
as traces of the drug may persist for long
periods & some reactions ,once initiated, may
continue for many days without re exposure to
the same drug
Page 6

7. Skin Testing
• Skin testing should be performed 6 weeks- 6
months after complete resolution of the reaction
• There are 3 types of skin testing:
1. PRICK TESTS- immediate hypersensitivity
reactions
2. PATCH TESTS- delayed hypersensitivity
reactions
3. INTRA DERMAL TESTS- immediate & delayed
hypersensitivity reactions
Page 7

8. PRICK TESTS
• Performed on the skin
of the volar aspects of
forearm with the
commercialized form
of the drug, but with
sequential dilutions
• Test reports are read
at 20 mins and at 24
hours
Page 8

9. PATCH TESTS
• Commercialized form of
the drug should be tested
at 30% in petroleum
jelly/water at the site most
effected in the initial
reaction
• Use lower concentrations
in severe adverse drug
reactions
• Read the test at day 2, 4
and preferably also at 1
week
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10. Page 10

11. INTRADERMAL TESTS
• They are performed
with sequential
dilutions (10-4,10-3,102,10-1) of 0.04 ml of a
pure sterile/injectable
form of the drug
• The test is read at 20
mins and at 24 hours
Page 11

12. Advantages
• Prick & Intradermal tests may be useful in
identification of patients who present with
immediate IgE hypersensitivity reactions to
certain drugs & thus may prevent anaphylaxis
(ex: penicillin & other beta lactam antibiotics
etc.)
• Drug Patch Tests are positive in 32-50% of
patients with a drug eruption, particularly of
value in maculopapular rashes , AGEP & FDE
• Patch test are of occasional use in SJS/TEN
Page 12

13. RESULTS
FALSE POSITIVE
FALSE NEGATIVE
• Can be due to an
excipient ( surfactant
polysorbate, emulsion
stabilizer, carboxy methyl
cellulose)
• Poor absorption through
skin
• Test is done too soon
after a reaction or too late
• A metabolite rather than
the substance
administered in the test is
the sensitizing antigen
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14. LIMITATIONS
• Usefulness of skin testing is limited by the fact
that the significant antigenic determinants are
unknown for most drugs
• Skin testing in not always safe as testing :
1. May induce a generalization of the drug
reaction
2. May lead to anaphylactic response
3. May lead to exfoliative dermatitis
Page 14

15. IN VITRO TESTS
• They are in trial stage and are not routinely used
for clinical purposes
• Various available tests are:
1. Basophil degranulation test
2. Histamine release test
3. Radioallergosorbent test
4. Leukocyte migration test
5. Lymphocyte transformation test
Page 15

16. DRUG PROVOCATION TESTS
• Defn: It is the controlled administration of a drug in order
to diagnose drug hypersensitivity reactions.
• DPT is widely considered to be the “gold standard” to
establish or exclude the diagnosis of hypersensitivity to a
certain drug
• DPTs are performed under medical surveillance.
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17. • Commercial preparation of the drug is administered
preferably by oral route at a starting dose which depends
on the type of drug, severity of drug hypersensitivity
reactions under investigation.
• Dosage is increased at regular intervals until the full
therapeutic dose is given or any severe adverse reaction
occurs
• DPT should never be performed on patients who have
experienced severe, life-threatening immunocytotoxic
reactions, vasculitic syndromes, exfoliative dermatitis,
erythema multiforme major/Stevens-Johnson syndrome,
drug induced hypersensitivity reactions (with
eosinophilia)/DRESS and toxic epidermal necrolysis
Page 17

18. TREATMENT OF DRUG ERUPTIONS
• Approach to the treatment of drug eruptions
depends on the severity of the reactions:
1. Mild conditions:( morbilliform rash, FDE, AGEP)
• Withdrawal of suspected drug
• Symptomatic treatment with emollients, mildmoderately potent topical corticosteroids &
systemic antihistamines
• If the patient is receiving multiple medications,
withdraw all medications, except the essential
ones & consider alternative , non cross reacting
drugs
Page 18

19. Management of severe drug reactions
1. Promptly discontinue any and all possible offending drugs
2. Admit the patient in an ICU or burns ward under aseptic conditions
3. Assess the condition of the patient to determine the prognosis
based on the SCORTEN score in cases of SJS/TEN
Page 19

20. Correct the fluid & electrolyte imbalance:
• Fluid loss and electrolyte imbalance should be
closely monitored and corrected
• The fluid requirement is calculated based on the
parklands formula & 3/4ths of this total amount is
given to a pt with TEN
Parkland’s formula = 4 ml/kg body wt × % BSA
involved according to the rule of nine
Page 20

21. Nutritional support:
• Patient should be allowed to eat a soft, easily
chewable diet if oral feeding is feasible
• If oral feeding is not possible, then nasogastric
tube feeding or parenteral feeding can be given
• Early and continuous feeding decreases the risk
of stress ulcers, reduces bacterial dislocation,
enterogenic infection
Temperature control:
• Should be maintained at 30-32° c to avoid heat
loss
Page 21

22. Wound care :
• Detached or detachable epidermis should be left
in position as a biological dressing & only the
denuded skin be covered with a dressing
• Condy’s compresses or petrolatum impregnated
gauzes can be used
• An air fluid bed / water bed may be used to make
the patient comfortable
Page 22

23. Ophthalmic care :
• 2 hourly instillation of eye drops ( saline or
antibiotic drops )
• Developing synechiae are disrupted by a blunt
instrument
ANTIBIOTICS:
• Are indicated if there is widespread epidermal
detachment
Page 23

24.  SPECIFIC TREATMENTS:
1. CORTICOSTEROIDS:
• Oral prednisolone (1-2 mg/kg/day) or parenteral steroids (
dexamethasone 8-16 mg daily or hydrocortisone) can be
started within the first 72 hours in a patient with limited
skin surface involvement to prevent wide spread diffusion,
and continue for 3-5 days followed by rapid tapering
• Role of corticosteroids is controversial
• Systemic corticosteroids may delay wound healing,
increase the risk of infection, mask early signs of sepsis,
and may precipitate gastrointestinal bleeding
Page 24

25. 2. CYCLOSPORINE:
• It acts by inhibiting the activated T lymphocytes,
macrophages & also interferes with the metabolism of
TNF-α and possesses anti apoptotic properties
• Cyclosporine interrupts the disease progression &
decreases the time taken for complete reepithelization
• Dose is 3-5 mg/kg/day oral or IV upto 2 weeks followed by
weaning over another 2 weeks
• Watch out septic complications and severe leukopenia
Page 25

26. 3. INTRAVENOUS IMMUNOGLOBULINS:
• Can be considered if pt is seen within 48-72 hrs of bulla
onset & in cases with active progressing lesions even
after 72 hrs
• Total dose is 2 gr/kg , which is given as 0.4 g/kg/day for 5
consecutive days
• Adverse effects are risk of thromboembolism, hemolysis,
vasomotor symptoms & anaphylactic reactions
• But the major limiting factor is its high cost
Page 26

27. PREVENTION OF DRUG ERUPTIONS
• Avoid drugs implicated in a previous reaction
• Where it is essential to readminister one of a group of
the drugs to a patient with previous history of a drug
eruption to related medication, then if possible
preliminary skin testing should be carried out to enable
identification of safe alternative therapy (under the cover
of oral corticosteroids and antihistamines to prevent
anaphylactic reaction)
• If no acceptable alternative for an essential drug is
available, then consider rapid desensitization therapy
Page 27

28. DESENSITIZATION THERAPY
• Defn: The induction of a state of unresponsiveness to a
compound responsible for a hypersensitivity reaction(
immediate IgE mediated reaction)
• It is a high risk procedure used only in patients in whom
alternatives are less effective or not available
• It is performed by administering increasing doses of the
medication over a short period of time ( from several hours
to a few days ) until the total cumulative therapeutic dose is
achieved & tolerated
• The starting doses range from 1/10000 to 1/100 of full
therapeutic dose( it is also determined by taking into
account the severity of previous reaction
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