CHAPTER 1

Epidemiology of Drug Allergy

REBECCA SAFF, MD, PHD

KEY POINTS

• Adverse drug reactions (ADRs) represent an important health concern, particularly with unpredictable hypersensitiv-
ity reactions, but accurate data on the prevalence of DHRs have been difficult to obtain, because of the difficulty in
classifying the type of reaction and the underlying mechanism.
• Cutaneous reactions are common, occurring in 2–10 per 1000 patients, and are frequently caused by antibiotics.
• Severe cutaneous adverse reactions (SCARs) are uncommon but can result in significant morbidity and mortality.
Anaphylaxis due to medications, particularly antibiotics, is more common in adults than in children and is associated
with more severe reactions, including fatal anaphylaxis.

Adverse drug reactions (ADRs) are defined by the World
Health Organization as any noxious, unintended, and
undesired effect of a drug that occurs at doses used for
prevention, diagnosis, and treatment.1 These are esti-
mated to account for 3%–6% of all hospital admissions
and to occur in 10%–15% of hospitalized patients.2 In
a national ambulatory care survey, 0.31% of visits were
because of adverse effects of medications, representing
an estimated 2.73 million visits annually.3 Cutaneous
reactions to drugs are among the most common clinical
manifestations of adverse drug events and had an annual
incidence of 2.26 per 1000 persons, with increasing inci-
dence in older adults.4 The actual incidence is likely even
greater, as physicians often either do not recognize ADRs
or attribute the symptoms to an underlying disease state.
Although some ADRs present as minor symptoms, many
are serious and can lead to death in about 0.2%–0.4% of
hospitalized patients.5 In addition, the cost of managing
ADRs can be high, whether they occur in the inpatient or
outpatient setting.
ADRs were originally classified into two types. Type
A ADRs are predictable and dose dependent, and they
comprise approximately 80% of reactions. Type A ADRs
include drug-induced toxicity, pharmacologic side effects,
and drug interactions, such as orthostatic hypotension
with antihypertensive medications or bleeding with war-
farin. Type B ADRs are unpredictable, dose independent,
and unrelated to the drug’s known pharmacology. Type B
ADRs make up 10%–15% of reactions and include drug
intolerance (an undesired drug effect produced by the
drug at therapeutic or subtherapeutic doses), idiosyncratic
reactions (uncharacteristic reactions that are not explain-
able in terms of the known pharmacologic effects of the
drug), and hypersensitivity reactions, which include both
immunologically and nonimmunologically mediated
events.6,7 Other types have now been added, including
chronic reactions related to both dose and time (Type C),
delayed reactions (Type D), effects due to withdrawal of
medication (Type E), and, most recently, the unexpected
failure of therapy (Type F).
The World Allergy Organization defines the term
hypersensitivity as objectively reproducible signs or
symptoms initiated by exposure to a defined stimulus
at a dose tolerated by normal persons and drug allergy
as a drug hypersensitivity reaction (DHR) with a dem-
onstrated immunologic mechanism.8 Therefore, DHRs
would include immune-mediated or allergic reactions as
well as nonimmune-mediated reactions, although these
terms are often used interchangeably in the literature
(Table 1.1). The 2010 Drug Allergy Practice Parameters
defines drug allergy as “an immunologically mediated
response to a pharmaceutical and/or formulation (excip-
ient) agent in a sensitized person.” Drug allergy may
be further classified by the Gell-Coombs classification
as follows: IgE mediated (type I), cytotoxic (type II),
immune complex (type III), and cellular mediated (type
IV).9 Although Gell-Coombs classification is helpful, it
does not account for many common clinical manifesta-
tions. The classification of drug allergies is limited by our
understanding of the underlying mechanisms.
Immune-mediated reactions include IgE-medi-
ated events, such as anaphylaxis, and T cell–medi-
ated events, including severe cutaneous adverse
reactions (SCARs). DHRs can also include reactions
that have an immunologic basis but do not require
sensitization, such as direct mast cell activation by

1
2 Drug Allergy Testing

TABLE 1.1
Classification of Adverse Drug Reactions
Adverse drug Type A (predictable) Drug-induced toxicity
reactions Pharmacologic side effects
Secondary side effects
Drug interactions
Type B (unpredictable) Drug intolerance
Idiosyncratic
Drug hypersensitivity reactions Immunologic
• IgE mediated
• T cell mediated
Non-immunologic
• Direct mast cell activation

intravenous contrast or vancomycin. Distinguishing
immune-mediated from nonimmune-mediated reac-
tions can be difficult, as the clinical findings (such as
urticaria from a nonsteroidal antiinflammatory drug
[NSAID]) can be similar and have multiple possible
underlying mechanisms.
Given the difficulty of defining the type of reac-
tion and the underlying mechanism, it has been hard
to determine the prevalence of DHR. Most studies are
performed retrospectively, and the reactions are based
primarily on clinical characteristics such as the symp-
toms and temporal relationship between drug use and
disease onset. There are very few studies that confirm
diagnosis of DHRs with in vivo or in vitro tests, and
these are often done in small referral populations.
DRUG HYPERSENSITIVITY REACTIONS
There are a number of studies that have attempted
to determine the rate of overall drug hypersensitivity
events in specific clinical settings using skin manifesta-
tions as a marker of reaction. One of the first major
studies that attempted to evaluate the prevalence of
drug allergy in a prospective population was the Bos-
ton Collaborative Drug Surveillance Program. This was
a prospective inpatient study initially reported in JAMA
in 1976 which included 565 drug-attributed skin reac-
tions that occurred among 22,227 monitored patients.10
Allergic skin reactions occurred in slightly over 2% of
hospitalized medical patients, and the primary cause
was β-lactam antibiotics (52 of 1000 patients receiving
ampicillin and 16 of 1000 patients receiving penicillin
G). Because the average patient received about eight
drugs, the rate of reactions per course of drug therapy
was approximately 3 in 1000 courses. A follow-up study
of the same population reported in 1986 confirmed the
reaction rate of 2.2% of patients, with the primary cause
being β-lactam antibiotics.11 Other prospective studies
found rates of approximately 3 reactions per 1000 hos-
pitalizations in inpatients, although these were limited
to cutaneous reactions.12–18 The most common cause
of a cutaneous reaction in these studies was antibiotics,
particularly β-lactam antibiotics, which were the impli-
cated drug in 20% of reactions.
A 2003 study, in France, of patients with cutaneous
allergic reactions verified by a dermatologist determined
a prevalence of 3.6 per 1000 hospitalized patients.18
Although the reactions were primarily exanthematous,
they were responsible for hospitalization in 18% of the
reacting patients and increased the duration of hospi-
talization in 14%. A 2006 prospective study in Mexico
showed a prevalence of 7 per 1000 hospitalized patients,
most frequently morbilliform rash, although 13% of the
patients with reactions were identified as having a severe
drug reaction.19 An incidence of 2.2 per 1000 was found
in a prospective study of Chinese patients, with mor-
billiform exanthema seen in 40% of patients.20 In all
these studies, antibiotics were the most common cause.
Overall, the literature seems to suggest the incidence of
cutaneous ADR ranges from 2 to 10 per 1000 patients,
although only a small percentage of these are severe.
DHRs in the ambulatory setting are not as well stud-
ied as reactions that occur in the inpatient setting. In
a review of ambulatory-based studies of adverse drug
events, the overall rate of ADRs in the ambulatory setting
was 15 per 1000 person-months, and skin symptoms,
such as rash, itching, or edema, which can be associated
with hypersensitivity reactions, were seen in 6.8% of the
ADRs.21 Using the National Ambulatory Care Survey
(1995–2000) and National Hospital Ambulatory Care
Survey (1995–2000), a rate of more than 100,000 out-
patient visits annually for severe cutaneous reactions and

about 2 million visits for likely drug-related immediate
hypersensitivity reactions was found.22 From these data,
it was estimated that there are more than 500,000 outpa-
tient visits for drug eruptions and drug allergies annually.
Given the difficulty of identifying true cases of DHRs
in a population, a number of methods have been used to
try to determine the true incidence. An electronic inpa-
tient drug allergy reporting system was used to identify
reactions in a general hospital in Singapore, which were
then verified by an allergist.17 Using this method, the inci-
dence of drug allergy was 4.2 per 1000 hospitalizations.
The rate of new DHRs during the course of inpatient treat-
ment was 2.07 per 1000 hospitalizations with a mortality
of 0.09 per 1000. Antimicrobials and antiepileptic drugs
comprised 75% of the drug allergies reported. Cutane-
ous eruptions were the most common clinical presenta-
tion (95.7%), with maculopapular rash being the most
common, and systemic manifestations occurred in 30%.
However, underreporting was a problem and this likely
underestimates the true incidence of DHRs. In Korea, a
mandatory reporting system was used to identify DHRs,
which were verified by allergists.23 The incidence of DHRs
was 1.8 per 1000 hospitalizations, with 70% cutaneous
symptoms and 30% with systemic symptoms.
Billing codes have also been used to try to deter-
mine the rate of DHRs in large populations. Billing
codes rely on heterogeneous coding of physicians and
staff and can therefore miss potential reactions but
could provide population data, allowing for a better
understanding of the true burden of disease. Using bill-
ing codes validated by a chart review to identify aller-
gic drug reactions, the estimated frequency of allergic
drug reactions was found to increase from 0.49% of
emergency department (ED) visits in 2001 to 0.94%
in 2012.24 Most reactions were attributed to antibiotics
(42%), intravenous contrast (7%), and NSAIDs (6%).
Validated codes could allow for better determination of
incidence of DHRs using large datasets.  organ involvement. It is reported to occur in 1 in 1000
SEVERE CUTANEOUS ADVERSE
REACTIONS
Severe cutaneous adverse reactions (SCARs) are delayed
in onset and are mediated by CD4+ and CD8+ T lym-
phocytes. These include Stevens-Johnson syndrome
(SJS), toxic epidermal necrolysis (TEN), drug-induced
hypersensitivity syndrome or drug rash with eosino-
philia and systemic symptoms (DIHS/DRESS), and
acute generalized exanthematous pustulosis (AGEP).
These reactions are rare but have severe morbidity
and high mortality rates. The estimated morality rate
is 10% for SJS, 30% for SJS/TEN, and almost 50% for
TEN, and drugs are known to be the most common
CHAPTER 1  Epidemiology of Drug Allergy 3
cause of reactions.25,26 As these reactions are primar-
ily diagnosed clinically, true estimates are difficult to
obtain. Because of the rarity of these reactions, with an
incidence of 1.4–6 per million person-years, most data
come from large retrospective studies.2
Both SJS and TEN are characterized by large areas of
necrotic epidermal detachment and mucosal erosions
and differ only in the amount of body surface areas
involved; they are considered a spectrum of the same dis-
order. Large registries have found that the time to onset is
typically within 4 weeks, although this varies depending
on the culprit drug.27,28 Antibiotics and antiepileptic med-
ications are the most common culprits. In a large retro-
spective study of a European registry (EuroSCAR), the use
of antibacterial sulfonamides, anticonvulsant agents, oxi-
cam NSAIDs, allopurinol, chlormezanone, and corticoste-
roids were associated with increased risk of SJS/TEN.29 In
2008, a follow-up study in this cohort not only confirmed
increased risk of SJS/TEN with antiinfective sulfonamides,
allopurinol, carbamazapine, phenobarbital, phenytoin,
and oxicam-NSAIDs but also reported increased risk asso-
ciated with nevirapine and lamotrigine.28 In Japan, drugs
were associated with 69% of cases of SJS and all cases of
TEN, and the most common culprits were anticonvul-
sants, antibiotics, and NSAIDs.30
A recent report of the prevalence of SJS/TEN caused
by medications in a large academic medical center in
the United States found a rate of 375 patients per mil-
lion, and antibiotics, particularly penicillins, cephalo-
sporins, and sulfonamides, as well as macrolides and
quinolones, were the most common culprits, followed
by antiepileptics (particularly lamotrigine, phenytoin,
carbamazepine, and phenobarbital) and NSAIDs.31
DIHS/DRESS is a rare, severe, and potentially fatal
cutaneous ADR characterized by generalized maculo-
papular eruptions or erythroderma, high fever, lymph-
adenopathy, eosinophilia, atypical lymphocytes, and
to 10,000 exposures, and its mortality is approximately
10%.32,33 Aromatic antiepileptic drugs were the first
described culprit medications, but many other drugs
have been reported to be associated, including allo-
purinol, sulfonamides, dapsone, and minocycline.34
The estimated risk at first or second prescription of
an aromatic antiepileptic drug is 1–4.5 in 10,000.35
In an Indian cohort, the most common culprits were
aromatic anticonvulsants, lamotrigine, minocycline,
salazopyrine, and dapsone.36 In a large European
case series, antiepileptic drugs were involved in 35%,
allopurinol in 18%, antimicrobial sulfonamides and
dapsone in 12%, and other antibiotics in 11%.37 Gly-
copeptides have been shown to be a common culprit in
some cohorts, particularly vancomycin.38,39
4 Drug Allergy Testing
AGEP is an acute drug reaction characterized by the
development of numerous small, nonfollicular, sterile
pustules accompanied by leukocytosis and fever. It has
been associated with aminopenicillins, pristinamycin,
quinolones, hydroxychloroquine, sulfonamide antibi-
otics, terbinafine, and diltiazem.40 AGEP is rare, with an
incidence of one to five patients per million per year.41
The EuroSCAR study found a mean age of 56 years and
a male:female ratio of 0.8:1.40 The predominance in
women was also seen in case series from Asia.42  1 in 5000, although this varies by country.2 The most
ANAPHYLAXIS
Anaphylaxis is a rapid, life-threatening hypersensitivity
reaction, typically representing an IgE-mediated reaction.
The incidence of anaphylaxis has been increasing over
time, and is estimated to be 50–100 cases per 100,000
person-years.43 Anaphylaxis is most commonly caused by
foods in pediatric populations, but drugs are a significant
trigger in older populations. In retrospective reviews of
patients treated in the emergency room for anaphylaxis,
drugs were the cause of anaphylaxis in 36% of cases in
Italy, 28% in Australia, and 46% in Belgium.44–46 In con-
trast, drugs were found as a cause in 5% of pediatric cases
of anaphylaxis seen in the emergency room in studies in
Australia.47,48 The European Anaphylaxis Registry also
found that only 5% of reactions were caused by medica-
tions in children, and these were predominantly in ado-
lescents, with antibiotics and analgesics being the most
common culprits.49 A study using data from ED visits in
Florida used a combination of billing codes to identify
patients with drug-related anaphylaxis, finding that adults
had twice as much relative risk as children.50 A study in
children seen in the ED for drug-related anaphylaxis, using
a combination of drug-specific billing codes and billing
codes for anaphylaxis, symptoms of anaphylaxis, or shock,
found a medication-induced anaphylaxis rate of 1.6 per
100,000 among children.51
In a retrospective review of acute anaphylaxis in adults
resulting in admission, drugs, particularly antibiotics and
NSAIDs, were the most common cause.52 Patients with
drug-induced anaphylaxis were older and more often
had cardiovascular symptoms. Drugs were identified as
the cause of anaphylaxis in 50% of cases in a retrospec-
tive review in Thailand, with 37% of cases occurring dur-
ing hospitalization.53 In a study of anaphylaxis occurring
during admission in China, 89.8% of cases were triggered
by medications, specifically antibiotics in 29.6%, radio-
contrast media in 16.7%, and chemotherapy in 11.1%.54
Antibiotics are most commonly implicated in ana-
phylaxis, particularly β-lactam antibiotics. IgE-mediated
reactions occur in 0.04%–0.015% of penicillin-treated
subjects, and anaphylaxis occurs in approximately
0.001%.55 NSAIDs and radiocontrast media are also
important causes of anaphylaxis, although these are
predominantly non-IgE mediated. NSAIDs (25.5%)
and antibiotics (23.5%) were the most common cause
of drug-induced anaphylaxis in a study in an emer-
gency room in Hong Kong.56
Drugs are an important cause of anaphylaxis in the
perioperative period, and the incidence of hypersen-
sitivity reactions during anesthesia is approximately
common culprits identified are antibiotics and neu-
romuscular blocking agents, with striking differences
between countries.57–59 In France, the most common
causes of anaphylaxis have consistently been neuro-
muscular blocking agents, latex, and antibiotics.60,61
In the United States, antibiotics are the more common
culprit, particularly cefazolin.57,62
Death from anaphylaxis is a rare event and occurs
in only 0.12 to 1.06 deaths per million person-years,
although medications have been associated with more
severe reactions and have been found as one of the most
common causes of fatal anaphylaxis.63,64 In a study of
anaphylaxis-related deaths in the US National Mortal-
ity Database using billing codes to identify patients,
58.8% of the 2458 anaphylaxis-related deaths were
due to medications, and there was a significant increase
over the 12 year study period, with antibiotics account-
ing for 40% of the cases in which a drug was specified.65 
PEDIATRIC DRUG ALLERGY
Although the reported incidence of ADRs is lower in
the pediatric populations as compared with adults,
they remain an important consideration. The overall
incidence of ADRs was 10.9% in hospitalized children
and 1.0% in outpatient children with a rate of hospital
admission due to ADRs of 1.8%.66 A review of ADRs in a
children’s hospital found that 0.4%–10.3% of all pediat-
ric hospital admissions were ADR-related (2.9% overall
incidence) and that 0.6%–16.8% of all children exposed
to a drug during hospital stay experienced an ADR.67
Antibiotics and antiepileptics were the most frequently
reported therapeutic class associated with ADRs in the
inpatient setting, and antibiotics and NSAIDS were fre-
quently reported as associated with ADRs in the outpa-
tient setting.67 These studies did not further characterize
ADRs into allergic and nonallergic. A 10-year retrospec-
tive review of ADRs at a pediatric hospital categorized
ADRs into pharmacologic or allergic/idiosyncratic.68 The
overall incidence was 1.6%, and 51% were allergic/idio-
syncratic. Similar to adults, antibiotics (33%) were the
most common drug class associated with ADRs, followed
by narcotic analgesics (12%) and anticonvulsants (11%).

Patients who experienced ADRs before hospital admis-
sion, or who reacted to medications during surgery, were
more likely to experience severe reactions. Of these severe
reactions, 40% were from chemotherapeutic agents and
24% were hypersensitivity reactions to anticonvulsants
and resulted in serious or fatal ADRs.  with increased ADRs and correlates with a decrease
LIMITATIONS IN DIAGNOSIS
Reported DHRs are common in the medical record
and are often overdiagnosed because of false asso-
ciation of symptoms with medications, improper
documentation, and incorrect classification. How-
ever, reactions may also be underreported and under-
diagnosis can lead to serious adverse consequences.
A predictive model for diagnosis of ADRs based on
variables in the clinical history estimated true ADRs to
occur in 20% of patients with reported allergies and
ruled out possible allergic reactions in 52%, although
mathematical modeling has limitations.69 A study
of over 1300 immediate DHRs in France in which
the authors confirmed the reaction with skin testing
and drug provocation tests found that only 17.6% of
patients were positive for immediate hypersensitiv-
ity reactions.70 The drugs responsible were β-lactams
(30.3%), aspirin (14.5%), other NSAIDs (11.7%),
paracetamol (8.9%), macrolides (7.4%), and quino-
lones (2.4%). A Spanish study of almost 5000 DHRs,
were carefully reviewed and the mechanism deter-
mined using in vivo and in vitro testing, confirmed
allergic cause in one-third of cases.71 Before evalua-
tion, based on clinical history, 37% of episodes were
attributed to NSAIDS, 29.4% to β-lactams, 15% to
non-β-lactam antibiotics, and 18.4% to other drugs.
Following evaluation, over 37.4% were found to have
an allergic cause with hypersensitivity to multiple
NSAIDs and β-lactams predominating.
Antibiotics represent the most common cause of
DHRs, with penicillin as the most common anti-
biotic causing allergy and reported in about 8% of
individuals using healthcare in the United States.72
However, after formal evaluation, greater than 90%
of patients can tolerate penicillins.73,74 There are
many causes for this discrepancy, including mis-
classification of the original reaction as well as the
known loss of sensitivity over time. Strategies to
evaluate reported penicillin allergy are being evalu-
ated, and there is evidence to show that penicil-
lin allergy increases hospital stay, cost of care, and
the use of broader-spectrum antibiotics, as well as
increased Clostridium difficile, methicillin-resistant
Staphylococcus aureus, and vancomycin-resistant
enterococci prevalence.75,76 Penicillin skin testing
CHAPTER 1  Epidemiology of Drug Allergy 5
can decrease the use of broad-spectrum antibiotics
and may potentially decrease the cost of care.73,74
Guidelines to increase penicillin skin testing and
the use of β-lactams in patients with reported allergy
have shown that appropriate use is not associated
in alternative antibiotic exposure.73,77 
RISK FACTORS
Reactions to drugs are complex responses that are influ-
enced by environmental factors, patient characteris-
tics, and properties of the drug itself. Risk factors for
cutaneous ADRs include viral infections, particularly
human immunodeficiency virus (HIV), connective tis-
sue disease including systemic lupus erythematosus,
viral and autoimmune hepatitis, and non-Hodgkin’s
lymphoma.18,19 Certain classes of drugs are associated
with a higher frequency of reaction as they can act as
haptens or prohaptens or bind covalently to immune
receptors, increasing the risk of reaction.
Females have been shown to develop DHRs more
frequently than males. Overall, females appear to be
more affected than males.71,78,79 In a study of allergy
consults, there were twice as many female consults
for drug allergy as male consults.80 As previously dis-
cussed, DHRs are more common in adults than in
children. Family history of drug allergy is a risk factor
for reactions, and ethnicity and genetics appear to be
increasingly important as we gain more insights into
the mechanisms of the reactions. 
GENETICS
Genetic factors that influence drug allergy are under
intense investigation but are still largely unknown. The
best understood mechanism is in SCAR, particularly
SJS/TEN, as the mechanism is understood to involve
the presentation of antigen in HLA to activate T cells.
Given that the frequency of HLA types varies in ethnic
populations, this has led to a better understanding of
increased risk of SJS/TEN in certain populations with
certain drugs. In 1982, the HLA-Bw44 antigen was
found to be associated with ocular involvement in Ste-
vens-Johnson in a white population.81 Since that time,
HLA associations have been described to a number of
drugs.
HLA-B*5801 has been clearly associated with allo-
purinol in both SJS/TEN and DIHS in a number of
populations, particularly SJS/TEN in Han Chinese from
Taiwan.82 This was subsequently seen in multiple popu-
lations, including Japanese and Europeans.83,84 A meta-
analysis found increased risk of allopurinol-induced
6 Drug Allergy Testing
SJS/TEN in both Asian and non-Asian populations with
HLA-B*5801, although the gene appears to be neces-
sary but not sufficient, and research continues into
other genetic factors that might be involved.85
HLA-B*15:02 was strongly associated with carba-
mazepine-induced SJS/TEN in Han Chinese popula-
tion.82 The association has been validated in many
populations in Southeast Asia, including Thailand,
Hong Kong, and India.86–88 Genetic screening of HLA-
B*1502 before the use of carbamazepine for patients
with Asian ancestry is recommended by US Food and
Drug Administration.
One of the best understood genetic predispositions
to drug allergy is seen in abacavir hypersensitivity reac-
tions. Abacavir causes a hypersensitivity reaction that
occurs in 5%–8% of patients during the first 6 weeks of
treatment resulting in fever, rash, and gastrointestinal
and respiratory symptoms. Immediate discontinuation
is required, and continued exposure or rechallenge can
lead to more severe and potentially life-threatening
reactions. In 2002, an association with a specific HLA
allele was reported.89,90 This was confirmed in multiple
subsequent studies. In 2008, the utility of screening
for HLA-B*5701 before starting abacavir was clearly
demonstrated, and screening is now a standard clinical
practice.91,92
In IgE-mediated reactions, studies reported in
multiple populations have shown that genes that are
involved in IgE production, particularly those of the
IL-13 and IL-4 pathways, are important in β-lactam
allergy.93,94 Polymorphisms in the IL-4/IL-13 axis and
related cytokines were reported to increase the risk of
β-lactam-mediated reactions.95 A strong association
seen in β-lactam allergy is with a polymorphism in
galectin-3, which binds IgE.96 Variants in genomewide
association studies in β-lactam allergy have shown the
likely importance of HLA-DRA.97 
CONCLUSIONS
ADRs represent an important health concern, particu-
larly with unpredictable hypersensitivity reactions,
but accurate data on the prevalence of DHRs have been
difficult to obtain, because of the difficulty in classify-
ing the type of reaction and the underlying mecha-
nism. Cutaneous reactions are common, occurring in
2–10 per 1000 patients, and are frequently caused by
antibiotics. SCARs are uncommon but can result in
significant morbidity and mortality. Anaphylaxis due
to medications, particularly antibiotics, is more com-
mon in adults than in children and is associated with
more severe reactions including fatal anaphylaxis.
Risk factors include environmental factors, proper-
ties of the drug itself, and patient characteristics with
pharmacogenetics increasingly recognized and pro-
viding an opportunity for screening. Moving forward,
standardizing terminology, improving our under-
standing of the immune mechanism, and validating
diagnosis with in vitro and in vivo testing will allow
for a better of understanding of DHRs and their pre-
vention and treatment.
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