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162 Textbook of Diagnostic and Therapeutic Procedures in Allergy
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Schmitt, J., Langan, S., Deckert, S., Svensson, A., von Kobyletzki, L., Thomas, K. et al. 2013. Assessment of
clinical signs of atopic dermatitis: a systematic review and recommendation. J. Allergy Clin. Immunol.
132(6): 1337–1347. doi:10.1016/j.jaci.2013.07.008.
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Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European Task Force on Atopic
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Swartz-Lamkins, and chlorazol black E fungal stains. Cutis 92(6): E8–10.
Sicherer, S. H. and Sampson, H. A. 1999. Food hypersensitivity and atopic dermatitis: pathophysiology,
epidemiology, diagnosis, and management. J. Allergy Clin. Immunol. 104(3 Pt 2): S114–122. doi:10.1016/
s0091-6749(99)70053-9.
Sidbury, R., Tom, W. L., Bergman, J. N., Cooper, K. D., Silverman, R. A., Berger, T. G. et al. 2014. Guidelines of care
for the management of atopic dermatitis: Section 4. Prevention of disease flares and use of adjunctive therapies
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Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD): The development and reliability
testing of a novel clinical outcome measurement instrument for the severity of atopic dermatitis. J. Am. Acad.
Dermatol. 83(3): 839–846. doi:10.1016/j.jaad.2020.04.104.
Singh, A. M., Anvari, S., Hauk, P., Lio, P., Nanda, A., Sidbury, R. et al. 2022. Atopic dermatitis and food allergy:
best practices and knowledge gaps-work group report from the AAAAI allergic skin diseases committee and
leadership institute project. J. Allergy Clin. Immunol. Pract. doi:10.1016/j.jaip.2021.12.037.
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Strid, J., Hourihane, J., Kimber, I., Callard, R. and Strobel, S. 2005. Epicutaneous exposure to peanut protein prevents
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2222.2005.02260.x.
Sukanto, H., Nater, J. P. and Bleumink, E. 1981. Influence of topically applied corticosteroids on patch test reactions.
Contact Dermatitis 7(4): 180–185. doi:10.1111/j.1600-0536.1981.tb04038.x.
Tam, I. and Yu, J. 2020. Allergic contact dermatitis in children: recommendations for patch testing. Curr. Allergy
Asthma Rep. 20(9): 41. doi:10.1007/s11882-020-00939-z.
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in patients referred for patch testing: Retrospective analysis of North American Contact Dermatitis Group data,
1994–2016. J. Am. Acad. Dermatol. 84(4): 953–964. doi:10.1016/j.jaad.2020.07.020.
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4(5): 379–385. doi:10.1097/00130832-200410000-00009.
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Chapter 7
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Drug Allergy
Saad Alshareef,* William Bermingham, Rashmeet Bhogal, Mohamed Omar and
Mamidipudi Thirumala Krishna
Introduction
Adverse drug reactions occur in around 15% of hospitalized patients and up to 25% of the patients
in ambulatory clinics. Drug allergy is less common as it accounts only for less than 10% of all
adverse drug reactions (Thong and Tan 2011). The prevalence of penicillin allergy labels has been
estimated to be between 5.9% and 10% in the UK and the USA’s population studies and up to 15%
of hospitalized patients. However, a number of studies have shown that, following comprehensive
allergy tests, 90–95% of penicillin allergy labels are inaccurate (West et al. 2019; Macy and Contreras
2014; Lee et al. 2000; National Institute for Health and Care Excellence 2014).
Adverse drug reactions can be broadly classified as either predictable (Type A) or
unpredictable (Type B) (Table 1). Predictable reactions are dose-dependent and related to a
known pharmacologic action of the drug. Common examples include drug toxicity, side effects
and drug interactions. The reaction could be due to an overdose or binding to “off-target”
receptors. Whereas unpredictable reactions are dose-independent and are unrelated to known
pharmacologic actions of the drug. Unpredictable reactions can be subdivided into drug intolerance,
drug idiosyncrasy, pseudoallergic reaction and hypersensitivity reactions (HSRs).
Gell-Coombs’ classification of hypersensitivity links the clinical presentation to an underlying
immunological mechanism (Table 2). A more recent classification emphasized the importance of
other pathomechanisms of delayed HSRs (Pichler 2019). In addition to allergic immune reactions
that occur secondary to antigens, there are also p-I (pharmacological interaction with immune
receptors) and pseudoallergic reactions (Table 3). In p-I mediated reaction, the drug binds directly to
the immune receptor and leads to T-cell mediated reactions, such as maculopapular exanthema, drug
1
International training fellow, University Hospitals Birmingham NHS Foundation Trust.
2
MRCP, FRCPath. Specialist trainee in Immunology. University Hospitals Birmingham NHS Foundation Trust.
3
Antimicrobial and Research Pharmacist Prescriber. Pharmacy department, University Hospitals of Birmingham NHS
Foundation Trust.
4
MRCP, FRCPath. Consultant Allergist and Immunologist. University Hospitals Birmingham NHS Foundation Trust.
5
FRCP, FRCPath, DNB. Consultant Allergist and Immunologist, University Hospitals Birmingham NHS Foundation Trust.
Honorary Professor in Allergy, Clinical Immunology and Global Health Institute of Immunology & Immunotherapy and
Institute of Clinical Sciences the University of Birmingham. Head of Postgraduate School of Pathology, West Midlands
Health Education England.
Emails: william.bermingham@nhs.net; rashmeet.bhogal@uhb.nhs.uk; Omar.Mohamed@uhb.nhs.uk; Thirumala.Krishna@
uhb.nhs.uk
* Corresponding author: saadmd3@gmail.com
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Table 1. Types of drug reactions.
Type of Adverse
Drug Reactions
A: Predicable
B: Unpredictable
Classication of Immunologically Mediated Drug Hypersensitivity Reactions (Gell-Coombs Classication)
Types Mechanism Notes/Symptoms Selected Examples
1 IgE mediated
hypersensitivity
reactions
2 Cytotoxic reactions Antibodies, in this case IgM or IgG,
3
Immune complex
reactions
4 Cell
mediated reactions
Features Examples
– Dose-dependent
– Due to the pharmacologic actions of
the drug
– Occurs in healthy individuals
– Dose-independent
– Unrelated to the pharmacologic actions of
the drug
– Some reactions occur in susceptible
individuals
Table 2. Gell-coombs classification of drug hypersensitivity.
Urticarial rash, pruritus, and wheezing.
Severe symptoms include hypotension,
laryngeal edema, and anaphylaxis.
(Within minutes-few hours depending
on the route of administration).
bind to cell bound antigens leading to
complement activation leading to cell
destruction.
Drugs can alter the cell surface,
generating new epitopes that could be
the target of these antibodies.
Antigen-antibody complexes deposition
causes complement activation and more
damage.
Fever, rash, urticaria, lymphadenopathy,
and arthralgia. It occurs few weeks after
exposure to the oending drug.
Can be subdivided into four categories
depending on the type of eector cells
recruited:
→ monocytes (IVa)
→ eosinophils (IVb)
→ CD4 or CD8 T cells (IVc)
→ neutrophils (IVd)
Drug toxicity
Side effects
Drug interactions
– Drug allergy
– Pseudoallergic reactions
– Drug intolerance:
• Example: aspirin-induced tinnitus
– Drug idiosyncrasy:
• Usually due to underlying abnormalities of
metabolism, excretion, or bioavailability
• Example: primaquine induced hemolytic
anemia in G6DP–deficient individuals
→ Anaphylaxis to penicillin, ciprooxacin,
rocuronium, atracurium, etc.
→ Haemolysis caused by
methyldopa and penicillin.
→ Thrombocytopenia caused by quinidine.
These reactions are very rare and not
amenable to skin tests.
→ Phenytoin induced vasculitis.
→ Penicillin induced serum sickness.
→ Contact dermatitis.
→ Allopurinol induced DRESS.
→ Carbamazepine induced
→ SJS/TEN.
→ Quinolones-induced AGEP
rash with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome SJS/Toxic
epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP) and hepatitis.
Some of these are mediated by delayed HSRs (HSRs; Type-4; see Table 2). In pseudoallergic
reactions, the drugs bind directly to effector cells or inflammatory cells and induce symptoms
depending on the receptor they bind to. For example, when a drug binds directly to the MRGPRX2
receptor on mast cells, it induces stimulation of the mast cells and release of mediators that can
cause anaphylaxis-like symptoms without the need for prior sensitization. Several agents are known
Table 3. Immune pathomechanism and classification of drug hypersensitivity.
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Drug Allergy 165
Type B Drug
Reactions
Allergic Immune
p-i
Pesudoallergic
(Pichler 2019)
Mechanism Example
– Formation of new antigen by the binding between the drug
or drug metabolite to proteins (hapten-protein complex)
– “Both” humoral and/or cellular immune responses can be
involved
– Drugs bind directly to immune receptors proteins
– Results in a T-cell mediated reactions which could have
features of both hypersensitivity and/or autoimmunity
– This is an example of a drug binding an off-target receptor
which leads to unwanted T-cell stimulation
– Some of these reactions occur in carriers of certain
HLA alleles (For example, abacavir-induced severe
hypersensitivity in carriers of HLAB*5701 allele)
– Drug directly activates effector inflammatory cells, and
hence the humoral and cellular immune systems are not
involved
– Dose dependent
– Prior sensitization is not required.
Any type of Coombs and Gell’s
hypersensitivity classification
DRESS
SJS/TEN
AGEP
– Some drugs can bind and
activate the MRGPRX2 on
mast cells, which leads to mast
cells activation and release of
mediators
– Examples include some of
the NMBA, e.g., atracurium,
and uoroquinolones, e.g.,
ciprooxacin
to cause such reactions, such as opiates, radiocontrast media, some neuromuscular blocking agents
and vancomycin.
Drug Hypersensitivity
Drug HSRs are immunologically mediated responses. Most are Type-1 or Type-4 HSRs, and a
small proportion is deemed secondary to p-I or pseudoallergic mechanisms (Demoly et al.
2014). The reactions are usually against active ingredients of the drug and rarely to excipients.
The reaction typically occurs following prior sensitization, which results in the production of
drug-specific antibodies, T cells or both.
History
Most of the available investigations have limited utility due to unknown predictive values, therefore
allergists rely on a systematic clinical history and scrutiny of available documentation in the
diagnostic process. Standard documentation of the drug reaction should include the following:
1. The name of the medication
2. The clinical indication for the medication
3. How long ago did the reaction occur?
4. The systems (e.g., cutaneous, respiratory and gastrointestinal) involved in the reaction and its
characteristics?
5. When during the treatment course did the reaction occur?
6. Was the patient taking concurrent medications at the time of the reaction? If yes, then what
are the medications? For how long he has been taking these medications? And is he still
taking them?
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7. The therapeutic management of the reaction?
8. Had the patient taken the same or a cross-reacting medication before the reaction?
9. Has the patient been re-exposed to the same or similar medication since the reaction?
10. Were any investigations done to evaluate the reaction?
11. Does the patient have an underlying condition (e.g., chronic spontaneous urticaria, mastocytosis)
that enhances the risk of reactions to certain medications?
Physical Examination
It is important to document all the physical signs that were observed during the allergic reaction.
Different cutaneous manifestations can accompany any drug reaction. Recognizing the pattern,
the timing and the morphology of the skin involvement is vital to reach an accurate diagnosis.
While urticaria and angioedema are common features of drug HSRs, bullous exanthem, mucosal
involvement and systemic symptoms are suggestive of more severe reactions, i.e., SJS and TEN.
Non-blanching petechiae or purpura may suggest “drug-induced vasculitis.”
Differential Diagnosis
Not every rash that occurs while the patient is taking a drug necessarily represents a drug allergy.
Rash that accompanies infections or chronic spontaneous urticaria is frequently misdiagnosed as a
drug allergy.
Infection
Different bacterial and viral infections are associated with a rash which could be precipitated
by commencing antimicrobials. A typical example is amoxicillin-induced rash in patients with
Epstein-Barr virus (EBV) infection. Patients typically lack other symptoms of allergy, pruritus,
mucocutaneous swelling, wheezing or hemodynamic instability. The rash is typically mild and
self-limiting. This is not an allergic reaction and patients are likely to tolerate future courses of the
antibiotic in the future.
Chronic Idiopathic Urticaria
Patients with chronic idiopathic urticaria experience urticarial rash randomly which can be triggered
by different factors including infections. Patients may notice urticarial rash when they have an
infection and start antibiotics and attribute the rash to drug allergy. Usually, these patients will report
similar episodes of spontaneous rash without taking on the drug.
Investigations
Serum Tryptase
An elevated acute serum tryptase level indicates mast cell activation. Samples ideally should be
collected within between 15 minutes and 3 hours (levels peak 1–2 hours) after symptoms onset
and should be rechecked > 24 hours after initial presentation. Baseline tryptase levels are usually
persistently elevated in patients with clonal mast cell disorders (e.g., systemic mastocytosis).
Discrimination between mature β-tryptase and total serum tryptase leads to greater specificity in
the diagnosis of anaphylaxis. Acute serum tryptase ≥ (2 + 1.2 × baseline tryptase levels) indicates
mast cell activation. However, it is worth noting that serum tryptase may not be elevated in a small
proportion of patients with anaphylaxis.
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Skin Tests
Skin tests are used to investigate Type-1 and Type-4 HSRs. They must always be interpreted in
conjunction with clinical history and an understanding of pre-test probability for HSRs. Skin
tests should not be used to “screen” patients for an allergy. They should not be used in the context
of Type-2 or Type-3 HSRs. Skin tests involve skin prick tests followed by intradermal tests.
Intradermal tests are performed when skin prick tests are negative or equivocal. There are published
Non-Irritant concentrations for skin tests of common drugs (Brockow et al. 2013; Broyles et
al. 2020; Joint Task Force on Practice Parameters 2010). Where non-irritant concentrations
are not available skin prick tests and intradermal tests may be considered at “neat”/1:10 and
1:1,000–1:10 of stock solutions. A positive skin prick test indicates the presence of drug (or excipient)
specific IgE. Similarly, a positive intradermal test at 15–20 minutes indicates sensitization (IgE) and
a delayed positive response (at 48–72 hours) indicates a T-cell mediated or delayed hypersensitivity
response (Mirakian et al. 2009). As with other allergens, antihistamines should be temporarily
withdrawn for 3–5 days prior to the tests. Concurrent therapy with high-dose corticosteroids and/or
immunosuppressive medications may affect delayed intradermal test response.
Immunoassay for Allergen-Specific IgE
Predictive values (sensitivity/specificity) are established only for very few drugs, making these tests
less useful when compared to skin testing. In general, they are very useful when tests are positive
in the context of a high pre-test probability (positive predictive value); however, negative results do
not exclude IgE-mediated allergy as most have poor negative predictive values. In other words, a
negative serum-specific IgE test on its own does an exclude an allergy. Antihistamines do not need
to be withdrawn prior to specific IgE testing.
The Basophil Activation Test (BAT) and Lymphocyte Transformation Test (LTT)
During BAT, the patient’s blood is incubated to the allergen (drug) in question. Basophil activation is
determined by flow cytometry using expression of CD63 and/or CD203c and indicates the presence
of drug-specific IgE. Whereas in the lymphocyte transformation test, the patient’s blood is incubated
with the allergen and the drug-specific T-cell proliferation is measured. While BAT can be useful in
the investigation of Type-1 HSRs, LTT is used to investigate Type-4 HSRs. Both tests have not made
their way into routine clinical practice as they are expensive and require specialist laboratory setup,
are labor intensive, require specialist interpretation and are not yet validated (Mirakian et al. 2015).
Drug Provocation Test (DPT)
DPT remains the gold standard in confirming or excluding drug allergies. Indications,
contraindications and practical aspects are listed in Table 4. Available protocols have not been
validated, and they should be customized to each patient. For example, patients with penicillin
allergy labels are stratified as “low risk” and “high risk.” Low-risk patients are deemed most
unlikely to be truly allergic based on the clinical history and/or review of clinical records. They
may be subjected to a “direct oral penicillin challenge” under supervision without undertaking
allergy tests or a single dose DPT has undertaken after demonstrating negative tests. On the other
hand, those stratified as “high risk” have a clinical history suggestive or either a Type-1 or Type-4
HSRs and/or an associated co-morbidity, such as severe or uncontrolled asthma, COPD, etc., and a
3–4 step graded challenge might be undertaken. An example of an amoxicillin oral challenge is
shown in Table 5 (Mirakian et al. 2015; Romano et al. 2020).
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Table 4. Indications, contraindications, safety and practical issues of the drug provocation tests.
Drug Provocation Test (DPT)
Indications
Contraindications
Safety and
Practical Issues
* In exceptional and/or urgent cases DPT can be undertaken without withdrawal of beta blocker. Glucagon should be
available as part of available resuscitation facilities to manage potential refractory anaphylaxis.
• To exclude allergy in cases where hypersensitivity is unlikely (i.e.: nonspecic or mild symptoms
not in keeping with an immune mediated reaction, e.g., refuting an inaccurate label of penicillin
allergy)
• As a nal step in evaluating drug allergy, after demonstrating absent sensitization
• As a proof of or reassurance for clinical tolerance to a potential cross-reacting drug. For example,
cephalosporin in a patient with a mild index reaction to penicillin, where skin test either cannot
be conducted or when skin tests are negative to penicillins and/or cephalosporin
• Strong clinical history (and positive skin test and/or SSIgE)
• If the index reaction was a severe cutaneous adverse reaction (e.g., SJS, TEN, etc.)
• History suggestive of type-2 or -3 hypersensitivity
• General anaesthetic agents (neuromuscular blocking agents, propofol, etc.)
• Patient choice
• Procedure must be done in a controlled environment with an immediate access to a resuscitation
cart and drugs for management of anaphylaxis
• Patients must be t for the procedure; haemodynamically stable, and do not have severe
uncontrolled cardiorespiratory diseases
• Preferable to withdraw antihistamines for 3-5 days prior where possible
• If patient is taking beta blocker*, it should be temporarily withheld for 24 hours prior to the
procedure after consulting with a cardiologist and/or patients family physician
• Protocol should be customized based on index reaction; longer observations between steps may
be undertaken
Table 5.
An example of oral amoxicillin challenge protocol (from our centre).
Time (minutes) Dose (mg) Cumulative
Dose (mg)
0 5 5
30 25 30
60 75 105
90 150 255
120 250 505
180 _________ ________
Practical Steps
• Obtain informed consent
• Check baseline HR, BP, and PEFR
• Repeat prior to dose escalations and ensure an allergic reaction has not occurred
• Monitor for 60 minutes post-last dose
• A prolonged dose of 250 mg twice daily is given for 3 days at our center in patients with an indeterminate history or those
where index reaction occurred during a course of therapy. This is done to exclude delayed or type-4 hypersensitivity
• Counsel patient regarding the outcome, amend clinical records appropriately and provide a written note
Heart Rate Blood
Pressure
Peak Expiratory
Flow Rate
Symptoms
Management
Promptly withdrawing the likely offending drug is the first step in the clinical management
of a suspected allergic reaction, in addition to avoiding re-exposure to the drug (or exposure to
cross-reacting drugs) in the future. Also, clear and thorough documentation is paramount to avoid
further reactions. Referral to allergy services should be considered for the following situations:
1. If the drug is considered indispensable, regardless of the severity of the index reaction
2. Multiple drug allergy/intolerance label
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3. Penicillin allergy label, particularly with an infection-related co-morbidity (e.g., hyposplenism,
immunodeficiency, immunosuppressed state, COPD, bronchiectasis, diabetes, etc.)
4. Perioperative anaphylaxis
Rapid Drug Desensitization
Rapid drug desensitization involves supervised administration of a drug to a patient with a history
of (or suspected history of) Type-1 HSRs, and there are no suitable alternatives (e.g., penicillin
in bacterial endocarditis, rifampicin in tuberculosis, cancer chemotherapy, etc.). This procedure
is also employed in non-IgE mediated reactions to aspirin in the context of those requiring dual
anti-platelet therapy prior to undertaking percutaneous coronary intervention or in the treatment of
aspirin-exacerbated respiratory disease (e.g., nasal polyp in Samter’s triad). There is some evidence
for employing this procedure in Type-4 HSR, in patients reporting mild mucocutaneous HSRs
(i.e., not severe cutaneous adverse reactions). The procedure induces a temporary immunological
tolerance to the drug, and the state of immunotolerance is maintained as long the treatment is not
interrupted for more than 24 hours.
The procedure is undertaken in a clinically supervised environment starting at a very small
dose (e.g., 10–6 of therapeutic target dose) with dose escalation at 15–20 minutes, usually involving
12–16 steps. Rapid drug desensitization can be undertaken either via oral and/or intravenous
routes depending on the formulation available and clinical indication. Baseline vital parameters
are checked, and the patient is monitored prior to each dose escalation and for 60 minutes
post-final dose. Further details are summarized in Table 6 (Krishna and Huissoon 2011; de Groot
et al. 2012; Scherer et al. 2013). Common case scenarios are discussed in scenarios 1 and 2 to put
basic principles into clinical perspective. An overall approach to drug allergy is summarized in
Flowchart 1 and key messages are in Table 7.
Table 6. Indications, contraindications and practical aspects of rapid drug desensitization.
Indications
Contraindications
Checklist • Written informed consent
• Conrmed type-1 hypersensitivity to a drug (positive skin test and/or specic IgE) or when there is
a strong history of type-1 hypersensitivity. No suitable alternative available and the drug is needed
(e.g., penicillin in bacterial endocarditis, rifampicin in TB, cancer chemotherapy drugs etc.)
• Can be considered for delayed or type-4 reaction, if the index reaction was mild cutaneous and not a
severe cutaneous adverse reaction
• Aspirin in the context of aspirin exacerbated respiratory disease/nasal polyps or percutaneous
coronary intervention with a need for double antiplatelet therapy (see main text)
• If the index reaction is severe cutaneous reaction such as SJS, TEN, and DRESS.
• If the index reaction is likely to represent Gell-Coombs type 2, or type 3 hypersensitivity
reaction.
• Severe uncontrolled respiratory disease (asthma, chronic obstructive pulmonary disease)
• Hemodynamic instability
• Poorly controlled cardiovascular diseases
• Inpatient procedure (intensive treatment unit or a regular ward)
• 1:1 supervision with availability of a clinician on-site
• Immediate access to cardiopulmonary resuscitation and critical care outreach team
• Ensure patient’s cardio-respiratory status is stable (e.g.: asthma, chronic obstructive pulmonary
disease, heart function)
• Beta blockers should be discontinued if deemed safe (otherwise keep glucagon ready for
treatment of refractory anaphylaxis)
• Antihistamine/s should be discontinued where possible
• Peripheral vein cannulation for IV access
• Check baseline vital parameters including heart rate, blood pressure, and peak expiratory ow
rate (PEFR) and prior to each step.
• Monitor the patient for symptoms of an allergic reaction.
Desensitization
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Flowchart 1. A general approach to drug allergy.
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Table 7. Drug allergy key messages.
• Structured clinical history
• Scrutinise clinical/prescription records – drugs, doses, temporal association with
symptoms
• Evaluate for systemic involvement and characterise clinical presentation
• Ask the question – ‘Is this a hypersensitivity (HSR) reaction’? consider dierential
diagnosis
Drug Allergy – ‘Clinical
Pearls’
• Stop suspected drug/s
• Consider referral to a specialist with experience in drug allergy
• Consider allergy tests
• Bear in mind: Predictive values not known for skin tests and in vitro tests for most drugs
not established
• Drug Provocative Tests (DPT) is ‘gold standard’ in diagnosis
• Consider DPT when allergy is unlikely and after undertaking a ‘risk-benet analysis’
• Ask the Q: ‘Is this drug really essential for this patient’?
• Basic knowledge of hypersensitivity reactions and immune mechanisms of drug allergy
is essential to work your way through!
Conclusion
Key to successful clinical outcomes in drug allergy management is to obtain a systematic clinical
history and review of clinical/prescription records. Current best practice involves performing and
interpreting skin tests (and specific IgE where available) in the context of the patient’s clinical
history. Prior knowledge of performance characteristics of allergy tests to individual drug classes is
needed in specialist clinical practice.
DPT should be undertaken in a safe clinical environment preferably by trained personnel
with immediate access to the management of anaphylaxis and access to critical care management.
Furthermore, knowledge of drugs implicated in specific types of non-immediate or Type-4 HSRs
and maintaining a broad differential diagnosis is key to underpinning accurate diagnosis and
management of serious systemic non-immediate HSRs.
Prospective data collection and characterization of adverse drug reactions and the application
of information technology and machine learning might provide a platform to generate more reliable
datasets regarding epidemiology and for the application of pharmaco-genomics to pave the way for
precision and personalized medicine.
1. A 60-year-old male patient was admitted via the emergency department with a case of
neurosyphilis. He has a documented history of anaphylaxis to penicillin 4 years ago. What
is the most appropriate approach?
Intravenous penicillin is the preferred treatment for neurosyphilis. Desensitization is the most
appropriate approach for this patient due to the following:
• There are no suitable alternatives to penicillin to treat neurosyphilis
• The initial reaction was an anaphylaxis
• The urgency to start antimicrobial
An example of a penicillin desensitization protocol is shown in Table 8. Desensitization can be
offered for patients with confirmed drug allergies or in cases where the drug is needed urgently, and
treatment cannot be postponed until the complete evaluation is done. It induces only a temporary
tolerance to the drug, so future courses of the drug should be introduced via desensitization. Also, it
is important to review the patient carefully for the presence of any contraindications. Please look at
Table 6 for the practical aspects of desensitization.
Common Scenarios
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