Aspirin induced urticaria in a recently diagnosed ischemic
stroke patient: A case report and literature review. Abhinav Dahal : Sukraraj Tropical and Infectious Disease Hospital, Teku,
Kathmandu, Nepal Email: abhinav.dahal333@gmail.com
Sushant gautam: Nepalgunj medical college, banke,Nepal
email:
gautamsushant1941@outlook.com
Aliza Shakya : Manipal college of medical sciences, Pokhara, Nepal
email:
shakyaaliza@gmail.com
Ashmita pant: Manipal college of medical sciences, Pokhara, Nepal
email:
ashmita.pant@gmail.com
Kriti Bhandari , Nepal Medical College, Jorpati, Kathmandu, Nepal
itirkbhandari977@gmail.com
Abhigan Babu Shrestha, M Abdur Rahim Medical College, Dinajpur,
Bangladesh.
Abigan17@gmail.com
Corresponding author:
ABS; M Abdur Rahim Medical College, Dinajpur, Bangladesh.
Abigan17@gmail.com
Abstract:
Aspirin and urticaria correlation has not been fully understood. The
pharmacological inference is suspected to be the diversion of
arachidonic acid metabolism. Aspirin sensitivity can aggravate
pre-existing chronic urticaria and in some instances causes acute
urticaria. We report a case of a 53-year old male, recently diagnosed
with stroke, who presented with complaints of multiple rash over trunk
and upper extremity with aspirin. NSAIDs induced urticarial are usually
neglected by physicians during diagnosis.
Keywords: Aspirin, urticarial, stroke, hemiplegiaIntroduction: Aspirin is a drug which is widely used to reduce the risk of stroke,
transient ischemic attack, and cardiovascular events. This is due to its
antithrombotic properties by irreversibly inhibiting the cyclooxygenase
enzyme, reducing the synthesis of Thromboxane A2 and thus subsequently
reducing platelet aggregation [1– 3]. Aspirin and NSAIDs’
pharmacological properties also result in adverse reactions like GI
upset, renal toxicity, and hemorrhagic complications, as well as
potentiate hypersensitivity reactions [4]. Aspirin Hypersensitivity
is reported by 0.9 to 1.5% of the general population [5].
Hypersensitivity reactions to NSAIDs are classified on the basis of
their involvement of the skin, like urticaria or angioedema, the airways
or other organs, their acute or delayed onset, the presence of
underlying diseases, and their cross reactivity[6]. In this report,
we document a case of aspirin induced urticaria in a patient with a
recent history of Ischaemic stroke and Hypertension.Case Description: A 53 years old male presented to the emergency department with a chief
complaint of multiple rashes with burning and itching sensation over
trunk and extremities. Figure 1 and 2.
The patient was a known case of hypertension with recent diagnosis of
left sided ischemic stroke with right sided hemiparesis 7 days back for
which he was admitted for 3 days. There were no significant reactions to
the treatment noticed during the hospital stay. He was discharged with a
daily dose of aspirin 75 mg o.d., enalapril 10 mg o.d., atorvastatin 20
mg o.d., omeprazole 20 mg b.d. He was advised for proper bed rest with
two hourly posture changes & physiotherapy.
He was solely on prescribed medications for the past 4 days. On the next
day, he was admitted following the appearance of cutaneous
manifestations with no other associated symptoms such as angioedema or
shortness of breath. He had no prior history of allergic reactions. On
further enquiry, he denied any changes to diet or environmental stimuli
including no exposure to any pets or animals. He also gave a negative
history of family members having such allergic manifestations.
On examination, multiple, pruritic, erythematous, blanching macules were
present on bilateral upper extremities and trunk(Figure 1). His vital
signs were within normal limits. Leukocytosis (wbc:12,000 cells/mm3)
with higher eosinophil count ( 550 per ml of blood) was noted while
other complete blood count and comprehensive metabolic panels were
unremarkable.
Medical history revealed he was taking enalapril 10 mg o.d. for the past
3 years for hypertension. As ACE inhibitors are commonly responsible for
causing the side effects such as allergies, drug rash & even
angioedema, it was replaced with amlodipine 5 mg o.d. He was started on
histacin 4 mg b.d for symptomatic management. However, there was no
significant improvement in his condition. Therefore, we decided to stop
the current medication one at a time to identify the culprit drug.
Aspirin was replaced with clopidogrel 75 mg o.d. & given daily. He was
kept under observation & followed up the next day with improvement.
Patient told that his itching and the degree of rash spread throught his
body were diminished. Three days later, the rashes almost fully subsided
& he was advised to continue histacin for 1 more week without stopping
clopidogrel intake. Aspirin was identified as the sole cause for the
rashes. He was discharged following complete recovery of cutaneous
symptoms after 3 days with proper counselling regarding his condition
and precaution to be taken for future aspirin use.Discussion: Aspirin and other NSAID are known to cause hypersensitivity reactions.
One of the manifestation of such reactions is urticaria. The prevalence
of aspirin induced urticaria is estimated to be around 0.3% excluding
individuals with recurrent urticaria, hay fever and chronic chest
disease [7]. Aspirin induced Urticaria(AIU) can be classified into
two types as aspirin intolerant acute urticaria(AIAU) and aspirin
intolerant chronic urticaria(AICU). The symptoms develop within minutes
to 24 hour in AIAU and lasts for less than 6 weeks whereas, in AICU
symptoms typically last for more than 6 weeks.[8]
Elevated IgE levels and atopy are suggested as a common
predisposingfactors for AIU according to a genetic study done in Korean
population[8]. In addition, HLA-DRB1 * 1302 - DQB1*0609 also has
been identified as a genetic marker[9]. Besides this, various
genetic studies have reported that high affinity IgE receptor[10] ,
histamine N‐methyltransferase[11] and adenosine A3
receptor[12] are other genetic determinants for AIU. These findings
allude that, causes leading to the release of inflammatory mediators
either by increased histamine release, faulty histamine degradation or
augmented mast cell signalling, contributes to the manifestation of AIU.
NSAIDs and Aspirin are known to be one of the common drugs causing
hypersensitivity drug reactions.(13) Drug Hypersensitivity Reactions
constitute about one third of all adverse drug reactions and affects
10-20% of hospitalized patients and 7% of
outpatients.[14]
Depending on the type of hypersensitivity reaction, patient can develop
an array of cutaneous manifestations ranging from urticaria/ angioedema,
fixed drug eruption, maculopapular exanthem to more severe
manifestations such as DRESS or SJS/TEN.[15] We have previously
encountered a case of Stevens Johnson Syndrome, Type III
Hypersensitivity Reaction due to an antibiotic namely Cefixime.[16]
In this case, we have encountered a case of Single NSAID Induced
Urticaria/ Angioedema or Anaphylaxis, a Type I Hypersensitivity
Reaction. Figure 3.
To date, there are only few case reports published in pubmed
highlighting the association of aspirin with urticaria. This may be due
to the fact that aspirin sensitivity is often neglected because of the
cross reaction with NSAIDs. One case report has documented urticaria in
three patients caused by aspirin where pharmaceutical excipients present
in the formulation of drug was found to be the sole cause for the
hypersensitivity reaction in two of those patients.[17]However,
acute urticaria is not uncommon and when patients present with an
urticarial reaction clinicians do not consider NSAIDs as the cause, as
the reaction occurs in context of different triggers and is thus
difficult to establish.
Beyond drug induced urticaria, differential diagnosis of acute urticaria
includes urticaria attributed to infections, foodstuffs, contact
dermatitis, solar urticaria, cholinergic urticaria, arthropod bite
reactions, autoimmune disorders, small vessel vasculitis. Diagnostic
workup for many of these etiologies rely on laboratory parameters and
histological evidence in addition to history. Initial laboratory
investigations revealed lekocytosis with a predominance of eosinophils.
However, access to further testing was limited due to patient’s refusal
and unfortunately no blood investigations or skin biopsy was taken at
presentation.
Management of NSAID induced urticaria includes strict culprit NSAID
avoidance along with symptomatic management of acute urticaria.[18]
Antihistamines are the first line treatment for management of acute
urticaria. In severe cases, corticosteroids can be added to control
symptoms.[19,20] Some types of NSAID hypersensitivity are known to
exhibit cross reactivity thus strict NSAID avoidance should be done
until potential of cross-intolerance is ruled out. If patient has
history suggesting selective NSAID induced urticaria, challenge to
chemically unrelated strong COX-1 inhibitor may be done to rule out
crossreactivity type hypersensitivity.[21] Once diagnosis of SNIUAA
is established, use of drug allergy passport and patient education help
both the medical provider and the patient know about the NSAID
hypersensitivity status, avoidance of the culprit NSAID as well as use
of chemically unrelated NSAIDs as safe alternatives. In this entity,
alternative drug to aspirin must be sought.[18,21] Therefore our
clinical reasoning is composed from detailed patient’s history, physical
examination and clinical course. Our patient did not have any history of
multisystem involvement, recent infection, past medical history of
atopy, inducible urticaria due to heat, cold or stress, recent contact
with common irritants or insect bite.
The patient had been taking Aspirin, Enalapril and Atorvastatin
following the diagnosis of Ischemic Stroke with Right Sided Hemiparesis.
The urticaria and pruritus should not be caused by Enalapril, since the
patient was tolerating the medication well for the past 3 years and the
patient’s symptoms worsened even after withdrawing of the drug. The
temporal correlation between the appearance of urticarial rash and
aspirin intake, and the resolution of urticarial rash and pruritus
following aspirin discontinuation suggests the possibility of Aspirin
Induced Urticaria. The causality assessment of the adverse drug reaction
(ADR) was carried out using the Naranjo Scale, a method for estimating
the probability of adverse drug reactions. The assessment revealed the
ADR to be ‘Probable’(+6) to be associated with
Aspirin.[22]The
patient’s history notably lacked presence of chronic urticaria. While
the drug provocation test for cross intolerance was not done, the
patient’s history reveals previous tolerance to other NSAIDs like
ibuprofen and paracetamol.