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\begin{document}

\title{BRUGADA SYNDROME UNMASKED BY DENGUE FEVER}



\author[1]{LOKESH KOUMAR Sivanandam}%
\author[2]{Shamal Roshan}%
\author[3]{Marah Hunjul}%
\author[4]{HIMABINDU BASANI}%
\author[5]{Vivek Sanker}%
\author[6]{Umang  Gupta}%
\affil[1]{SLIMS}%
\affil[2]{Government Medical College Thrissur}%
\affil[3]{Al-Najah National University}%
\affil[4]{Lyceum Northwestern University}%
\affil[5]{Noorul Islam Institute of Medical Science and Research Foundation Medicity}%
\affil[6]{Nepalgunj Medical College}%


\vspace{-1em}



  
  \date{May 26, 2024}


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\selectlanguage{english}
\begin{abstract}
Brugada syndrome is a genetic arrhythmia syndrome characterized by a
coved type of ST segment elevation in the ECG.The patients are usually
asymptomatic, with unmasking of the disease under certain conditions.We
are reporting the case of such a patient who was diagnosed during an
attack of dengue fever%
\end{abstract}%



\sloppy


\textbf{INTRODUCTION:}

Brugada syndrome, described in 1992 by brothers Josep and Pedro Brugada,
is a genetic arrhythmia syndrome caused due to gene defects involving
the sodium, calcium, and potassium channels of the cardiac musculature
among others. Around 18-30\% of defects can be attributed to SCN5A gene
mutation affecting the alpha subunit of the cardiac sodium channel(1).
The syndrome is characterized by a typical ECG pattern of
\textgreater{}0.2 mV of ST-segment elevation with a coved ST segment and
negative T-wave in more than one anterior precordial lead (V1-V3) along
with Right bundle branch block in a structurally normal heart(2). This
is accompanied by a risk of sudden death due to ventricular
fibrillation, or syncope resulting from polymorphic ventricular
tachycardia.

Most patients with this syndrome are asymptomatic. Nevertheless,
diagnosing the syndrome, which is by its specific ECG pattern, is
essential, as the first manifestation of the disease may even be sudden
cardiac death. An Implantable cardioverter defibrillator (ICD) is
indicated for patients who have had unexplained syncope or have been
resuscitated from cardiac arrest(3). Anti-arrhythmic drugs like
quinidine and catheter ablation of abnormal regions have been beneficial
in suppressing VT. This help to reduce the incidence of sudden death to
an extent.

The characteristic ST-elevation crucial for diagnosis may not be present
always. It fluctuates with time and is precipitated by various
factors(3). Most important among them are acute illnesses and fever. The
syndrome can unmask itself in the event of a febrile illness and as a
result, the disease may present itself for the first time, during such
an episode.

In a region where febrile illnesses, such as dengue; and Brugada
syndrome are both prevalent, such as Southeast Asia, case reports such
as these become relevant. So the factors responsible for precipitating
arrhythmias, such as febrile illnesses like dengue need to be analyzed
and their relation needs to be understood.

\textbf{CASE REPORT:}

A 56-year-old male presented with a 3 days history of intermittent fever
with associated non-productive cough. The fever temporarily subsided on
taking medications. The patient also had headaches described as,
generalized, pricking, and continuous. He has no history of syncope,
palpitations, chest pain, shortness of breath, or any cardio-pulmonary
symptoms. The patient is diabetic, hypertensive, and non-compliant with
medications. The patient does not have a family history of sudden
cardiac death or any cardiac diseases. He has no significant past
medical or surgical history. This case has been reported in line with
the SCARE criteria (4)..

On physical examination, the patient was febrile (102.7F), and
tachycardic, otherwise, the findings were unremarkable. The laboratory
findings showed positive for Dengue NS1 antigen and IgM , with a
platelet count of 187\selectlanguage{ngerman}× 10\textsuperscript{3} /\selectlanguage{greek}μ\selectlanguage{english}L.

The patient was admitted and managed with intravenous fluids,
broad-spectrum antibiotics, and acetaminophen. On the evening of
admission, the complete blood count was repeated, showing a platelet
count of 29 \selectlanguage{ngerman}× 10\textsuperscript{3} /\selectlanguage{greek}μ\selectlanguage{english}L, hematocrit 45.4\%, hemoglobin
15.8g/dL, WBC 8.24 \selectlanguage{ngerman}× 10\textsuperscript{3} /\selectlanguage{greek}μ\selectlanguage{english}L, and lymphocytes 60.2\%
with suspected thrombocytopenia, large immature cells, and atypical
cells. On day 2 of admission complete blood count showed a platelet
count of 26 \selectlanguage{ngerman}× 10\textsuperscript{3} /\selectlanguage{greek}μ\selectlanguage{english}L, hematocrit 42.6\%, hemoglobin
14.8g/dL, WBC 8.56\selectlanguage{ngerman}× 10\textsuperscript{3} /\selectlanguage{greek}μ\selectlanguage{english}L, and lymphocytes 65.2\%
with suspected thrombocytopenia, lymphocytosis, and large immature
cells. Serum electrolytes, urea, and creatinine were all within the
normal range.\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
& \textbf{On the day of admission} & \textbf{Day 2} & \textbf{On
Discharge}\tabularnewline
\midrule
\endhead
Temperature & 103\selectlanguage{ngerman}°F & 102\selectlanguage{ngerman}°F & 100\selectlanguage{ngerman}°F\tabularnewline
Platelets & 29\selectlanguage{ngerman}× 10\textsuperscript{3} /\selectlanguage{greek}μ\selectlanguage{english}L & 26 \selectlanguage{ngerman}× 10\textsuperscript{3}
/\selectlanguage{greek}μ\selectlanguage{english}L & 56 \selectlanguage{ngerman}× 10\textsuperscript{3} /\selectlanguage{greek}μ\selectlanguage{english}L\tabularnewline
Trop T & 0.01 ng/ml (normal) & &\tabularnewline
CK-MB & Normal & &\tabularnewline
\bottomrule
\end{longtable}

The patient had cyclic fevers during his hospital stay which were
managed with IV and oral acetaminophen. The sequence of ECG findings was
documented showing RBBB with ST-segment elevation. Diagnosed as Brugada
syndrome Type 1 unmasked by Dengue fever (Fig. 1 \& 2).\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\textbf{Fig. 1 -- ECG taken at the time of Admission {[}J point
elevation of 2mm from PQ with rectilinear ST Depression with T
inversion, Satisfying the criteria for Type 1 Brugada Syndrome, Similar
Pattern seen in aVR, Sinus rhythm at 78 /minute, QRS axis Normal, QRS
Narrow complex, No Atrial or ventricular hypertrophy pattern, QTc
interval -- 350 ms{]}}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

\textbf{Fig. 2 -- ECG taken at the time of Discharge {[}J point
elevation of 2mm from PQ with rectilinear ST Depression with T
inversion, Satisfying the criteria for Type 1 Brugada Syndrome, Similar
Pattern seen in aVR, Sinus rhythm at 70/minute, QRS axis Normal, QRS
Narrow complex, No Atrial or ventricular hypertrophy pattern, QTc
interval -- 350 ms{]}}

\textbf{DISCUSSION:}

Brugada syndrome is an inherited sodium channel defect that gives rise
to fatal ventricular arrhythmia and sudden death(5). Brugada disease is
an autosomal dominant inherited disease that runs in families, however,
more than 60\% of cases are sporadic. The gene involved is SCN5A which
encodes the alpha portion of the sodium channels in cardiac muscles. (6)
There's not enough evidence to connect this disease with structural
changes in the heart (5).

There are 3 types of Brugada Syndrome, which differ in their ECG
presentation. Only type 1, when present is considered a diagnostic
criterion, whereas the other 2 are suggestive of the disease rather than
diagnostic(7). Type 1 is characterized by ST-segment elevation [?]2 mm in
more than 1 lead in the pericardial leads ( V1, V2, V3) followed with T
inversion (8). Type 2 is the same ST elevation criteria but followed by
biphasic or normal T wave, and Type 3 where ST elevation is [?]1 mm(9).

Brugada syndrome can be considered as a differential diagnosis when
there is a family history, previous cardiac arrhythmia, previous
syncope, previous ventricular tachycardia or fibrillation (10).

To diagnose Brugada syndrome a new scoring system was made, namely the
Shanghai Score System which was built on the previous clinical research
and data available(11). This score takes into consideration the ECG
Changes, past medical history, genetics, and family history. If the
score is 2-3 , Brugada is a possible diagnosis, if the score is [?]3.5
it's a definite diagnosis(12).

The Proposed Shanghai Score System for diagnosis of Brugada syndrome
(12) -\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
& Points\tabularnewline
\midrule
\endhead
I. ECG (12-Lead/Ambulatory) &\tabularnewline
A. Spontaneous type 1 Brugada ECG pattern at nominal or high leads &
3.5\tabularnewline
B. Fever-induced type 1 Brugada ECG pattern at nominal or high leads &
3\tabularnewline
C. Type 2 or 3 Brugada ECG pattern that converts with provocative drug
challenge & 2\tabularnewline
\emph{Only award points once for highest score within this category. One
item from this category must apply}. & *\emph{Only award points once for
highest score within this category. One item from this category must
apply}.\tabularnewline
II. Clinical History* &\tabularnewline
A. Unexplained cardiac arrest or documented VF/ polymorphic VT &
3\tabularnewline
B. Nocturnal agonal respirations & 2\tabularnewline
C. Suspected arrhythmic syncope & 2\tabularnewline
D. Syncope of unclear mechanism/unclear etiology & 1\tabularnewline
E. Atrial flutter/fibrillation in patients \textless{}30 years without
alternative etiology & 0.5\tabularnewline
\emph{Only award points once for highest score within this category}. &
*\emph{Only award points once for highest score within this
category}.\tabularnewline
III. Family History &\tabularnewline
A. First- or second-degree relative with definite BrS & 2\tabularnewline
B. Suspicious SCD (fever, nocturnal, Brugada aggravating drugs) in a
first- or second-degree relative & 1\tabularnewline
C. Unexplained SCD \textless{}45 years in first- or second- degree
relative with negative autopsy & 0.5\tabularnewline
\emph{Only award points once for highest score within this category.} &
*\emph{Only award points once for highest score within this
category.}\tabularnewline
IV. Genetic Test Result &\tabularnewline
A. Probable pathogenic mutation in BrS susceptibility gene &
0.5\tabularnewline
Score (requires at least 1 ECG finding) &\tabularnewline
[?]3.5 points: Probable/definite BrS &\tabularnewline
2--3 points: Possible BrS &\tabularnewline
\textless{}2 points: Non diagnostic &\tabularnewline
\bottomrule
\end{longtable}

\textbf{BrS = Brugada syndrome; SCD = sudden cardiac death; VF =
ventricular fibrillation; VT = ventricular tachycardia.}

Several studies linked the new discovery of Brugada syndrome with fever
(13, 14), fever associated with illness such as tonsillitis or
pneumonia, unmasking Brugada, and eventually leading to fatal
arrhythmias and possible death(15). It has been discovered that the gene
SCN5A encodes Thr1620Met which forms the alpha unit of the sodium
channel in the heart. This protein is affected by temperature, the
higher the temperature, the faster the decay of this protein and that's
what reveals the syndrome (16). Another study indicates that Brugada ECG
changes are 20 times more obvious when associated with high fever (17).

\textbf{CONCLUSION:}The characteristic ECG findings of Brugada Syndrome
are more pronounced in febrile illnesses such as dengue fever. The
syndrome can thus be diagnosed by taking ECG during such febrile
episodes. Patients presenting with arrhythmias can be managed
accordingly, to prevent the progression and complications. In
conclusion, Doctors treating patients with febrile illnesses should have
high index of suspicion and be ready to manage it. Febrile illnesses
need to be taken care of, by quick control of temperature. Further
studies on this subject should be done to understand more about the
degree of association, other precipitating factors and various treatment
modalities.

\textbf{CONFLICTS OF INTEREST:}

None declared.

\textbf{AUTHOR CONTRIBUTION:}

All the authors contributed equally in drafting, editing, revising and
finalizing the case report.

\textbf{ETHICAL APPROVAL:~}

The ethical approval was not required for the case report as per the
country's guidelines.

\textbf{CONSENT:}

Written informed consent was obtained from the patient to publish this
report.

\textbf{DATA AVAILABILITY STATEMENT:}

The data that support the findings of this article are available from
the corresponding author upon reasonable request.

\textbf{REFERENCES:}

\begin{enumerate}
\tightlist
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\selectlanguage{english}
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