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\begin{document}

\title{Unusual Manifestations of Takayasu Arteritis: A Diagnostic challenge}



\author[1]{Tahseen  Al-kinani}%
\author[1]{Ali Al-yacopy}%
\author[2]{Ahmed Alhatemi}%
\author[3]{Hashim Talib Hashim}%
\author[4]{Rand Abdulhussain }%
\author[5]{Ali Talib Hashim}%
\affil[1]{Al Nasiriyah Heart Hospital }%
\affil[2]{Al Nasiriyah Teaching Hospital }%
\affil[3]{University of Warith Al Anbiyaa}%
\affil[4]{University of Huddersfield Department of Pharmacy}%
\affil[5]{Golestan University of Medical Sciences and Health Services}%


\vspace{-1em}



  
  \date{June 17, 2024}


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\textbf{Unusual Manifestations of Takayasu Arteritis: A Diagnostic
challenge}

Dr.Tahseen Ali Al-kinani1, Dr.Ali Akeel Al-yacopy2, Dr.Ahmed Qasim
Mohammed Alhatemi3, Dr.Hashim Talib Hashim4, Ms.Rand Abdulhussain 5, Ali
Talib Hashim 6.

\begin{enumerate}
\tightlist
\item
  Consultant cardiologist, Coronary Care unit, Al Nasiriyah Heart
  Hospital, Thi Qar, Iraq. tahssein.ali@utq.edu.iq
\item
  Fellow Iraqi board of cardiology , Coronary Care Unit, Al Nasiriyah
  Heart Hospital, Thi Qar, Iraq. Aliteam2004yousif@gmail.com
\item
  Internal Medicine Trainee, Internal Medicine, Al Nasiriyah Teaching
  Hospital, Thi Qar, Iraq. dr.ahmedqasim95@gmail.com
\item
  Head of research department, Warith Al Anbiyaa university, Karbala,
  Iraq. Hashim.talib@uowa.edu.iq
\item
  University of Huddersfield, Huddersfield, UK.
  randkabdulhussain@gmail.com
\item
  Golestan University of medical sciences, Gorgan, Iran.
  Talibhashim42@gmail.com
\end{enumerate}

\textbf{Corresponding author} : Ali Talib Hashim, Golestan University of
medical sciences, Gorgan, Iran. Talibhashim42@gmail.com

\textbf{Data availability statement}

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

\textbf{Consent for publication}

Written consent form for publication of his details was obtained from
the patient.

\textbf{Competing interests}

The authors declare that they have no competing interests.

\textbf{Funding}

No source of funding were received.

\textbf{Authors contribution}

\textbf{Tahseen Ali Al-kinani}

Investigation

Project administration

\textbf{Ali Akeel Al-yacopy}

Investigation

Supervision

\textbf{Ahmed Qasim Mohammed Alhatemi}

Project administration

Writing -- original draft

Writing -- review \& editing

\textbf{Hashim Talib Hashim}

Methodology

Project administration

\textbf{Rand Abdulhussain}

Validation

Visualization

\textbf{Ali Talib Hashim}

Project administration

\textbf{Key clinical message:}

Timely recognition of atypical Takayasu arteritis is paramount. CT
angiogram plays a pivotal role in precise diagnosis, guiding the
initiation of targeted immunosuppressive.

\textbf{Keywords:}

Cardiology, Rheumatology, Immunology, Emergency Medicine, Radiology and
Imaging.

\textbf{Introduction:}

Takayasu Arteritis (TA), a rare, chronic vasculitis primarily affecting
large vessels, is conventionally characterized by stenosis, occlusion,
or aneurysm formation in the aorta and its main branches (1).However,
emerging research and clinical observations have begun to shed light on
its less typical manifestations, presenting a more complex and diverse
spectrum of the disease than previously understood. This burgeoning
awareness is pivotal in broadening the diagnostic and therapeutic
approaches for TA (2).

Traditionally, TA has been identified through its classic symptoms:
pulselessness, vascular bruits, and differences in blood pressure
between limbs. Nonetheless, recent studies and case reports have
unveiled a range of atypical presentations (3). These unusual
manifestations often lead to diagnostic challenges, as they can mimic
other medical conditions and delay accurate recognition of TA. For
instance, patients might present with symptoms resembling neurological
disorders, renal impairments, or gastrointestinal complications, which
are not immediately identifiable as consequences of vascular
inflammation (3).

The significance of these unusual presentations lies not only in their
diagnostic challenge but also in their potential impact on the
management and prognosis of TA (4). The disease's progression with
atypical symptoms may alter the traditional therapeutic strategies,
necessitating a more tailored and holistic approach. The complexity of
these manifestations requires a high index of suspicion and a
multidisciplinary approach involving rheumatologists, cardiologists,
neurologists, and other specialists, depending on the affected organ
systems (5).

This introduction aims to delve into these atypical presentations of
Takayasu Arteritis, exploring their clinical implications, challenges in
diagnosis, and impact on management strategies. Understanding these
unusual manifestations is crucial for clinicians to provide timely and
accurate diagnosis, preventing disease progression and improving patient
outcomes in this rare but impactful condition (5)

\textbf{Case history and examination}

A 42-year-old male presented to our cardiology clinic with a three-week
history of low-grade fever, backache, and exertional dyspnoea,
progressing to severe dyspnoea at rest after one week.

He has history of smoking 20 pack-year and no chronic drugs use. His
family history includes paternal myocardial infarction at 50 and
maternal type two diabetes diagnosed at 55.

On examination, an averagely built, fully conscious male was sitting in
distress with dyspnoea. He exhibited normal vesicular breathing without
added sounds. Cardiac examination revealed muffled heart sounds and an
elevated jugular venous pressure (JVP) at 9cm. His abdomen was soft,
non-tender, with no visible pulsating mass. No cyanosis or peripheral
oedema was noted. Vital signs were as follows: BP 111/87 mmHg, RR 26
breath/min, PR 87 beat/min, Temp 39.1 Celsius, and oxygen saturation at
88\% on room air.

\textbf{Deferential diagnosis, investigation and management}

Oxygen mask at 100\% was started immediately and rapid strep ECG
revealed multiple premature ventricular contractions PVCs. (figure1)\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\textbf{Figure 1. Baseline ECG showing multiple PVCs with compensatory
pause.}

Chest X-ray was ordered to exclude spontaneous pneumothorax and aortic
dissection, revealing an enlarged cardiac shadow most likely due to
pericardial effusion (Figure 2).\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

\textbf{Figure 2. Chest X-ray PA view revealing enlarged cardiac
shadow.}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

We preceded with transthoracic echocardiogram which revealed a large
pericardial effusion (figure 3A).

\textbf{Figure 3A. Initial transthoracic echocardiogram TTE four chamber
view showing large pericardial effusion PE.}

Urgent pericardiocentisis was performed, resulting in complete
evacuation of 1.5 litters of clear serous fluid, as observed in his
echocardiogram (Figure 3B). This led to an improvement in the patient's
dyspnoea. Subsequently, he was admitted for further assessment and
diagnosis.

\textbf{Hosted file}

\verb`image4.tmp`  available at \url{https://authorea.com/users/756238/articles/727204-unusual-manifestations-of-takayasu-arteritis-a-diagnostic-challenge}

\textbf{figure 3B. Repeated transthoracic echocardiogram TTE four
chamber view revealing no pericardial effusion one day after
pericardiocentisis}

Laboratory testing at the time revealed normal white blood cell count,
haemoglobin, and platelets count of 7.0 \selectlanguage{ngerman}× 111/L, 125 g/L, and 288 ×
109/L, respectively. The patient's electrolytes and renal function were
also normal (sodium 144 mmol/L, potassium 3.8 mmol/L, and creatinine 77
\selectlanguage{greek}μ\selectlanguage{english}mol/L)

A comprehensive analysis of pericardial fluid, encompassing cytology,
culture, biochemistry, and ADA levels, was conducted to rule out
atypical tuberculosis. Imaging studies, including chest X-ray and chest
CT were inconclusive. Given the high prevalence and ambiguity of
tuberculosis in Iraq, screening, including AFB swap and Gene Xpert,
yielded negative results. Despite this, a trial of anti-tuberculosis
therapy was initiated for two months with regular biweekly follow-ups.
Serial echocardiograms showed no significant pericardial effusion, yet
recurrent symptoms, such as high-grade fever, back pain, and exertional
dyspnoea, persisted.

\textbf{Results and follow up~}

A decision was made to continue the tuberculosis regimen and pursue
further evaluation. Tuberculosis of the spine was considered, and an MRI
of the spine returned normal results.

Serial blood tests, including a complete blood count (CBC), syphilis
screen, thyroid function test, and autoimmune workup -- which included
testing for antinuclear antibodies, double-stranded DNA,
antineutrophilic cytoplasmic antibody, rheumatoid factor, cryoglobulin
panel, and antiphospholipid antibodies -- yielded negative. However, an
elevated erythrocyte sedimentation rate (ESR) of 100 mm/hr was observed.
Despite the negative immune screening, the persistent elevation in ESR
prompted further investigation into potential underlying causes for the
increased inflammatory marker.

Further assessment indicated a difference in blood pressure between the
left arm (110/70 mmHg) and right arm (160/95 mmHg), leading to a CT
angiogram that confirmed large vessel vasculitis with aortic enhancement
(Figure 4 A, B, C, D). Additionally, mild aortic regurgitation and trace
pericardial effusion were observed on echocardiography.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image5/image5}

\end{center}
\end{figure}

\textbf{Figure 4.A) CT angiogram of the aorta shows normal contrast
filling in the main aortic arch branches with no aneurysm observed.
Marked wall thickening is noted at the left common carotid artery (CCA)
and left subclavian artery (SCA), with severe stenosis at the origin and
proximal segment of the left subclavian artery (white arrows).}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image6/image6}

\end{center}
\end{figure}

\textbf{figure 4.B) CT angiogram axial view shows narrow and tapered
proximal left subclavian artery SCA with increased aortic arch wall
thickness (white arrows)}

\textbf{Hosted file}

\verb`image7.tmp`  available at \url{https://authorea.com/users/756238/articles/727204-unusual-manifestations-of-takayasu-arteritis-a-diagnostic-challenge}

\textbf{figure 4.C) CT angiogram three dimensional (3D) view revealing
marked wall thickening at the left common carotid artery (CCA) and left
subclavian artery (SCA), with severe stenosis at the origin and proximal
segment of the left subclavian artery (white arrows).}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image8/image8}

\end{center}
\end{figure}

\textbf{figure 4.D) CT angiogram sagittal view shows marked wall
thickness with enhancement at the left subclavian artery (SCA) (white
arrow).}

While the vasculitis screen returned negative, the CT angiogram findings
suggest large vessel vasculitis, specifically Takayasu arteritis.
Management commenced with Prednisone (1mg/kg QD) and methotrexate 10mg
per week as induction, alongside metoprolol 100mg QD and Lisinopril 10
mg QD. However, no notable improvement in the patient's condition was
observed after three months. During the follow-up, the patient developed
recurrent attacks of fever, myalgia, and frequently had elevated
inflammatory markers. This condition was labelled as a flare-up under
rheumatologist supervision. Medication changes were implemented, and the
patient was kept on prednisone 20 mg QD, leflunomide 20mg QD, colchicine
1mg BD, and adalimumab 40mg subcutaneous Q 2wk for 3 months, leading to
clinical and laboratory improvement. After that, scheduled prednisone
tapering was initiated until reaching 7.5 mg QD.

The patient's condition remained stable throughout the follow-up period,
with consistent improvement observed in serial ECGs (Figure 5) and
normal echocardiograms during monthly visits to our cardiology
outpatient clinic.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image9/image9}

\end{center}
\end{figure}

\textbf{Figure 5.follow-up ECG conducted after 6 months, illustrating
premature ventricular contractions (PVCs).}

\textbf{Discussion} :

Aortitis, characterized by inflammation of the aorta, is a condition
with the potential for life-threatening consequences. The diagnostic
exploration of aortitis is guided by a differential diagnosis that
categorizes causes into inflammatory and infectious origins. The
principal contributors to non-infectious aortitis are the large-vessel
vasculitis, specifically giant-cell arteritis and Takayasu arteritis,
affecting the aorta and its primary branches (6).

Takayasu Arteritis (TA), a rare form of vasculitis, primarily affects
large vessels, such as the aorta and its main branches. While classic
presentations include limb claudication, reduced or absent pulses, and
vascular bruits, TA can also manifest in unusual ways, adding complexity
to its diagnosis and management (7).

One of the less common manifestations of TA is renal involvement, which
may present as renovascular hypertension due to renal artery stenosis.
This can lead to significant morbidity if not recognized and managed
promptly (7). Another atypical presentation is neurological symptoms,
ranging from headaches and dizziness to more severe complications like
strokes or transient ischemic attacks, attributed to the involvement of
carotid or vertebral arteries (8).

Gastrointestinal (GI) involvement, although rare, is another unusual
manifestation of TA. Patients may experience abdominal pain, ischemic
bowel disease, or even acute abdomen, often resulting from mesenteric
artery stenosis or aneurysms (9). Pulmonary artery involvement can also
occur, leading to symptoms like dyspnoea, chest pain, or haemoptysis.

Cardiac manifestations, including aortic regurgitation, coronary artery
disease, and myocardial infarction, are also reported in TA patients,
posing significant risks (10).

These atypical manifestations highlight the need for a high index of
suspicion and comprehensive evaluation in patients with TA. A
multidisciplinary approach involving rheumatologists, cardiologists,
neurologists, and other specialists is often necessary for optimal
management. Understanding and recognizing these unusual presentations
are crucial for early diagnosis and treatment, which can significantly
alter the disease course and improve patient outcomes (10).

\textbf{References} :

\begin{enumerate}
\tightlist
\item
  Kim, Esther SH, and Joshua Beckman. ``Takayasu arteritis: challenges
  in diagnosis and management.'' Heart (2017).
\item
  Mason, Justin C. ``Takayasu arteritis---advances in diagnosis and
  management.'' Nature reviews rheumatology 6.7 (2010): 406-415.
\item
  Russo, Ricardo AG, and Mar\selectlanguage{ngerman}ía M. Katsicas. ``Takayasu arteritis.''
  Frontiers in pediatrics 6 (2018): 265.
\item
  Kerr, Gail S., et al. ``Takayasu arteritis.'' Annals of internal
  medicine 120.11 (1994): 919-929.
\item
  Mwipatayi, Bibombe P., et al. ``Takayasu arteritis: clinical features
  and management: report of 272 cases.'' ANZ journal of surgery 75.3
  (2005): 110-117.
\item
  Gornik HL, Creager MA. Aortitis. Circulation. 2008 Jun
  10;117(23):3039-51. doi: 10.1161/CIRCULATIONAHA.107.760686. PMID:
  18541754; PMCID: PMC2759760.
\item
  Watson, L., et al. ``Diagnosis and assessment of disease activity in
  Takayasu arteritis: a childhood case illustrating the challenge.''
  Case Reports in Rheumatology 2014 (2014).
\item
  Direskeneli, Haner. ``Clinical assessment in Takayasu's arteritis:
  major challenges and controversies.'' Clin Exp Rheumatol 35.Suppl 103
  (2017): 189-93.
\item
  Keser, Gökhan, Kenan Aksu, and RAF\selectlanguage{polish}İ \selectlanguage{english}HANER D\selectlanguage{polish}İ\selectlanguage{english}RESKENEL\selectlanguage{polish}İ. \selectlanguage{english}``Takayasu
  arteritis: an update.'' Turkish journal of medical sciences 48.4
  (2018): 681-697.
\item
  Schmidt, Jean, et al. ``Diagnostic features, treatment, and outcomes
  of Takayasu arteritis in a US cohort of 126 patients.'' Mayo Clinic
  Proceedings. Vol. 88. No. 8. Elsevier, 2013.
\item
  Chatterjee, Soumya, et al. ``Clinical diagnosis and management of
  large vessel vasculitis: Takayasu arteritis.'' Current cardiology
  reports 16 (2014): 1-10.
\end{enumerate}\selectlanguage{english}
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