Delayed diagnosis of Granulomatosis with Polyangiitis in a
39-year-old woman with
situs inversus totalis: A Case Report
Authors: Hanie Forouzandeh¹Ahmadreza
Rajabi¹, Abbas Ali Torfeh
Esfahani², Farzin
Khorvash², Mansoor
Karimifar³
Affiliations: ¹ School of Medicine, Isfahan University
of Medical Sciences, Isfahan, Iran.
² Department of Infectious Diseases and
Tropical Medicine, School of Medicine, Isfahan University of Medical
Sciences, Isfahan, Iran.
³ Department of Rheumatology, Alzahra
Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.Corresponding author: Abbas Ali Torfeh Esfahani Department of Infectious Diseases and Tropical Medicine, School of
Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Email Address:
abas1793@gmail.com Full postal address: P.O. Box 791 – Al-Zahra Hospital – Soffe St. –
Isfahan - Iran Tel: (+98) 31-36202086
https://orcid.org/0000-0002-4950-5806-haniforouzandeh80@gmail.com
Ahmadreza Rajabi :
https://orcid.org/0009-0002-7584-9124-ahmadrezarajabi96@gmail.com
Abbas Ali Torfeh Esfahani :
https://orcid.org/0000-0001-9713-1549-abas1793@gmail.com
Farzin Khorvash :
https://orcid.org/0000-0003-2542-9885-khorvash@med.mui.ac.ir
Mansoor Karimifar:
https://orcid.org/0000-0003-4688-991X-karimifar@med.mui.ac.ir
Compliance with Ethical Standards Data availability statement: Data sharing is not applicable to
this article as no new data were created or analyzed in this study.Funding statement: None.Conflict of interest disclosure: None.Ethics approval statement: not applicable.Patient consent statement: Written informed consent was
obtained from all individual participants included in the study.Permission to reproduce material from other sources: not
applicable.Clinical trial registration: not applicableAuthor Contributions Hanie Forouzandeh: Writing – original draft, Data curation, study
design, Supervision, Project administration
Ahmadreza Rajabi: Writing – original draft, Data curation
Abbas Ali Torfeh Esfahani: Supervision, Writing – review & editing,
Conceptualization, Project administration
Farzin Khorvash: Writing – review & editing, Conceptualization
Mansoor Karimifar: Writing – review & editing, ConceptualizationAcknowledgments Conflict of interest All the authors have
declared no competing interests.Human and Animal Rights This article does not contain any
studies with human participants or animals performed by any of the
authors.Informed consent Informed consent was obtained from all
individual participants included in the study. Author’s
contribution All authors contributed to the study design, data
collection, and writing the draft of the study. All read and confirmed
the final version of the manuscript.
AbstractSitus inversus totalis (SIT) is a rare congenital condition
characterized by the transposition of both abdominal and thoracic
organs. Individuals with Situs inversus totalis (SIT) may also have
Kartagener syndrome, which is characterized by a triad of situs
inversus, bronchiectasis, and recurrent sinusitis. Granulomatosis with
polyangiitis (GPA), also known as Wegener’s granulomatosis, is a rare
condition. GPA involves granulomatous inflammation in tissues and blood
vessels, potentially leading to organ damage. To date, no cases of Situs
inversus totalis (SIT) individuals with Wegener’s granulomatosis have
been reported in the literature. Our study aims to report a case with
misleading information in medical history, leading to a delayed
diagnosis of Granulomatosis with polyangiitis (GPA). Keywords: situs inversus totalis, Kartagener syndrome, Granulomatosis
with polyangiitis, Wegener’s granulomatosiskey clinical message: The main clinical point in this article
is being aware of all possible differential diagnoses despite all
misleading data on the patient’s history. It is also very interesting
that we have a patient who has a rare congenital condition with a
diagnosis of a rare disease.IntroductionSitus inversus totalis (SIT) is an extremely rare congenital condition
characterized by the transposition of both abdominal and thoracic
organs. This rare condition occurs in approximately 1:10,000
individuals(1). Even most professional
surgeons may encounter only 1 to 2 cases throughout their entire
career(2). Typically, these cases are
discovered incidentally during medical procedures or imaging
tests(3). Sometimes these people have
Kartagener Syndrome which is defined by a triad of situs inversus,
bronchiectasis, and recurrent sinusitis(1).
Granulomatosis with polyangiitis (GPA), also known as Wegener’s
granulomatosis, is a rare condition with an unknown cause. It affects
approximately 3 in every 100,000 people and typically occurs around the
age of 45 in both males and females. Granulomatosis with polyangiitis
(GPA) is characterized by inflammation in the tissues, known as
granulomatous inflammation, as well as inflammation in the blood vessels
(vasculitis), which can lead to organ damage. While the sinuses, lungs,
and kidneys are the most commonly affected areas, GPA can impact any
part of the body(4).
We herein present a patient with situs inversus totalis who has been
diagnosed with GPA (Wegener’s granulomatosis) at Alzahra Medical &
Educational Center \RL of Isfahan.
Case presentationWe present a case of a 39–year–old woman with situs inversus totalis
and a previous history of Kartagener syndrome and hypothyroidism. She
came to the emergency department with intermittent petechiae and purpura
in her lower limbs and intermittent high-grade fever and true chills
from 3 months ago. She was giving a history of traveling to the
Malaria-endemic region. Rashes and fever started right after her trip.
She was giving a history of mild weight loss, nausea, and vomiting.
Vital signs demonstrated a fever of 38.5°C, blood pressure (BP) 95/60,
pulse rate (PR) 100, respiratory rate (RR) 24, and O2sat 88%. In the
physical examination, we found a mild crackle in lung auscultation.
Rashes were non-blanching. Laboratories were remarkable for leukocytosis
of 14.05 with left shifting and thrombocytosis of 535. ESR was 101 and
CRP was 88. Serum creatinine was 1.4 at first and then rose to 1.7 in
three days. CXR showed evidence of mild infiltration in the lower lobe
of the left lung and mild pleural effusion on the left side
(Figure1). We tapped the pleural effusion.
It had an exudative pattern in analysis. With a suspicion of Malaria, we
performed PBS but it didn’t confirm Malaria. We requested blood culture,
sputum culture, wright test, PPD skin test, Widal test, and viral
markers, which all were negative. U/A was remarkable for protein (++),
blood (+++), RBC (many, 40% dysmorphic), and granular casts (1-2).
Urine culture was negative. The stool exam was normal and the stool
culture was negative. Endoscopy was performed for continuous nausea and
vomiting and food intolerance, too. It showed erosive gastropathy. We
also ruled out endocarditis with a normal echocardiography with no
evidence of vegetation. Then we changed our approach from infectious
diseases that were related to her travel, to rheumatologic diseases. So,
we requested rheumatologic tests, and C-ANCA (Anti PR3) and ANA and RF
were positive among them (The results are in
Table1). We also performed a Chest M.D.C.T
that showed cystic bronchiectasis(Figure2),
mild infiltration in the lower lobe of the left lung, and mild pleural
effusion on the left side (figure3) and we
did a normal Abdominal M.D.C.T Scan.Differential diagnosis:Differential diagnoses of fever and rash included infectious diseases
like mononucleosis, Meningitis, Endocarditis, Malaria, Dengue fever,
Scarlet fever, malignancies like Lymphoma, or autoimmune diseases like
Vasculitis, SLE, and Still’s.
Treatment plan:At first, we had started antibiotics for her because of our suspicion of
infectious diseases but she had a fever for the next 3 days despite
antibiotic therapy, then after the positivity of autoimmune tests, we
changed our treatment. First, the patient was started on three
consecutive pulse doses (1gr) of Methylprednisolone Sodium Succinate
then she received 1gr Rituximab, and this dose was repeated fourteen
days later. We continued her therapy with a Prednisolone Tab (10mg/three
times a day), Azathioprine Tab (daily), and Calcium D Tab (daily). Then
a month after the second dose of Rituximab, we increased the dose of
Azathioprine Tab to 50mg twice a day and we slowly tapered Prednisolone.
This is important to mention that we chose Rituximab among other common
treatments because the patient was of reproductive age and treatments
like Cyclophosphamide could lead to infertility. We also added
Cotrimoxazole 400/80mg Tab for prevention of Pneumocystis Carinii.Follow up:To date when we write this report, the patient’s signs and symptoms are
improved. Serum creatine decreased to 1.3 and urine analysis turned to
normal.
DiscussionAntineutrophil cytoplasmic antibody ANCA-associated vasculitis (AAV)
encompasses a group of multisystem disorders that cause inflammation in
the small blood vessels. This group includes granulomatosis with
polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic
granulomatosis with polyangiitis
(EGPA)(5)\RL.
As described in the classification criteria for granulomatosis with
polyangiitis, PR3-ANCA is most frequently linked with granulomatosis
with polyangiitis (GPA), but MPO-ANCA is more prevalent in microscopic
polyangiitis (MPA)(6)\RL. Advances in the diagnosis and treatment of
ANCA-associated vasculitis (AAV) have significantly improved outcomes,
changing it from a rapidly fatal disease with an untreated 1-year
mortality rate of 80% to a condition that has relapsing and remitting
episodes, albeit with ongoing morbidity and mortality in the long term.
Pulmonary complications, both acute and chronic, are common in
ANCA-associated vasculitis (AAV), affecting 25% to 80% of cases
according to references. Lung involvement is increasingly recognized as
a key contributor to the persistent morbidity and mortality in
ANCA-associated vasculitis (AAV), with early pulmonary manifestations
being linked to severe organ damage and poor outcomes in
GPA(6)\RL.Conclusion Although there are few articles about the association between
ANCA-associated vasculitis (AAV) and pulmonary involvements such as
bronchiectasis(6), there is no published
article about situs inversus individuals with GPA or association between
Kartagener syndrome and ANCA-associated vasculitis (AAV). Additionally,
our case had a history of traveling to malaria-endemic regions, which
misled us in our approach to limb petechiae and fever and it made our
case more noteworthy to report. However, further tests led to the
diagnosis of ANCA-associated vasculitis (AAV).