A case report of Cardiovascular Disease caused by
Anti-neutrophil Cytoplasmic Antibody (ANCA) -associated vasculitis
Zulhumar Aysa1 M.S ;Zhan-neng Yang 1M.D; Yong Qiao2 Ph.D ; Gao-Liang
Yan2 Ph.D ; Cheng-Chun Tang3Ph.D ;
Author Information
1 School of Medicine, Southeast University, Nanjing 210009, Jiangsu
Province, China.
2 Department of Cardiology, Zhongda Hospital, Southeast University,
Nanjing 210009, Jiangsu Province, China.
3Department of Cardiology, Zhongda Hospital, Southeast University,
Nanjing 210009, Jiangsu Province, China. Corresponding author
Email:tangchengchun@hotmail.com
Abbreviations: ANCA=Anti- neutrophil cytoplasmic antibodies,
AAV=Anti-neutrophil cytoplasmic antibodies (ANCA) -associated vasculitis
Ethics approval and consent to participate was not applicable.
Written informed consent for publication was obtained from the patient.
All patient information was obtained from the Department of Cardiology,
Affiliated Hospital &Southeast University, Nanjing, Jiangsu, China. All
data used and analyzed in the current study are included in this
article.
Funding was not applicable.
The authors have no conflicts of interest to disclose.
Data sharing not applicable to this article as no datasets were
generated or analyzed during the current study.
Abstract
Rationale:
Anti-neutrophil cytoplasmic antibody (ANCA) -associated vasculitis is a
group of systemic small vessel vasculitis characterized by the detection
of ANCA in serum, which mainly affects small vessels (arterioles,
arterioles, venules, and capillaries)but may also have middle artery
involvement. In recent years, with the deepening of studies on ANCA)
-associated vasculitis , reports of coronary artery involvement have
also repeatedly emerged, updating the view that AAV only involves small
vessels in the past. We report a case of ANCA -associated vasculitis.
Patient concerns:
We reported a-49-year-old women with dizziness and fatigue for one half
year , who visited several hospitals during this period ,and her
symptoms recurred.
Diagnoses:
In the event of clinical suspicion of AAV, ANCA should first be
determined using an antigen-specific immunoassay for proteinase 3‑ANCA
and myeloperoxidase-ANCA, according to current consensus
recommendations.
Outcomes:
The symptoms relieved significantly.
Lessons:
In recent years, with the deepening of the studies on antineutrophil
cytoplasmic antibody (ANCA) -associated vasculitis (AAV), reports of
coronary artery involvement have also repeatedly emerged, updating the
view that AAV only involves small vessels in the past. Cardiovascular
involvement is an independent risk factor for death in patients with
AAV, with a 4.811-fold increased risk of death compared to patients who
do not develop cardiovascular involvement [1].
Although the proportion of cardiovascular involvement is relatively
small in the lungs and kidneys, if it is not diagnosed and treated in
time, the consequences are serious. The mortality rate of AAV patients
with evidence of cardiac involvement (electrocardiogram,
echocardiography, cardiac magnetic resonance imaging, coronary
angiography, myocardial biopsy, etc.) has significantly
increased[2]. Therefore, clinical attention should
be paid to the screening of routine cardiac involvement in patients with
AAV.ANCA-associated vasculitis rarely accumulates in the coronary
arteries and has a poor prognosis and a high risk of early death.
This case was used as the object of this study to further investigate
the clinical features of ANCA-associated vasculitis in order to provide
a practical and detailed reference for improving the diagnosis and
treatment of this disease.
keywords:
Anti-neutrophil cytoplasmic antibody-associated vasculitis; coronary
heart disease; prevention
1. Introduction
A 49-year-old women presented to the first local hospital for diagnosis
and treatment in July 2021 because of dizziness and fatigue for one
month. One month prior , the patient had dizziness, fatigue, poor
appetite without obvious cause, and numbness of both feet, accompanied
by a needling sensation, and visited the first local hospital. Routine
blood examination showed: WBC:6.68*1^ 09/l;HGB:332*10^
9/l;PLT:332*10^ 9/l,liver and kidney function, urine routine,
fecal occult blood showed no significant abnormality , anemia was
considered, and blood transfusion and other symptomatic treatments were
administered. The patient was discharged after the symptom improved.
Later, the patient experienced aggravated fatigue and went to a second
local hospital for treatment. A 13, 2021-13, bone marrow puncture was
performed on August 13,2021. The results showed hyperplastic anemia with
a granulocyte maturation disorder. The patient‘s condition improved and
she was discharged after symptomatic and supportive treatment.
On October 10, the patient developed fever and was diagnosed and treated
at the third local hospital. Her body temperature returned to normal
after symptomatic treatment. The patient was discharged after the
symptom improved.
On November 2, 2021, the patient experienced dizziness and fatigue
again, and visited the fourth hospital for treatment. The patient
received a blood transfusion ,fluid infusion , other symptomatic, and
supportive treatments. The results of bone marrow aspiration (November
8, 2021) showed that bone marrow hyperplasia was significantly active.
Fe staining: extracellular iron (+); the positive rate of intracellular
iron was 10%, of which type I accounted for 9% and type II accounted
for 1%. On November 8, 2021, whole body CT showed mucosal thickening of
the sphenoid sinus and maxillary sinus ,hypertrophy of right inferior
turbinate ,left diploic mastoid process, left middle ear mastoiditis,
several solid nodules in both lungs, ground-glass nodules in the upper
lobe of the left lung, (all less than 5 mm),and a small amount of
pericardial effusion.On November 10, 2021, the patient visited our
outpatient clinic for diagnosis and treatment. Blood routine: WBC: 9.25
× 10 9/L, HGB: 88g/l, PLT: 525 ×
10 9/L, Na +: 159.6 mmol/l, CI: 123.3 mmol/l. The
patient was admitted by our hematology department as an outpatient due
to ”Anemia ”. During the course of the disease, the patient had clear
consciousness, poor spirit, poor appetite, normal urination, and
constipation, with a weight loss of 5 kg in recent the previous 3
months. She was healthy in the past, had a history of anxiety disorder
for 2 years, had not taken regular medication recently, had thyroid
nodules (TMAI8), and had not received special treatment.On admission,
her mental status was normal. Her body temperature was 36.5 °C, pulse
rate was 115 beats/min and regular, respiratory rate was 20 breaths/min,
and blood pressure was 93/66 mmHg
. Upper abdominal discomfort with tenderness below the xiphoid process.
The patient was initially diagnosed with the following conditions
(Department of Hematology ): 1. Anemia ; 2. Anxiety disorder; 3.
Thyroid nodule
A series of laboratory tests were performed after admission. Laboratory
results indicated: WBC:9.81×
10 9/L;HBG:78g/;PLT:431×
10 9/L;CRP-HS:105.33mg/Lt;RF:55IU/mLt;Na+:165.0mmo1/L,CI:125.6mmo1/f;ferritin761.19ug/l
,EPO:70.02pg/l,TGAb:1500IU/mlt、Anti-nuclear antibody series (13 items):
negative; Coob’s test: negative; Aspergillus immunological test: 0.113
μg/L; fungus-D glucan quantitative G test: negative. Gastrointestinal
endoscopy,1. Chronic gastritis with biliary obstruction 2. Gastric
polyps (biopsy removal) 3. portal inflammation 4. Rough hemorrhoids of
the colonic mucosa. The positive rate of intracellular iron in bone
marrow aspiration in other hospitals was low, and the patient was given
symptomatic treatment such as improving anemia, acid suppression ,
stomach protection, and anti-anxiety. The possibility of autoimmune
diseases was considered after admission, the body temperature fluctuated
between 36.5℃ and 38.9℃ (as shown in Figure 1), and the conjunctiva was
congested with hyperplasia. After further analysis of changes in the
condition. The examination of autoimmune disease-related markers was
immediately perfected: ANCA: positive; MPO-IgG: 336.37 RU/ml1, anti-CCP
antibody: 1.805 KU/ml;
The patient was transferred to the Department of Rheumatology and
Immunology at our hospital, and the revised diagnosis was made 1.
ANCA-associated vasculitis, 2. Iron-deficiency anemia, 3. Hypernatremia
4. Anxiety Disorders 5. Thyroid nodules 6. chronic gastritis with bile
7. Gastric polyps; methylprednisolone 20 mg ivdrip, hydroxychloroquine
sulfate tablets 0.2g po qd ,and the other treatments were the same as
above; (November 22, 2021-22) the patient developed chest discomfort,
emergency examination of aTnI: 3.2379, ECG (Figure 2) showed: 1.Sinus
tachycardia 2. abnormal T-waves3.low QRS; consultation was given,
considering that the patient’s age, blood pressure, blood glucose, blood
lipid, etc. were not significantly abnormal, without coronary heart
disease factors; emergency left and right coronary angiography (Figure
3) was performed on November 23, 2021, which showed no significant
stenosis of the left main coronary artery, slow total blood flow in the
left anterior descending branch, plaque infiltration, complete occlusion
of the middle and distal segments; plaque infiltration in the left
circumflex artery, 95% stenosis in the middle segment.
The patient was transferred to the hospital and underwent relevant
examinations. ECG (Figure 4) showed the following: 1. sinus rhythm 2.
Limb QRS wave low voltage, V3-V6 chest low voltage; echocardiography
(Figure 5) showed: FE: 0.52, E/A < 1; abnormal wall motion;
mild tricuspid valve; reduced left ventricular function. The modified
diagnoses were as follows: 1. Coronary heart disease, acute
non-ST-segment elevation myocardial infarction, coronary spontaneous
dissection Killip II 2. ANCA-associated vasculitis 3. Iron deficiency
anemia 4. Anxiety Disorders 5. Thyroid vein nodule 6.Chronic gastritis
Carditis. (November 23, 2021) underwent coronary artery stenting under
local anesthesia (Figure 6) and was treated with dual antibody,
lipid-lowering, and ventricular rate control. Other treatments were the
same as above, and the patient’s chest tightness symptoms improved.
(November 26, 2021) was transferred to the Department of Rheumatology
and Immunology of our hospital for further treatment of the primary
disease .Because the patient’s vasculitis accumulated in the great
vessels, she was administered 100 mg intravenous drip for two days each
on the basis of the previous treatment. Reexamination of the ECG showed
revealed the following : 1. sinus rhythm 2.The Q wave was abnormal
(Figure 7),and reexamination of blood (result: 1) showed that all
indicators were lower than before, the condition was stable, and the
patient was discharged on December 9, 2021.The patient was instructed to
receive an intravenous drip of rituximab 100 mg 1 week after discharge
(December 15, 2021), and the discharge medications included
methylprednisolone, hydroxychloroquine sulfate tablets, total glucosides
of paeony capsules, double antibody, lipid regulation, acid suppression
, stomach protection, and anti-anxiety.The patient was followed up at
discharge to monitor changes in the patient’s condition.
On January 7, 2022, the patient came to the hospital for re-examination
and recovered well, and all laboratory indicators decreased, as shown in
Table 1. This demonstrates that our diagnostic and therapeutic
approaches were correct.
2.Discussion
ANCA-associated vasculitis is a systemic, oligoimmune complex
necrotizing vasculitis, and there are no uniform diagnostic criteria
that need to be combine with clinical manifestations, serum ANCA
examination, characteristic pathological changes, imaging examination to
make a comprehensive diagnosis. Its clinical manifestations include
fatigue, fever, weight loss, arthralgia, sinusitis, cough, hemoptysis,
dyspnea, urinary abnormalities, purpura, pericarditis, myocardial
lesions and neurological dysfunction. Its pathogenesis is still not very
clear, but it is affected by various factors such as environmental
exposure, genetic susceptibility, cytokines, complement, ANCA, and
immune cells [3]. In this case, the patient was
initially treated for anemia at another hospital and our hospital, and
the symptoms were not significantly relieved after improving anemia
treatment. Combined with the patient’s symptoms, signs, and imaging
findings, ANCA-associated vasculitis was initially highly suspected, and
the author reported this case to improve the clinicians’ understanding
of the disease.
On the first admission, the patient only experienced dizziness, fatigue,
and poor appetite, and was preliminarily diagnosed with anemia. The
symptoms were relieved after symptomatic treatment, and similar symptoms
recurred after discharge. The symptoms lacked specificity and were not
diagnosed at an early stage. The diagnosis was delayed for half a year
.The diagnosis of ANCA-associated vasculitis is usually delayed or
missed because the disease has few characteristic symptoms and most
patients present systemically with multisystem damage, which can lead to
early failure to make an accurate diagnosis if changes in each system
are considered separately[4].When the diagnosis is
delayed or missed, there is a significant difference in the prognosis of
patients: only 11 percent of patients survive for more than two years
without treatment[5].If detected in a timely
manner, ANCA-associated vasculitis responds well to immunosuppressive
therapy and has a prognosis similar to that of other chronic
inflammatory diseases .In a foreign randomized controlled trial, 60-90%
of patients achieved remission of the disease, and the 2-year survival
rate was as high as 90-97%[6, 7].On the 13th day
after admission, the patient had chest discomfort, emergency examination
of aTnI was3.2379 ng/ml, coronary angiography results showed 95%
stenosis in the middle segment of the right coronary artery, and the
patient was diagnosed with coronary heart disease. The patient’s blood
pressure, blood glucose, and blood lipids were within the normal range,
without chest tightness, chest pain ,or other symptoms after activity,
no smoking history, and no family history of coronary heart disease
;therefore coronary artery stenting was suspected to be caused by
vasculitis. If the diagnosis was confirmed for the first time,
vasculitis was likely not to involve the coronary artery. Since the
coronary artery was involved, the patient’s prognosis would be worse and
the risk of early death would be higher.
Treatment strategies for ANCA-associated vasculitis are mainly based on
disease classification and severity and are generally divided into three
stages: induction of remission (3 to 6 months), maintenance of remission
(at least 18 months), and prevention of relapse .In recent decades,
high-dose glucocorticoids and cyclophosphamide have historically been
the mainstay treatment for ANCA-associated vasculitis .This regimen is
highly likely to transform the usual treatment outcome of severe
ANCA-associated vasculitis from death to disease control and temporary
remission[8] However, not all patients can achieve
remission with this drug combination, and those who do often experience
flares of disease that require repeated
treatment[9-14].In addition, the side effects of
cyclophosphamide, as well as the multiple side effects of long-term
glucocorticoid therapy, are major causes of long-term illness and death[9-11, 13-17].Recent years have demonstrated that
rituximab is an effective alternative to cyclophosphamide, and
rituximab-based regimens are more effective than cyclophosphamide-based
regimens in inducing remission in patients with relapsed disease.
Methylprednisolone and hydroxychloroquine sulfate tablets were started
when the patient was definitively diagnosed with ANCA-associated
vasculitis; however, coronary artery involvement occurred during
hospitalization; therefore, rituximab was used in combination to better
relieve symptoms and improve the prognosis. In summary, ANCA-associated
vasculitis is a syndrome with an unclear etiology, diverse clinical
manifestations, easy misdiagnosis and missed diagnosis, and rapid
progression of the disease in critically ill patients. Numerous studies
have reported that ANCA-associated vasculitis easily involves the
kidneys and lungs, while there are few reports of cardiovascular
involvement;therefore we are inexperienced in vasculitis involving the
heart and easily ignore the problem of the heart, so cardiovascular
accidents should be considered as early as possible when vasculitis is
encountered, as well as to prevent further aggravation. The possibility
of vasculitis is considered when non-specific symptoms such as
unexplained fever, weight loss, loss of appetite, and chronic sinusitis
occur. Autoimmune antibody screening should be performed as early as
possible, and timely detection and treatment should be performed to save
patients’ lives.
3.Author contributions
Zulhumar Aysa contributed to patient information acquisition and
manuscript writing; Yong Qiao 、Gao-Liang Yan 、 Cheng-Chun
Tangparticipated in the diagnosis and treatment of the patients.
Zhan-neng Yang revised the manuscript and all authors have read and
approved the final manuscript.