International Journal of Medical Sciences And Clinical Research
40
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VOLUME
Vol.05 Issue03 2025
PAGE NO.
40-45
10.37547/ijmscr/Volume05Issue03-08
Evaluation of the efficiency of methods of diagnostics of
various variants of granulomatosis with polyangiitis
Berdieva D.U.
Tashkent Medical Academy, Uzbekistan
Received:
29 January 2025;
Accepted:
28 February 2025;
Published:
31 March 2025
Abstract:
Early diagnosis of granulomatosis with polyangiitis (GPA) is a difficult clinical task and requires a
thorough examination of the patient using modern research methods to identify pathognomonic symptoms. It is
necessary to specifically search for respiratory tract damage by performing rhinoscopy, laryngoscopy, computer
tomography of the paranasal sinuses, and lung scans, as the disease may be asymptomatic or have minimal clinical
symptoms for a long time. Only 50% of patients are diagnosed within the first 3-6 months of disease onset, while
in 7%, GPA remains undetected for 5-16 years after the first symptoms appear.
In the active period of the disease, non-specific signs are revealed in the laboratory examination: normochromic
anemia, thrombocytosis, neutrophilic leukocytosis and an increase in ESR, rheumatoid factor, positivity of C-
reactive protein. Clinical analysis of urine: hematuria, erythrocyte casts, proteinuria. Along with the urinary
syndrome, azotemic indicators increase and the glomerular filtration rate decreases rapidly.
Keywords:
Granulomatosis with polyangiitis, diagnosis, ANCA.
Introduction:
ANCA is a group of immunoglobulin G
(IgG) antibodies directed against the cytoplasm of
neutrophil granulocytes and monocytes, the presence
of which in blood serum can be detected indirectly by
immunofluorescence. In PAG, antigens are detected for
proteinase 3 (PR3) and myeloperoxidase (MPO). ANCA
against these antigens is therefore called PR3-ANCA
and MPO-ANCA. The detection of ANCA is important.
Among serological methods for the detection of ANCA,
immunofluorescence
and
enzyme-linked
immunosorbent assays are widely used. In indirect
immunofluorescence in the presence of ethanol-fixed
neutrophils, antibodies specific for proteinase-3 and
myeloperoxidase produce different fluorescences: they
are c-ANCA (cytoplasmic antineutrophil cytoplasmic
antibodies) and p-ANCA (perinuclear antineutrophil
cytoplasmic antibodies). c-ANCA is mainly associated
with serum containing PR3-ANCA and is specific for
PAH (>90%). c-ANCA has a sensitivity of 91% and
specificity of 99% for active HPA [1-7]. However, ANCA
is an important diagnostic marker of PAH and has a low
value for monitoring disease activity, because they can
be present in the serum during complete clinical
remission and may not be detected in relapses despite
high vasculitis activity. Although high ANCA activity is
common in GPA, ANCA is unlikely to be a major factor
in the development of the disease [8-11]. In systemic
GPA, c-ANCA is found in approximately 90% of patients,
and in 80-95% of these patients, antibodies are
directed against PR3. c-ANCA has a sensitivity of 91%
and specificity of 99% for active GPA.
Purpose
: To evaluate the effectiveness of methods of
diagnosis of various variants of polyangiitis
granulomatosis
METHODS
The study subjects were 60 patients with GPA who
were treated inpatiently in the rheumatology and
cardiorheumatology
departments
of
the
Multidisciplinary Clinic of the Tashkent Medical
Academy in 2018-2022 and who were monitored and
treated on an outpatient basis in the arthrological IADC
department.
The subjects of the study included patients' blood
serum, radiological and ultrasound examination
methods, as well as materials for determining the level
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International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
of disease activity (BVAS) and determining the
vasculitis damage index (VDI).
The study used a clinical questionnaire, laboratory
tests,
immunological
(ANCA),
nasopharyngeal
bacteriological culture, BVAS and VDI indicators,
instrumental (paranasal sinus and lung CT, X-ray
examination) and statistical methods.
General examination of patients was carried out
according to the plan adopted in the clinic. During the
study of the anamnesis, special attention was paid to
the activity of the disease, the presence of damage to
various organs and systems.
In the detailed anamnesis study, the premorbid
background more than 6 months before the onset of
GPA and the conditions that preceded the appearance
of GPA symptoms and could cause its development
were analyzed. Manifest symptoms of the first month
of the disease, clinical manifestations of the
exacerbation phase and subsequent relapses were
compared.
The BVAS scale (Bermingham Vasculitis Activity Index)
was used to assess activity. Remission of the disease
was considered to be a BVAS score of 1 or less, and
exacerbation of GPA was considered to be a BVAS score
of 2 or more. Organ damage was assessed in all patients
using the VDI index. The damage index takes into
account the organ damage observed since the onset of
vasculitis. Patients often have additional diseases that
arose before the development of vasculitis, which
should not be taken into account.
RESULTS
Patients with exacerbation of GPA had significantly
higher erythrocyte sedimentation rate and C-reactive
protein levels compared with patients in remission of
GPA. The main laboratory parameters are presented in
Table 1.
TABLE 1
Laboratory indicators in patients with PAG according to the form and period of the
disease
General
Disease form
Disease period
N=60
Local
(n=29)
Generalized
(n=31)
Intensification
(n=32)
Remission
(n=28)
Glomerular
filtration rate
less than 60
ml/min/1.73
m2
19 (31.7%)
0
19 (50.0%)
11 (34.4%)
8 (28.6%)
Proteinuria
18 (%)
0
18 (47.4%)
9 (28.%)
9 (28.1%)
Proteinuria
more than
0.5 g/day
10 (16.7%)
0
10 (26.3%)
6 (18.8%)
4 (14.3%)
Elevated
creatinine
levels in
blood
16 (26.7%)
0
16 (42.1%)
10 (31.3%)
6 (10.0%)
Mean value
of creatinine,
mg/dl
1.29±1.1
0.91±0.2
1.5±1.3
1.48±1.4
1.08±0.4
GFR reading
CKDEPI,
ml/min
67.3±28.3
80.1±19.9
59.9±28.2
62.5±28.1
72.7±28.0
Hematuria
12 (20.0%)
0
12 (31.6%)
8 ( 25.0%)
4 (14.3%)
Average
daily
0.21±0.6
0.03±0.1
0.32±0.7
0.26±0.7
0.16±0.3
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International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
proteinuria,
g/day
Elevated
ESR
29 (48.3%) 7 (31.8%)
22 (57.9%)
20 (62.5%)
9 (32.1%)
Average
ESR value,
mm/s
18.02±16.8 12.23±7.3
21.37±19.8
23.69±20.6
11.54±7.1
Increased
CRP
13
(21.67%)
2 (9.1%) 11 (28.9%)
12 (37.5%)
1 (3.6%)
A decrease in glomerular filtration rate of more than
50% was found in 19 (31.67%) GPA patients with renal
vasculitis. TRGN development was noted in 1 (1.7%)
patient (increased creatinine from 5 mg/dL to 8.3
mg/dL). In patients with PAG, urinary syndrome was
mainly manifested by hematuria and proteinuria (PU
up to 1 g per day - 16 (89.5%), 1-3 g per day - 1 (5.3%),
more than 3 g per day (nephrotic syndrome) - 1 (5.3%),
which was observed more often in patients with an
exacerbation of GPA.
Thus, the expressed stage of GPA is characterized by
the development of upper respiratory tract pathology,
usually with necrotic/ulcerative involvement of
rhinosinusitis (96%), the organ of hearing (41.6%) and
the larynx (3.3%), the formation of foci/infiltrates
prone to resorption in the lungs (53.3%), can be
asymptomatic and develop GN with hematuria (38.3%),
fever and arthralgia/arthritis in every third case
(13.3%). Less skin lesions (8.3%), eyes (41.6%),
cardiovascular pathology (3.3%). In the diffuse type of
GPA, i.e., group 2, significantly higher indicators of CRP
and ESR were also distinguished (Fig. 1).
ANCA was detected in 58 (93.3%) patients, 2 (3.3%)
patients remained ANCA-negative throughout the
entire follow-up period. Antibodies to PR-3 were
detected in 48 (80%) patients, more often than anti-
MPO antibodies, with a female predominance in both
groups (11 and 19, respectively).
The titer of antineutrophil cytoplasmic antibodies,
ANCA, which is an immunological marker of GPA, was
significantly lower in the local type than in the diffuse
type (Figure 2).
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International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
According to statistical data, a high titer of ANCA
indicates more damage to internal organs. Our
scientific study confirmed this conclusion, showing a
higher frequency of organ damage in GPA patients with
ANCA titer higher than 5. (Table 2)
No significant difference was found in the titer of ANCA
in the course of GPA. The frequency of short-term and
long-term recurrences did not differ significantly
between the two disease types. However, GPA with
higher ANCA titer had higher clinical severity of
relapses (Figure 3).
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International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
In the group of patients with PR-3-AT, the frequency of
visual organ damage (p=0.05) and the presence of
areas of consolidation in the lungs at the end of follow-
up (p=0.009) were significantly higher than in the group
of patients with MPO-AT. At the same time, patients
with PR-3-ANCA had higher creatinine levels at the
initial onset of the disease (p=0.025). There was no
significant difference in lung, kidney, or other organ
damage. There were also no significant differences in
mortality, seizure frequency, activity parameters, or
nonreversibility of lesions.
During the recurring period, ANCA levels may exceed
those detected at the onset of the disease. Of particular
interest is the ANCA-negative variant of GPA. In this
sample, 2 patients with ANCA-negative status were
identified, 1 female, 1 male, mean age 49.4 years, and
follow-up period 20.5 months. There were no
differences in the values of BVAS and VDI indices when
compared. These patients had severe clinical
manifestations of GPA, as a result of which diffuse
alveolar hemorrhage developed in 1 patient, and in 1
patient, renal function increased to stage 3B and higher
at the end of observation.
CONCLUSION
Early diagnosis and exacerbation of GPA allow us to
conclude that patients with high serum ANCA and CRP
titers have a higher incidence of internal organ damage
and, at the same time, are predictors of severe
outcomes.
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