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COMPARATIVE EFFECTIVENESS OF PULSE THERAPY IN CHILDREN WITH
SYSTEMIC LUPUS ERYTHEMATOSUS
Abdulxakova R.M., Abduraxmonov I.T., Arifxujayev A.T.
Andijan State Medical Institute
The study included 18 patients with SLE, of which 9 were in the control group. A group of
patients with ineffective standard therapy and high activity of the process was selected, i.e.
the study included patients with a polysyndromic picture of systemic lupus erythematosus,
all with more than 5-8 ARA criteria.
To standardize the assessment of the dynamics of clinical and laboratory parameters, we
used the results of clinical symptoms, clinical blood tests with the calculation of index
parameters of white blood cells, and the results of acute phase activity of the inflammatory
process.
In order to objectify the assessment of the effectiveness of combination therapy, we
compared the results of treatment with prednisolone alone and in combination with
cyclophosphamide (control group). The results of the dynamics of clinical manifestations of
SLE in patients receiving pulse therapy (Group 1) and standard therapy (Group II) are
presented in Table 1. Analysis of the obtained results showed that the use of combination
therapy was effective in relation to most extrarenal manifestations of the disease already in
the first days after the end of treatment. Almost complete disappearance of the joint
syndrome, significant reduction in skin and mucous membrane lesions, disappearance
Table 1.
Dynamics of clinical manifestations of SLE in patients receiving pulse therapy and standard
therapy
Clinical sign
Patient groups
I (n=9)
II (n=9)
Before
treatment
On the 7th
day of
therapy
Before
treatment
On the
7th day
of
therapy
Fever
8
-
7
6
Articular syndrome
9
1
6
8
Skin and mucous membrane lesions
6
-
4
6
Lupus nephritis
6
1
6
6
Nervous system lesions
6
1
8
8
Vasculitis
6
1
4
4
Serositis
7
2
7
7
Lymphadenopathy
8
2
7
6
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Thrombocytopenia
2
-
1
1
Anemia
9
9
9
9
Leukopenia
7
5
6
6
ESR>15 mm/hour
9
3
9
9
lymphadenopathy, a decrease in the manifestations of carditis and polyserositis were
observed in all patients. In 5 of 6 patients, we observed either a complete disappearance or a
significant decrease in Raynaud's syndrome. As for the manifestations of lupus nephritis, in
4 of 6 patients with nephrotic syndrome, a decrease in edema syndrome, a decrease and
stabilization of blood pressure were observed already on the 3rd day. During the days of
combined therapy, such patients showed a significant increase in diuresis. Hematuria and
proteinuria decreased in more than half of the patients.
In patients of the second group, who received standard therapy with the inclusion of
prednisolone orally at a dose of 1-3 mg / day, at the end of the first week of therapy, no clear
positive changes in clinical indicators were noted. Thus, fever and articular syndrome
continued to persist. Skin and mucous membrane lesions were noted in two more patients.
Lupus nephritis, vasculitis, serositis, leukopenia did not have positive changes in any patient.
Analysis of the results of the peripheral blood picture showed (Table 2) that in patients of
the first group, who received pulse therapy, at the end of the 7th day there was
Table 2.
Dynamics of peripheral blood parameters in patients with SLE who received pulse therapy
and standard therapy
Indicators
In healthy people
Group I (n=9)
II group (n=9)
Erythrocytes
3,78±0,03
3,17±0,46
3,06±0,54
3,33±0,43
3,02±0,62
Hemoglobin, g/l
123,20±0,10
67,61±2,47
71,39±2,31
82,41±3,19
68,88±3,12
Color index
0,95±0,01
0,77±0,01
0,79±0,86
0,81±0,01
0,76±0,01
SHE, (in pg)
30,21±0,14
28,48±0,18
28,59±0,15
30,40±0,19
29,04±0,17
SSHE, (in %)
31,90±0,18
27,92±0,26
28,90±0,19
31,54±0,35
28,73±0,23
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ESR, (µm3)
94,59±0,27
101,49±0,82
102,69±0,59
95,80±0,76
100,62±0,47
Leukocytes
6,72±0,17
4,95±0,87
4,88±0,76
6,74±1,09
5,01±0,61
Band
3,02±0,20
4,93±0,26
4,78±0,20
2,12±0,14
4,41±0,09
Segmented
54,35±1,18
63,51±0,90
62,93±0,73
53,06±1,49
60,34±0,78
Lymphocytes
35,29±1,00
26,56±0,69
25,81±0,61
37,96±1,30
30,49±0,65
Monocytes
5,03±0,30
3,16±0,17
4,40±0,19
4,65±0,28
4,59±0,18
Eosinophils
2,31±0,20
1,84±0,09
2,15±0,08
2,20±0,19
2,17±0,14
ESR mm/h
7.50±0,06
43,56±2,33
39,23±3,11
24,91±3,12
40,51±4,08
Note: MCH - mean corpuscular hemoglobin; MCH - mean corpuscular hemoglobin
concentration; ESR - mean corpuscular volume.
The numerator shows the values before treatment. The denominator shows the
normalization of erythrocyte balance values 7 days after the start of therapy: the
erythrocyte content significantly increased, although it still remained lower than in healthy
children. The hemoglobin concentration increased significantly (severe anemia became
moderate), and the color index returned to normal. MCH, MCH, and ESR values did
not differ from those in healthy children. In terms of leukocyte content and leukocyte
formula values, patients in Group 1 did not differ from healthy children in the second period
of the study. The erythrocyte sedimentation rate in patients in this group significantly
decreased compared to the value upon admission. This indicates the onset of the stage of
attenuation of the immune-inflammatory process and the favorability of pulse therapy.
Unfavorable results were obtained in patients of group II in the second period of the study.
Thus, none of their indicators returned to normal in the second period of the study. Moderate
hypochromic anemia became severe, the indicators of SSGE, SGE and ESR were still
abnormal, which indicates the onset of severe anemia. Leukopenia, neutrophilia with a shift
to the left, relative and absolute lymphopenia, persistent acceleration of the erythrocyte
sedimentation rate still persisted. These general clinical laboratory data indicate the
continued activity of the inflammatory process and its unfavorable course.
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A comparative assessment of the treatment results showed that in patients of group II, the
overall clinical effect was worse than in patients of group I, which is confirmed by persistent
fever, articular syndrome, an increase in the frequency of lesions of the skin and mucous
membranes, lupus nephritis, vasculitis, serositis, leukopenia and negative indicators of white
blood. The results of the study of white blood index indicators are presented in Table 3.
Table 3.
Dynamics of white blood cell index values in patients with SLE who received pulse
therapy and standard therapy
Indicators
In healthy
people
In patients
Group I
Group II
Leukocyte intoxication index
(LII)
0,57±0,02
1,16±0,08
0,94±0,07
0,49±0,06
0,69±0,05
Left shift index (LSI)
5,67±0,08
7,76±0,19
7,59±0,17
4,10±0,59
4,03±0,14
Granulocyte-agronulocyte index
(GAI)
1,52±0,02
2,48±0,10
2,48±0,08
1,38±0,09
1,91±0,04
General intoxication index (GII)
7,77±0,14
11,38±0,26
11,01±0,21
5,98±0,14
6,64±0,14
Neutrophil-lymphocyte ratio
index (NLR)
1,67±0,02
2,75±0,23
2,83±0,18
1,49±0,10
2,14±0,10
Neutrophil-monocyte ratio index
(NMR)
12,44±0,31
31,95±0,64
20,52±0,35
14,67±0,42
18,76±0,84
Lymphocyte-monocyte ratio
index (LMR)
7,53±0,27
12,60±0,38
7,94±0,24
10,03±0,76
6,64±0,89
Lymphocyte-eosinophil ratio
index (LER)
15,79±0,76
10,88±1,04
10,44±0,76
23,35±1,00
18,26±0,68
Note: the numerator shows the values before treatment, the denominator shows the
values on the 7th day of therapy.
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Among the index indicators in patients of the 1st group, complete normalization occurred for
LII due to a significant decrease in band neutrophils, GAI due to a decrease in the absolute
and relative number of neutrophils, and ISNL due to a decrease in the number of neutrophils
in peripheral blood. Normalization has not yet been noted for the ISI, OII, ISLM and ISLE
indicators. It should be noted that the ISLE indicator in patients of this group has
significantly increased due to an increase in the relative number of lymphocytes compared to
the data upon admission. In our opinion, this additionally indicates the onset of the stage of
attenuation of the immune-inflammatory process.
It should be emphasized that in most cases, patients of the 1st group showed a clear
correlation between the positive dynamics of index indicators and clinical manifestations of
SLE. In patients of the second group who received standard therapy, none of the studied
index parameters normalized, with the exception of ISLM, which was restored due to a
slight decrease in the number of lymphocytes and an increase in the number of monocytes.
Here, correlative connections were also noted between the index parameters of white blood
cells and the clinical manifestations of SLE.
The dynamics of biochemical parameters in the observed patients with SLE are presented in
Table 4.
The data in the table indicate that complex therapy led to a significant normalization of
biochemical parameters in the observed patients, but the degree of their normalization was
different in the studied groups (Table 4). Thus, the concentration of sialic acids was
completely normalized only in patients of group I, while in patients of group II, despite their
significant decrease in comparison with the results upon admission (P < 0.001), complete
normalization did not occur (P < 0.001). According to the concentration of diphenylamino
acid, significant normalization occurred in patients of the first group. However, this
indicator remained reliably high in patients of both groups. The latter indicator, in our
opinion, is the most reliable among the indicators of acute-phase inflammation activity.
Malen's test, detected in all patients, by the end of the observation was the most positive in
patients of group II (P<0.001) and the least positive in patients of group I (P<0.001).
Interesting results were obtained when setting up the Veltman test. Thus, in patients of
group II at the last stage of observation, a shift of the test to the right was noted (P<0.01),
indicating the chronicity of the inflammatory process, and in patients of group I, statistical
differences were not found compared with the control group.
Table 4.
Dynamics of biochemical blood parameters in patients with SLE who received pulse therapy
and standard therapy
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Indicators
In healthy people
In patients
Group I
Group II
Sialic acids, units of optical density
187,73
1,64
326,1±6,87
311,7±3,01
189,8±4,26*
264,1±2,24*
Diphenylamine acid, units of
optical density
0,160
0,01
0,343±0,04
0,335±0,02
0,204±0,03*
0,257±0,02*
Malena test
Отр
Положительная у 100% больных
22,2%*
77,7%*
Veltman test
0,36
0,01
0,20±0,01
0,20±0,01
0,34±0,01*
0,40±0,01*
C-reactive protein, mm.:
Отр
3,30±0,06
3,24±0,05
0,59±0,14*
1,91±0,07*
Blood protein, g/l
70,76
0,50
68,32±0,80
68,60±0,81
69,21±0,28
65,53±0,23*
Albumins, in %:
59,19
0,41
48,10±0,41
48,01±0,43
54,37±0,56*
52,18±0,23*
α-globulins
13,31
0,66
21,37±0,40
20,69±0,45
15,02±0,33*
17,13±0,14*
β-globulins
11,97
0,35
14,21±0,31
14,56±0,29
12,28±0,33
8,93±0,20*
-globulins
15,53
0,37
16,32±0,36
16,74±0,32
18,33±0,46*
21,76±0,32*
Despite the therapy, CRP was detected in all the studied groups, with its highest content
noted in patients of group II, and the lowest - in patients of group I (P < 0.01-0.001). This
indicator most fully determines the degree of activity of the inflammatory process. In
patients of group I, pulse therapy did not have a significant effect on total blood protein, and
in patients of group II, hypoproteinemia occurred against the background of treatment (P <
0.001). Blood albumins still remained low in all compared groups (P < 0.001). Serum α-
globulins, characterizing the severity of the inflammatory process, still remained high in all
patients, with the highest in patients of group II (P < 0.001), and relatively low in patients of
group I (P < 0.01). β-globulins were elevated in all groups of patients, and by the end of the
observation - in patients of group II (P < 0.05) they significantly decreased, while in patients
of group I at this time of the study no reliable differences were found. Serum γ-globulins in
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all patients at the last observation period significantly increased (P < 0.001), which indicated
the chronicity of the inflammatory process, or indirectly one can assume the suppression of
antidiv formation or hyperimmunoglobulinemia. At the same time, the highest
concentration of gamma globulins was recorded in patients of group II, rather than in
patients of group I (P < 0.05). In general, in patients in this study, pulse therapy with
methylprednisolone was effective in 77.7% of patients with SLE, persistent remission was
noted in 66.6% of patients. In 22.2% of patients, despite the therapy, no noticeable clinical
and laboratory effect was observed. As for standard therapy, for patients with high activity
of the inflammatory process, with persistent vasculitis, visceritis, this method is ineffective
and requires further improvement in relation to the use of pulse therapy.
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