Проблемы назначения нестероидных противовоспалительных препаратов женщинам репродуктивного возраста с анкилозирующим спондилитом

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line medications for ankylosing spondylitis (AS); their action is associated with blockade of the enzyme cyclooxygenase 2 and with a mediated decrease in the synthesis of prostaglandins (PGs). However, PGs play an important role in regulating the functions of the female reproductive system. The paper presents an update on the participation of PG in folliculogenesis, ovulation, implantation, and development of the embryo, and labor activity. Based on experimental and clinical findings, the authors discuss whether due to inhibition of the synthesis of PGs, NSAIDs are able to cause ovulation failure, including luteinized unovulated follicle syndrome and spontaneous abortions. Further investigation is justified to determine the most optimal NSAID therapy regimens when planning pregnancy and during gestation in women with AS.Нестероидные противовоспалительные препараты (НПВП) являются препаратами первого ряда в терапии анкилозирующего спондилита (АС), их действие связано с блокадой фермента циклооксигеназы 2 и опосредованным снижением синтеза простагландинов (ПГ). Однако ПГ играют важную роль в регулировании функций женской репродуктивной системы. В статье представлены современные данные об участии ПГ в фолликулогенезе, овуляции, имплантации и развитии эмбриона, родовой деятельности. На основании данных экспериментальных и клинических исследований обсуждается возможность НПВП за счет ингибирования синтеза ПГ вызывать нарушения овуляции, в том числе синдром лютеинизации неовулировавшего фолликула и спонтанные аборты. Обоснованно проведение дальнейших исследований с целью определения наиболее оптимальных схем терапии НПВП при планировании беременности и во время гестации у женщин с АС

Relationship of the clinical characteristics of rheumatoid arthritis to work capacity and efficiency

Objective: to study the impact of the clinical characteristics of rheumatoid arthritis (RA) on work efficiency. Subjects and methods. One hundred and thirty-seven patients (116 women and 21 men) with RA were examined. Their mean age was 52.03+13.17 years; mean age at disease onset was 42.12+14.43 years. Median RA duration was 84 (range 24-174) months. DAS 28 for RA was moderate. The HAQ score was 1.42+0.82. Results. Fifty-nine (43%) of the 137 patients were in work. Absenteeism was 28.2%. It was equal to 0 in 28 of the 59 working subjects. The mean presenteeism was 42.3±27.9%. The reduction of overall work efficiency was 54.8±34.4%. The day-to-day activity determined in all the patients was reduced by 53.6±25.7%. Absenteeism turned out to be negatively related to RA duration (R = 0.26). DAS 28 scores were directly related to all WPAI indicators: absenteeism (R = 0.28), presenteeism (R = 0.63), lower overall work efficiency (R = 0.47), day-to-day activity (R = 0.64). The WPAI indicators (R >0.5), exclusive of absenteeism, were noted to have the strongest correlation with VAS pain intensity. The HAQ score was unassociated with absenteeism, but its association with presenteeism, lower overall work efficiency, and day-to-day activity proved to be high (R = 0.65; R = 0.43; R = 0.75, respectively). The correlation of the WPAI components with the transformed index of a patient's physical state (SF-36 PCS) was much higher than that with mental one (MCS). Conclusion. RA activity had a major influence on work efficiency. Presenteeism was much stronger related to the clinical characteristics of RA than with absenteeism. All WPAI scores were associated with activity, degree of functional defect, quality-of-life values, and fatigability. At the same time, absenteeism was least related to the clinical characteristics of RA

EVALUATION OF A DECRESE IN WORK PRODUCTIVITY IN PATIENTS WITH RHEUMATOID ARTHRITIS

Objective. To study the association between the clinical manifestations and work ability in patients with rheumatoid arthritis (RA) and to elaborate mathematical methods for predicting work productivity indicators according to the evaluation of the functional status of patients and disease activity.Material and Methods. A total of 185 RA patients were examined; 105 of them were employed. The mean age was 48.2±11.3 years; RA duration was 77.9±70.7 months; DAS28 4.68±1.53; visual analogue scale (VAS) score was 40.6±22.2; HAQ was 1.3±0.7. The employed patients in the test group had a longer duration but weaker activity of RA according to DAS28 as compared to those in the control group (p<0.05). The WPAI indicators in the test and control groups, respectively, were as follows: presenteeism – 39.0±26.3 vs. 57.9±16.8%; total productivity decrease (TPD) – 54.6±34.1 vs. 65.2±23.3%; daily activity (DA) – 52.3±26.3 vs. 55.3±14.8%. The multiple regression method was used to create prognostic equations. A significant divergence of the distribution of absenteeism rates from the normal distribution prevented selection of regression equations.Results. HAQ, VAS pain, and DAS28 turned out to be optimal for selecting equations. The Spearman correlation coefficients with WPAI indicators were higher than 0.4 in all the cases. The following prognostic equations were obtained:Presenteeism (%) = 0.66 + 11.31 • HAQ + 0.44 • VAS pain + 2.17 • DAS28 (R2 = 0.46), TPD (%) = 8.53 + 3.90 • HAQ + 0.47 • VAS pain + 4.73 • DAS28 (R2 = 0.28), DA (%) = 11.27 + 11.87 • HAQ + 0.36 • VAS pain + 1.96 • DAS28 (R2 = 0.44).Verification of the predicted WPAI values using the data of an additional group has demonstrated the coincidence of the predicted and actual values for presenteeism and TPD. However, the correlation coefficient between the predicted and actual presenteeism indicators was considerably higher (0.68 vs. 0.51). The predicated DA differed considerably from the actual ones.Conclusion. Multiple regression analysis was used to obtain and verify the prognostic equations for presenteeism, TPD, and DA. The resulting regression equation for calculating presenteeism is characterized by sufficient significance for predicting this indicator in RA patients. HAQ and RA duration (months) are the most significant variables for predicting work ability

Применение ингибиторов фактора некроза опухоли α у женщин с анкилозирующим спондилитом во время беременности

Objective: to present our own experience of tumor necrosis factor α (TNFα) inhibitors (iTNFα) usage during pregnancy in women with ankylosing spondylitis (AS), to assess AS activity and outcomes of gestation.Patients and methods. A prospective observation of 55 pregnant women with AS who met the modified New York criteria of 1984. Fifty-six pregnancies were followed. The average age of the patients was 31.7±4.7 years, the duration of the disease was 132.2±85.4 months. The median BASDAI for pregnancy trimesters was 2.4 [1.2; 4.4], 2.7 [1.4; 4.2] and 2.2 [1.5; 4.0], respectively. 14 women received iTNFα 3 months before pregnancy.Results and discussion. In the first trimester, TNFα was used in 9 (16.1%) patients, in the second – in 9 (16.1%) and in the third – in 5 (9.3%); the median BASDAI for trimesters was 2.3 [1.0; 3.7], 3.4 [1.2; 3.5], 3.0 [0.8; 3.4], respectively. All patients who discontinued iTNFα just before or in early pregnancy had indications for resuming therapy in the second half of gestation. Cancellation of iTNFα at the end of the second trimester was not a risk factor for high activity in the third trimester. There was 1 adverse pregnancy outcome. In other cases, childbirth occurred at 38.9±1.4 weeks, newborns' body weight was 3273.1±435.6 g.Conclusion. Women with AS who plan a pregnancy should be prescribed drugs with the maximum allowed duration of use during gestation. Cancellation of iTNFα before and in early pregnancy is a risk factor for high AS activity, while renewal of iTNFα therapy during pregnancy is not always effective.Цель исследования – представить собственный опыт применения ингибиторов фактора некроза опухоли (иФНОα) во время беременности у женщин с анкилозирующим спондилитом (АС), оценить активность АС и исходы гестации.Пациенты и методы. Проведено проспективное наблюдение 55 беременных с АС, соответствовавших модифицированным Нью-Йоркским критериям 1984 г. Прослежено 56 беременностей. Средний возраст пациенток составлял 31,7±4,7 года, продолжительность болезни – 132,2±85,4 мес. Медиана BASDAI по триместрам беременности – 2,4 [1,2; 4,4], 2,7 [1,4; 4,2] и 2,2 [1,5; 4,0] соответственно. ИФНОα за 3 мес до наступления беременности получали 14 женщин.Результаты и обсуждение. В I триместре иФНОα применяли 9 (16,1%) пациенток, во II – 9 (16,1%) и в III – 5 (9,3%); медиана BASDAI по триместрам составляла 2,3 [1,0; 3,7], 3,4 [1,2; 3,5], 3,0 [0,8; 3,4] соответственно. Все пациентки, отменившие иФНОα накануне или на ранних сроках беременности, имели показания к возобновлению терапии во второй половине гестации. Отмена иФНОα в конце II триместра не являлась фактором риска высокой активности в III триместре. Имел место 1 неблагоприятный исход беременности. В остальных случаях роды произошли на сроке 38,9±1,4 нед, масса тела новорожденных – 3273,1±435,6 г.Заключение. Женщинам с АС, планирующим беременность, необходимо назначать препараты с максимально разрешенным сроком применения во время гестации. Отмена иФНОα перед беременностью и на ее ранних сроках – фактор риска высокой активности АС, при этом возобновление терапии иФНОα во время беременности не всегда эффективно

Features of effector lymphocyte subsets in patients with uveal melanoma in recurrent and chronic herpesvirus infection

The aim of the study is to conduct a comparative analysis of percentages for peripheral blood effector lymphocyte subsets in patients with uveal melanoma manifested by recurrent and chronic herpesvirus infection. There were 141 subjects enrolled: 70 patients with uveal melanoma, 38 patients with corneal ulcers and involvement of the uveal tract as well as 33 healthy donors. Immunophenotyping was performed by using laser flow cytometry with panel of monoclonal antibodies to differentiate lymphocyte subpopulations. IgM and IgG antibodies to herpesvirus infections were determined by using enzyme-linked immunosorbent assay on an automatic ELISA analyzer Lazurit (USA) with diagnostic kits of CJSC “Vector-Best” (Koltsovo). The data obtained showed that the absolute number of blood lymphocytes (CD45+) in patients with uveal melanoma did not differ from those in healthy donors. In contrast, patients with corneal ulcers and involvement of the uveal tract had this parameter increased. A decreased relative and absolute count of T cells (CD3+) in uveal melanoma, but increased absolute CD3+ number in inflammation was observed. No difference in relative and absolute content of the CD3+CD4+ helper/inducer subpopulation in patients with recurrent herpesvirus infections was found. Corneal ulcers in cancer patients revealed significantly increased absolute level of CD3+CD4+ helpers/inductor cells. Chronic herpesvirus infection in uveal melanoma patients showed increased relative and absolute number of cytotoxic T lymphocytes (CD3+CD8+). Recurrent herpesvirus infection was featured with decreased relative number of T lymphocytes (CD3+CD8+), upon inflammation, there was noted increased absolute and decreased relative number compared with healthy subjects. Double positive T cells increased in tumor and inflammation. B lymphocytes (CD19+) increased in melanoma and inflammation. The relative number of blood natural killer cells (CD16+CD56+) in uveal melanoma increased upon recurrent infection. Inflammation was coupled to decreased relative level of natural killer cells (CD16+CD56+). Melanoma showed no changes in CD4+/ CD8+ ratio; upon inflammation, its increase was noted in acute and chronic herpesvirus infections (p < 0.05). The suppression of the immune system in uveal melanoma, restricting antiviral defense, was revealed. The data obtained seem to be important for development of personalized approaches to prognosis and treatment of patients with uveal melanoma

Анкилозирующий спондилит и беременность : современный взгляд на проблему

Ankylosing spondylitis (AS) more often develops in the 3rd and 4th decade of life when many women think about motherhood. Today, the view which has prevailed since the middle of the 20th century on AS as a male disease has been revised; the male to female ratio for this disease is approaching 1:1, which makes it urgent to study the problem of pregnancy in AS. The review gives the data available in the literature on fertility in AS, the interaction of the latter and pregnancy, and drug therapy during gestation. There is evidence for further investigations to clarify the course of AS, to optimize the assessment of its activity and patients' functional status, to identify markers for an exacerbation of the disease during pregnancy and after childbirth, and to standardize drug therapy when preparing for pregnancy and during the latter.Анкилозирующий спондилит (АС) чаще развивается в 3–4-м десятилетии жизни, когда многие женщины задумываются о материнстве. Сегодня пересмотрено господствовавшее с середины XX в. мнение об АС как о мужской болезни: соотношение мужчин и женщин, страдающих этим заболеванием, приближается к 1 : 1, что обусловливает актуальность изучения проблемы беременности при АС. В обзоре приведены данные литературы о фертильности при АС, взаимовлиянии АС и беременности, лекарственной терапии при гестации. Обосновано проведение дальнейших исследований, направленных на уточнение течения АС, оптимизацию оценки его активности и функционального состояния больных, выявление маркеров обострения заболевания во время беременности и после родов, стандартизацию лекарственной терапии как на этапе подготовки к беременности, так и на ее фоне

Features of systemic cytokine production in Behcet's disease associated with uveitis without ocular lesions

Behcet's disease (BD) is a systemic disease underlyed by chronic vasculitis. Hyperactivity of innate and adaptive immunity plays important role in its pathogenesis. Uveitis occurs in 30-70% of the patients, often recurring and reducing visual function. The objective of our work was to study the features of systemic production of immune mediators in BD patients, depending on presence and activity of uveitis. 116 BD patients were divided into 3 groups: (1) 41 patients with active uveitis (UA), (2) 64 subjects with uveitis remission (UR), (3) 11 uveitis-free BD patients (WU). Control group (CG) comprised 34 conditionally healthy people. Detection rate (%) and contents (pg/ml) were measured for IL-1β IL-2, IL-4, IL-5, IL-6, IL-12p70, IL-13, IL-18, IFNγ, CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL5/RANTES, CCL11/Eotaxin, СXCL1/GRO-α, CXCL8/IL-8, CXCL10/IP-10, CXCL12/SDF-1α, GM-CSF, TNFα in blood serum by means of multiplex analysis using MAGPIX analyzer (Luminex Corp., USA), Procarta Plex “Human Th1/Th2&Chemokine Panel 20 plex” kits (Bioscience, Austria). TGF-P1, TGF-P2 levels were assayed by ELISA-test (“Vfector-Best”). All the BD patients showed high detection rates of CXCL1/GRO-α (but not its level) in comparison with CG. Detection rate and levels of IL-6, IL-8 were increased in 1st and 2nd BD groups, compared to CG. In UR, unlike UA and WU groups, IL-4 was detected more often than in CG. WU patients showed increased detection rate of only CXCL1/GRO -α. When compared with UA, WU patients had lower serum concentrations of IFNγ, MCP-1, IP-10, MIP-1a, SDF-1α, TGF-β1; UR patients also showed decreased serum levels of IL-18, Eotaxin, GRO-α, RANTES, TGF-β2. Our results indicate the importance of angiogenic and proinflammatory chemokines and cytokines in pathogenesis of BD uveitis, as well as imbalanced production of various immunomediators. Higher detection rates and levels of IL-6 and IL-8 in UA and UR patients may result from weak persistent intraocular inflammation, even upon relief of clinical symptoms, thus, probably, requiring therapeutic correction

EFFECT OF HUMAN HERPES VIRUS REACTIVATION ON SYSTEMIC CYTOKINE PRODUCTION IN PATIENTS WITH BEHCET’S DISEASE AND UVEITIS

Behcet’s disease (BD) is a systemic autoinflammatory-autoimmune disease (chronic systemic vasculitis) of unknown etiology, almost 70% of patients develop uveitis. BD pathogenesis is complex, human herpesviruses (HHV) play an important role among infectious trigger factors. Ability of herpesviruses to modulate cytokine production and evade host’s immune response is known.Aim of the study was to assess the effect of Herpes simplex virus type 1, Herpes simplex virus type 2, Cytomegalovirus, Epstein-Barr virus on systemic levels of chemokines, pro- and anti-inflammatory cytokines in BD with and without uveitis. Serum samples were collected from 116 BD patients chronically infected with HHV and examined in ELISA-test for markers of HHV reactivation (IgG-antibodies to immediate early HSV antigens 1, 2 and CMV, early EBV antigen). Concentration of IL-1β, IFNγ, MCP-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-12p70, IL-13, IL-18, TNFα, GMCSF, Eotaxin, GRO-α, IP-10, MIP-1α, MIP-1β, SDF-1α, RANTES detected in multiplex analysis. TGF-β1, TGF-β2 were measured in ELISA-test. Depending on presence and activity of uveitis 3 groups of patients with BD were identified: group 1 – active uveitis, group 2 – remission of uveitis, group 3 – BD without ocular manifestations. After serological study 2 subgroups were highlighted in each group: a) patients with antibody markers of reactivation of at least one HHV, b) patients chronically infected with HHV, without serological signs of reactivation. Mean level and detection rate of cytokines and chemokines in patients with active uveitis (1a, 1b) and in remission (2a, 2b) were compared with patients without eye damage (3a, 3b). Chronic HHV infection (subgroup “b”) was compared with reactivation (subgroup “a”). A significant increase of MCP-1/ CCL2, MIP-1α/CCL3, MIP-1β/CCL4, RANTES/CCL5, IP-10, SDF-1α chemokines in serum, as well as IFNγ, TGF-β1, and TGF-β2 was observed in patients with uveitis (regardless of their activity) and HHV reactivation compared to patients without uveitis. Our data indicate that systemic production of cytokines and chemokines in BD patients and uveitis could be affected by the activity of chronic herpesvirus infections, and the greatest changes are related to chemokines

Течение анкилозирующего спондилита на фоне беременности: промежуточные данные проспективного наблюдения

The onset of ankylosing spondylitis (AS) more frequently occurs at the end of the third decade of life, which corresponds to the time of marriage and the birth of the first child and determines the relevance of a study of the interaction of AS and pregnancy.Objective: to describe the clinical presentations of AS and its therapy during pregnancy and to study AS activity dynamics and the patients' functional status during gestation.Patients and methods. The investigation enrolled 19 pregnant women who met the 1984 modified New York AS criteria. The mean age of the women was 32.2±1.1 years; their mean age at the onset of AS was 22.6±3.1 years; the duration of the disease was 147±20.7 months. The patients visited their physician at 10–11, 20–21, and 31–32 weeks of pregnancy. The investigators determined AS activity by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS) and functional status by the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Metrology Index (BASMI). The Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) was used to assess enthesitis.Results and discussion. At the time of conception, 78.9% of the patients had inflammatory back pain with an intensity of 2.2±0.4 on a numerical rating scale; during pregnancy, 95% of the pregnant women experienced pain, its intensity increased by the second trimester (4.6±0.7) and remained at this level in the third trimester (p<0.05 between the month of conception and the second and third trimesters). By the third trimester, the nature of the pain changed: 55.5 and 61.1% of the patients reported reduced pain at rest and after exercise, respectively. The frequency and severity of enthesitis increased with gestational age: the MASES scores were higher in the third trimester (2.3±0.5) than that in the first-trimester (0.4±0.22; p<0.05). The frequency of extra-axial and extra-skeletal manifestations did not increase during gestation. Coxitis was detected in 27.8% of the pregnant women.The BASDAI increased from the time of conception (1.7±0.3) to the second trimester (3.3±0.5; p<0.05) and remained at this level in the third trimester. Multiple regression analysis revealed that the predictors of BASDAI levels in the third trimester were BASDAI scores (R2 =0.7) and back pain (R2 =0.9) at the time of conception, the use of biological agents 3 months before gestation (R2 =0.7) with their cumulative impact. Throughout pregnancy, the BASDAI was determined by a set of factors: the severity of pain in the back (β=0.6) and entheses (β=0.3) and weakness (β=0.6). By the end of the first trimester, the increased BASDAI scores were provided mainly by the higher level of general weakness (by 68.5%) and back pain (by 24.1%). In the second trimester, the higher BASDAI was due to the increased severity of enthesitis (by 30.7%) and back pain (by 27%).There were no changes in ASDAS-C-reactive protein (ASDAS-CRP), but there was its upward tendency in the second trimester as compared with the beginning of pregnancy. The BASMI did not change significantly (1.3±0.9; 1.8±0.2; 2.1±0.3, respectively, for trimesters). The BASFI increased by the third trimester (3.9±0.7) versus the first trimester (1.4±0.3; p<0.05).In the third trimester, this rise was due to difficulties in performing the actions related to both AS activity and pregnancy (forward bends; questions 1, 2, and 4).According to the trimesters, 31.6, 73.7, and 66.7% of the pregnant women took nonsteroidal anti-inflammatory drugs. The need for glucocorticoids was noted in 22% of patients in the second trimester and in 53% in the third trimester.Conclusion. The clinical activity of AS is increased by the second trimester of pregnancy and remains moderate and high until the end of gestation. The activity of AS at the time of conception can determine the activity of the disease throughout pregnancy. In the third trimester, mechanical back pain becomes concurrent in half of the patients. Functional impairments increase with gestational age, and this is due to both the activity of AS and pregnancy itself in the third trimester. Анкилозирующий спондилит (АС) чаще дебютирует в конце третьего десятилетия жизни, что соответствует времени вступления в брак и рождения первого ребенка и обусловливает актуальность изучения вопросов взаимовлияния АС и беременности.Цель исследования – описание клинической картины и терапии АС во время беременности, изучение динамики активности АС и функционального статуса больных при гестации.Пациенты и методы. В исследование включено 19 беременных, соответствующих модифицированным Нью-Йоркским критериям АС (1984). Средний возраст – 32,2±1,1 года, средний возраст на момент начала АС – 22,6±3,1 года, продолжительность болезни – 147±20,7 мес. Пациентки посещали врача на 10–11-й, 20–21-й и 31–32-й неделях беременности. Активность АС определяли по индексам BASDAI и ASDASсрб, функциональный статус – по индексам BASFI и BASMI. Для оценки энтезита использовали счет MASES.Результаты и обсуждение. На момент зачатия 78,9% пациенток имели боль в спине воспалительного ритма, интенсивностью 2,2±0,4 по числовой рейтинговой шкале; в течение беременности боль испытывали 95% беременных, интенсивность ее увеличивалась ко II триместру (4,6±0,7) и оставалась на этом уровне в III триместре (p<0,05 между месяцем зачатия и II, III триместрами). К III триместру характер боли изменился: 55,5% пациенток отметили уменьшение боли в покое, 61,1% – усиление боли после физических упражнений.Частота и выраженность энтезита увеличивались со сроком беременности: счет MASES в III триместре (2,3±0,5) был выше, чем в I (0,4±0,22; p<0,05). Частота внеаксиальных и внескелетных проявлений в ходе гестации не возрастала. Коксит выявлен у 27,8% беременных.BASDAI возрастал от момента зачатия (1,7±0,3) ко II триместру (3,3±0,5; p<0,05) и оставался на этом уровне в III триместре. При анализе с использованием множественной регрессии предикторами уровня BASDAI в III триместре были значения BASDAI (R2 =0,7) и боли в спине (R2 =0,9) на момент зачатия, использование генно-инженерных биологических препаратов за 3 мес до гестации (R2 =0,7) при их совокупном влиянии. На всем протяжении беременности BASDAI детерминировался совокупностью факторов: выраженностью боли в спине (β=0,6) и энтезисах (β=0,3), слабости (β=0,6). Прирост значений BASDAI к концу I триместра обеспечивался в основном за счет повышения уровня общей слабости (на 68,5%), боли в спине (на 24,1%). Увеличение BASDAI во II триместре происходило за счет усиления выраженности энтезита (на 30,7%), боли в спине (на 27%).Динамики индекса ASDASсрб не наблюдалось, но имелась тенденция к его повышению во II триместре по сравнению с началом беременности. BASMI значимо не изменялся (1,3±0,9; 1,8±0,2; 2,1±0,3 соответственно по триместрам). BASFI увеличивался к III триместру (3,9±0,7) по сравнению с I триместром (1,4±0,3; p<0,05). В III триместре это увеличение было обусловлено трудностями при выполнении действий, связанными как с активностью АС, так и с беременностью (наклоны вперед; вопросы 1, 2, 4).Нестероидные противовоспалительные препараты принимали по триместрам: 31,6; 73,7 и 66,7% беременных. Потребность в глюкокортикоидах во II триместре отмечена у 22% пациенток, в III – у 53%.Выводы. Клиническая активность АС увеличивается ко II триместру беременности и остается умеренной и высокой до конца гестации. Активность АС на момент зачатия может определять его активность в течение всей беременности. В III триместре у половины больных присоединяется боль в спине механического ритма. Функциональные нарушения увеличиваются со сроком беременности, причем в III триместре это связано как с активностью АС, так и с самой беременностью.

Боль в спине и функциональный статус у пациенток с анкилозирующим спондилитом на фоне беременности

Inflammatory rhythm back pain and enthesitis are one of the main clinical manifestations of ankylosing spondylitis (AS), which increase in severity during pregnancy. However, addition of back pain and, possibly, enthesis in the second half of gestation, which is associated with normal pregnancy, needs to make a differential diagnosis for clarifying the genesis of pain and choosing the right management tactics, which determines the relevance of this study.Objective: to investigate the course of pain in the back, enthesis, and inguinal region, as well as the functional status in AS patients during pregnancy and to reveal clinical signs that most accurately reflect inflammatory activity during gestation.Patients and methods. A study included 36 pregnant women with a reliable diagnosis of AS according to the modified New York criteria (1984). Their mean age was 31.6±4.8 years, the mean age at the onset of AS was 21.8±10.9 years; the duration of the disease was 134.9±89.3 months. A control group comprised 30 healthy pregnant women with no history of back pain and arthritis; their mean age was 28.2±4.5 years. The pregnant women of both groups were matched for parity. They made visits at 10–11, 20–21, and 31–32 weeks of pregnancy. Pain intensity was estimated using the numerical pain rating scale (NPRS) and the functional status was assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI). The Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) was used to assess enthesitis.Results and discussion. During pregnancy, 94% of AS patients had back pain; its intensity by trimesters was 3 [2; 4], 4 [3; 5.5], 3 [2; 7] and was higher than in healthy pregnant women (p<0.0001). In the study group, there was a rise in pain intensity at night with increasing gestational age (n=23–28): 2 [1; 4] in the first trimester; 3 [0; 5] II in the second trimester; 3 [1; 6] in the third trimester (p< when comparing the first, second, and third trimesters) and an increase in the duration of morning stiffness (n= ): 10 [5; 20], 15 [10; 55], and 15 [5; 60] min, respectively. Moreover, the number of women who reported improvements after exercise (85–63%) and no improvement at rest (88–56%) declined (p<0.05 when comparing the first, second, and third trimesters).In the control group, 1 and 3 patients had morning back stiffness and night pain, respectively. The healthy pregnant women more frequently reported a reduction in back pain after exercise in the third trimester (66.7% of those with pain) than in the first trimester (20% of those with pain) (p<0.05).By the third trimester, the patients with AS showed a change in the nature of back pain: 43.7% of the patients reported an improvement at rest; 42.4% noted an increase in pain after exercise, while the frequency of elements of mechanical back pain was less than that in the control group (p < 0.05).The intensity of groin pain (2.4±1.9, 3.3±2.4, and 4.3±3.0 in the first, second, and third trimesters, respectively) did not differ in AS patients with and without coxitis or pelvic enthesitis. The frequency of enthesitis and MASES scores in the study group were higher than in the control group (p<0.05), the MASES scores increased with gestational age, amounting to 0 [0; 1] in the first trimester and 2 [0; 3] in the third trimester (p<0.05).Functional disorders during pregnancy increased in both groups; there was a difference in BASFI scores between the groups only in the third trimester: 3.5±2.8 and 1.7±1.2, respectively (p<0.05).Conclusion. Back pain and functional disorders increase in AS patients during gestation. Night back pain, morning stiffness, and enthesitis reflect the inflammatory activity of AS during pregnancy. Mechanical back pain joins in 40% of women with AS in the third trimester. The criteria for inflammatory back pain and BASFI require adaptation when used in pregnant women.Боль в спине воспалительного ритма и энтезиты – одни из основных клинических проявлений анкилозирующего спондилита (АС), их выраженность увеличивается в течение беременности. Однако присоединение во второй половине гестации боли в спине и, возможно, в энтезисах, связанной с физиологически протекающей беременностью, требует проведения дифференциальной диагностики для уточнения генеза боли и выбора правильной тактики ведения пациенток, что и обусловливает актуальность данного исследования.Цель исследования – изучить динамику боли в спине, энтезисах и паховой области, а также функционального статуса у пациенток с АС в течение беременности и выявить клинические признаки, наиболее точно отражающие воспалительную активность на фоне гестации.Пациенты и методы. В основную группу включено 36 беременных с достоверным диагнозом АС по модифицированным Нью-Йорским критериям (1984). Средний возраст – 31,6±4,8 года, средний возраст на момент начала АС – 21,8±10,9 года, продолжительность болезни – 134,9±89,3 мес. В контрольную группу вошли 30 здоровых беременных с отсутствием боли в спине и артритов в анамнезе, средний возраст – 28,2±4,5 года. Беременные обеих групп были сопоставимы по паритету. Визиты проводились на 10–11-й, 20–21-й и 31–32-й неделях беременности. Интенсивность боли оценивали по числовой рейтинговой шкале (ЧРШ), функциональный статус – по BASFI. Для оценки энтезита использовали счет MASES.Результаты и обсуждение. В течение беременности боль в спине беспокоила 94% больных АС, ее интенсивность по триместрам составила 3 [2; 4], 4 [3; 5,5], 3 [2; 7] и была выше, чем у здоровых беременных (p<0,0001). В основной группе с увеличением срока гестации отмечалось нарастание интенсивности ночной боли (n=23–28): I триместр – 2 [1; 4]; II – 3 [0; 5]; III – 3 [1; 6] (p<0,05 при сравнении I и II, I и III триместров) и продолжительности утренней скованности (n=28–30): 10 [5; 20], 15 [10; 55] и 15 [5; 60] мин соответственно. При этом количество женщин, отметивших улучшение после физических упражнений (85–63%) и отсутствие улучшения в покое (88–56%), уменьшилось (p<0,05 при сравнении I и II, III триместров).В контрольной группе утренняя скованность в спине была у 1, а ночная боль – у 3 пациенток. На уменьшение боли в спине после физических упражнений здоровые беременные чаще указывали в III триместре (66,7% имеющих боль) по сравнению с I (20% имеющих боль; p<0,05).У больных АС К III триместру наблюдалось изменение характера боли в спине: 43,7% пациенток отметили улучшение в состоянии покоя, 42,4% – усиление боли после физических упражнений, при этом частота элементов механической боли в спине была меньше, чем в контрольной группе (p<0,05).Интенсивность боли в паховой области (2,4±1,9; 3,3±2,4; 4,3±3,0 соответственно в I и II, III триместрах) не различалась у больных АС с кокситом и энтезитом в области таза и без них. Частота энтезита и счет MASES в основной группе были выше, чем в контрольной (p<0,05), счет MASES увеличивался со сроком беременности, составляя 0 [0; 1] в I триместре и 2 [0; 3] в III триместре (p<0,05).Функциональные нарушения в ходе гестации нарастали в обеих группах, различие значений BASFI между группами выявлено только в III триместре: 3,5±2,8 и 1,7±1,2 соответственно (p<0,05).Выводы. В ходе гестации боль в спине и функциональные нарушения у больных АС усиливаются. Ночная боль в спине, утренняя скованность и энтезит отражают воспалительную активность АС на фоне беременности. В III триместре у 40% женщин с АС присоединяется механическая боль в спине. Критерии воспалительной боли в спине и BASFI требуют адаптации для их использования у беременных