Международный эндокринологический журнал Том 19, №2, 2023
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Особливості діагностичного пошуку та досвід лікування хронічної кропивниці у хворих на ожиріння з легеневою патологією
Авторы: N.M. Kaspruk, S.O. Batranovska
Bukovinian State Medical University, Chernivtsi, Ukraine
Рубрики: Эндокринология
Разделы: Клинические исследования
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Резюме
Актуальність. В останні десятиліття поряд із зростанням частоти алергічних захворювань спостерігається прогресуюче збільшення кількості людей із надмірною масою тіла різного ступеня вираженості, про що свідчать численні епідеміологічні дослідження. Тому як алергія, так і ожиріння через їх високу поширеність та медико-соціальну значимість належать до глобальних проблем сучасної охорони здоров’я. Мета: аналіз етіологічних факторів хронічної кропив’янки (ХК) у хворих на ожиріння з легеневою патологією, оптимізація діагностики й лікування ХК для подальшого планування профілактичних заходів. Матеріали та методи. Обстежено 250 пацієнтів, які звернулися за медичною допомогою до обласної клінічної лікарні м. Чернівці з приводу ХК, асоційованої з легеневою патологією та ожирінням. На підставі аналізу отриманих даних сформовано групу зі 140 пацієнтів для подальшого клініко-анамнестичного обстеження: збору анамнезу, визначення ступеня тяжкості кропив’янки, оцінки якості життя, контролю симптомів кропив’янки, загальноклінічних лабораторних досліджень, тестів для верифікації кропив’янки. Алерготестування виконували, коли анамнестичні дані хворого свідчили про його доцільність. Обстеження проводилося протягом одного місяця і включало діагностичний період та 3 консультації кожні 7–10 днів. Результати. Серед причин ХК у пацієнтів пульмонологічного профілю домінують непереносимість лікарських засобів та паразитарна інфекція. Поєднання кількох етіологічних факторів спостерігається в 60 % випадків. Відмінностями ХК у хворих пульмонологічного профілю з ожирінням є тривала персистенція кропив’янки або інших елементів висипки, недостатня ефективність терапії антигістамінними препаратами другого й третього поколінь та глюкокортикостероїдами. Висновки. Отримані результати свідчать про позитивний ефект застосування похідного хінуклідинів хіфенадину при лікуванні ХК у хворих на легеневу патологію та ожиріння. Задовільні ефекти були отримані в 91,43 % пацієнтів. Найгірші результати (8,57 %) зафіксовано в пацієнтів з етіологічним значенням факторів хімічного походження (у тому числі професійних), що пов’язано з більш проблематичним дотриманням режиму елімінації в цієї категорії пацієнтів.
Background. In recent decades, along with the growth of allergic diseases, there has been a progressive increase in the number of people with overweight of varying severity, as evidenced by numerous epidemiological studies. Therefore, both allergies and obesity are among the global problems of modern healthcare due to their high prevalence and medical and social significance. The purpose of the study was analysis of the etiological factors of chronic urticaria (CU) in obese patients with pulmonary pathology, optimization of diagnosis and treatment of CU for further planning of preventive measures. Materials and methods. We examined 250 patients who applied for medical care to the regional clinical hospital in Chernivtsi and had CU associated with pulmonary pathology and obesity. Based on the analysis of the obtained data, a group of 140 patients was formed for further clinical and anamnestic examination: analysis of the anamnesis, determination of the severity of urticaria, assessment of quality of life, control of urticaria symptoms, general clinical laboratory studies, tests for verification of urticaria. Allergy testing was carried out when the patient’s anamnestic data indicated its expediency. The survey was carried out for one month and included a diagnostic period and 3 consultations every 7–10 days. Results. Among the causes of CU in patients with pulmonary disease, drug intolerance and parasitic infection dominate. Polyetiology is observed in 60 % of cases. Differences in CU in obese patients are the long-term persistence of urticaria or other elements of the rash, the lack of effectiveness of therapy with the second- and third-generation antihistamines and glucocorticosteroids. Conclusions. The results obtained indicate a positive effect of the quinuclidine derivative quifenadine for the treatment of CU in patients with pulmonary pathology and obesity. Complete and significant effects were obtained in 91.43 % of patients. The worst results (8.57 %) were demonstrated by patients with the etiological significance of chemical factors (including occupational ones), which is associated with more problematic compliance with the elimination regimen in this category of patients.
Ключевые слова
легенева патологія; хронічна кропив’янка; ожиріння; хіфенадин
pulmonary pathology; chronic urticaria; obesity; quifenadine
Introduction
Urticaria is a heterogeneous and extremely common group of allergic diseases initiated by various etiological factors. International guidelines systematize the division of urticaria forms based on the duration and course of the disease [1, 2].
Constant pollution of air, soil and water bodies due to the use of a wide range of different chemicals, often exaggerated and uncontrolled, on the one hand, and on the other hand, the increasing use of products with a long shelf life, as well as polypharmacy and self-medication due to the abundance of advertising in the media and the availability of most over-the-counter drugs, in turn, are also the driving force behind the growth of various allergic reactions in the population [3, 4]. At the same time, along with the growth of allergic diseases, also for known reasons, there is a progressive increase in the number of overweight people of varying severity, as evidenced by numerous epidemiological studies. Therefore, both allergies and obesity, due to their high prevalence and medical and social significance, are among the global problems of modern healthcare [5, 6]. Considering the constant increase in the allergization of the population in the world and in Ukraine, in particular, and, accordingly, taking into account socio-economic factors and far from encouraging forecasts for a further increase in the incidence of various allergies, including chronic urticaria (CU), the question arises of the availability of effective and affordable methods of both its treatment and prevention [7].
CU, so-called hives, is a long-term condition. It is not known exactly why this happens, but it can accompany a chronic or autoimmune disease. A patient with chronic urticaria may have hives every day for months or years. It is impossible to get hives from another person. However, in some cases, urticaria occurs with a contagious infection. If a person suffers from hives, they are at risk of developing a life-threatening condition called anaphylaxis. It is important to be aware of other symptoms of this condition, such as swelling of the face, tongue, or throat, fast heart rate, or dizziness. Anyone who might have anaphylaxis should receive urgent medical care [2, 3].
Allergy and obesity are diseases that form a stable inflammatory process in the body. In the first case, it can be local, concentrated in the skin, walls of the respiratory tract or gastrointestinal tract, in the second case, it is often more widespread, affecting many organs and systems to a greater extent. The conditions for maintaining such inflammation and its further strengthening may be: the involvement of large volumes of adipose tissue in this process; the participation of factors of innate and adaptive immunity in it. At the same time, the formation, course and severity of allergic inflammation may depend on the severity of adipose tissue hyperplasia and the activity of the inflammatory process in it. For example, the mass of adipose tissue is one of the factors of severe uncontrolled, therapy-resistant forms of bronchial asthma in patients suffering from obesity since childhood [8]. And in case of food allergy, conditions arise for the development of immune inflammation due to disruption of the processes of elimination of immunocompetent cells, changes in the metabolism of adipocytes and other processes, as a result of which the development of complications, including insulin resistance, is induced [9].
According to the literature, the prevalence of CU in the general population varies from 0.5 to 5 %, in certain countries the incidence can reach 15 %. According to our data, this figure is 8 % [7]. The direct relationship of skin manifestations of allergy, in particular CU, with other chronic diseases once again confirms the great practical importance of differentiating its various types in clinical practice. The high prevalence of urticaria, the variety of forms of comorbid pathology, the presence of pathology mainly in patients of working age, the frequent ineffectiveness of diagnostic measures determines the relevance of the problem and require further study of this pathology [9, 10]. CU is a heterogeneous disease, so it is fair to consider it an interdisciplinary problem that not only allergists, but also therapists, pediatricians, and family doctors constantly encounter [11, 12].
The purpose of the current study was to analyze the etiological factors of CU in patients with pulmonary disease and obesity, to optimize the diagnosis and treatment of chronic urticaria for further planning of preventive measures.
Materials and methods
For the period from 2016 to 2021, we examined 250 patients who applied for medical care to the regional clinical hospital in Chernivtsi, in whom CU was associated with pulmonary pathology against the background of obesity, and bronchopulmonary pathology was in remission.
The diagnosis of obesity and the degree of obesity was made based on body mass index (38.2 ± 5.4 kg/m2) according to the recommendations of the WHO and International Obesity Task Force. All patients underwent a clinical examination, including anthropometry and immunological examination.
A clinical and anamnestic examination was carried out: history taking, evaluation of complaints, determination of the severity of urticaria, assessment of quality of life, control of symptoms of urticaria; laboratory research: clinical blood test, determination of C-reactive protein, concentration of thyroid hormones and antibodies to thyroid structures, tests for verification of physical urticaria, test with autologous serum, determination of rheumatoid factor, eosinophilic cationic protein, total IgE, antinuclear antibodies, complement C3/C4 components, protein fractions, coagulogram, fecal analysis for protozoa and eggs of worms.
Allergy testing was carried out when the patient’s anamnestic data indicated its expediency. The examination was carried out for one month and it included a diagnostic period and 3 consultations every 7–10 days, during which the patients received diet therapy using a low-calorie version of the standard diet and the exclusion of causally significant products according to the allergology examination.
Based on the analysis of the obtained data, a group of 140 patients was formed with the following inclusion/exclusion criteria in the study.
Criteria for inclusion in the study:
1. Age of patients: 22–70 years.
2. Duration of urticaria more than 6 weeks (up to 6 years).
3. Persistent course of CU with clinical manifestations at least 2 times a week.
4. Unsatisfactory effectiveness of the second- and third-generation antihistamines antihistamines and insufficient — glucocorticosteroids.
5. The diagnosis of obesity and the degree of obesity was made on the basis of body mass index.
Criteria for exclusion from the study:
1. CU with a previously established cause (predominantly atopic form, physical environmental factors).
2. Rheumatological diseases.
3. Continuous use of oral systemic corticosteroids.
4. Pregnancy.
5. Concomitant decompensated diseases: cardiovascular, neurological, hematological, gastrointestinal.
6. Oncological diseases.
The causes of CU we identified in patients of the study group were distributed as follows (Table 1).
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All patients were prescribed drug of the quinuclidine derivatives group quifenadine at a dose of 50 mg 3 times a day. The duration of therapy was 14 days. The substance quifenadine is an antagonist of H1-histamine receptors, blocks serotonin 5-HT1 receptors, weakening the action of allergy mediators — histamine and serotonin. Quifenadine prevents or weakens the spasmodic effect of histamine and serotonin on the smooth muscles of the bronchi and intestines, and also reduces the intoxication caused by these allergy mediators, and the dilation of capillaries with impaired permeability of their walls and the development of edema. It has a pronounced antipruritic and anti-exudative effect of a long-term nature. Quifenadine affects the immunological reactivity of the body, reducing the number of antibody-forming and rosette-forming cells in the spleen, bone marrow, lymph nodes, and also reduces the increased concentration of immunoglobulins of classes A and G [7, 13, 14].
Clinical efficacy of quifenadine was assessed using self-observation diaries, which paid attention to the intensity of itching, the severity of skin rashes, sleep disturbance due to itching, and a general decrease in quality of life. These symptoms were proposed to be assessed on a 3-point scale. In addition, patients were asked to record possible side effects: drowsiness, impaired attention in professional activities, dry mucous membranes, and others. At the end of the study a general assessment of the effectiveness of therapy was carried out.
Ethical approval. The study fully ensured standards described in the 1975 Helsinki Declaration of Human Rights (amended in 2008). The participants completed and signed a written informed consent before enrolling voluntarily in the research. Approval was obtained from the local ethics committee (protocol 5, 16.02.2022).
Results
Positive results of treatment with antimediator drug of the quifenadine at a therapeutic dose (complete and significant effects) were obtained in 128 patients (91.43 %). The worst results (8.57 %) were demonstrated by 12 patients with the etiological significance of factors of chemical origin (including occupational ones), which is associated with more problematic compliance with the elimination regimen in this category of patients.
Most patients noted good tolerability of the drug, side effects developed only in 10 (7.14 %) patients (increased drowsiness). Five patients noted increased sleepiness during the day, although patients with sleep disorders and whose work does not require increased attention noted the positive aspects of this effect. Three patients noted worsening of the symptoms, three patients suffered from nausea and headache after taking the drug. These symptoms did not require the administration of additional medications, resolved spontaneously (within 1–3 days), in two cases it was proposed to cancel the therapy with the studied group of drugs (Fig. 1).
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Discussion
Chronic spontaneous urticaria is one of the commonest diseases in allergological and dermatological practice. It constitutes an interdisciplinary problem, and its pathogenesis is not always easily determined. It has been suggested that metabolic syndrome and hyperlipidaemia are more frequent in patients with urticaria, but the influence of overweight and obesity on the development of urticaria has not been thoroughly investigated.
In typical situations, the diagnosis of urticaria does not cause difficulties for clinicians. However, with atypical manifestations of the disease, there are difficulties in differential diagnosis due to the variability of clinical manifestations, complex interdisciplinary aspects of pathology, and insufficient awareness of practitioners about rare diseases and syndromes that occur with urticarial or urticaria like rashes [2, 9, 10].
In classical cases, the diagnosis of urticaria does not cause difficulties and is established during the collection of anamnesis and physical examination of the patient. However, clinical situations requiring differential diagnosis of urticaria with other diseases, including autoinflammatory diseases, often present diagnostic difficulties for practitioners. Complex interdisciplinary aspects of differential diagnosis can lead to erroneous diagnoses and untimely appointment of adequate therapy [12, 13].
Given the presence of transitional forms between urtica–ria and urticarial vasculitis, sometimes it is possible to clarify the diagnosis only with dynamic observation of patients. Often the question of the need for differential diagnosis of urticaria arises with resistance to ongoing therapy. Thus, the clinical efficacy of antihistamines may also be of diagnostic value [1, 14, 15].
The differential diagnosis of urticaria, as a comorbidity problem, is carried out with the participation of allergo–logists, endocrinologist, dermatologists, rheumatologists and infectious disease specialists, gastroenterologists, and otorhinolaryngologists. In a targeted analysis of the history data, it turned out that drug intolerance most often occurred in patients with additional inflammatory processes in the upper respiratory tract (21 %), diseases of the bronchopulmonary system (44 %), chronic diseases of the biliary system (23.5 %), diseases of the stomach and intestines (10 %), diseases of the genitourinary system (9 %), diseases of the cardiovascular system (24 %). It should be emphasized that almost all patients had multiple foci of infection. In some cases, a combination of nosologies was observed in the same patient (about 15 %). Careful analysis of clinical associations in an individual patient and an interdiscipli–nary approach are essential for verifying the diagnosis and optimizing therapy.
According to our data, one of the most significant triggers of exacerbation of urticaria were drugs (44.28 % of cases). Most often, they were characterized by the occurrence of rashes with the same localization with repeated use of the causally significant drug [3, 4, 7]. The most common cau–ses of these fixed rashes in our study were NSAIDs, sulfona–mides, and antibiotics. Difficulties in differential diagnosis with urticaria were often due to the evolution of skin elements in fixed drug rashes, which at different stages resembled urticaria. The initial elements were represented by dark red spots with a bluish tint, which often progressed to a pa–pule or plaque, in 3 patients led to the formation of a bubble. As the rash resolved, the center of the skin elements became grayish in color, and the rash regressed with the formation of hyperpigmentation. When resolved, the elements took on a brown color and the shape of rings and garlands and resembled urticarial elements. The rash was accompanied by itching and burning, and in 30 % of cases persisted for more than a month.
Analysis of the incidence of our patients by months of the year did not reveal significant differences and any seasonality. Thirty-two patients, by the nature of their professional activities, had contact with medicinal or chemical substances (17 with antibiotics, 8 with disinfectants, 5 with acids and alkalis, 7 additionally with varnishes and paints).
Conclusions
Among the causes of CU in patients with pulmonary disease, drug intolerance and parasitic infection dominate. Polyetiology is observed in 60 % of cases.
The plan for the differential diagnosis of recurrent urticaria should definitely include parasitological studies and a thorough study of the pharmacological history.
Patients with obesity may be recommended to conduct an immunological examination in order to timely detect food allergies, followed by the implementation of the principles of personalized diet therapy.
Differences in CU in patients with pulmonary disease is the long-term persistence of urticaria or other elements of the rash, the lack of effectiveness of therapy with the second- and third-generation antihistamines and glucocorticosteroids.
The group of quinuclidine derivatives is highly effective for the treatment of recurrent urticaria in obese patients with pulmonary pathology: clinically significant positive changes occur 2–4 days after the start of treatment.
Received 03.01.2023
Revised 02.03.2023
Accepted 09.03.2023
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