PATHOMORPHOSIS OF EXTRAPULMONARY TUBERCULOSIS IN CHILDREN

Aim. To study clinical and epidemiological aspects of pathomorphosis of extrapulmonary tuberculosis clinical forms. Materials and Methods. Retrospective analysis of 138 case histories in children aged to 15 years, obtaining extrapulmonary tuberculosis treatment in a specialized children’s hospital during 1988–2015 was carried out. Among them, in 103 children, clinical forms of extrapulmonary tuberculosis combined with respiratory tuberculosis and in 35 children independent forms of extrapulmonary tuberculosis were found. Studied stage (1988–2015) was divided into 3 periods: I – 1988–1997, II – 1998–2007, III – 2008–2015. During 2008–2015, in comparison to previous periods, the number of cases of peripheral lymph node tuberculosis (PLN), meninges and central nervous system tuberculosis, bones and joints tuberculosis, and ocular tuberculosis decreased. In 2008–2015, the share of combined forms of meninges and central nervous system tuberculosis and ocular tuberculosis remained at 1998–2007 level. During 2008–2015, skin tuberculosis was not diagnosed. Nevertheless, in 2008–2015, in 6.8±10.2 % of cases extrapulmonary tuberculosis combined with miliary tuberculosis, and in 5.8±10.4 % of cases the process characterized by lethal outcome, moreover 4.9±10.7 % from them – in recent years. It is important that during period I, in 19.6±13.2 % of cases extrapulmonary tuberculosis combined with respiratory tuberculosis in reverse development phases, during period II – in 12.9±19.3 % of cases, during period III – in 23.8±21.2 % of cases. Conclusion. Despite the reduction, extrapulmonary tuberculosis combined with severe forms of respiratory tuberculosis, which led to lethal outcome in children in 5.8±10.4 % of cases. Tuberculosis epidemiological situation worsening, reversion of severe forms of tuberculosis with the development of extrapulmonary one and several organs injuries in children shows the necessity of social, preventive and therapeutic measures intensification among children.


Introduction
A significant increase in morbidity and mortality in 90-s changed the tuberculosis epidemiological situation. In this case, unlike raised respiratory tuberculosis morbidity, extrapulmonary tuberculosis morbidity increased slightly [1]. Nevertheless, some scientists point to the growth of extrapulmonary tuberculosis and a significant increase of patients with extrapulmonary tuberculosis hospitalization [2,3]. Besides, the share of extrapulmonary tuberculosis in developed countries is between 1/4 (Austria, Switzerland, Germany) to 1/3 (US, Iran), and even 1/2 (Canada) of all identified patients [4].
Some scholars point to delayed identification of extrapulmonary tuberculosis [5], other -to difficulties in its diagnosis, which leads to late detection [6].
Peculiarities of national accounting systems are also worth mentioning. In some countries, including Ukraine, pleural and intrathoracic lymph node (ITLN) tuberculosis are considered as extrapulmonary tuberculosis [7].
It should be noted, that issues of extrapulmonary tuberculosis in adults are often highlighted in literature; publications on this issue inchildren are insignificant and inconsistent. Some scientists pay attention, that despite the growth of morbidity among children, extrapulmonary tuberculosis remains stable, some of them point to extrapulmonary tuberculosis indicators increasing [6], and other point to their decreasing [7]. This fact raises interest and stimulates the study of clinical and epidemiological aspects of pathomorphosis of extrapulmonary tuberculosis in children.

Aim
To study clinical and epidemiological aspects of pathomorphosis of extrapulmonary tuberculosis clinical forms during 1988-2015.

Materials and Methods
Retrospective analysis of 138 case histories in children aged to 15 years, obtaining extrapulmonary tuberculosis treatment in a specialized children's hospital during 1988-2015 was carried out. Among them, in 103 children, clinical forms of extrapulmonary tuberculosis combined with respiratory tuberculosis and in 35 children independent forms of extrapulmonary tuberculosis were found.
Children with tuberculosis outside the chest organs lesions were classified as extrapulmonary tuberculosis. Combinations of extrapulmonary tuberculosis local forms and respiratory tuberculosis were considered as combined forms of extrapulmonary tuberculosis. Independent forms of extrapulmonary tuberculosis were such extrapulmonary tuberculosis local forms, which didn't show any specific features of respiratory organs lesions after X-Ray detection. Clinical forms of pleural and ITLN tuberculosis were classified as respiratory tuberculosis.
To research clinical and epidemiological aspects of pathomorphosis of extrapulmonary tuberculosis clinical forms, the studied stage (1988-2015) was divided into 3 periods (the first -1988-1997; the second -1998-2007; the third -2008-2015). Changes in structure of extrapulmonary tuberculosis clinical forms and both combined and independent forms during studied periods were considered as pathomorphosis.
According to the case histories data, following information was analyzed: extrapulmonary tuberculosis clinical forms, respiratory tuberculosis clinical forms, combined clinical forms of extrapulmonary tuberculosis with respiratory tuberculosis, the number of affected organs.
All material of our research was statistically analyzed. To determine significant difference of selected options share, in percentage, Fisher formula was used [8]. In particular, the arithmetic mean (M), the average error (m), the probability index (t) and the probability difference (P) were determined by Student's table [9].

Results of Research
Among 1886 children treated from tuberculosis local forms in specialized children's hospital during 1988-2015, the share of extrapulmonary tuberculosis was 7.3±2.2 % (138).
The distribution of extrapulmonary tuberculosis clinical forms during different periods is shown in Table 1. The distribution of combined and independent forms of extrapulmonary tuberculosis during different periods is shown in Table 2. As it is shown in Table 2, the highest share of both combined (49.5±7.0 % -51) and independent (45.7±12.9 % -16) forms was in period I, the lowest -in period III (20.4±9.0 % -21 and 22.9±15.9 % -8, respectively).
The distribution of combined and independent forms of PLN tuberculosis during different periods is shown on Fig. 2.

Fig. 2. The distribution of combined and independent forms of PLN tuberculosis during different periods
As it is shown on Fig. 2, the highest share (60.5±10.4 % -23) of combined forms of PLN tuberculosis is in period I, the lowest (18.4±15.8 % -7) is in period III. Independent forms were detected mostly in period II -45.5±24.8 % (5), and the least in period III -18.2±13.6 % (9).
The distribution of combined and independent forms of meninges and CNS tuberculosis during different periods is shown on Fig. 3.   Fig. 3. The distribution of combined and independent forms of meninges and CNS tuberculosis during different periods As it is shown on Fig. 3, the highest share (42.3±15.6 % -11) of combined forms of meninges and CNS tuberculosis was in period I, but in periods II and III it was the same (19.2±19.6 % -5). Independent forms in periods I and III had the same ratios (50.0±35.3 % -3), and were not observed in period II.
The distribution of combined and independent forms of bones and joints tuberculosis during different periods is shown on As it is shown on Fig. 4, the share of combined forms of bones and joints tuberculosis was almost the same (38.9±19.9 % -7 and 44.4±18.7 % -8) in periods I and II, and it was the lowest in period III (16.7±26.3 % -3). The share of independent forms was the highest in period I (46.2±22.2 % -6) and the lowest in period III (23.1±29.8 % -3).
The distribution of combined and independent forms of ocular tuberculosis during different periods is shown on Fig. 5.   Fig. 4. The distribution of combined and independent forms of bones and joints tuberculosis during different periods As it is shown on Fig. 5, most often combined forms of ocular tuberculosis were identified in period I (77.8±16.9 % -7), in periods II and III their share was in the same ratio (to 11.1 % -1). Independent forms were frequently identified in period II (66.7±47.1 % -2), and were not identified in period III.
The distribution of combined and independent forms of extrapulmonary tuberculosis of another localization during different periods is shown on Fig. 6.
The share of combined forms of another localization of tuberculosis was the highest in period III (41.7±24.6 % -5), the lowest -in period I (25.0±30.6 % -3). Independent forms were observed only in period I. with miliary tuberculosis) died. Besides, despite the fact that during 2008-2015, in comparison to 1988-1997, the share of combined forms of meninges and CNS tuberculosis became lower, the mentioned disease characterized by lethal outcome in three cases.
It's worth mentioning, that despite the fact that the number of cases of bones and joints tuberculosis became lower in 2008-2015, in child aged 1 year and 2 months suffering from hip joint tuberculosis combined with bilateral lesions of ITLN, meninges, eyes and cervical lymph nodes, disease characterized by lethal outcome.
The Therefore, in recent 30 years extrapulmonary tuberculosis in children had clinical and epidemiological pathomorphosis, which manifested in its significant decrease and a slight reduction in its clinical and combined forms. However, combined forms of meninges and CNS tuberculosis, as well as ocular tuberculosis, during 2008-2015 remained on the 1998-2007 level, and skin tuberculosis was not diagnosed. Nevertheless, extrapulmonary tuberculosis in 6.8±10.2 % of cases combined with miliary tuberculosis, and in 5.8±10.4 % of cases the disease characterized by lethal outcome, moreover, 4.9±10.7 % of them happened in the last years. Recently, extrapulmonary tuberculosis combined with respiratory tuberculosis in reverse development phases more often than in previous years. It point to the late detection of respiratory tuberculosis, which led to extrapulmonary tuberculosis forms development. The mentioned above shows tuberculosis epidemiological situation worsening, reversion of severe forms of tuberculosis with the development of extrapulmonary one and several organs lesions in children, and the necessity of social, preventive and therapeutic measures among children.

Conclusion
1. Among children, suffering from local forms of tuberculosis, the share of extrapulmonary tuberculosis is 7.3±2.2 %.
2. In recent 30 years, extrapulmonary tuberculosis in children had clinical and epidemiological pathomorphosis, which manifested in its significant decrease (21.0±7.6 % to 48.6±6.1 %; р<0.05) and a slight reduction in its clinical and combined forms.
3. Despite the decrease, extrapulmonary tuberculosis combined with severe forms of respiratory tuberculosis, which in 5.8±10.4 % of cases led to children death.
4. Tuberculosis epidemiological situation worsening, reversion of severe forms of tuberculosis with the development of extrapulmonary one and several organs lesions in children, and the necessity of social, preventive and therapeutic measures among chldren.