Extrapulmonary tuberculosis (EPTB) describes the various conditions caused by Mycobacterium tuberculosis infection of organs or tissues outside the lungs. There are many forms of EPTB, affecting every organ system in the body. Some forms, such as TB meningitis and TB pericarditis, are life-threatening, while others such as pleural TB and spinal TB can cause significant ill-health and lasting disability. Diagnosis of EPTB in rural areas itself is a challenge and bears considerable patient cost and time. Regional hospitals like ours have limited diagnostic facilities and patients have to travel to tertiary levels for further work up, diagnosis and management. Purpose of the study is to evaluate the spectrum of disease, its demographic profile and effectiveness of various modalities used in patient workup and diagnosis.
EPTB accounts for about 25% cases of tuberculosis [1]. WHO defines extrapulmonary tuberculosis as an infection by M. tuberculosis which affects tissues and organs outside the pulmonary parenchyma. Extrapulmonary tuberculosis is mostly underdiagnosed due to high rates of smear negativity in these cases. The burden of EPTB is high, ranging from 15-20 percent of all TB cases in HIV-negative patients, while in HIV-positive people, it accounts for 40-50 per cent of new TB cases [2]. India is the worst affected country in the world and shares one fifth of global burden. The theme for 2021 was' The Clock is Ticking’.Diagnosis of EPTB is often difficult and requires invasive tests to collect samples from relatively inaccessible sites. Focus of diagnosis relies on lymph node, pleural and other sites specific EPTB diagnostic test for which can be done in rural setup. Molecular diagnostic test like CB-NAAT & TrueNat are being used in diagnosis of EPTB as recommended by WHO in our hospital. Spectrum of EPTB includes pleural effusion, lymph node, abdominal, tubercular bacterial meningitis (TBM), genitourinary (GU), spine, bone and others like reproductive tract, pericardial, ocular, disseminated, skin etc. Diagnosis of such diverse site specific disease requires advanced diagnostic facilities, burden of such cases at tertiary care center like medical colleges is thus unavoidable.
Pleural TB is one of the most common forms of EPTB. Pleural TB can be complicated by massive effusion leading to respiratory compromise in the short term and pleural thickening, fibrosis and pleural adhesions causing impaired respiratory function in the medium to long term. When assessing pulmonary TB regimens, relapse rates of 5 per cent are generally considered acceptable [3]. However, relapse of TBM is fearsome as it is a life-threatening condition and can lead to severe neurodisability. Thus, whether any risk of relapse is tolerable for TBM is to be considered when establishing TBM regimens. However, longer ATTs reduce compliance and increase drug toxicity and costs [4]. The standard first-line regimen for drug-sensitive TBM, according to the WHO guidelines [5], is a two- month intensive phase with isoniazid, rifampicin, pyrazinamide and ethambutol or streptomycin followed by a 10- month continuation phase with isoniazid and rifampicin (2HRZE or S/10HR). Several different regimens are used in the current practice, with variations regarding doses, selection of the fourth drug and duration of treatment from six to more than 24 months. Steroids are recommended for TB meningitis in HIV-negative people. Duration of steroid treatment should be for at least four weeks with tapering as appropriate. Abdominal TB can present with isolated involvement of any of the following sites: peritoneal, intestinal, upper gastrointestinal (esophageal, gastroduodenal), hepatobiliary, pancreatic and perianal. Bone TB is a form of TB that affects the spine, long bones and the joints. Spinal TB also known as potts spine. The thoracic region of the vertebral column is most frequently affected. Formation of cold abscess around lesion is another characteristic feature, paraplegia is a dreaded complication of spinal TB. The kidney is the most common site of GUTB. Sterile pyuria is a classical finding in GUTB.
The study was conducted by analyzing data of the last three consecutive years from 2019-2021 in tribal district Kinnaur of Himachal Pradesh. Out of all TB cases notified data of EPTB cases diagnosed, type of EPTB including method of diagnosis was analyzed by simple statistical test.
Routine investigations were done in every suspect with EPTB. Chest X –ray, USG abdomen, ZN staining, mantoux test were other tests usually done. The skin of the patient, over the suspected lymph node to be aspirated was cleaned with betadine or spirit. The lymph node was then fixed between the thumb and index finger of the left hand, then an 18 gauge needle attached to a 10 ml syringe was introduced into the lymph node. Vacuum was created in the syringe by pulling the plunger and the needle was carefully moved in all directions to dislodge the material. Sample size of 0.5ml-1ml was considered adequate however if sample was inadequate then also it was diluted in distilled water/saline in Falcon tube and sent to lab immediately. USG guided pleural aspiration, CSF in TBM collected under aseptic technique and sample processed in similar fashion. Results were reported as positive or negative.
Table 1: Age Wise Distribution of Patients in Years.
Years | >5 | 10 | 15 | 20 | 25 | 30 | 35 | 40 | 45 | 50 | 55 | 60 | >61+ | Total |
2019 | 2 | 1 | 7 | 16 | 11 | 5 | 9 | 6 | 3 | 2 | 2 | 6 | 9 | 79 |
2020 | 3 | 2 | 3 | 12 | 11 | 12 | 3 | 12 | 4 | 3 | 6 | 4 | 5 | 80 |
2021* | 1 | 0 | 4 | 12 | 10 | 7 | 6 | 5 | 5 | 4 | 3 | 4 | 4 | 67 |
Table 2: Yearly Distribution of EPTB Patients with %Age and Total Resident/Non-Resident
Year | Eptb(Rh) | Eptb(Outside) | % Rh Eptb Diagnosis | (Total)(R/Nr) |
2019 | 5 | 74 | 6.7% | 79(71/8) |
2020 | 25 | 55 | 31.25% | 80(70/10) |
2021 * | 12 | 55 | 17.9% | 67(51/16) |
Total | 42 | 184 | 18.5% | 226(192(85%)//34(15%) |
Table 3: Yearly Distribution of PTB and EPTB Patients with Gender in District Kinnaur
Parameters | PTB | EPTB(M/F) | TOTAL | EPTB % |
2019 | 142 | 79(46/33) | 221 | 35.7% |
2020 | 112 | 80(45/35) | 192 | 41.6% |
2021* | 111 | 67(34/33) | 178 | 37.6% |
TOTAL | 365 | 226(125/101) | 591 | 38.2% |
Table 4: Sex and Site-Specific Distribution of EPTB in Each Age Group RH.
Eptb Site Specific Rh | Age Group | ||||||||||||||
0-20 years | 21-40 | 41-60 | 61-80 | TOTAL | |||||||||||
M | F | T | M | F | T | M | F | T | M | F | T | M | F | Total(%age) | |
Pleural Effusion | 2 | 3 | 5 | 4 | 5 | 9 | 4 | 1 | 5 | 2 | 1 | 3 | 12 | 10 | 22(53%) |
Lymph Node | 1 | 0 | 1 | 3 | 1 | 4 | 2 | 1 | 3 | 0 | 0 | 0 | 6 | 2 | 8(19%) |
Other sites | 1 | 1 | 2 | 4 | 4 | 8 | 0 | 2 | 2 | 0 | 0 | 0 | 5 | 7 | 12(28%) |
Total | 4 | 4 | 8 | 11 | 10 | 21 | 6 | 4 | 10 | 2 | 1 | 3 | 23 | 19 | 42 |
Table 5: Yearly Sex and Site Specific Distribution with Age Group EPTB
YEAR | EPTB SITE | TPE | LN | OTH | ABD | GU | TBM | Spine | Bone | ||||||||
2019 | Age group | M | F | M | F | M | F | M | F | M | F | M | F | M | F | M | F |
0-20 | 4 | 1 | 3 | 2 | 4 | - | 2 | - | - | - | 1 | - | - | - | - | - | |
21-40 | 3 | 4 | 1 | 3 | 4 | 4 | 3 | 3 | - | 1 | 3 |
| 1 | - | - | 1 | |
41-60 | 4 | 2 | - | 3 | 3 | 2 | 1 | 2 | - | - | - | - | 1 | - | 1 | 1 | |
>61 | 2 | - | - | 1 | 4 | 2 | - | - | - | - | - | - | - | 1 | - | - | |
2020 | 0-20 | 5 | - | 2 | 1 | 1 | - | 2 | 4 | - | - | - | 1 | 1 | 1 | 1 | - |
21-40 | 5 | 7 | 7 | 1 | 5 | 4 | 2 | 1 | - | 1 | - | 1 | 2 | 1 | - | 1 | |
41-60 | 7 | 3 | 2 | 2 | 3 | 2 | - | - | - | 1 | - | - | - | - | - | - | |
>61 | - | - | - | - | 2 | 2 | - | 1 | - | - | - | - | - | - | - | - | |
2021 | 0-20 | 4 | 2 | 1 | - | - | - | 1 | 2 | - | 1 | - | - | - | - | - | - |
21-40 | 8 | 7 | 2 | 2 | 3 | - | 2 | 3 | - | 2 | - | 1 | 1 | - | - | 1 | |
41-60 | 3 | 1 | 2 | 2 | 1 | 4 | 2 |
| - | 1 | - | - |
| 3 | - | - | |
2021 | >61 | 3 | 0 | - | - | 1 | 1 | - | - | - | - | - | - | 1 | - | - | - |
| Total | 48 | 27 | 20 | 17 | 31 | 19 | 15 | 16 | 0 | 7 | 4 | 3 | 7 | 6 | 2 | 4 |
%age | 75(33%) | 37(16.) | 50(22%) | 31(13%) | 7(3%) | 7(3%) | 13(5.7% | 6(2.6%) |
Table 6: Basis of Diagnosis of EPTB Cases Site Wise of Distt Kinnaur in Last 3 Years at RH and Outside
EPTB site wise | Pleural effusion (PL) | Lymph node (LN) | Other site(OS) | Spine | TBM | Abdominal (AB) | Genitourinary | Bone | Total | Outside total 0 | |||
Basis of diagnosis | RH PEO | Outside | RH PEO |
| RH PEO | Outside |
|
|
|
|
|
|
|
CBNAAT | 4 | 0 | 5 | 11 | 7 | 1 | 1 | 1 | 2 | 2 | 0 | 34 | 18 |
TRUENAT | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 3 | 2 |
CXR | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 |
ZNS | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 |
OTHER TEST | 16 | 50 | 3 | 17 | 4 | 36 | 12 | 6 | 29 | 5 | 6 | 184 | 171 |
LPA | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
TOTAL % | 22 | 53 | 8 | 29 | 12 | 38 | 13 | 7 | 31 | 7 | 6 | 226 | 184 |
Other tests used for diagnosis like pleural fluid analysis, low glucose, proteins>3g/dl exudative, ADA>40 IU/L, LDH> 2/3rd serum were used to confirm diagnosis of pleural effusion. FNAC, biopsy for HPE sent of lymph node and infertility patients respectively. Urine for AFB for 3 consecutive days used to diagnose GUTB. The following observations were made:
Age wise distribution of patients shows no age group is spared in EPTB over the last three years even when the age group is kept at 5 years. Total patients of EPTB were 79, 80 & 67 in the year 2019, 2020 and 2021 respectively at Regional Hospital Reckong Peo (RH). Maximum number of patients were seen in the age group 20-25 followed by 25-30 years (Table 1).
In 2019 only 5(6.7%) patients out of 79 were diagnosed at RH, 25(31.2%) patients out of 80 in 2020 and 12(17.9%) out of 67 patients diagnosed were of this year. Total 34(15%) out of 226 were non residents and 192(85%) were residents over 3 years (Table 2).
Year wise distribution of PTB and EPTB patients in district Kinnaur shows EPTB were 79(35.7%), 80(41.6%) and 67(37.6%) in 2019, 2020 & 2021 respectively. Male patients were more than females in all three years (Table 3).
Total 22(53%) out of 42 patients diagnosed at RH were of pleural effusion followed by 12(28%) of 42 other sites and at least 8(19%) of 42 of lymph nodes. Pleural effusion was more common in 20-40 years age group total 9(41%) cases out of 22 with 5 females and 4 males (Table 4).
75(33%) out of 226 cases were of pleural effusion followed by 50(22%) of others, 37(16.7%) of lymph node (LN), 31(13.7%) abdominal (ABD), 13(5.75%) of spinal, 7(3%) each of GU and tubercular bacterial meningitis (TBM) and lastly1 (2.6%) of bone tuberculosis (Table 5).
In RH overall 4/19(21.05%) of pleural effusions were diagnosed in three years. 5/5(100%) cases of lymph node tuberculosis were detected by CBNAAT in 2020. CBNAAT detected 16(47%) out of 34 cases at RH,18(9.7%) cases out of 184 outside RH (Table 6).
EPTB is a significant public health issue which represents a diagnostic challenge.In our study age distribution of patients over three years shows the maximum number of patients were in the age group 20-25 years followed by 25-30 years. However, no age group is exempt from EPTB in our study. Total E&P TB cases notified in district were 79(36%), 80(42%) and 67(38%) in 2019, 2020 and 2021 respectively As per RNTCP, the prevalence of EPTB in non-HIV patients was 15%-20% , but in our study it was overall 38.2%,which is more than the RNTCP statistics. In another hospital based retrospective study conducted at Nepal it showed an EPTB percentage of 48.5% [6].
Overall 75(33.1%) out of 226 cases of EPTB were TPE followed by 50(22%) of others, 37(16.7%) of LN, 31(13.7%) ABD, 13(5.75%) of spinal, 7(3%) each of GU /TBM and lastly 1(2.6%) of bone tuberculosis.. LN was the most common site in EPTB as per RNTCP statistics but in our study TPE was commonest. In our study ratio of M:F was 1.8:1 with 48M(64%)/27F (36%) of all cases of TPE over 3 years which is consistent with other study,TPE predominates in men, with overall male- to- female ratio of 2:1 [7]. LN TB most frequently affects children and young adults. It accounts for between 30 and 40% of all EPTB cases [8]. The most common location is cervical lymphadenopathy (63-77%) although it can also affect other areas such as supraclavicular, axillary, thoracic and abdominal nodes [9].
Overall 42(18.5%) of all 226 EPTB patients were diagnosed at RH in the last three years. EPTB diagnosis involves clinical, radiological, microbiological, histopathological, biochemical/ immunological, and molecular methods, facilities for which are available at medical colleges only and majority of patients were diagnosed there in our study also. GUTB was seen in all 7 female patients 7% of overall EPTB in females. Other sites CBNAAT detected 7(87.5%) out of 8 cases at RH. Overall 34(15%) of 226 cases CBNAAT was the basis of diagnosis in our study.The operational feasibility studies conducted under the RNTCP have demonstrated the feasibility of the machine to efficiently work under Indian settings [10].
Spectrum of EPTB is wide enough to span any age group, gender and site of the body. Incidence of EPTB in our district is above national level and is cause of concern. EPTB diagnosis at district level is mostly dependent on TrueNat / CBNAAT as evident in our study.TBM and pericardial effusion have high mortality and morbidity for which prompt diagnosis with primary management and early referral is prerequisite.
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