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Extrapulmonary Tuberculosis*

Emelita P. Ang, M.D.,** Estelita M. Quimosing, M.D.*** and Bienvenido D. Alora, M.D.****

(*Read at 6th Animal Convention, PSMID, November 1981; **Senior Resident in Medicine, Santo Tomas University

Hospital; ***Junior Consultant in Medicine, STUH; ****Consultant and Chief, Section of Infectious and Tropical

Diseases, STUH)

SUMMARY

Extrapulmonary tuberculosis occurs in any age group but more in the 2nd and 3rd decades of life with a male

preponderance. Fever, anorexia, abdominal pain and cough are more common in those with positive chest x-rays but

these objective findings did not differ in both groups. A negative chest x-ray does not exclude the presence of

extrapulmonary tuberculosis because it present can present as pleural effusion, mediastinal mass, metastatic cancer,pneumonia, pneumothorax, pulmonary neoplasm and atelectasis.

Of the patients whose chest x-rays were compatible with tuberculosis only 27% showed miliary pattern.

Anemia was a more prominent feature in those with positive chest x-rays and neutrophilia rather than lymphocytosis

was predominant in both groups but higher in those with positive chest x-rays.

All except the meningitis cases were diagnosed histologically. [Phil J Microbiol Infect Dis 1982; 11(2):115-123]

Key Words: tuberculosis,M. tuberculosis , extrapulmonary, pulmonary

INTRODUCTION

Extrapulmonary tuberculosis is the result of dissemination of tubercle bacilli from aninitial focus in the lungs soon after primary infection.

1The dissemination is primarily by way of

the lympho-hematogenous route,2

with seeding of virulent tubercle bacilli in almost all of theorgans and tissues of the body. Although in most patients, both pulmonary and extrapulmonarylesions heal, clinically subtle granulomas contain tubercle bacilli which can remain viable fordecades.

3Subsequent breakdown of these lesions can lead to reactivation of extrapulmonary

disease. Reactivation may be clinically deceptive for the usual features of infection are often

absent. Indeed, the infection may be far advanced before any observable symptom occurs. Thereare reports of clinically unsuspected extrapulmonary tuberculosis diagnosed only duringnecropsy.

4-6Thus up to the present time extrapulmonary tuberculosis continuous to present as a

clinical problem as reflected by reports of cases with atypical clinical and pathological features,including negative chest roentgenograms.

4,7,8

This study was undertaken to present the clinical features of extrapulmonary tuberculosisas seen at the Santo Tomas University Hospital Clinical Division with a view of increasingawareness of its existence thereby facilitating early treatment. To determine how many of thesepatients have chest x-rays signs of tuberculosis and to compare the clinical features of patientswhose chest x-rays were positive and those whose chest x-rays were read as negative fortuberculosis.

MATERIALS AND METHODS

Records of patients admitted at the Santo Tomas University Hospital Clinical Divisionfrom January 1976 to December 1980 with a diagnosis of "Extrapulmonary Tuberculosis" werereviewed. Included in this study are all patients with chest x-rays and who had extrapulmonaryTB as determined by one or more of the following criteria: (1) biopsy or necropsy demonstrationof caseating, epitheloid granulomas in one or more organs and (2) clinical presentation consistentwith tuberculosis with marked improvement after anti-tuberculosis therapy.


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The subjects were divided into 2 groups: Group I - those chest x-rays were positive fortuberculosis and Group II - those whose chest x-rays were interpreted as either negative or non-tuberculous in nature. Tests of significance of any differences between these 2 groups were doneby the chi square test or T test.

RESULTS

This series comprised 87 patients. Fifty nine percent were males and forty one percentwere females. The age ranged from 4 months to 77 years. The mean age for both groups was 30years. Eighty seven percent of our patients are below 50 years, the majority belonging to agegroup 21-30 years (Table 1).

There were 25 cases of TB meningitis, 14 cases of TB adenitis, 8 genitourinary TB, and 7each for ileocecal and hepatobiliary tuberculosis and 12 cases had disseminated tuberculosis. Outof 87 cases, 44 or 51% had chest x-rays positive for tuberculosis while 43 or 49% had eithernegative or non-tuberculous roentgenographic findings (Table 2).

Table 1. Age and Sex Distribution

Chest X-ray TB (+) Chest X-ray TB (-)

Age in Years Male Female Male Female Total

10 5 4 1 1 11

11 - 30 0 4 6 5 15

21 - 30 3 3 13 4 2331 - 40 5 5 0 4 14

41 - 50 7 3 3 0 13

51 - 60 3 0 1 2 6

61 - 70 0 0 2 0 2

71 - 80 1 1 1 0 3Total 24 20 27 16 87

Table 2. Chest X-ray

Organs Involved Number of Cases Chest X-ray TB (+) Chest X-ray TB (-)

Meninges 25 13 12Lymph Node, Cervical 14 1 13

Genito-Urinary 8 6 2

Ileocecal 7 6 1

Hepatobiliary 7 3 4Peritoneum 5 3 2

Pleura 5 2 3

Spine 4 3 1

Disseminated 12 7 5

Twenty seven percent of patients in Group I (Chest x-ray TB+) had miliary pattern in thechest x-ray while 73% showed non-miliary pattern. In Group II (Chest X-ray TB-), 70% was readas negative and 30% was interpreted as having abnormalities other than tuberculosis (Table 3).

The majority of patients with TB in the chest x-ray had symptoms usually associated withtuberculosis in general like fever, anorexia, and cough. Although they were present in Group II,they occurred at a much lower frequency (P 38.5C occurred on admission in 21 and 14 cases respectively.There was a relatively high incidence of findings referable to the central nervous system like neck


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rigidity, stupor or coma. This was probably related to the great number of meningitis cases (28%)included in this series (Table 5).

Table 3. Roentgenographic Features

Chest X-ray TB (+) N = 44 Chest X-ray TB (-) N = 43

Miliary Pattern 12 (27%) Negative 30 (70%)Non Miliary 32 (73%) Pleural effusion, alone 3

PTB, minimal 9 Mediastinal mass 2

Moderately advanced 3 Metastatic carcinoma 1

Far advanced 1 Pneumonia 4Primary complex 5 Pneumothorax 1

Hilar adenopathy 2 Pulmonary neoplasm 1

TB pneumonia 1 Atelectasis 1

PTB plus pleural effusion 3

PTB plus atelectasis 1Healed PTB 7

Table 4. Major Symptoms

Symptoms Chest X-ray TB (+) N = 146 Chest X-ray TB (-) N = 74 p Value

Fever 33 (75%) 20 (46%) p < 0.02Anorexia 20 (45%) 8 (19%) p < 0.02

Weight loss 16 (36%) 7 (16%)

Abdominal pain 17 (39%) 6 (14%) p < 0.02

Headache 12 (27%) 11 (26%)Cough 15 (34%) 4 (9%) p < 0.02

Vomiting 10 (23%) 8 (19%)

Dyspnea 9 (20%) 3 (7%)

Chills 6 (14%) 5 (12%)

Night Sweats 8 (18%) 2 (5%)Convulsion 5 (11%) 3 (7%)

Melena/Hematochysia 5 (11%) 2 (5%)

Malaise 4 (9%) 3 (7%)

Urinary symptoms 6 (13%) 1 (2%)

Pleuritic pain 4 (9%) 2 (5%)

Joint pain 1 (2%) 4 (9%).Pruritus 1 (2%) 1 (2%)

Hemoptysis 1 (2%) 0

Table 5. Clinical Findings

Findings Chest X-ray B (+) N = 92 Chest X-ray TB (-) N = 53

Adenopathy 25 (57%) 16 (37%)

Fever > 38.5OC 21 (48%) 14 (32%)

Hepatomegaly 9 (20%) 3 (7%)Stiff Neck 6 (14%) 6 (20%)

Abdominal Mass 6 (14%) 3 (7%)

Pleural Effusion 5 (11%) 3 (7%)

Jaundice 5 (11%) 3 (7%)

Ascites 4 (9%) 3 (7%)Rales/Rhonchi 6 (14%) 1 (2%)

Stupor/Coma 5 (11%) 1 (2%)

Neurological 7 (16%) 6 (14%)

Edema 3 (7%) 3 (7%)

Abscess 3 (7%) 1 (2%)Ecchymosis/Pallor 3 (7%) 1 (2%)

Scrotal Mass 2 (5%) 0

Splenomegaly 1 (2%) 1 (2%)


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Twenty five cases or 56% of Group I had hemoglobin values < 12 gms while it was

present in only 13 cases or 30% of Group II (P < 0.05), Figure 1.

Figure 1. Hemoglobin in Grams

Fifty two percent of cases in Group I had leukocytosis greater than 10,000/mm3

while inGroup II it was present in 37% of cases (p > 0.05), Figure 2. A patient who died however, whobelonged to Group II had leukocytosis greater than 50,000/mm

3and the peripheral smear showed

atypical cells. The differential count is shown in Table 6.

Figure 2. White Blood Cell Count

Table 6. Differential Count

Chest X-ray TB (+) Chest X-ray TB (-)

Neutrophils< 60% 10 (23%) 20 (47%)

60 - 70% 10 (23%) 11 (26%)> 70% 24 (54%) 12 (28%) p< 0.05

Lymphocytes< 30% 28 (64%) 17 (40%)

30 - 40% 7 (16%) 17 (40%)

> 40% 9 (20%) 9 (21%)

Eosinophils > 3% 7 (16%) 16 (37%)

Monocytes > 5% 0 2 (3%)Atypical Cells 0 1 (2%)


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Fifty four percent in Group I had polymorphonuclear leukocytosis greater than 70% ascompared to Group II which was 28% (p < 0.05 Chi square), and both groups significantlymphocytosis and monocytosis were not observed. It was noted that eosinosinophilia waspresent in 16% of Group I and 37% of Group II (p < 0.05).

History of exposure to tuberculosis was common in both groups followed by cigarettesmoking and alcohol intake. History of pulmonary tuberculosis was observed in 12 cases Table7).

Table 7.Associated Conditions

Chest X-Ray TB (+) N = 44 Chest X-Ray TB (-) N = 43 Total

Exposure to TB 14 11 25Cigarette Smoking 10 10 20

Alcohol Intake 7 11 18

History of PTB 6 6 12

Associated Illness 4 3 7Associated Pregnancy 2 1 3

Steroid Therapy 1 0 1

Table 8. Methods of Diagnosis

Extrapulmonary Involvement Therapeutic Trial Biopsy Operation Necropsy

Meningitis 25TB Adenitis 14

Genito-Urinary TB 1 7

Ileocecal TB 7Hepatobiliary TB 3 4

TB Peritonitis 5

TB Pleura 5

Pott's Disease 4

Disseminated TB 25 1* 3 8Total 24 30 8

*Biopsy of cervical lymph nodes consistent with TB miliary pattern on chest x-ray. X-ray of skull, cervical spineconsistent with TB

Of the 25 patients with meningitis, 15 presented with headache, 8 had neck rigidity andvomiting, 5 had convulsion and 3 had stupor or coma. Cerebrospinal fluid obtained from thecases showed leukocyte count ranging from 25-500/mm

3and more than 50% were lymphocytes,

increased protein to more than 15mg% and the CSF glucose was < 60 mg%. These patients wereimmediately given triple TB therapy (isoniazid, ethambutol and streptomycin or rifampicin).None of the patients were given other antibiotics and all responded favorably.

The 14 cases of TB adenitis had very few signs and symptoms. Their main complaint wascervical mass or masses. Lymph node biopsy in all revealed caseating granulomas.

Eight cases of genitourinary tuberculosis were included in this series (4 kidneys andureters, 2 ovaries and uterus, 1 penis and 1 testis). All patients with renal TB had symptoms

referable to the urinary tract like frequency and nocturia, 2 had palpable kidneys and 2complained of flank pain. Examination of the urine revealed pyuria in 2, hematuria in one andalbuminuria in one. Blood urea nitrogen was normal in all while the creatinine level was elevatedin one.

The patients with TB of the ovaries and uterus were admitted because of abdominal mass.Diagnosis in all was established by surgery biopsy and subsequent histopathological examination.

Of the 7 patients with Ileocecal tuberculosis, three presented with vague abdominal pain,2 with abdominal mass and 2 patients had developed abscesses in an appendectomy sites. All four


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who had barium enema showed features compatible with ileocecal TB. The presence of TB wasconfirmed by surgery and histopathological examination.

There were seven patients with hepatobiliary TB, 6 of them presented with jaundice andhepatomegaly. Four out of five had elevated bilirubin level, predominantly the conjugated type.The alkaline phosphatase was elevated in 3/3 and serum albumin was low in 1/5 patients. Allcases had normal prothrombin time. In 3 patients, diagnosis was confirmed by blind liver biopsy,

3 by biopsy under peritoneoscopic guidance, and one by exploratory laparotomy, the initialimpression which was jaundice secondary to choledocolithiasis.

The presenting symptoms of patients TB peritonitis were abdominal in 4, weight loss in 5and low grade fever in 2. All had exudative type of ascitic fluid. A case was diagnosed byexploratory laparotomy and four cases by peritoneoscopy, which showed the presence of milletseeds in the visceral and parietal peritoneum.

The patients with pleural effusion presented with respiratory signs and symptoms likecough and dyspnea. Thoracentesis and pleural biopsy were done and the biopsied specimenrevealed chronic granulomatous inflammation.

In addition to the presence of signs symptoms of tuberculosis, in general, the patientswith TB of the spine presented with neurological manifestations like weakness and numbness ofthe lower extremities in 4, urinary and fecal incontinence in 2, back pain in 3 and gibbus in 2. All

underwent laminectomy or anterior spinal fusion. The specimen obtained showed chronicgranulomatous inflammation.

Of the 12 patients diagnosed to have disseminated tuberculosis, eight were diagnosedafter death, 3 by laparotomy and one by biopsy of cervical lymph node. This patient had miliarypattern in the chest x-ray and x-ray of the spine and the skull showed findings compatible withtuberculosis.

Of the 8 who were autopsied, 8 had involvement of the lungs although in 5 cases theywere interpreted as non-tuberculous radiologically.

DISCUSSION AND CONCLUSION

In this Study, the age and sex cases distribution of our patients were similar to that

reported by Gelb.9

The peak age incidence was during the second and third decades of life. Ascontrasted to the study by Proudfoot

4and Biehl

10where 65% and 52% of cases respectively were

after the fifth decade of life. Barret-Connor7

points out that the higher incidence of tuberculosis asone grows older is due to the presence of an underlying illness, which is more common in theadvanced age group and to the faltering immunity associated with the aging process. Theapparent high incidence of cases in the2nd-3

rddecades of life for the present study may be due to

the wider age group included and the high prevalence of tuberculosis in the country so that eventhe younger generation is infected. Moreover, the presence of an associated illness believed topredispose to the reactivation of dormant infection was observed in a significant number of cases.

One of the factors that cause delay or erroneous diagnosis as evident in this study was theabsence of signs of tuberculosis in the chest radiographs. The chest x-rays in five of the eightcases autopsied were interpreted as non-tuberculous but on autopsy, there was miliary

involvement of the lungs. One reason that may lead to erroneous interpretations is that the lesionis too small (< 2 mm) to be seen in the x-ray plate or it is masked by the presence of otherabnormalities such as hydrothorax and consolidation. Hussen et al in 1971

11showed that forty

patients out of 367 cases with negative chest x-ray but suspected clinically to have active PTBgave positive sputum cultures. So the chest x-ray films alone cannot be relied upon exclusively todiscover all cases of PTB.

The presenting signs and symptoms in this study were similar to those seen in pulmonarytuberculosis. However, localizing signs like lymphadenopathy, neck rigidity and hepatomegalyare important diagnostic clues for detecting extrapulmonary tuberculosis and should be looked


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for. Some interesting observations in our patients are the following: (1) milder symptoms inpatients whose chest x-rays were negative for PTB (2) anemia and polymorphonuclearleukocytosis were more pronounced in patients where chest x-rays were positive for PTB. Thesefindings may be secondary to the lesser degree of infection of the patients with negative chest x-rays.

Majority of our cases were diagnosed by demonstrating caseating granulomas in biopsied

specimen. Although this is a presumptive evidence of tuberculous infection, when taken togetherwith the clinical manifestations of a patient in our country, they are very suggestive ofextrapulmonary tuberculosis.

REFERENCES

1. Youmans G. Tuberculosis. Philadelphia: WB Saunders Co. 1979.

2. Simon H, Weinstein A. Genitourinary tuberculosis - clinical features in a general hospital population. 1977; Am J Med 63:410-419.

3. Youmans G. Tuberculosis. In: Hunter G, Swartswerlder J (eds). Tropical Medicine, 5th ed. Pkiladelphia: WB Saunders Co.,1976. 193-211.

4. Proudfoot AT. Miliary tuberculosis in adults. Br Med J 1969; 2:273-276.5. Jacques J, SIoan JM. The changing pattern of miliary tuberculosis. Thorax 1970; 25:237.6. Bottiger IE, Nordenstein HN. Disseminated tuberculosis as a cause of fever of obscure origin. Lancet 1962; 1:19.

7. Gricco MN. Acute disseminated tuberculosis as a diagnostic problem - a clinical study based on twenty eight cases. Am RevRespir Dis 1974; 109:554-564.8. Banner A. Tuberculosis - clinical aspects and diagnosis. Arch Intern Med 1979; 139:1387-1390.9. Gelb AF, Loftier C. Miliary tuberculosis. Am Rev Respir Dis 1973; 108:1327-1333.

10. Biehl JP. Miliary tuberculosis: A review of 68 Adult patients admitted to a municipal general hospital. Am Rev Tuberculosis158, 77, 605.

11. Hussen MD, Fulkerson L. Pulmonary tuberculosis with negative findings on chest x-ray films: A study of 40 cases. Chest 1971;6:540-542.

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