4.7 Features and diagnostic approach of EPTB

The lymph nodes most commonly involved are the cervical nodes. Other sites may also be involved including submandibular, supraclavicular, inguinal or axillary nodes. Involvement of lymph nodes may result from direct extension of infection or from haematogenous spread.

The usual course of lymph node disease is as follows:

• Initially they are firm and discrete.
• Later become fluctuant and matted together followed by abscess formation.
• The skin may then breakdown leading to chronic sinus formation and.
• Ultimately healing with scarring.

Diagnosis is based on FNAC (smears for AFB, Xpert MTB/RIF, or ULTRA cultures for MTB) and or biopsy (Histopathology).

Miliary TB results from widespread blood-borne dissemination of TB bacilli; usually in children. Although it is often the consequence of a recent (primary) infection however, in adults, it may be due to either recent infection or reactivation of old disseminated foci.

Patients present with constitutional features rather than respiratory symptoms. They may have hepato-splenomegaly and choroidal tubercles on fundoscopy. Often the presentation is associated with fever of unknown origin and wasting may be marked. A rare presentation seen in the elderly is cryptic miliary tuberculosis which has a chronic course and remains undiagnosed unless there is a high degree of suspicion. Very rarely an acute septicaemic form, non-reactive miliary tuberculosis, occurs due to massive haematogenous spread of the tubercle bacilli.

Diagnosis is based on chest X-ray. It shows diffuse, uniformly distributed, small miliary shadows. "Miliary" means "like small millet seeds". Various haematological abnormalities may be seen including anaemia, leukopenia, neutrophilic leucocytosis and leukemoid blood reactions. Liver function tests may be abnormal. Bacteriological confirmation (smear or culture) is sometimes possible from sputum, cerebrospinal fluid, bone marrow, liver or blood. Granulomas are evident in liver or bone marrow biopsy specimen from many patients. Testing of broncho alveolar lavage is more likely to lead to bacteriological confirmation.

The presentation is usually with constitutional and local features. Microscopy/Xpert MTB/RIF of the aspirate from tuberculous serous effusions rarely shows AFB because the fluid forms as an inflammatory reaction to TB lesions in the serous membrane. TB culture, even if available, is of no immediate help. The white cell content is variable, usually with predominant lymphocytes and. The aspirate is an exudate (i.e. protein content is more than 30 g/l). Interpret the laboratory result of protein concentration in any aspirated fluid with caution. If there has been a delay in laboratory analysis, a protein clot may have formed in the sample. The laboratory result may then be falsely low.

The clinical and chest X-ray diagnosis of a pleural effusion is straightforward. Ultrasound can confirm the presence of fluid in the pleural space in case of doubt. Always perform diagnostic pleural aspiration if a patient has a pleural effusion. The fluid is usually straw-colored. The white cell count is usually high with predominant lymphocytes. Occasionally the fluid is blood-stained. The presence of pus on aspiration indicates an empyema (purulent effusion). If facilities are available, closed pleural biopsy using an Abrams needle is useful for histological diagnosis. Since the distribution of TB lesions in the pleura is patchy, the diagnostic yield of closed pleural biopsy is about 75%. Multiple biopsies increase the diagnostic yield. A small open pleural biopsy increases the yield even further.

The diagnosis usually rests on suggestive constitutional and cardiovascular features and investigation findings (ECG, chest X-ray and echocardiography).

Ascites results from peritoneal TB. Routes of spread of TB to the peritoneum include the following: a) from tuberculous mesenteric lymph nodes; b) from intestinal TB (pulmonary TB patients may develop intestinal ulcers and fistulae as a result of swallowing infected sputum); c) blood-borne. Patients  present with constitutional features and ascites. There may be palpable abdominal masses (mesenteric lymph nodes). Aspirated fluid is exudative with high protein content and leucocytosis with predominantly lymphocytes. The yield of direct smear microscopy/GeneXpert and culture for AFB is relatively low; culture of a large volume ascitic fluid can increase the yield. Ultrasound may show features consistent with TB, including enlarged mesenteric or retroperitoneal lymph nodes. Definitive diagnosis rests on a peritoneal biopsy. Blind percutaneous needle biopsy of the peritoneum has a low pick-up rate and a high complication rate. In experienced hands, laparoscopy under local anaesthetic has a high pick-up rate. Laparoscopy enables direct visualization and biopsy of peritoneal TB lesions. Laparotomy will confirm the diagnosis in nearly every case but is too invasive for routine use.

Any portion of the gastrointestinal tract may be affected by tuberculosis. The terminal ileum and caecum are the sites most commonly involved. Abdominal pain (at times similar to that of appendicitis), chronic diarrhoea, subacute obstruction, haematochezia and a right iliac fossa mass are common findings at presentation. Fever, weight loss and night sweats are also frequent. A 'doughy abdomen' due to extensive intra-abdominal inflammation may also be detected. Diagnosis rests on barium examination of the small and large intestine or on colonoscopy.

The sites most commonly involved are the lower thoracic vertebrae (with T-10 being the most common) and upper lumbar spine but the cervical spine can also be affected. TB starts in an intervertebral disc and spreads along the anterior and longitudinal ligaments before involving the adjacent vertebral bodies. With advanced disease, collapse of vertebral bodies results in kyphosis (gibbus). A para-vertebral cold abscess may also form. This may track to sites such as the lower thoracic cage or below the inguinal ligament (Psoas abscess).

Plain X-ray of the spine is usually diagnostic. The typical appearance is erosion of the anterior edges of the superior and inferior borders of adjacent vertebral bodies. The disc space is narrowed. CT scan or MRI reveals the lesions more correctly. Aspiration of the abscess or bone biopsy confirms the tuberculous etiology by histopathology and culture. The main differential diagnoses are malignancy and pyogenic spinal infections. Malignant deposits in the spine tend to erode the pedicles and spinal bodies, leaving the disc intact. Pyogenic infection tends to be more acute than TB, with more severe pain.

Weight bearing joints are mostly affected. Tuberculosis of the hip joints causes pain and limping. TB of the knee produces pain and swelling. A history of previous trauma is often elicited. Systemic symptoms are present in about half of the patients. Pulmonary TB is detected in approximately half of these patients. Radiological abnormalities include bone erosions, joint space narrowing, and ultimately joint destruction. Diagnosis requires synovial biopsy.

Tuberculosis can involve any part of genitor-urinary tract. It is usually due to haematogenous seedling following primary infection. Local symptoms predominate. Urinary frequency, dysuria, haematuria, and loin pain are common presentations. However, patient may be asymptomatic and the disease discovered after severe destructive lesions of the kidneys have developed. Urine analysis gives abnormal result in 90% of cases, revealing pyuria and haematuria. Sterile pyuria first raises the suspicion of renal tuberculosis. An intravenous pyelography helps in the diagnosis. Calcification and ureteric stricture are suggestive findings. AFB/Xpert MTB/RIF from centrifuge urine specimen helps in diagnosis. Culture of three consecutive morning urine specimens yields a definitive diagnosis in nearly 90% cases. Severe ureteric strictures may lead to hydronephrosis and renal damage.

Genital tuberculosis is more common in female than in male. In female patients, it affects the fallopian tubes and endometrium and may cause infertility, pelvic pain and menstrual irregularities. Diagnosis requires biopsy and/or culture of specimens obtained by dilatation and curettage (D and C). In male patients, tuberculosis preferentially affects the epididymis (producing a slight tender mass), orchitis and prostatitis may also develop. In almost half of cases of genitourinary tuberculosis, urinary tract disease is also present.

Disseminated TB may involve the liver or spleen and can cause diagnostic confusion. Solitary or multiple abscesses may develop. Ultrasound or CT scan and guided FNAC give diagnosis in most of the cases.

Less common extra-pulmonary forms

Tuberculosis may cause chorioretinitis, uveitis, panopthalmitis, phlyctenular conjunctivitis. In the nasopharynx, tuberculosis may simulate Wegner's granulomatosis. Cutaneous manifestations of tuberculosis include primary infection due to direct inoculation, abscess and chronic ulcers, scrofuloderma, lupus vulgaris, miliary lesions, and erythema nodosum. Adrenal tuberculosis is a manifestation of advanced disease presenting as sign of adrenal insufficiency.

This is described under the childhood tuberculosis (but it can also occur in adults).