Made by DATEXIS (Data Science and Text-based Information Systems) at Beuth University of Applied Sciences Berlin
Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
Testing for miliary tuberculosis is conducted in a similar manner as for other forms of tuberculosis, although a number of tests must be conducted on a patient to confirm diagnosis. Tests include chest x-ray, sputum culture, bronchoscopy, open lung biopsy, head CT/MRI, blood cultures, fundoscopy, and electrocardiography. The tuberculosis (TB) blood test, also called an Interferon Gamma Release Assay or IGRA, is a way to diagnose latent TB.
A variety of neurological complications have been noted in miliary tuberculosis patients—tuberculous meningitis and cerebral tuberculomas being the most frequent. However, a majority of patients improve following antituberculous treatment. Rarely lymphangitic spread of lung cancer could mimic miliary pattern of tuberculosis on regular chest X-ray.
The tuberculin skin test, commonly used for detection of other forms of tuberculosis, is not useful in the detection of miliary tuberculosis. The tuberculin skin test fails due to the high numbers of false negatives. These false negatives may occur because of higher rates of tuberculin anergy compared to other forms of tuberculosis.
1)positive tuberclin test
2)chest radiograph
3)CT scan
4)cytology/biopsy (FNAC)
5)AFB staining
6)mycobacterial culture
Incision drainage with proper evacuation of the fluid followed by anti-tubercular medication.
If left untreated, miliary tuberculosis is almost always fatal. Although most cases of miliary tuberculosis are treatable, the mortality rate among children with miliary tuberculosis remains 15 to 20% and for adults 25 to 30%. One of the main causes for these high mortality rates includes late detection of disease caused by non-specific symptoms. Non-specific symptoms include: coughing, weight loss, or organ dysfunction. These symptoms may be implicated in numerous disorders, thus delaying diagnosis. Misdiagnosis with tuberculosis meningitis is also a common occurrence when patients are tested for tuberculosis, since the two forms of tuberculosis have high rates of co-occurrence.
The Mantoux tuberculin skin test is often used to screen people at high risk for TB. Those who have been previously immunized may have a false-positive test result. The test may be falsely negative in those with sarcoidosis, Hodgkin's lymphoma, malnutrition, and most notably, active tuberculosis. Interferon gamma release assays, on a blood sample, are recommended in those who are positive to the Mantoux test. These are not affected by immunization or most environmental mycobacteria, so they generate fewer false-positive results. However, they are affected by "M. szulgai", "M. marinum", and "M. kansasii". IGRAs may increase sensitivity when used in addition to the skin test, but may be less sensitive than the skin test when used alone.
Diagnosis can be achieved through blood cultures, or cultures of other bodily fluids such as sputum. Bone marrow culture can often yield an earlier diagnosis, but is usually avoided as an initial diagnostic step because of its invasiveness.
Many people will have anemia and neutropenia if bone marrow is involved. MAC bacteria should always be considered in a person with HIV infection presenting with diarrhea.
The diagnosis requires consistent symptoms with two additional signs:
- Chest X-ray or CT scan showing evidence of right middle lobe (or left lingular lobe) lung infection
- Sputum culture or bronchoalveolar lavage culture demonstrating the infection is caused by MAC
Disseminated MAC is most readily diagnosed by one positive blood culture. Blood cultures should be performed in patients with symptoms, signs, or laboratory abnormalities compatible with mycobacterium infection. Blood cultures are not routinely recommended for asymptomatic persons, even for those who have CD4+ T-lymphocyte counts less than 100 cells/uL.
Diagnosing active tuberculosis based only on signs and symptoms is difficult, as is diagnosing the disease in those who are immunosuppressed. A diagnosis of TB should, however, be considered in those with signs of lung disease or constitutional symptoms lasting longer than two weeks. A chest X-ray and multiple sputum cultures for acid-fast bacilli are typically part of the initial evaluation. Interferon-γ release assays and tuberculin skin tests are of little use in the developing world. Interferon gamma release assays (IGRA) have similar limitations in those with HIV.
A definitive diagnosis of TB is made by identifying "M. tuberculosis" in a clinical sample (e.g., sputum, pus, or a tissue biopsy). However, the difficult culture process for this slow-growing organism can take two to six weeks for blood or sputum culture. Thus, treatment is often begun before cultures are confirmed.
Nucleic acid amplification tests and adenosine deaminase testing may allow rapid diagnosis of TB. These tests, however, are not routinely recommended, as they rarely alter how a person is treated. Blood tests to detect antibodies are not specific or sensitive, so they are not recommended.
lymphadenopathy is a common biopsy finding, and may often be confused with malignant lymphoma. It may be separated into major morphologic patterns, each with its own differential diagnosis with certain types of lymphoma. Most cases of reactive follicular hyperplasia are easy to diagnose, but some cases may be confused with follicular lymphoma. There are seven distinct patterns of benign lymphadenopathy:
- Follicular hyperplasia: This is the most common type of reactive lymphadenopathy.
- Paracortical hyperplasia/Interfollicular hyperplasia: It is seen in viral infections, skin diseases, and nonspecific reactions.
- Sinus histiocytosis: It is seen in lymph nodes draining limbs, inflammatory lesions, and malignancies.
- Nodal extensive necrosis
- Nodal granulomatous inflammation
- Nodal extensive fibrosis (Connective tissue framework)
- Nodal deposition of interstitial substance
These morphological patterns are never pure. Thus, reactive follicular hyperplasia can have a component of paracortical hyperplasia. However, this distinction is important for the differential diagnosis of the cause.
A CT scan provides a computer-generated picture of the lungs that can show pockets of fluid. It also may show signs of pneumonia, a lung abscess, or a tumor.
In arterial blood-gas sampling, a small amount of blood is taken from an artery, usually in the wrist. The blood is then checked for oxygen and carbon-dioxide levels. This test shows how well the lungs are taking in oxygen.
MAC in patients with HIV disease is theorized to represent recent acquisition rather than latent infection reactivating (which is the case in many other opportunistic infections in immunocompromised patients).
The risk of MAC is inversely related to the patient's CD4 count, and increases significantly when the CD4 count decreases below 50 cells/mm³. Other risk factors for acquisition of MAC infection include using an indoor swimming pool, consumption of raw or partially cooked fish or shellfish, bronchoscopy and treatment with granulocyte stimulating factor.
Disseminated disease was previously the common presentation prior to the advent of highly active antiretroviral therapy (HAART). Today, in regions where HAART is the standard of care, localized disease presentation is more likely. This generally includes a focal lymphadenopathy/lymphadenitis.
A study conducted on 452 patients revealed that the genotype responsible for higher IL-10 expression makes HIV infected people more susceptible to tuberculosis infection. Another study on HIV-TB co-infected patients also concluded that higher level of IL-10 and IL-22 makes TB patient more susceptible to Immune reconstitution inflammatory syndrome (IRIS). It is also seen that HIV co-infection with tuberculosis also reduces concentration of immunopathogenic matrix metalloproteinase (MMPs) leading to reduced inflammatory immunopathology.
This is a group of tests that use polymerase chain reaction (PCR) to detect mycobacterial nucleic acid. These test vary in which nucleic acid sequence they detect and vary in their accuracy. The two most common commercially available tests are the amplified mycobacterium tuberculosis direct test (MTD, Gen-Probe) and Amplicor. In 2007, review concluded that for diagnosing tuberculous meningitis "Individually, the AMTD test appears to perform the best (sensitivity 74% and specificity 98%)", they found the pooled prevalence of TB meningitis to be 29%.
The differential diagnosis of Rosai–Dorfman disease includes both malignant and nonmalignant diseases, such as granulomatosis with polyangiitis, Langerhans cell histiocytosis, Langerhans cell sarcoma, lymphoma, sarcoidosis, and tuberculosis. The disease is diagnosed by biopsy of affected tissues. Microscopic examination of stained specimens will show histiocytes with lymphocytes and possibly other types of cells trapped within them, a phenomenon known as emperipolesis. Upon immunohistochemical staining, the histiocytes will be positive for S100, CD68, and CD163 but negative for CD1a.
Once a pleural effusion is diagnosed, its cause must be determined. Pleural fluid is drawn out of the pleural space in a process called thoracentesis, and it should be done in almost all patients who have pleural fluid that is at least 10 mm in thickness on CT, ultrasonography, or lateral decubitus X-ray and that is new or of uncertain etiology. In general, the only patients who do not require thoracentesis are those who have heart failure with symmetric pleural effusions and no chest pain or fever; in these patients, diuresis can be tried, and thoracentesis is avoided unless effusions persist for more than 3 days. In a thoracentesis, a needle is inserted through the back of the chest wall in the sixth, seventh, or eighth intercostal space on the midaxillary line, into the pleural space. The use of ultrasound to guide the procedure is now standard of care as it increases accuracy and decreases complications. After removal, the fluid may then be evaluated for:
1. Chemical composition including protein, lactate dehydrogenase (LDH), albumin, amylase, pH, and glucose
2. Gram stain and culture to identify possible bacterial infections
3. White and red blood cell counts and differential white blood cell counts
4. Cytopathology to identify cancer cells, but may also identify some infective organisms
5. Other tests as suggested by the clinical situation – lipids, fungal culture, viral culture, tuberculosis cultures, lupus cell prep, specific immunoglobulins
The diagnosis is confirmed by a skin biopsy and a positive culture for acid-fast bacilli. A PPD test may also result positive.
Diagnosis of TB meningitis is made by analysing cerebrospinal fluid collected by lumbar puncture. When collecting CSF for suspected TB meningitis, a minimum of 1ml of fluid should be taken (preferably 5 to 10ml). The CSF usually has a high protein, low glucose and a raised number of lymphocytes. Acid-fast bacilli are sometimes seen on a CSF smear, but more commonly, "M. tuberculosis" is grown in culture. A spiderweb clot in the collected CSF is characteristic of TB meningitis, but is a rare finding. ELISPOT testing is not useful for the diagnosis of acute TB meningitis and is often false negative, but may paradoxically become positive after treatment has started, which helps to confirm the diagnosis.
A pleural effusion appears as an area of whiteness on a standard posteroanterior chest X-ray. Normally, the space between the visceral pleura and the parietal pleura cannot be seen. A pleural effusion infiltrates the space between these layers. Because the pleural effusion has a density similar to water, it can be seen on radiographs. Since the effusion has greater density than the rest of the lung, it gravitates towards the lower portions of the pleural cavity. The pleural effusion behaves according to basic fluid dynamics, conforming to the shape of pleural space, which is determined by the lung and chest wall. If the pleural space contains both air and fluid, then an air-fluid level that is horizontal will be present, instead of conforming to the lung space. Chest radiographs in the lateral decubitus position (with the patient lying on the side of the pleural effusion) are more sensitive and can detect as little as 50 mL of fluid. At least 300 mL of fluid must be present before upright chest X-rays can detect a pleural effusion (e.g., blunted costophrenic angles).
Chest computed tomography is more accurate for diagnosis and may be obtained to better characterize the presence, size, and characteristics of a pleural effusion. Lung ultrasound, nearly as accurate as CT and more accurate than chest X-ray, is increasingly being used at the point of care to diagnose pleural effusions, with the advantage that it is a safe, dynamic, and repeatable imaging modality. To increase diagnostic accuracy of detection of pleural effusion sonographically, markers such as boomerang and VIP signs can be utilized.
Lymph node enlargement is recognized as a common sign of infectious, autoimmune, or malignant disease. Examples may include:
- Reactive: acute infection ("e.g.," bacterial, or viral), or chronic infections (tuberculous lymphadenitis, cat-scratch disease).
- The most distinctive sign of bubonic plague is extreme swelling of one or more lymph nodes that bulge out of the skin as "buboes." The buboes often become necrotic and may even rupture.
- Infectious mononucleosis is an acute viral infection caused by Epstein-Barr virus and may be characterized by a marked enlargement of the cervical lymph nodes.
- It is also a sign of cutaneous anthrax and Human African trypanosomiasis
- Toxoplasmosis, a parasitic disease, gives a generalized lymphadenopathy ("Piringer-Kuchinka lymphadenopathy").
- Plasma cell variant of Castleman's disease - associated with HHV-8 infection and HIV infection
- Mesenteric lymphadenitis after viral systemic infection (particularly in the GALT in the appendix) can commonly present like appendicitis.
Less common infectious causes of lymphadenopathy may include bacterial infections such as cat scratch disease, tularemia, brucellosis, or prevotella.
- Tumoral:
- Primary: Hodgkin lymphoma and non-Hodgkin lymphoma give lymphadenopathy in all or a few lymph nodes.
- Secondary: metastasis, Virchow's Node, neuroblastoma, and chronic lymphocytic leukemia.
- Autoimmune: systemic lupus erythematosus and rheumatoid arthritis may have a generalized lymphadenopathy.
- Immunocompromised: AIDS. Generalized lymphadenopathy is an early sign of infection with human immunodeficiency virus (HIV), the virus that causes acquired immunodeficiency syndrome (AIDS). "Lymphadenopathy syndrome" has been used to describe the first symptomatic stage of HIV progression, preceding a diagnosis of AIDS.
- Bites from certain venomous snakes such as the pit viper
- Unknown: Kikuchi disease, progressive transformation of germinal centers, sarcoidosis, hyaline-vascular variant of Castleman's disease, Rosai-Dorfman disease, Kawasaki disease, Kimura disease
It is currently recommended that HIV-infected individuals with TB receive combined treatment for both diseases, irrespective of CD4+ cell count. ART (Anti Retroviral Therapy) along with ATT (Anti Tuberculosis Treatment) is the only available treatment in present time. Though the timing of starting ART is the debatable question due to the risk of immune reconstitution inflammatory syndrome (IRIS). The advantages of early ART include reduction in early mortality, reduction in relapses, preventing drug resistance to ATT and reduction in occurrence of HIV-associated infections other than TB. The disadvantages include cumulative toxicity of ART and ATT, drug interactions leading to inflammatory reactions are the limiting factors for choosing the combination of ATT and ART.
A systematic review investigated the optimal timing of starting antiretroviral therapy in adults with newly diagnosed pulmonary tuberculosis. The review authors included eight trials, that were generally well-conducted, with over 4500 patients in total. The early provision of antiretroviral therapy in HIV-infected adults with newly diagnosed tuberculosis improved survival in patients who had a low CD4 count (less than 0.050 x 109 cells/L). However, such therapy doubled the risk for IRIS. Regarding patients with higher CD4 counts (more than 0.050 x 109 cells/L), the evidence is not sufficient to make a conclusion about benefits or risks of early antiretroviral therapy.
Tuberculous pericarditis is a form of pericarditis.
Pericarditis caused by tuberculosis is difficult to diagnose, because definitive diagnosis requires culturing "Mycobacterium tuberculosis" from aspirated pericardial fluid or pericardial , which requires high technical skill and is often not diagnostic (the yield from culture is low even with optimum specimens). The Tygerberg scoring system helps the clinician to decide whether pericarditis is due to tuberculosis or whether it is due to another cause: night sweats (1 point), weight loss (1 point), fever (2 point), serum globulin > 40g/l (3 points), blood total leucocyte count <10 x 10/l (3 points); a total score of 6 or more is highly suggestive of tuberculous pericarditis. Pericardial fluid with an interferon-γ level greater than 50/ml is highly specific for tuberculous pericarditis.
There are no randomized trials which evaluate the length of anti-tuberculosis treatment required for tuberculous pericarditis. There is a small but not conclusive benefit for treatment with a schedule of steroids with anti-tuberculosis drugs. Open surgical drainage of fluid though effective in preventing cardiac tamponade was associated with more deaths.
Some patients have no symptoms, spontaneous remission, or a relapsing/remitting course, making it difficult to decide whether therapy is needed. In 2002, authors from Sapienza University of Rome stated on the basis of a comprehensive literature review that "clinical observation without treatment is advisable when possible."
Therapeutic options include surgery, radiation therapy, and chemotherapy. Surgery is used to remove single lymph nodes, central nervous system lesions, or localized cutaneous disease. In 2014, Dalia and colleagues wrote that for patients with extensive or systemic Rosai–Dorfman disease, "a standard of care has not been established" concerning radiotherapy and chemotherapy.
Diagnosis of mycetoma is usually established clinically in endemic areas.
X rays and ultrasonography may be employed in evaluating the extent of the disease. X rays findings are extremely variable. The disease is most often observed at an advanced stage that exhibits extensive destruction of all bones of the foot. Rarely, a single lesion may be seen in the tibia where the picture is identical with chronic osteomyelitis. Cytology of fine needle aspirate or pus from the lesion, and tissue biopsy may be undertaken sometimes. Some publications have claimed a "dot in a circle sign" as a characteristic MRI feature for this condition (this feature has also been described on ultrasound).
The following clinical conditions may be considered before diagnosing a patient with mycetoma:
1. Tuberculous ulcer
2. Kaposi's sarcoma, a vascular tumour of skin usually seen in AIDS.
3. Leprosy
4. Syphilis
5. Malignant neoplasm
6. Tropical ulcer
7. Botryomycosis, a skin infection usually caused by the bacteria Staphylococcus aureus.
About 30% of people with viral pericarditis or pericarditis of an unknown cause have one or several recurrent episodes.