Miliary tuberculosis is a form of

tuberculosis Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...

that is characterized by a wide dissemination into the human body and by the tiny size of the

lesion A lesion is any damage or abnormal change in the tissue of an organism, usually caused by injury or diseases. The term ''Lesion'' is derived from the Latin meaning "injury". Lesions may occur in both plants and animals. Types There is no de ...

s (1–5 mm). Its name comes from a distinctive pattern seen on a chest

radiograph Radiography is an imaging technique using X-rays, gamma rays, or similar ionizing radiation and non-ionizing radiation to view the internal form of an object. Applications of radiography include medical ("diagnostic" radiography and "therapeu ...

of many tiny spots distributed throughout the

lung The lungs are the primary Organ (biology), organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the Vertebral column, backbone on either side of the heart. Their ...

fields with the appearance similar to

millet Millets () are a highly varied group of small-seeded grasses, widely grown around the world as cereal crops or grains for fodder and human food. Most millets belong to the tribe Paniceae. Millets are important crops in the Semi-arid climate, ...

seeds—thus the term "miliary" tuberculosis. Miliary TB may infect any number of organs, including the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

, and

spleen The spleen (, from Ancient Greek '' σπλήν'', splḗn) is an organ (biology), organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The spleen plays important roles in reg ...

Signs and symptoms

Patients with miliary tuberculosis often experience non-specific signs, such as coughing and enlarged lymph nodes. Miliary tuberculosis can also present with enlarged liver (40% of cases), enlarged spleen (15%), inflammation of the pancreas (<5%), and multiple organ dysfunction with

adrenal insufficiency Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones. The adrenal glands—also referred to as the adrenal cortex—normally secrete glucocorticoids (primarily cortisol), mineraloco ...

(

adrenal gland The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer adrenal corte ...

s do not produce enough steroid hormones to regulate organ function). Stool may also be diarrheal in nature and appearance. Other symptoms include

fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...

hypercalcemia Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range for total calcium is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L def ...

, choroidal tubercles, and cutaneous lesions. Firstly, many patients can experience a fever lasting several weeks with daily spikes in morning temperatures. Secondly, hypercalcemia prevails in 16–51% of tuberculosis cases. It is thought that hypercalcemia occurs as a response to increased

macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...

activity in the body. Such that, 1,25 dihydroxycholecalciferol (also referred to as calcitriol) improves the ability of macrophages to kill bacteria; however, higher levels of calcitriol lead to higher calcium levels, and thus hypercalcemia in some cases.Soofi, A., Malik, A., Khan, J., & Muzzafer, S. (2004). Severe Hypercalcemia in Tuberculosis. J Pak Med Assoc, 54(4), 213–215. Thus, hypercalcemia proves to be an important symptom of miliary tuberculosis. Thirdly, chorodial tubercules, pale lesions on the optic nerve, typically indicate miliary tuberculosis in children. These lesions may occur in one eye or both; the number of lesions varies between patients. Chorodial tubercules may serve as important symptoms of miliary tuberculosis, since their presence can often confirm suspected diagnosis. Lastly, 10–30% of adults and 20–40% of children with miliary tuberculosis have tuberculosis meningitis. This relationship results from mycobacteria from miliary tuberculosis spreading to the brain and the subarachnoid space; as a result, leading to tuberculosis meningitis. The risk factors for contracting miliary tuberculosis are being in direct contact with a person who has it, living in unsanitary conditions, and poor nutrition. In the U.S., risk factors for contracting the disease include homelessness and

HIV/AIDS The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...

Cause

Miliary tuberculosis is a form of tuberculosis that is the result of ''

Mycobacterium tuberculosis ''Mycobacterium tuberculosis'' (M. tb), also known as Koch's bacillus, is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' ha ...

'' travelling to extrapulmonary organs, such as the liver, spleen and kidneys. Although it is well understood that the bacteria spread from the pulmonary system to the lymphatic system and eventually the blood stream, the mechanism by which this occurs is not well understood. One proposed mechanism is that tuberculous infection in the lungs results in erosion of the epithelial layer of alveolar cells and the spread of infection into a pulmonary vein.Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; & Mitchell, Richard N. (2007). ''Robbins Basic Pathology'' (8th ed.). Saunders Elsevier. pp. 516–522 Once the bacteria reach the left side of the heart and enter the systemic circulation, they may multiply and infect extrapulmonary organs. Once infected, the cell-mediated immune response is activated. The infected sites become surrounded by macrophages, which form granuloma, giving the typical appearance of miliary tuberculosis. Alternatively, the bacteria may attack the cells lining the alveoli and enter the lymph node(s). The bacteria then drain into a systemic vein and eventually reach the right side of the heart. From the right side of the heart, the bacteria may seed—or re-seed as the case may be—the lungs, causing the eponymous "miliary" appearance.

Diagnosis

Testing for miliary tuberculosis is conducted in a similar manner as for other forms of

, although a number of tests must be conducted on a patient to confirm diagnosis. Tests include

chest x-ray A chest radiograph, chest X-ray (CXR), or chest film is a Projectional radiography, projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures. Chest radiographs are the most common fi ...

sputum culture A sputum culture is a test to detect and identify bacteria or fungi that infect the lungs or breathing passages. Sputum is a thick fluid produced in the lungs and in the adjacent airways. Normally, fresh morning sample is preferred for the bac ...

, bronchoscopy, open lung

biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, an interventional radiologist, or an interventional cardiology, interventional cardiologist. The process involves the extraction of sampling (medicine), sample ...

, head CT/

MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and rad ...

, blood cultures,

fundoscopy Ophthalmoscopy, also called funduscopy, is a test that allows a health professional to see inside the fundus of the eye and other structures using an ophthalmoscope (or funduscope). It is done as part of an eye examination and may be done as part ...

, and

electrocardiography Electrocardiography is the process of producing an electrocardiogram (ECG or EKG), a recording of the heart's electrical activity through repeated cardiac cycles. It is an electrogram of the heart which is a graph of voltage versus time of t ...

. 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. A case of miliary tuberculosis in an 82-year-old woman: File:Chest radiograph of miliary tuberculosis 1.jpg, X-ray, 13 days after onset, showing bilateral interstitial infiltrates File:CT of miliary tuberculosis.jpg, CT, 16 days after onset, showing extensive pulmonary parenchymal involvement consisting of irregular septal thickenings with ground-glass areas and centrilobular nodules with a peri-lymphatic distribution File:Chest radiograph of miliary tuberculosis 2.jpg, X-ray, 22 days after onset, showing extensive bilateral reticulo-nodular infiltrates File:Gross pathology of miliary tuberculosis.jpg,

Gross pathology Gross pathology refers to macroscopic manifestations of disease in organ (anatomy), organs, Tissue (biology), tissues, and body cavity, body cavities. The term is commonly used by anatomical pathology, anatomical pathologists to refer to diagnosti ...

of the lung, spleen and kidney, showing micronodules (1–4 mm in diameter) which resemble millet seeds File:Microscopy of tuberculous micronodules.jpg,

Histopathology Histopathology (compound of three Greek words: 'tissue', 'suffering', and '' -logia'' 'study of') is the microscopic examination of tissue in order to study the manifestations of disease. Specifically, in clinical medicine, histopatholog ...

, showing epithelioid granulomas with multinucleated giant cells and acid-fast bacilli

Treatment

The standard treatment recommended by the

WHO The World Health Organization (WHO) is a specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Geneva, Switzerland, and has 6 regional offices and 15 ...

is with

isoniazid Isoniazid, also known as isonicotinic acid hydrazide (INH), is an antibiotic used for the treatment of tuberculosis. For active tuberculosis, it is often used together with rifampicin, pyrazinamide, and either streptomycin or ethambutol. F ...

and rifampicin for six months, as well as

ethambutol Ethambutol (EMB, E) is a medication primarily used to treat tuberculosis. It is usually given in combination with other tuberculosis medications, such as isoniazid, rifampicin and pyrazinamide. It may also be used to treat ''Mycobacterium avi ...

and

pyrazinamide Pyrazinamide is a medication used to treat tuberculosis. For active tuberculosis, it is often used with rifampicin, isoniazid, and either streptomycin or ethambutol. It is not generally recommended for the treatment of latent tuberculosis. It i ...

for the first two months. If there is evidence of

meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, intense headache, vomiting and neck stiffness and occasion ...

, then treatment is extended to twelve months. The U.S. guidelines recommend nine months' treatment. "Common medication side effects a patient may have such as inflammation of the liver if a patient is taking pyrazinamide, rifampin, and isoniazid. A patient may also have drug resistance to medication, relapse, respiratory failure, and

acute respiratory distress syndrome Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Symptoms include shortness of breath (dyspnea), rapid breathing (tachypnea), and bluish skin co ...

Prognosis

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 15–20% and for adults 25–30%. 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.

History

John Jacob Manget described a form of disseminated tuberculosis in 1700 and expressed its resemblance to numerous millet seeds in size and appearance and coined the term from Latin word , meaning ''related to millet seed''.

References

External links

* {{Authority control Tuberculosis Mycobacterium-related cutaneous conditions