Tuberculosis (Clinical)

Overview

Definition^[1,5]

Tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis ( TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis) is an infectious disease affecting the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy and, sometimes, other organs. Tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis is caused by Mycobacterium tuberculosis Mycobacterium tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis complex (MTBC) bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology.

Epidemiology^[5,13]

• TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis is the deadliest infectious disease in the world, with approximately 1.4 million deaths per year.
• 30% of the world’s population is infected with TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis.
• 10% of infected people will develop the active form of the disease.
• In 2019, 10 million people contracted TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis.
• TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis is the leading cause of death in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with human immunodeficiency Immunodeficiency Chédiak-Higashi Syndrome virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology ( HIV HIV Anti-HIV Drugs).
• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: 2.7 per 100,000 people in the United States (2019)
• Regions with the highest incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis:
  • Southeast Asia ASIA Spinal Cord Injuries
  • Africa
  • The Western Pacific
• Risk factors:
  • Institutionalized patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • Intravenous drug use
  • HIV HIV Anti-HIV Drugs or other immunodeficiency Immunodeficiency Chédiak-Higashi Syndrome
  • Travel to high-risk regions

Pathophysiology

Etiologic agent^[2]

The M. tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis complex is a group of species that can cause TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis in humans or other animals Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, animalia was one of the kingdoms. Under the modern three domain model, animalia represents one of the many groups in the domain eukaryota. Cell Types: Eukaryotic versus Prokaryotic.

Key species:

• M. tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis
• M. bovis
• M. africanum
• M. microti
• M. canetti

Characteristics:

• Acid-fast:
  • Property conferred by mycolic acid Mycolic acid Long fatty acids found in the cell walls of some actinobacteria, including Mycobacterium tuberculosis. Tuberculosis
  • Do not destain by acid alcohol after being stained with aniline dyes
• Gram stain Gram stain Klebsiella:
  • Usually cannot penetrate MTBC waxy cell wall Cell wall The outermost layer of a cell in most plants; bacteria; fungi; and algae. The cell wall is usually a rigid structure that lies external to the cell membrane, and provides a protective barrier against physical or chemical agents. Cell Types: Eukaryotic versus Prokaryotic
  • Most commonly produce no stain or variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables results
• Slow-growing
• Obligate aerobes Obligate aerobes Bacteriology

Virulence factors Virulence factors Those components of an organism that determine its capacity to cause disease but are not required for its viability per se. Two classes have been characterized: toxins, biological and surface adhesion molecules that affect the ability of the microorganism to invade and colonize a host. Haemophilus:

• Cell envelope Envelope Bilayer lipid membrane acquired by viral particles during viral morphogenesis. Although the lipids of the viral envelope are host derived, various virus-encoded integral membrane proteins, i.e. Viral envelope proteins are incorporated there. Virology:
  • Major constituent: mycolic acid Mycolic acid Long fatty acids found in the cell walls of some actinobacteria, including Mycobacterium tuberculosis. Tuberculosis
  • Mycolic acid Mycolic acid Long fatty acids found in the cell walls of some actinobacteria, including Mycobacterium tuberculosis. Tuberculosis is attached to glycolipids Glycolipids Lipid attached to carbohydrate, outward-facing. The Cell: Cell Membrane.
  • Glycolipids Glycolipids Lipid attached to carbohydrate, outward-facing. The Cell: Cell Membrane are responsible for “cord formation” on microscopy (grossly corresponds to granuloma formation).
• Catalase-peroxidase: resists host cell oxidative response
• Sulfatides Sulfatides Mycobacterium and trehalose dimycolate Trehalose dimycolate Toxic glycolipids composed of trehalose dimycolate derivatives. They are produced by Mycobacterium tuberculosis and other species of Mycobacterium. They induce cellular dysfunction in animals. Mycobacterium: triggers toxicity Toxicity Dosage Calculation
• Lipoarabinomannan ( LAM LAM Tuberous Sclerosis): induces cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response

Transmission:

• Exclusively airborne
• From patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with active TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis

Pathogenesis^[1,2,5,9]

• 1st step is inhalation of aerosol droplets Droplets Varicella-Zoster Virus/Chickenpox.
• Droplets Droplets Varicella-Zoster Virus/Chickenpox are deposited in the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy.
• 3 possible outcomes:
  • Clearance of bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology
  • Primary active disease
  • Latent infection (clinical disease may occur many years later)

Primary active disease:

• Proliferation of bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology within alveolar macrophages Alveolar macrophages Round, granular, mononuclear phagocytes found in the alveoli of the lungs. They ingest small inhaled particles resulting in degradation and presentation of the antigen to immunocompetent cells. Acute Respiratory Distress Syndrome (ARDS)
• Cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response produced by macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation attract other phagocytic cells.
• A tubercle (granulomatous structure) forms.
• Tubercle expands into lung parenchyma → Ghon complex
• Bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology then can spread to draining lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy → lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy
• Ghon complex Ghon complex Tuberculosis + lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy/calcification → Ranke complex
• If spread is not controlled by the immune cells, bacteremia Bacteremia The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. Glycopeptides with seeding Seeding The local implantation of tumor cells by contamination of instruments and surgical equipment during and after surgical resection, resulting in local growth of the cells and tumor formation. Grading, Staging, and Metastasis of other organs may occur → miliary TB Miliary TB An acute form of tuberculosis in which minute tubercles are formed in a number of organs of the body due to dissemination of the bacilli through the bloodstream. Tuberculosis
• When bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology erode into airways (caseating granulomas Granulomas A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. Sarcoidosis), the patient becomes contagious.
• Infection may progress to a chronic stage, with episodes of healing and subsequent scarring Scarring Inflammation of the lesions.
• Spontaneous eradication is rare.

Latent infection:

• Lifetime risk of reactivation Reactivation Herpes Simplex Virus 1 and 2 is 5%–10%.
• Immunosuppression is a definite factor in reactivation Reactivation Herpes Simplex Virus 1 and 2.
• Risk factors:
  • HIV HIV Anti-HIV Drugs
  • Kidney disease
  • Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
  • Steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors
  • Lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum
  • Advanced age
  • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases

Clinical Presentation

Primary TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis^[1,2,9]

• Symptomatic primary disease develops in only about 10% of infected people.
• Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever:
  • Most common symptom
  • Mostly low grade, but may be up to 39°C (102.2°F)
  • Lasts up to 10 weeks, but on average 14–21 days
• Pleuritic chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways (may or may not be associated with effusion)
• Retrosternal/interscapular pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways (due to bronchial lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy)
• Cough
• Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
• Arthralgia Arthralgia Pain in the joint. Rheumatic Fever
• Pharyngitis Pharyngitis Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis

Reactivation Reactivation Herpes Simplex Virus 1 and 2 TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis^[2,9]

• Apical segments of upper lobes and superior segments of lower lobes are most commonly involved, likely because of:
  • Increased oxygen tension
  • Poor lymphatic drainage
• Onset of symptoms is gradual; may go undiagnosed for 2–3 years
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever:
    • Low grade first, worsening with more advanced disease
    • Classically diurnal: peaks in the afternoon, afebrile at night and in the early morning
  • Night sweats Night sweats Tuberculosis
  • Cough:
    • Mild first, gradually worsening
    • Initially only in the mornings
    • Becomes more productive (greenish-yellow sputum) as disease progresses
    • Nocturnal cough and hemoptysis Hemoptysis Hemoptysis is defined as the expectoration of blood originating in the lower respiratory tract. Hemoptysis is a consequence of another disease process and can be classified as either life threatening or non-life threatening. Hemoptysis can result in significant morbidity and mortality due to both drowning (reduced gas exchange as the lungs fill with blood) and hemorrhagic shock. Hemoptysis: advanced disease
  • Pneumothorax Pneumothorax A pneumothorax is a life-threatening condition in which air collects in the pleural space, causing partial or full collapse of the lung. A pneumothorax can be traumatic or spontaneous. Patients present with a sudden onset of sharp chest pain, dyspnea, and diminished breath sounds on exam. Pneumothorax or effusions may present with dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea (rare).
  • Anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa, wasting, malaise Malaise Tick-borne Encephalitis Virus
  • Ulcers of mouth, tongue Tongue The tongue, on the other hand, is a complex muscular structure that permits tasting and facilitates the process of mastication and communication. The blood supply of the tongue originates from the external carotid artery, and the innervation is through cranial nerves. Lips and Tongue: Anatomy, larynx Larynx The larynx, also commonly called the voice box, is a cylindrical space located in the neck at the level of the C3-C6 vertebrae. The major structures forming the framework of the larynx are the thyroid cartilage, cricoid cartilage, and epiglottis. The larynx serves to produce sound (phonation), conducts air to the trachea, and prevents large molecules from reaching the lungs. Larynx: Anatomy, and esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy: due to infected expectorated secretions

Extrapulmonary and miliary TB Miliary TB An acute form of tuberculosis in which minute tubercles are formed in a number of organs of the body due to dissemination of the bacilli through the bloodstream. Tuberculosis^[2,7,9]

• Can develop in the course of primary or reactivation Reactivation Herpes Simplex Virus 1 and 2 disease
• In up to 15%–20% of active cases
• Most common in children and immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis individuals
• Extrapulmonary manifestations (can affect any organ system):
  • Tuberculous pleurisy Pleurisy Pleuritis, also known as pleurisy, is an inflammation of the visceral and parietal layers of the pleural membranes of the lungs. The condition can be primary or secondary and results in sudden, sharp, and intense chest pain on inhalation and exhalation. Pleuritis 
  • Adrenal gland insufficiency
  • Meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis
  • Spondylitis tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis (Pott’s disease, TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis infection of > 1 vertebra)
  • Constrictive pericarditis Constrictive pericarditis Inflammation of the pericardium that is characterized by the fibrous scarring and adhesion of both serous layers, the visceral pericardium and the parietal pericardium leading to the loss of pericardial cavity. The thickened pericardium severely restricts cardiac filling. Clinical signs include fatigue, muscle wasting, and weight loss. Pericarditis
  • Lupus vulgaris (reddish-brown nodules that usually appear on the face around the nose Nose The nose is the human body’s primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Nose Anatomy (External & Internal), eyelids Eyelids Each of the upper and lower folds of skin which cover the eye when closed. Blepharitis, lips Lips The lips are the soft and movable most external parts of the oral cavity. The blood supply of the lips originates from the external carotid artery, and the innervation is through cranial nerves. Lips and Tongue: Anatomy, cheeks Cheeks The part of the face that is below the eye and to the side of the nose and mouth. Melasma, ears, and neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess)
  • Scrofula (cervical lymphadenitis Lymphadenitis Inflammation of the lymph nodes. Peritonsillar Abscess)
  • Sterile Sterile Basic Procedures pyuria Pyuria The presence of white blood cells (leukocytes) in the urine. It is often associated with bacterial infections of the urinary tract. Pyuria without bacteriuria can be caused by tuberculosis, stones, or cancer. Urinary Tract Infections (UTIs)
• Miliary TB Miliary TB An acute form of tuberculosis in which minute tubercles are formed in a number of organs of the body due to dissemination of the bacilli through the bloodstream. Tuberculosis:
  • Massive spread of infection through blood and lymphatics
  • Small granulomatous lesions through multiple organs

Diagnosis

History^[7,9,10]

• Travel to endemic areas
• Exposure to individuals with known or suspected active infection
• HIV HIV Anti-HIV Drugs or other immune deficiencies
• Working in healthcare
• Living in a homeless shelter or correctional institution

Physical exam^[7,9,10]

• Findings are often non-specific.
• Pulmonary:
  • Dullness to percussion Percussion Act of striking a part with short, sharp blows as an aid in diagnosing the condition beneath the sound obtained. Pulmonary Examination (effusions)
  • Crackles on auscultation
  • Distant hollow breath sounds
• Extrapulmonary (depends on organ involvement):
  • Cervical lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy
  • Hepatomegaly/ splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly
  • Ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites, jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice
  • Meningismus Meningismus Subarachnoid Hemorrhage, altered mental status Altered Mental Status Sepsis in Children
  • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions changes (lupus vulgaris)

Imaging^[7,9,10]

• Chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests:
  • Can be normal in primary TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis
  • Hilar lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy
  • Ghon complex Ghon complex Tuberculosis: enlarged hilar lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy + local shadowing
  • Assmann’s focus: infraclavicular infiltration
  • Pleural effusions
  • Reactivation Reactivation Herpes Simplex Virus 1 and 2 TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis:
    • Simon foci (calcified small scar Scar Dermatologic Examination from primary infection Primary infection Herpes Simplex Virus 1 and 2)
    • Infiltrates in apical segments and upper segments of lower lobes
    • Cavities with air-fluid levels
• Computed tomography (CT) scan:
  • More sensitive than plain X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests
  • Used if chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests is non-specific or alternative diagnosis is considered

Laboratory identification Identification Defense Mechanisms

Active pulmonary TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis:^[5,7,9,10]

• Sputum:
  • 3 specimens, at least 1 in the early morning (volume of at least 3 mL; optimal amount is 5–10 mL)
  • Acid-fast bacillus Bacillus Bacillus are aerobic, spore-forming, gram-positive bacilli. Two pathogenic species are Bacillus anthracis (B. anthracis) and B. cereus. Bacillus ( AFB AFB Mycobacterium) smear
  • Mycobacterial culture (both liquid and solid) with drug susceptibility for rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis and isoniazid Isoniazid Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. Antimycobacterial Drugs
  • Nucleic acid amplification Nucleic acid amplification Laboratory techniques that involve the in-vitro synthesis of many copies of DNA or RNA from one original template. Septic Arthritis (NAA) test
• Bronchoscopy Bronchoscopy Endoscopic examination, therapy or surgery of the bronchi. Laryngomalacia and Tracheomalacia:
  • Perform with bronchoalveolar lavage Bronchoalveolar lavage Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. Pulmonary Fibrosis and brushings if sputum samples are inadequate.
  • If rapid diagnosis is needed, perform transbronchial biopsy Transbronchial biopsy Pneumocystis jirovecii/Pneumocystis Pneumonia (PCP).

Extrapulmonary TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis:^[7,10]

• Consider biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma and needle aspiration Needle aspiration Using fine needles (finer than 22-gauge) to remove tissue or fluid specimens from the living body for examination in the pathology laboratory and for disease diagnosis. Peritonsillar Abscess of involved tissue(s), assessing advantages and disadvantages.
• For liquid specimens (e.g., pleural fluid, cerebrospinal fluid Cerebrospinal Fluid A watery fluid that is continuously produced in the choroid plexus and circulates around the surface of the brain; spinal cord; and in the cerebral ventricles. Ventricular System: Anatomy (CSF)):
  • Send for cell count and chemistries in amenable fluid specimens such as ascitic, pleural, cerebrospinal, and joint fluids.
  • Obtain adenosine Adenosine A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. Class 5 Antiarrhythmic Drugs deaminase ( ADA ADA An enzyme that catalyzes the hydrolysis of adenosine to inosine with the elimination of ammonia. Purine and Pyrimidine Metabolism): ≥ 79% sensitivity and ≥ 83% specificity for detecting TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis in CSF, pleural fluid, peritoneal fluid, and pericardial fluid Pericardial fluid Watery fluid produced in the serous and visceral pericardium surrounding the surface of the heart. Heart: Anatomy
  • Obtain free interferon ( IFN IFN Interferon (IFN) is a cytokine with antiviral properties (it interferes with viral infections) and various roles in immunoregulation. The different types are type I IFN (IFN-ɑ and IFN-β), type II IFN (IFN-ɣ), and type III IFN (IFN-ƛ). Interferons)-γ levels: ≥ 89% sensitivity and ≥ 97% specificity for detecting TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis in pleural fluid and peritoneal fluid
• Area(s) affected and specimen:
  • Pleura Pleura The pleura is a serous membrane that lines the walls of the thoracic cavity and the surface of the lungs. This structure of mesodermal origin covers both lungs, the mediastinum, the thoracic surface of the diaphragm, and the inner part of the thoracic cage. The pleura is divided into a visceral pleura and parietal pleura. Pleura: Anatomy:
    • Sputum: send for microscopy, culture, histology
    • Pleural fluid: send for microscopy, culture, histology, ADA ADA An enzyme that catalyzes the hydrolysis of adenosine to inosine with the elimination of ammonia. Purine and Pyrimidine Metabolism, free IFN-γ
    • Pleural biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma
  • Central nervous system Central nervous system The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. Nervous System: Anatomy, Structure, and Classification:
    • Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma of suspected tuberculoma: send for microscopy, culture, histology
    • CSF: send for microscopy, culture, histology, nucleic acid amplification Nucleic acid amplification Laboratory techniques that involve the in-vitro synthesis of many copies of DNA or RNA from one original template. Septic Arthritis test (NAAT), ADA ADA An enzyme that catalyzes the hydrolysis of adenosine to inosine with the elimination of ammonia. Purine and Pyrimidine Metabolism
  • Lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node:
    • Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma: send for microscopy, culture, histology, NAAT
    • Aspirate: send for microscopy, culture, histology, NAAT
  • Pericardium Pericardium A conical fibroserous sac surrounding the heart and the roots of the great vessels (aorta; venae cavae; pulmonary artery). Pericardium consists of two sacs: the outer fibrous pericardium and the inner serous pericardium. The latter consists of an outer parietal layer facing the fibrous pericardium, and an inner visceral layer (epicardium) resting next to the heart, and a pericardial cavity between these two layers. Heart: Anatomy:
    • Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma: send for microscopy, culture, histology
    • Pericardial fluid Pericardial fluid Watery fluid produced in the serous and visceral pericardium surrounding the surface of the heart. Heart: Anatomy: send for microscopy, culture, histology, NAAT, ADA ADA An enzyme that catalyzes the hydrolysis of adenosine to inosine with the elimination of ammonia. Purine and Pyrimidine Metabolism
  • Gastrointestinal:
    • Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma of omentum Omentum Peritoneum: Anatomy, liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy: send for microscopy, culture, histology
    • Ascitic fluid Ascitic fluid The serous fluid of ascites, the accumulation of fluids in the peritoneal cavity. Ascites: send for microscopy, culture, histology, ADA ADA An enzyme that catalyzes the hydrolysis of adenosine to inosine with the elimination of ammonia. Purine and Pyrimidine Metabolism
  • Genitourinary:
    • Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma: send for microscopy, culture, histology
    • Urine: culture
  • Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types and joint:
    • Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma or aspiration of abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease: culture
    • Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma of joint
    • Aspirate of joint fluid
  • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions: biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma (send for microscopy, culture, histology)

Latent TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis:^[5,10]

• Tuberculin Tuberculin A protein extracted from boiled culture of tubercle bacilli (Mycobacterium tuberculosis). It is used in the tuberculin skin test (tuberculin test) for the diagnosis of tuberculosis infection in asymptomatic persons. Type IV Hypersensitivity Reaction skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions test (TST; purified protein derivative (PPD) or Mantoux test):
  • Intradermal injection of tuberculin Tuberculin A protein extracted from boiled culture of tubercle bacilli (Mycobacterium tuberculosis). It is used in the tuberculin skin test (tuberculin test) for the diagnosis of tuberculosis infection in asymptomatic persons. Type IV Hypersensitivity Reaction antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination (0.1 mL of PPD)
  • Can detect active or latent infection
  • Measure induration Induration Dermatologic Examination area in 48–72 hours; positive if:
    • ≥ 5 mm in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with HIV HIV Anti-HIV Drugs, immunosuppression, with radiologic or clinical evidence of current or past TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis or recent contact with TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis
    • ≥ 10 mm in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship from high-risk countries, IV drug users, medical and lab workers
    • ≥ 15 mm in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with no known risk factors for TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis
• Ifn-γ release assay ( IGRA IGRA The assay of interferon-gamma released from lymphocytes after their exposure to a specific test antigen, to check for immunologic memory resulting from a previous exposure to the antigen. The amount of interferon-gamma released is usually assayed by an enzyme-linked immunosorbent assay. Tuberculosis): blood test detecting immune reactivity to M. tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis but offers no distinction between active and inactive TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis
  • Available IGRAs:
    • QuantiFERON assay
    • T-SPOT. TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis assay
  • Preferably performed on patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship age ≥ 5 years who:
    • Are suspected to have M. tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis infection
    • Have low-to-intermediate risk of disease progression
    • Need to be tested for latent TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis
  • TST is an alternative if IGRA IGRA The assay of interferon-gamma released from lymphocytes after their exposure to a specific test antigen, to check for immunologic memory resulting from a previous exposure to the antigen. The amount of interferon-gamma released is usually assayed by an enzyme-linked immunosorbent assay. Tuberculosis is not available or is too costly.
• Neither TST nor IGRA IGRA The assay of interferon-gamma released from lymphocytes after their exposure to a specific test antigen, to check for immunologic memory resulting from a previous exposure to the antigen. The amount of interferon-gamma released is usually assayed by an enzyme-linked immunosorbent assay. Tuberculosis can distinguish between active and latent TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis.
• Exclude active TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis with thorough history, chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests, and possible sputum laboratories (if chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests is suggestive of active TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis).

Management

The following recommendations are based on US and UK guidelines.

Goals^[6–8]

• Cure infected individuals while minimizing morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status and mortality Mortality All deaths reported in a given population. Measures of Health Status
• Reduce person-to-person transmission
• Prevent occurrence of drug resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing

Case management^[7,8]

• Patient education
• In-person visits
• Coordination Coordination Cerebellar Disorders of care with specialist and home care
• Reminders
• Incentives

Pharmacologic management^[6‒8]

• The mainstay of treatment is anti-mycobacterial drugs.
• Directly observed therapy (DOT) is preferred:
  • Medications are administered to patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.
  • Administration by healthcare providers ensures compliance Compliance Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. Veins: Histology and correct administration.
• Usually 2 treatment phases: intensive and continuation

Intensive phase

4-drug regimen: Rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis, Isoniazid Isoniazid Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. Antimycobacterial Drugs, Pyrazinamide Pyrazinamide A pyrazine that is used therapeutically as an antitubercular agent. Antimycobacterial Drugs, Ethambutol Ethambutol An antitubercular agent that inhibits the transfer of mycolic acids into the cell wall of the tubercle Bacillus. It may also inhibit the synthesis of spermidine in mycobacteria. The action is usually bactericidal, and the drug can penetrate human cell membranes to exert its lethal effect. Antimycobacterial Drugs (RIPE):^[6–9] 

• 2 months of treatments
• May discontinue ethambutol Ethambutol An antitubercular agent that inhibits the transfer of mycolic acids into the cell wall of the tubercle Bacillus. It may also inhibit the synthesis of spermidine in mycobacteria. The action is usually bactericidal, and the drug can penetrate human cell membranes to exert its lethal effect. Antimycobacterial Drugs (EMB) if drug susceptibility results show susceptibility to isoniazid Isoniazid Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. Antimycobacterial Drugs (INH) and rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis (RIF)
• Daily dosing recommended: DOT (5-days-a-week administration) is acceptable.
• Thrice-weekly regimens for:
  • Low relapse Relapse Relapsing Fever risk: drug-susceptible TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis, initially noncavitary and/or smear-negative
  • HIV-negative
• If daily or thrice-weekly administration difficult, may consider twice-weekly administration after 2 weeks of daily dosing in cases with:
  • Low risk for relapse Relapse Relapsing Fever: drug-susceptible TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis, initially noncavitary and/or smear-negative
  • No HIV HIV Anti-HIV Drugs infection
• Risk factors for relapse Relapse Relapsing Fever:
  • Cavitation Cavitation Imaging of the Lungs and Pleura on initial chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests
  • Positive culture by month 2 of treatment
• Monitoring:
  • Monthly sputum collection ( AFB AFB Mycobacterium smear and culture) until 2 consecutive specimens are negative
  • Chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests at baseline, 2nd month, and end of treatment
  • Clinical: symptoms, weight, vision Vision Ophthalmic Exam, adherence to treatment
  • Baseline laboratory tests: CBC, hepatic and renal profiles, HIV HIV Anti-HIV Drugs, hepatitis B Hepatitis B Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Most individuals with acute HBV infection are asymptomatic or have mild, self-limiting symptoms. Chronic infection can be asymptomatic or create hepatic inflammation, leading to liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B Virus and C, diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus screen
  • Subsequent laboratory tests: monthly CBC, hepatic and renal profile

Newer 4-drug regimen: Rifapentine Rifapentine Antimycobacterial Drugs, isoniazid Isoniazid Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. Antimycobacterial Drugs, pyrazinamide Pyrazinamide A pyrazine that is used therapeutically as an antitubercular agent. Antimycobacterial Drugs ( PZA PZA A pyrazine that is used therapeutically as an antitubercular agent. Antimycobacterial Drugs), moxifloxacin Moxifloxacin A fluoroquinolone that acts as an inhibitor of DNA topoisomerase II and is used as a broad-spectrum antibacterial agent. Fluoroquinolones:^[9,12]

• 8 weeks
• Daily dosing
• Candidates:
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship ≥ 12 years of age and with body weight ≥ 40 kg
  • Drug-susceptible TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis
  • HIV HIV Anti-HIV Drugs patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship must have CD4 counts ≥ 100 cells/mm³ and be on efavirenz-based antiretroviral regimen.
  • Those with low mycobacterial burden lung disease (culture-negative) and no HIV HIV Anti-HIV Drugs infection
• Contraindicated in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who are pregnant or breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding

Additional considerations in treating active TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis:

• Pyridoxine (vitamin B₆):
  • Given with INH to those at risk of neuropathy Neuropathy Leprosy (e.g., pregnant women, breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding infants; patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with HIV HIV Anti-HIV Drugs, diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus, alcoholism Alcoholism A primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. Wernicke Encephalopathy and Korsakoff Syndrome, malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries, chronic renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome, or advanced age)
  • Dosing: 25–50 mg a day (daily INH), 50 mg a week (weekly INH/ rifapentine Rifapentine Antimycobacterial Drugs)
• INH, RIF, and PZA PZA A pyrazine that is used therapeutically as an antitubercular agent. Antimycobacterial Drugs can lead to drug-induced liver injury Drug-induced liver injury Drug-induced liver injury (DILI) is the most common cause of acute liver failure (ALF). Hepatotoxic drugs can cause injury to the hepatocytes directly in a predictable dose-dependent way or through idiosyncratic reactions. The injury mechanisms can have the following effects: hepatitis, cholestasis, vascular lesions, or overlapping changes. Drug-Induced Liver Injury (DILI).

Continuation phase

• RIPE:^[6–8]
  • 2-drug regimen: rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis and isoniazid Isoniazid Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. Antimycobacterial Drugs
  • 4–7 months
  • Daily dosing recommended (thrice-weekly administration may be used if needed)
• Rifapentine-moxifloxacin regimen:^[9,12]
  • 3-drug regimen: rifapentine Rifapentine Antimycobacterial Drugs, moxifloxacin Moxifloxacin A fluoroquinolone that acts as an inhibitor of DNA topoisomerase II and is used as a broad-spectrum antibacterial agent. Fluoroquinolones, and isoniazid Isoniazid Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. Antimycobacterial Drugs
  • 9 weeks
  • Daily dosing

Latent TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis^[7,9,11]

• 3- or 4-month, rifamycin-based course (see daily dosing in Table 1)
  • Recommended because of easier adherence
  • Options:
    • Isoniazid Isoniazid Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. Antimycobacterial Drugs + rifapentine Rifapentine Antimycobacterial Drugs for 3 months (≥ 2 years of age) or for 4 months (all ages)
    • Isoniazid Isoniazid Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. Antimycobacterial Drugs + rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis for 3 months (all ages)
• 6- or 9-month isoniazid Isoniazid Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. Antimycobacterial Drugs monotherapy (see daily dosing in Table 1)

Prevention^[7,9,11]

• TST screening Screening Preoperative Care for individuals at high risk
• Isolation of individuals with active pulmonary infection
• BCG BCG An active immunizing agent and a viable avirulent attenuated strain of Mycobacterium bovis, which confers immunity to mycobacterial infections. It is used also in immunotherapy of neoplasms due to its stimulation of antibodies and non-specific immunity. Cancer Immunotherapy (bacille Calmette-Guérin) vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination:
  • A nonvirulent form of M. bovis used as a live vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination to provide active immunity against severe forms of TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis
  • Not recommended as a universal vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination in countries with low TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis burden
  • May be considered for some individuals at high risk of exposure: infants and adolescents < 16 years of age in a high-incidence country
  • 70%–80% effective against most severe forms of TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis ( miliary TB Miliary TB An acute form of tuberculosis in which minute tubercles are formed in a number of organs of the body due to dissemination of the bacilli through the bloodstream. Tuberculosis, tuberculous meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis)
  • Reduced effect against respiratory TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis
  • No proof of effectiveness in adults > 35
  • Contraindicated in positive tuberculin Tuberculin A protein extracted from boiled culture of tubercle bacilli (Mycobacterium tuberculosis). It is used in the tuberculin skin test (tuberculin test) for the diagnosis of tuberculosis infection in asymptomatic persons. Type IV Hypersensitivity Reaction reactions, AIDS AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS, or immunosuppression
  • Vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination administration will result in a positive TST.

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas^[4]

• Treatment with anti-mycobacterial drugs is 85% successful worldwide.
• 15% mortality Mortality All deaths reported in a given population. Measures of Health Status rate worldwide
• 2.5%–5% rate of treatment failure or relapse Relapse Relapsing Fever in the United States

Differential Diagnosis

• Chronic bronchitis Chronic bronchitis A subcategory of chronic obstructive pulmonary disease. The disease is characterized by hypersecretion of mucus accompanied by a chronic (more than 3 months in 2 consecutive years) productive cough. Infectious agents are a major cause of chronic bronchitis. Rhinovirus: a type of chronic obstructive pulmonary disease Pulmonary disease Diseases involving the respiratory system. Blastomyces/Blastomycosis ( COPD COPD Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD)) involving inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and swelling Swelling Inflammation of the airways, leading to productive cough for > 3 months in a year for > 2 consecutive years. Diagnosis is established by history, physical exam, and pulmonary function tests. Treatment involves bronchodilators Bronchodilators Asthma Drugs and steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors.
• Atypical pneumonia Atypical pneumonia Mycoplasma: a form of pulmonary infection that typically has a slow onset and progression and presents with a non-productive, dry cough Dry Cough Strongyloidiasis and extrapulmonary symptoms such as fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, malaise Malaise Tick-borne Encephalitis Virus, and headaches. Diagnosis is made from history, physical exam, and chest imaging. Atypical pneumonia Atypical pneumonia Mycoplasma is usually treated with antibiotics.
• M. avium complex (MAC) infection: an AIDS-defining condition. Mycobacterium avium Mycobacterium avium A bacterium causing tuberculosis in domestic fowl and other birds. In pigs, it may cause localized and sometimes disseminated disease. The organism occurs occasionally in sheep and cattle. It should be distinguished from the m. avium complex, which infects primarily humans. Mycobacterium complex is an opportunistic infection caused by nontuberculous mycobacteria Mycobacteria Mycobacterium is a genus of the family Mycobacteriaceae in the phylum Actinobacteria. Mycobacteria comprise more than 150 species of facultative intracellular bacilli that are mostly obligate aerobes. Mycobacteria are responsible for multiple human infections including serious diseases, such as tuberculosis (M. tuberculosis), leprosy (M. leprae), and M. avium complex infections. Mycobacterium species that typically affects immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship. Manifests with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, night sweats Night sweats Tuberculosis, weight loss Weight loss Decrease in existing body weight. Bariatric Surgery, abdominal pain Abdominal Pain Acute Abdomen, and diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea. Treatment includes antibiotics ( macrolides Macrolides Macrolides and ketolides are antibiotics that inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit and blocking transpeptidation. These antibiotics have a broad spectrum of antimicrobial activity but are best known for their coverage of atypical microorganisms. Macrolides and Ketolides and ethambutol Ethambutol An antitubercular agent that inhibits the transfer of mycolic acids into the cell wall of the tubercle Bacillus. It may also inhibit the synthesis of spermidine in mycobacteria. The action is usually bactericidal, and the drug can penetrate human cell membranes to exert its lethal effect. Antimycobacterial Drugs).
• Lung mycoses Mycoses Diseases caused by fungi. Mycology: fungal diseases usually due to opportunistic pathogens that infect patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with immune deficiencies; includes candidiasis Candidiasis Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis, cryptococcosis Cryptococcosis Cryptococcosis is an opportunistic, fungal infection caused by the Cryptococcus species. The principal pathogens in humans are C. neoformans (primary) and C. gattii. The majority of affected patients are immunocompromised. Patients with AIDS, chronic steroid use, and organ transplant are particularly affected. Cryptococcosis is an AIDS-defining illness and typically associated with CD4 count < 100 cells/μL. Cryptococcus/Cryptococcosis, and aspergillosis Aspergillosis Aspergillosis is an opportunistic fungal infection caused by Aspergillus species, which are common spore-forming molds found in our environment. As Aspergillus species are opportunistic, they cause disease primarily in patients who are immunocompromised. The organs that are most commonly involved are the lungs and sinuses. Aspergillus/Aspergillosis. Symptoms may include cough, hemoptysis Hemoptysis Hemoptysis is defined as the expectoration of blood originating in the lower respiratory tract. Hemoptysis is a consequence of another disease process and can be classified as either life threatening or non-life threatening. Hemoptysis can result in significant morbidity and mortality due to both drowning (reduced gas exchange as the lungs fill with blood) and hemorrhagic shock. Hemoptysis, dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, fevers, weight loss Weight loss Decrease in existing body weight. Bariatric Surgery, and fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia. Diagnosis is made by imaging and histologic examination. Treatment involves systemic antifungal Antifungal Azoles medications.
• Bronchial carcinoma: a type of lung cancer Lung cancer Lung cancer is the malignant transformation of lung tissue and the leading cause of cancer-related deaths. The majority of cases are associated with long-term smoking. The disease is generally classified histologically as either small cell lung cancer or non-small cell lung cancer. Symptoms include cough, dyspnea, weight loss, and chest discomfort. Lung Cancer that arises within the main airways. Frequently presents with cough, hemoptysis Hemoptysis Hemoptysis is defined as the expectoration of blood originating in the lower respiratory tract. Hemoptysis is a consequence of another disease process and can be classified as either life threatening or non-life threatening. Hemoptysis can result in significant morbidity and mortality due to both drowning (reduced gas exchange as the lungs fill with blood) and hemorrhagic shock. Hemoptysis, and constitutional symptoms Constitutional Symptoms Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis. Diagnosis is established by imaging and biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. Treatment depends on the stage and includes surgical resection, adjuvant Adjuvant Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (freund’s adjuvant, bcg, corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Vaccination radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma, and chemotherapy Chemotherapy Osteosarcoma.
• Granulomatous diseases Granulomatous diseases A defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. When chronic granulomatous disease is caused by mutations in the cybb gene, the condition is inherited in an X-linked recessive pattern. When chronic granulomatous disease is caused by cyba, ncf1, ncf2, or ncf4 gene mutations, the condition is inherited in an autosomal recessive pattern. Type IV Hypersensitivity Reaction:
  • Sarcoidosis Sarcoidosis Sarcoidosis is a multisystem inflammatory disease that causes noncaseating granulomas. The exact etiology is unknown. Sarcoidosis usually affects the lungs and thoracic lymph nodes, but it can also affect almost every system in the body, including the skin, heart, and eyes, most commonly. Sarcoidosis: a chronic inflammatory disease characterized by the formation of noncaseating granulomas Noncaseating granulomas Crohn’s Disease, typically in the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy and, less commonly, in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, eyes, and skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions. Pulmonary sarcoidosis Sarcoidosis Sarcoidosis is a multisystem inflammatory disease that causes noncaseating granulomas. The exact etiology is unknown. Sarcoidosis usually affects the lungs and thoracic lymph nodes, but it can also affect almost every system in the body, including the skin, heart, and eyes, most commonly. Sarcoidosis presents with cough, dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, and constitutional symptoms Constitutional Symptoms Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis. Definitive diagnosis is established by histology. Some cases are self-limited, while others are treated with steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors and immunosuppressive drugs Immunosuppressive drugs Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-cells or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. Organ Transplantation. 
  • Pneumoconiosis Pneumoconiosis Pneumoconiosis is an occupational disease that results from the inhalation and deposition of mineral dusts and other inorganic particles in the lung. It can be categorized according to the type of causative particle involved or by the type of response provoked. Pneumoconiosis: an occupational disease that consists of a group of restrictive interstitial lung diseases Interstitial Lung Diseases Interstitial lung diseases are a heterogeneous group of disorders characterized by the inflammation and fibrosis of lung parenchyma, especially the pulmonary connective tissue in the alveolar walls. It may be idiopathic (e.g., idiopathic pulmonary fibrosis) or secondary to connective tissue diseases, medications, malignancies, occupational exposure, or allergens. Interstitial Lung Diseases caused by inhalation of toxic dust. Presents with cough and progressive dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea. Diagnosed by imaging and histology. Management is largely supportive.
  • Histoplasmosis Histoplasmosis Histoplasmosis is an infection caused by Histoplasma capsulatum, a dimorphic fungus. Transmission is through inhalation, and exposure to soils containing bird or bat droppings increases the risk of infection. Most infections are asymptomatic; however, immunocompromised individuals generally develop acute pulmonary infection, chronic infection, or even disseminated disease. Histoplasma/Histoplasmosis: an infection caused by the fungus Histoplasma capsulatum Histoplasma capsulatum Histoplasma/Histoplasmosis. Presents with symptoms of pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia. Can also cause diffuse systemic infection in immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis individuals. Diagnosis is established histologically. Treatment involves antifungal Antifungal Azoles medications.