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. M. tuberculosis are acid-fast, slowly growing bacteria that can survive in macrophages, allowing for a latent infection that can remain asymptomatic for decades, posing a challenge to diagnosis, therapy, and prevention. The diagnosis is established with tuberculin skin test, sputum culture, and lung imaging. The mainstay of management is anti-mycobacterial drugs.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Overview

Definition

Tuberculosis (TB) 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 and, sometimes, other organs. Tuberculosis is caused by Mycobacterium Mycobacterium 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 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: Overview.

Epidemiology

  • TB 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.
  • 10% of infected people will develop the active form of the disease.
  • In 2019, 10 million people contracted TB.
  • TB is the leading cause of death in patients with human immunodeficiency 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: Overview (HIV).
  • Incidence: 2.7 per 100,000 people in the United States (2019)
  • Regions with the highest incidence of TB: 
    • Southeast Asia
    • Africa
    • The Western Pacific
  • Risk factors:
    • Institutionalized patients
    • Intravenous drug use
    • HIV or other immunodeficiency
    • Travel to high-risk regions
Prevalence of tuberculosis

Estimated prevalence of tuberculosis per 100,000 people in 2007, per country

Image: “Estimated prevalence of tuberculosis” by Eubulides. License: Public Domain

Pathophysiology

Etiologic agent

The M. tuberculosis complex is a group of species that can cause TB in humans or other animals.

Key species:

  • M. tuberculosis
  • M. bovis
  • M. africanum
  • M. microti
  • M. canetti

Characteristics:

  • Acid fast:
    • Property conferred by mycolic acid
    • Do not destain by acid alcohol after being stained with aniline dyes
  • Gram stain:
    • Usually cannot penetrate MTBC waxy cell wall
    • 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
Acid fast stain of mycobacterium tuberculosis

Acid-fast stain of M. tuberculosis

Image: “ Mycobacterium Mycobacterium 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 tuberculosis 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: Overview” by CDC/Dr. George P. Kubica. License: Public Domain

Virulence factors:

  • Cell envelope:
    • Major constituent: mycolic acid
    • Mycolic acid is attached to glycolipids.
    • Glycolipids are responsible for “cord formation” on microscopy (grossly corresponds to granuloma formation).
  • Catalase-peroxidase: resists host cell oxidative response
  • Sulfatides and trehalose dimycolate: triggers toxicity
  • Lipoarabinomannan (LAM): induces cytokines

Transmission:

  • Exclusively airborne
  • From patients with active TB

Pathogenesis

  • 1st step is inhalation of aerosol droplets.
  • Droplets 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.
  • 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: Overview
    • 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: Overview within alveolar macrophages
  • Cytokines produced by macrophages attract other phagocytic cells.
  • A tubercle (granulomatous structure) forms.
  • Tubercle expands into lung parenchyma → Ghon’s complex
  • Bacteria then can spread to draining lymph nodes → 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’s complex + 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 with seeding of other organs may occur → miliary TB
  • 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: Overview erode into airways (caseating granulomas), the patient becomes contagious.
  • Infection may progress to a chronic stage with episodes of healing and subsequent scarring of the lesions.
  • Spontaneous eradication is rare.

Latent infection:

  • Lifetime risk of reactivation is 5%–10%.
  • Immunosuppression is a definite factor in reactivation.
  • Risk factors:
    • HIV
    • Kidney disease
    • Diabetes
    • Steroids
    • Lymphoma
    • Advanced age
    • Smoking

Clinical Presentation

Tuberculosis clinical presentation

Schematic diagram depicting the various clinical presentations of tuberculosis along with the characteristic pathologic mechanisms of each presentation

Image by Lecturio. License: CC BY-NC-SA 4.0

Primary TB

  • 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 Chest Pain Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies. Chest Pain (may or may not be associated with effusion)
  • Retrosternal/interscapular pain (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
  • Arthralgia
  • 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 TB

  • 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
    • 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, wasting, malaise
    • 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. Oral Cavity: Lips and Tongue, 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, 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: due to infected expectorated secretions

Extrapulmonary and miliary TB

  • Can develop in the course of primary or reactivation disease
  • In up to 15%–20% of active cases
  • Most common in children and immunocompromised individuals
  • Extrapulmonary manifestations (can affect any organ system): 
    • Tuberculous pleurisy 
    • 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 tuberculosa (Pott’s disease, TB infection of > 1 vertebra)
    • Constrictive pericarditis Pericarditis Pericarditis is an inflammation of the pericardium, often with fluid accumulation. It can be caused by infection (often viral), myocardial infarction, drugs, malignancies, metabolic disorders, autoimmune disorders, or trauma. Acute, subacute, and chronic forms exist. 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. Anatomy of the Nose, eyelids, 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. Oral Cavity: Lips and Tongue, cheeks, ears, and neck)
    • Scrofula (cervical lymphadenitis)
    • Sterile pyuria
  • Miliary TB:
    • Massive spread of infection through blood and lymphatics
    • Small granulomatous lesions through multiple organs

Diagnosis

History

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

Physical exam

  • Findings are often non-specific.
  • Pulmonary:
    • Dullness to percussion (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, altered mental status
    • Skin changes (lupus vulgaris)

Imaging

  • Chest X-ray:
    • Can be normal in primary TB
    • 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’s complex: enlarged hilar lymph nodes + local shadowing
    • Assmann’s focus: infraclavicular infiltration
    • Pleural effusions
    • Reactivation TB: 
      • Simon foci (calcified small scar from primary infection)
      • 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
    • Used if chest X-ray is non-specific or alternative diagnosis is considered

Laboratory identification

  • Sputum:
    • 3 specimens, at least 1 in the early morning
    • 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) smear
    • Mycobacterial culture
    • Nuclear acid amplification (NAA) test
  • Blood or urine mycobacterial culture: in HIV or immunocompromised patients
  • Tuberculin 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. Structure and Function of the Skin test (TST; purified protein derivative (PPD) or Mantoux test): 
    • Intradermal injection of tuberculin antigen
    • Can detect active or latent infection
    • Measure induration area in 48–72 hours; positive if: 
      • > 5 mm in patients with HIV, immunosuppression, or recent contact with TB
      • > 10 mm in patients from high-risk countries, IV drug users, medical and lab workers
      • > 15 mm in patients with no known risk factors for TB
  • lnterferon-y release assay (IGRA): no distinction between active and inactive TB

Management

Pharmacologic management

  • The mainstay of treatment is anti-mycobacterial drugs.
  • Usually 2 treatment phases: intensive and stabilization
  • Directly observed therapy (DOT) is preferred:
    • Medications are administered to patients.
    • Administration by healthcare providers ensures compliance and correct administration.

Summary of anti-tuberculosis regimens

Table: Tuberculosis treatment regimens
Initial phase Stabilization phase
Active TB
  • Isolation for 4–6 weeks
  • 2 months of RIPE:
    • Rifampin (RIF)
    • Isoniazid (INH)
    • Pyrazinamide (PZA)
    • Ethambutol (EMB)
  • 4 months of:
    • INH
    • RIF
  • Monitoring of sputum for 2 years
Latent TB Treatment options:
  • RIF for 4 months
  • INH for 6–9 months
  • INH + RIF for 3 months
  • INH + rifapentine (RPT) for 3 months

Prevention

  • TST screening for individuals at high risk
  • Isolation of individuals with active pulmonary infection
  • BCG (bacille Calmette-Guérin) vaccine Vaccine A vaccine is usually an antigenic, non-virulent form of a normally virulent microorganism. Vaccinations are a form of primary prevention and are the most effective form due to their safety, efficacy, low cost, and easy access. Vaccination:
    • A nonvirulent form of M. bovis used as a live vaccine Vaccine A vaccine is usually an antigenic, non-virulent form of a normally virulent microorganism. Vaccinations are a form of primary prevention and are the most effective form due to their safety, efficacy, low cost, and easy access. Vaccination to provide active immunity against severe forms of TB
    • Not recommended as a universal vaccine Vaccine A vaccine is usually an antigenic, non-virulent form of a normally virulent microorganism. Vaccinations are a form of primary prevention and are the most effective form due to their safety, efficacy, low cost, and easy access. Vaccination in countries with low TB 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 (miliary TB, tuberculous meningitis)
    • Reduced effect against respiratory TB
    • No proof of effectiveness in adults > 35
    • Contraindicated in positive tuberculin 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 administration will result in a positive TST.

Prognosis

  • Treatment with anti-mycobacterial drugs is 85% successful worldwide.
  • 15% mortality rate worldwide
  • 2.5%–5% rate of treatment failure or relapse in the United States

Differential Diagnosis

  • Chronic bronchitis: a type of chronic obstructive pulmonary disease Chronic obstructive pulmonary disease 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) ( 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 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 and steroids.
  • Atypical 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: a form of pulmonary infection that typically has a slow onset and progression and presents with a non-productive, dry cough and extrapulmonary symptoms such as fatigue, malaise, and headaches. Diagnosis is made from history, physical exam, and chest imaging. Atypical 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 is usually treated with antibiotics.
  • M. avium complex (MAC) infection: an 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-defining condition. Mycobacterium Mycobacterium 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 avium complex is an opportunistic infection caused by nontuberculous mycobacteria species that typically affects immunocompromised patients. Manifests with fever, night sweats, weight loss, abdominal pain, 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).
  • Lung mycoses: fungal diseases usually due to opportunistic pathogens that infect patients 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, and fatigue. Diagnosis is made by imaging and histologic examination. Treatment involves systemic antifungal 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. Diagnosis is established by imaging and biopsy. Treatment depends on the stage and includes surgical resection, adjuvant radiation, and chemotherapy.
  • Granulomatous diseases:
    • 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, 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 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, 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. Structure and Function of the Skin. Pulmonary 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 Chest Pain Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies. Chest Pain, and constitutional symptoms. Definitive diagnosis is established by histology. Some cases are self-limited, while others are treated with steroids and immunosuppressive drugs. 
    • 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 Histoplasma Histoplasmosis is an infection caused by Histoplasma capsulatum, a dimorphic fungus. The fungus exists as a mold at low temperatures and as yeast at high temperatures. H. capsulatum is the most common endemic fungal infection in the US and is most prevalent in the midwestern and central states along the Ohio and Mississippi River valleys. Histoplasma/Histoplasmosis capsulatum. 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 individuals. Diagnosis is established histologically. Treatment involves antifungal medications.

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  5. Tuberculosis (TB). Centers for Disease Control and Prevention. Retrieved January 13, 2021, from https://www.cdc.gov/tb/default.htm

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