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Histoplasma/Histoplasmosis

Histoplasmosis is an infection caused by Histoplasma capsulatum, a dimorphic fungus. The fungus exists as a mold Mold Mycology at low temperatures and as yeast Yeast A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are saccharomyces cerevisiae; therapeutic dried yeast is yeast, dried. Mycology 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. Transmission is through inhalation, and exposure Exposure ABCDE Assessment to soils containing bird or bat droppings increases the risk of infection. Most infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease are asymptomatic; however, 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 generally develop acute pulmonary infection, chronic infection, or even disseminated disease. Diagnosis is via different modalities, with the visualization and/or growth of the causative organism made using direct microscopy, histopathology, or culture studies. Management is dependent on disease severity. The antifungal Antifungal Azoles medications that are used include amphotericin B Amphotericin B Macrolide antifungal antibiotic produced by streptomyces nodosus obtained from soil of the orinoco river region of venezuela. Polyenes and itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles.

Last updated: Apr 1, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

General Characteristics of Histoplasma

Features

  • Morphology: thermally dimorphic fungus
    • Ambient (low) temperature: mold Mold Mycology form
    • Body (high) temperature: yeast Yeast A general term for single-celled rounded fungi that reproduce by budding. Brewers’ and bakers’ yeasts are saccharomyces cerevisiae; therapeutic dried yeast is yeast, dried. Mycology form
  • Characteristics:
    • Obligate aerobe Obligate aerobe Nocardia/Nocardiosis
    • Mold Mold Mycology form:
      • Septate mycelium Mycelium The body of a fungus which is made up of hyphae. Mycology: thin and branching
      • Produce microconidia and tuberculate macroconidia
    • Yeast Yeast A general term for single-celled rounded fungi that reproduce by budding. Brewers’ and bakers’ yeasts are saccharomyces cerevisiae; therapeutic dried yeast is yeast, dried. Mycology form:
      • Reproduce by budding Budding Mycology
      • Slightly oval
      • 2–4 µm in diameter
      • Found exclusively in 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

Clinically relevant species

  • H. capsulatum var. capsulatum
  • H. capsulatum var. duboisii: exists primarily in Africa

Forms of disease

  • Pulmonary histoplasmosis:
    • Asymptomatic
    • Symptomatic
    • Acute diffuse
    • Chronic pulmonary
  • Disseminated histoplasmosis:
    • CNS
    • GI
    • 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 lesions
    • Adrenal glands Adrenal Glands The adrenal glands are a pair of retroperitoneal endocrine glands located above the kidneys. The outer parenchyma is called the adrenal cortex and has 3 distinct zones, each with its own secretory products. Beneath the cortex lies the adrenal medulla, which secretes catecholamines involved in the fight-or-flight response. Adrenal Glands: Anatomy

Mnemonic

Histoplasmosis is an infection caused by a dimorphic fungus. Remember the following mnemonic to recall how the fungus exists:

  • Mold Mold Mycology in the cold”
  • Yeast Yeast A general term for single-celled rounded fungi that reproduce by budding. Brewers’ and bakers’ yeasts are saccharomyces cerevisiae; therapeutic dried yeast is yeast, dried. Mycology in the heat Heat Inflammation

Epidemiology

Frequency

  • Most common fungal infection endemic in the US
  • 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 in the US: 500,000 new infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease annually
  • Geographic prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency:
    • US: Midwestern and Central US, Ohio and Mississippi River valleys
    • Worldwide:
      • South and Central America
      • Africa
      • India
    • Australia

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

  • Outcomes can vary depending on severity, duration, and host immune state.
  • Mild disease: typically good outcomes
  • Mortality Mortality All deaths reported in a given population. Measures of Health Status of severe disease (despite hospitalization Hospitalization The confinement of a patient in a hospital. Delirium): 
    • 5% in children
    • 8% in adults
  • Chronic pulmonary histoplasmosis is more likely in individuals with underlying lung disease (particularly emphysema Emphysema Enlargement of air spaces distal to the terminal bronchioles where gas-exchange normally takes place. This is usually due to destruction of the alveolar wall. Pulmonary emphysema can be classified by the location and distribution of the lesions. Chronic Obstructive Pulmonary Disease (COPD)).
  • Disseminated histoplasmosis:
    • Immunocompetent adults: 1 per 2,000 cases of histoplasmosis
    • 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: 4%–27% mortality Mortality All deaths reported in a given population. Measures of Health Status in severe cases
Map of united states areas endemic for histoplasmosis

Map of the United States illustrating the areas endemic for histoplasmosis

Image: “Map showing areas endemic for histoplasmosis in the US” by CDC. License: Public Domain

Pathogenesis

Infectious Infectious Febrile Infant process

  • Habitat:
    • Found in soil contaminated with bird or bat droppings
    • Droppings increase nitrogen Nitrogen An element with the atomic symbol n, atomic number 7, and atomic weight [14. 00643; 14. 00728]. Nitrogen exists as a diatomic gas and makes up about 78% of the earth’s atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. Urea Cycle content → favorable for sporulation
    • Common sites:
      • Chicken coops
      • Farm buildings
      • Abandoned buildings
      • Caves
  • Transmission:
    • Inhalation via the respiratory tract
    • Deposition in the pulmonary alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS)
    • Exposures are seen in spelunkers and individuals involved in construction or agriculture.
  • 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:
    • Siderophores Siderophores Low-molecular-weight compounds produced by microorganisms that aid in the transport and sequestration of ferric iron. Klebsiella: support intracellular yeast Yeast A general term for single-celled rounded fungi that reproduce by budding. Brewers’ and bakers’ yeasts are saccharomyces cerevisiae; therapeutic dried yeast is yeast, dried. Mycology growth
    • Melanin Melanin Insoluble polymers of tyrosine derivatives found in and causing darkness in skin (skin pigmentation), hair, and feathers providing protection against sunburn induced by sunlight. Carotenes contribute yellow and red coloration. Seborrheic Keratosis:
      • Found in the 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
      • Decreases host defense mechanisms Defense mechanisms Defense mechanisms are normal subconscious means of resolving inner conflicts between an individual’s subjective moral sense and their thoughts, feelings, or actions. Defense mechanisms serve to protect the self from unpleasant feelings (anxiety, shame, and/or guilt) and are divided into pathologic, immature, mature, neurotic, and other types. Defense Mechanisms
      • Decreases the susceptibility of yeast Yeast A general term for single-celled rounded fungi that reproduce by budding. Brewers’ and bakers’ yeasts are saccharomyces cerevisiae; therapeutic dried yeast is yeast, dried. Mycology to antifungal Antifungal Azoles agents
    • Heat Heat Inflammation shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis (HSPs):
      • HSP60: prevents significant activation of phagocytes
      • HSP82: role in yeast Yeast A general term for single-celled rounded fungi that reproduce by budding. Brewers’ and bakers’ yeasts are saccharomyces cerevisiae; therapeutic dried yeast is yeast, dried. Mycology development and cellular stress
    • Yeast-phase-specific (YPS)3 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics:
      • Found in 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
      • Unknown function
    • Calcium-binding protein optimizes phagolysosomal conditions for yeast Yeast A general term for single-celled rounded fungi that reproduce by budding. Brewers’ and bakers’ yeasts are saccharomyces cerevisiae; therapeutic dried yeast is yeast, dried. Mycology growth.
    • α-(1,3)-glucan: antigenic function
  • Pathogenicity and disease process:
    • Microconidia are phagocytized 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.
    • Conversion to yeast Yeast A general term for single-celled rounded fungi that reproduce by budding. Brewers’ and bakers’ yeasts are saccharomyces cerevisiae; therapeutic dried yeast is yeast, dried. Mycology form occurs.
    • Yeast Yeast A general term for single-celled rounded fungi that reproduce by budding. Brewers’ and bakers’ yeasts are saccharomyces cerevisiae; therapeutic dried yeast is yeast, dried. Mycology multiply in 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).
    • Dividing yeast Yeast A general term for single-celled rounded fungi that reproduce by budding. Brewers’ and bakers’ yeasts are saccharomyces cerevisiae; therapeutic dried yeast is yeast, dried. Mycology destroys 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 and is then ingested by the recruited phagocytes.
    • H. capsulatum survives by capturing iron Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements and modulating pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance (to neutral), thereby decreasing the killing effect of phagolysosomes.
    • The cycle Cycle The type of signal that ends the inspiratory phase delivered by the ventilator Invasive Mechanical Ventilation continues and allows the infection to spread to the 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.
    • 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 help spread the organism via the lymphatic system Lymphatic system A system of organs and tissues that process and transport immune cells and lymph. Primary Lymphatic Organs.

Host risk factors

  • HIV HIV Anti-HIV Drugs infection
  • Primary immunodeficiencies
  • Immunosuppressive disorders
  • Transplant recipients
  • 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:
    • Most common fungal infection in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship on TNF-α inhibitors
    • Glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids
    • Antirejection therapies for solid organ transplants
  • Extremes of age
  • Heavy inoculation exposure Exposure ABCDE Assessment

Clinical Presentation

General findings

Clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor varies depending on host immune status and underlying risk factors.

  • Exposure Exposure ABCDE Assessment to Histoplasma in endemic regions is extremely common.
  • The majority of infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease are asymptomatic or subclinical.

Pulmonary histoplasmosis

  • < 5% of individuals develop symptomatic disease after low-level exposure Exposure ABCDE Assessment.
  • Symptomatic pulmonary histoplasmosis:
    • Presents several weeks after exposure Exposure ABCDE Assessment
    • Symptoms:
      • 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
      • Chills Chills The sudden sensation of being cold. It may be accompanied by shivering. Fever
      • Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
      • Myalgias Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus
      • 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
      • Cough
      • 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
    • Examination:
    • Chest X-ray Chest X-ray X-ray visualization of the chest and organs of the thoracic cavity. It is not restricted to visualization of the lungs. Pulmonary Function Tests: may be normal, or may show focal infiltrates with/without hilar or mediastinal lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node involvement
  • Acute diffuse pulmonary histoplasmosis
    • Associated with large inoculum
    • Abrupt onset of symptoms
    • Chest X-ray Chest X-ray X-ray visualization of the chest and organs of the thoracic cavity. It is not restricted to visualization of the lungs. Pulmonary Function Tests: diffuse pulmonary infiltrates (reticulonodular)
    • ARDS ARDS Acute respiratory distress syndrome is characterized by the sudden onset of hypoxemia and bilateral pulmonary edema without cardiac failure. Sepsis is the most common cause of ARDS. The underlying mechanism and histologic correlate is diffuse alveolar damage (DAD). Acute Respiratory Distress Syndrome (ARDS) can develop within days.
    • 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 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 may persist for months after treatment.
  • Chronic pulmonary histoplasmosis
    • Underlying lung disease ↑ risk
    • Symptoms:
      • Productive 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
      • 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
      • Sweats
      • 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
    • Radiography/CT: 
      • Fibrotic apical infiltrates with cavitation Cavitation Imaging of the Lungs and Pleura
      • Can be confused for 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
    • Areas of chronic infection have increased predisposition for:
      • Aspergilloma Aspergilloma Aspergillus/Aspergillosis
      • Atypical 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
      • Chronic or recurrent 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
  • Broncholithiasis
    • Lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node calcification or pulmonary granuloma calcification can occur years after the initial infection.
    • The calcification may erode into the adjacent bronchi Bronchi The larger air passages of the lungs arising from the terminal bifurcation of the trachea. They include the largest two primary bronchi which branch out into secondary bronchi, and tertiary bronchi which extend into bronchioles and pulmonary alveoli. Bronchial Tree: Anatomy.
    • Patient may report expectoration of:
      • Small stones
      • Gravel
      • Gritty material
    • Symptoms:
      • Chronic cough
      • Purulent sputum
      • Wheezing Wheezing Wheezing is an abnormal breath sound characterized by a whistling noise that can be relatively high-pitched and shrill (more common) or coarse. Wheezing is produced by the movement of air through narrowed or compressed small (intrathoracic) airways. Wheezing
      • 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
      • 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
      • Chills Chills The sudden sensation of being cold. It may be accompanied by shivering. Fever
  • Other pulmonary manifestations:

Disseminated histoplasmosis

  • Most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship experience asymptomatic dissemination.
  • Can present acutely or years later
    • Acute: 
      • In infants 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
      • Can be rapidly fatal
    • Chronic: older patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who are immunocompetent
  • Symptoms:
    • 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
    • Malaise Malaise Tick-borne Encephalitis Virus
    • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
  • Examination:
    • Hepatosplenomegaly Hepatosplenomegaly Cytomegalovirus
    • 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
    • Pallor
    • Petechiae Petechiae Primary Skin Lesions: if pancytopenic
    • Oral ulcerations
    • 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 lesions
  • Severe disease:
    • Sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock
    • Disseminated intravascular coagulation Disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation
    • 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
    • Hepatic failure Hepatic failure Severe inability of the liver to perform its normal metabolic functions, as evidenced by severe jaundice and abnormal serum levels of ammonia; bilirubin; alkaline phosphatase; aspartate aminotransferase; lactate dehydrogenases; and albumin/globulin ratio. Autoimmune Hepatitis
    • Acute respiratory distress
  • CNS:
    • 5%–20% of cases
    • Presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor:
      • 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
      • Isolated chronic meningitis Chronic Meningitis Meningitis
      • Cerebral vasculitis Vasculitis Inflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body. Systemic Lupus Erythematosus
      • Focal brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification lesions
      • Encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis
      • Localized spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy involvement
  • GI disease:
    • Although 70% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship have GI involvement, < 10% present clinically.
    • Can occur throughout the GI tract (most common in the ileum Ileum The distal and narrowest portion of the small intestine, between the jejunum and the ileocecal valve of the large intestine. Small Intestine: Anatomy and colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy)
    • Manifestations:
      • Oral ulcers Oral ulcers A loss of mucous substance of the mouth showing local excavation of the surface, resulting from the sloughing of inflammatory necrotic tissue. It is the result of a variety of causes, e.g., denture irritation, aphthous stomatitis; necrotizing gingivitis, toothbrushing, and various irritants. Chédiak-Higashi Syndrome
      • Colonic perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis
      • Polypoid-like mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast
  • 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:
    • 10%–15% of cases
    • More often in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with 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
    • Lesions:
  • Adrenal glands Adrenal Glands The adrenal glands are a pair of retroperitoneal endocrine glands located above the kidneys. The outer parenchyma is called the adrenal cortex and has 3 distinct zones, each with its own secretory products. Beneath the cortex lies the adrenal medulla, which secretes catecholamines involved in the fight-or-flight response. Adrenal Glands: Anatomy:
    • Involvement is common; however, < 10% of individuals have overt insufficiency
    • Can be unilateral or bilateral
    • Perivasculitis → thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus → infarction of the adrenal glands Adrenal Glands The adrenal glands are a pair of retroperitoneal endocrine glands located above the kidneys. The outer parenchyma is called the adrenal cortex and has 3 distinct zones, each with its own secretory products. Beneath the cortex lies the adrenal medulla, which secretes catecholamines involved in the fight-or-flight response. Adrenal Glands: Anatomy
    • Adrenal insufficiency Adrenal Insufficiency Conditions in which the production of adrenal corticosteroids falls below the requirement of the body. Adrenal insufficiency can be caused by defects in the adrenal glands, the pituitary gland, or the hypothalamus. Adrenal Insufficiency and Addison’s Disease:
      • Electrolyte abnormalities
      • Orthostatic hypotension Orthostatic hypotension A significant drop in blood pressure after assuming a standing position. Orthostatic hypotension is a finding, and defined as a 20-mm hg decrease in systolic pressure or a 10-mm hg decrease in diastolic pressure 3 minutes after the person has risen from supine to standing. Symptoms generally include dizziness, blurred vision, and syncope. Hypotension
      • Hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia 
  • Others: less common:
    • Cardiopulmonary: endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis, 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, pleuritis Pleuritis 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
    • GI/abdominal: peritonitis Peritonitis Inflammation of the peritoneum lining the abdominal cavity as the result of infectious, autoimmune, or chemical processes. Primary peritonitis is due to infection of the peritoneal cavity via hematogenous or lymphatic spread and without intra-abdominal source. Secondary peritonitis arises from the abdominal cavity itself through rupture or abscess of intra-abdominal organs. Penetrating Abdominal Injury, pancreatitis Pancreatitis Inflammation of the pancreas. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of chronic pancreatitis. The two most common forms of acute pancreatitis are alcoholic pancreatitis and gallstone pancreatitis. Acute Pancreatitis, cholecystitis Cholecystitis Cholecystitis is the inflammation of the gallbladder (GB) usually caused by the obstruction of the cystic duct (acute cholecystitis). Mechanical irritation by gallstones can also produce chronic GB inflammation. Cholecystitis is one of the most common complications of cholelithiasis but inflammation without gallstones can occur in a minority of patients. Cholecystitis
    • Skeletal: osteomyelitis Osteomyelitis Osteomyelitis is an infection of the bone that results from the spread of microorganisms from the blood (hematogenous), nearby infected tissue, or open wounds (non-hematogenous). Infections are most commonly caused by Staphylococcus aureus. Osteomyelitis, septic arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis
    • Chorioretinitis Chorioretinitis Chorioretinitis is the inflammation of the posterior segment of the eye, including the choroid and the retina. The condition is usually caused by infections, the most common of which is toxoplasmosis. Some of these infections can affect the fetus in utero and present as congenital abnormalities. Chorioretinitis
    • Mastitis Mastitis Mastitis is inflammation of the breast tissue with or without infection. The most common form of mastitis is associated with lactation in the first few weeks after birth. Non-lactational mastitis includes periductal mastitis and idiopathic granulomatous mastitis (IGM). Mastitis
    • Thrombotic microangiopathy
    • Hemophagocytic syndrome
    • Hypercalcemia Hypercalcemia Hypercalcemia (serum calcium > 10.5 mg/dL) can result from various conditions, the majority of which are due to hyperparathyroidism and malignancy. Other causes include disorders leading to vitamin D elevation, granulomatous diseases, and the use of certain pharmacological agents. Symptoms vary depending on calcium levels and the onset of hypercalcemia. Hypercalcemia: due to calcitriol Calcitriol The physiologically active form of vitamin d. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (calcifediol). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption. Parathyroid Glands: Anatomy 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

Diagnosis

Diagnostic approach

  • Diagnosis cannot be made on clinical information alone.
  • The approach will vary depending on presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor and test limitations Limitations Conflict of Interest.
  • Multiple tests including culture, direct microscopy, and histopathology can help in diagnosis.
    • Time consuming (> 14 days)
    • 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 sensitivity Sensitivity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Blotting Techniques
    • Culture is most effective when the fungal burden is high.
  • Histopathology:
  • Culture:
    • Medium: Sabouraud’s dextrose Dextrose Intravenous Fluids agar
    • Growth: 2–6 weeks
    • Sources:
      • Tissue
      • Sputum and/or 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 (BAL)
      • Blood
      • 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 marrow
  • Antigen detection Antigen detection Respiratory Syncytial Virus:
    • ELISA ELISA An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. St. Louis Encephalitis Virus for antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination testing
    • Allows for rapid diagnosis, particularly in disseminated disease
    • Sensitivity Sensitivity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Blotting Techniques increases with disease severity (most sensitive test in disseminated disease).
    • False positives can occur with other fungal diseases.
    • Sources:
  • Direct microscopy:
    • Wright’s stained smear (blood)
    • Least expensive
    • Can allow for rapid and confirmatory diagnosis
    • Limited by low sensitivity Sensitivity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Blotting Techniques (< 10%)
  • Others:
    • Antibody tests (immunodiffusion test and complement fixation test)
    • PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR)

Imaging

  • Chest X-ray Chest X-ray X-ray visualization of the chest and organs of the thoracic cavity. It is not restricted to visualization of the lungs. Pulmonary Function Tests and chest CT:
    • Can be normal
    • Findings:
      • Focal infiltrates
      • Hilar and/or mediastinal 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
      • Calcified granulomas Granulomas A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. Sarcoidosis
      • Pulmonary nodules Pulmonary nodules A number of small lung lesions characterized by small round masses of 2- to 3-mm in diameter. They are usually detected by chest ct scans. Such nodules can be associated with metastases of malignancies inside or outside the lung, benign granulomas, or other lesions. Granulomatosis with Polyangiitis
      • Diffuse interstitial or reticulonodular infiltrates
      • Cavitary lesions (rare)
      • Pleural effusions
  • CT (other areas):
    • Head CT:
    • Abdominal CT:
      • Can demonstrate adrenal involvement, if suspected
      • The findings typically demonstrate adrenal enlargement.
Chest_x-ray_acute_pulmonary_histoplasmosis

Chest X-ray Chest X-ray X-ray visualization of the chest and organs of the thoracic cavity. It is not restricted to visualization of the lungs. Pulmonary Function Tests:
Diffuse pulmonary infiltration due to acute pulmonary histoplasmosis caused by Histoplasma capsulatum

Image: “This chest film shows diffuse pulmonary infiltration due to acute pulmonary histoplasmosis caused by H. capsulatum” by CDC/M. Renz. License: Public Domain

Management

Principles

  • Treatment varies depending on disease severity.
  • Most cases are self-limiting Self-Limiting Meningitis in Children and do not require treatment.
  • Individuals with large inoculum exposure Exposure ABCDE Assessment and patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who are 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 usually require treatment.
  • Antifungal Antifungal Azoles drugs are the mainstay of treatment.
Table: Treatment of histoplasmosis
Condition Treatment
Moderate pulmonary disease Pulmonary disease Diseases involving the respiratory system. Blastomyces/Blastomycosis or symptoms lasting > 4 weeks Itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles
Moderately severe to severe pulmonary disease Pulmonary disease Diseases involving the respiratory system. Blastomyces/Blastomycosis Amphotericin B Amphotericin B Macrolide antifungal antibiotic produced by streptomyces nodosus obtained from soil of the orinoco river region of venezuela. Polyenes + itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles
Chronic pulmonary histoplasmosis Itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles
Mild disseminated histoplasmosis: mild symptoms with single focus Focus Area of enhancement measuring < 5 mm in diameter Imaging of the Breast (no CNS involvement) Itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles
Severe disseminated histoplasmosis without CNS involvement Amphotericin B Amphotericin B Macrolide antifungal antibiotic produced by streptomyces nodosus obtained from soil of the orinoco river region of venezuela. Polyenes + itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles
CNS involvement Amphotericin B Amphotericin B Macrolide antifungal antibiotic produced by streptomyces nodosus obtained from soil of the orinoco river region of venezuela. Polyenes (prolonged) + itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles

Acute pulmonary histoplasmosis

  • No treatment for:
    • Asymptomatic individuals
    • Individuals with mild symptoms
  • Prolonged symptoms (> 4 weeks) or moderate pulmonary disease Pulmonary disease Diseases involving the respiratory system. Blastomyces/Blastomycosis:
  • Moderately severe to severe pulmonary disease Pulmonary disease Diseases involving the respiratory system. Blastomyces/Blastomycosis:
    • Amphotericin B Amphotericin B Macrolide antifungal antibiotic produced by streptomyces nodosus obtained from soil of the orinoco river region of venezuela. Polyenes for 1–2 weeks, followed by itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles for 12 weeks
    • Methylprednisone for 1–2 weeks for ARDS ARDS Acute respiratory distress syndrome is characterized by the sudden onset of hypoxemia and bilateral pulmonary edema without cardiac failure. Sepsis is the most common cause of ARDS. The underlying mechanism and histologic correlate is diffuse alveolar damage (DAD). Acute Respiratory Distress Syndrome (ARDS)

Chronic pulmonary histoplasmosis

Disseminated histoplasmosis

  • If mild clinical symptoms and single focus Focus Area of enhancement measuring < 5 mm in diameter Imaging of the Breast of disease (without CNS involvement): itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles for 1 year ( loading dose Loading Dose Dosage Calculation for the 1st 3 days)
  • All other cases:
    • Amphotericin B Amphotericin B Macrolide antifungal antibiotic produced by streptomyces nodosus obtained from soil of the orinoco river region of venezuela. Polyenes for 1–2 weeks (with CNS involvement: 4–6 weeks)
    • Itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles for at least 1 year ( loading dose Loading Dose Dosage Calculation for the 1st 3 days)

Suppressive therapy

  • Relapse Relapse Relapsing Fever can occur if immune recovery is not maintained with antiretroviral therapy Antiretroviral therapy Antiretroviral therapy (ART) targets the replication cycle of the human immunodeficiency virus (HIV) and is classified based on the viral enzyme or mechanism that is inhibited. The goal of therapy is to suppress viral replication to reach the outcome of undetected viral load. Anti-HIV Drugs in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with 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.
  • Itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles is effective in preventing up to 95% of cases.
  • For 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 having CD4 counts < 150 cells/µL → long-term itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles

Differential Diagnosis

  • Opportunistic fungal infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease: a group of infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease that occur in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with weakened immune systems (especially individuals with CD4 counts < 200 cells/μL). Healthy individuals with normal immune systems are typically not affected. The general signs and symptoms can be similar to those of histoplasmosis. Exposure Exposure ABCDE Assessment history, microscopy, and culture of sputum or BAL to identify specific organisms can help differentiate fungal infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease.
  • Community-acquired pneumonia Community-Acquired Pneumonia Pneumonia in Children: the typical symptoms (cough, 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, 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) are usually of a shorter duration than those seen in histoplasmosis 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 chest X-ray Chest X-ray X-ray visualization of the chest and organs of the thoracic cavity. It is not restricted to visualization of the lungs. Pulmonary Function Tests will typically demonstrate lobar consolidation Consolidation Pulmonary Function Tests (typical) or bilateral interstitial infiltrates (atypical). Gram staining Gram staining Bacteriology of the sputum and culture often reveals neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation and 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 that are not part of the normal flora. Antibiotics are the general mainstay of treatment.
  • 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: an autoimmune disorder Autoimmune Disorder Septic Arthritis that can present with clinical findings similar to those of histoplasmosis. The common findings include diffuse pulmonary infiltrates, mediastinal 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, erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion nodosum, 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, and non-caseating granulomas Granulomas A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. Sarcoidosis. Although ↑ ACE levels are seen in both diseases, the elevation is classically associated with 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.
  • Blastomycosis Blastomycosis Blastomycosis is an infection caused by inhalation of the spores of the fungus, Blastomyces. Blastomyces species thrive in moist soil and decaying material and are common in the Ohio and Mississippi River valleys and the Great Lakes regions of the United States and Canada. Although most patients are asymptomatic, some can develop pneumonia. Blastomyces/Blastomycosis: a pulmonary disease Pulmonary disease Diseases involving the respiratory system. Blastomyces/Blastomycosis caused by inhaling the spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax of Blastomyces Blastomyces Blastomycosis is an infection caused by inhalation of the spores of the fungus, Blastomyces. Blastomyces species thrive in moist soil and decaying material and are common in the Ohio and Mississippi River valleys and the Great Lakes regions of the United States and Canada. Although most patients are asymptomatic, some can develop pneumonia. Blastomyces/Blastomycosis. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship can develop 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 or disseminated extrapulmonary disease Extrapulmonary disease Blastomyces/Blastomycosis. Clinically, pulmonary manifestations can be difficult to distinguish from histoplasmosis. Unlike in histoplasmosis, the 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 is the most common site of dissemination in blastomycosis Blastomycosis Blastomycosis is an infection caused by inhalation of the spores of the fungus, Blastomyces. Blastomyces species thrive in moist soil and decaying material and are common in the Ohio and Mississippi River valleys and the Great Lakes regions of the United States and Canada. Although most patients are asymptomatic, some can develop pneumonia. Blastomyces/Blastomycosis. Blastomyces Blastomyces Blastomycosis is an infection caused by inhalation of the spores of the fungus, Blastomyces. Blastomyces species thrive in moist soil and decaying material and are common in the Ohio and Mississippi River valleys and the Great Lakes regions of the United States and Canada. Although most patients are asymptomatic, some can develop pneumonia. Blastomyces/Blastomycosis is endemic to the regions of the Great Lakes and the Ohio and Mississippi River valleys. Diagnosis is made by cultures Cultures Klebsiella and imaging.
  • 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: an infectious Infectious Febrile Infant disease caused by 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 of the 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. Like histoplasmosis, 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 usually infects 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 but can also spread to other parts of the body. Both 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 and histoplasmosis are associated with a period of latency and can present with similar signs and symptoms. Look for a history of exposure Exposure ABCDE Assessment to an environment 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 prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency (healthcare setting, homeless shelters, etc ETC The electron transport chain (ETC) sends electrons through a series of proteins, which generate an electrochemical proton gradient that produces energy in the form of adenosine triphosphate (ATP). Electron Transport Chain (ETC).). A CD4 count of < 300 cells/μL is typically associated 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. The diagnosis is established with a 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, blood tests, sputum culture, and lung imaging.
  • Coccidioidomycosis Coccidioidomycosis Coccidioidomycosis, commonly known as San Joaquin Valley fever, is a fungal disease caused by Coccidioides immitis or Coccidioides posadasii. When Coccidioides spores are inhaled, they transform into spherules that result in infection. Coccidioidomycosis is also a common cause of community-acquired pneumonia and can cause severe disease in the immunocompromised. Coccidioides/Coccidioidomycosis: a pulmonary or hematogenously spread fungal disease caused by Coccidioides Coccidioides Coccidioidomycosis, commonly known as San Joaquin Valley fever, is a fungal disease caused by Coccidioides immitis or Coccidioides posadasii. When Coccidioides spores are inhaled, they transform into spherules that result in infection. Coccidioidomycosis is also a common cause of community-acquired pneumonia and can cause severe disease in the immunocompromised. Coccidioides/Coccidioidomycosis species. Like histoplasmosis, coccidioidomycosis Coccidioidomycosis Coccidioidomycosis, commonly known as San Joaquin Valley fever, is a fungal disease caused by Coccidioides immitis or Coccidioides posadasii. When Coccidioides spores are inhaled, they transform into spherules that result in infection. Coccidioidomycosis is also a common cause of community-acquired pneumonia and can cause severe disease in the immunocompromised. Coccidioides/Coccidioidomycosis is acquired through inhalation. The endemic regions for Coccidioides Coccidioides Coccidioidomycosis, commonly known as San Joaquin Valley fever, is a fungal disease caused by Coccidioides immitis or Coccidioides posadasii. When Coccidioides spores are inhaled, they transform into spherules that result in infection. Coccidioidomycosis is also a common cause of community-acquired pneumonia and can cause severe disease in the immunocompromised. Coccidioides/Coccidioidomycosis are distinct from Histoplasma and include southern California, Arizona, New Mexico, and West Texas.

References

  1. Baddley, J.W. (2021). Diagnosis and treatment of histoplasmosis in patients with HIV. UpToDate. Retrieved June 18, 2021, from https://www.uptodate.com/contents/diagnosis-and-treatment-of-histoplasmosis-in-patients-with-hiv
  2. Guimarães, A.J., Nosanchuk, J.D., Zancopé-Oliveira, R.M. (2006). Diagnosis of histoplasmosis. Braz J Microbiol 37, 1–13.
  3. Kauffman, C.A. (2020). Histoplasmosis: A clinical and laboratory update. Clin Microbiol Rev 20, 115–132.
  4. Kauffman, C.A. (2021). Diagnosis and treatment of pulmonary histoplasmosis. UpToDate. Retrieved June 18, 2021, from https://www.uptodate.com/contents/diagnosis-and-treatment-of-pulmonary-histoplasmosis
  5. Kauffman, C.A. (2021). Pathogenesis and clinical features of pulmonary histoplasmosis. UpToDate. Retrieved June 18, 2021, from https://www.uptodate.com/contents/pathogenesis-and-clinical-features-of-pulmonary-histoplasmosis
  6. Kauffman, C.A. (2021). Pathogenesis and clinical manifestations of disseminated histoplasmosis. UpToDate. Retrieved June 18, 2021, from https://www.uptodate.com/contents/pathogenesis-and-clinical-manifestations-of-disseminated-histoplasmosis
  7. Linder, K.A., Kauffman, C.A. (2019). Histoplasmosis: Epidemiology, diagnosis, and clinical manifestations. Curr Fungal Infect Reports 13, 120–128.
  8. Mihu, M.R., Nosanchuk, J.D. (2012). Histoplasma virulence and host responses. Int J Microbiol 2012, 268123.

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