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Aspergillus/Aspergillosis

Aspergillosis is an opportunistic fungal infection caused by Aspergillus Aspergillus A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family trichocomaceae. Echinocandins species, which are common spore Spore The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Microsporidia/Microsporidiosis-forming molds found in our environment. As Aspergillus Aspergillus A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family trichocomaceae. Echinocandins species are opportunistic, they cause disease primarily in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who are 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. The organs that are most commonly involved are the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy and sinuses. Invasive aspergillosis can spread hematogenously and may involve the 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, heart, and skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions. Symptoms may vary depending on the organ involved, but pulmonary symptoms may include shortness of breath Shortness of breath 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, 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, 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. The diagnosis is made based on imaging studies, fungal cultures Fungal cultures Dermatophytes/Tinea Infections, and analysis of serologic or respiratory samples. Management depends on the 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 but can include antifungal Antifungal Azoles therapy and surgical resection in severe disease.

Last updated: 4 May, 2021

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

General Characteristics of Aspergillus

Characteristics:

Morphology:

  • Hyphae Hyphae Microscopic threadlike filaments in fungi that are filled with a layer of protoplasm. Collectively, the hyphae make up the mycelium. Mycology
    • Long, filamentous structures
    • Frequent septae 
    • Form dichotomous branches (45-degree angles)
    • Walls are typically parallel
  • Conidia Conidia Mycology
    • Asexual, nonmotile spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax
    • Spherical
    • Originate from conidiophores (specialized hyphal branch)

Clinically relevant species

Over 250 species of Aspergillus Aspergillus A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family trichocomaceae. Echinocandins exist; however, only the following species are most commonly associated with aspergillosis:

  • A. fumigatus (most common)
  • A. niger
  • A. flavus
  • A. terreus

Forms of aspergillosis

Aspergillosis can have 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 clinical presentations, with the most commonly involved organ systems being the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy and 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. These disease presentations include:

  • Allergic bronchopulmonary aspergillosis (ABPA)
  • Aspergillus Aspergillus A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family trichocomaceae. Echinocandins sinusitis Sinusitis Sinusitis refers to inflammation of the mucosal lining of the paranasal sinuses. The condition usually occurs concurrently with inflammation of the nasal mucosa (rhinitis), a condition known as rhinosinusitis. Acute sinusitis is due to an upper respiratory infection caused by a viral, bacterial, or fungal agent. Sinusitis
  • Aspergilloma
  • Chronic pulmonary aspergillosis
  • Invasive aspergillosis
  • Cutaneous aspergillosis

Epidemiology and Pathogenesis

Epidemiology

Limited statistics are available on aspergillosis.

  • ABPA potentially affects: 
    • 1%–15% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with cystic Cystic Fibrocystic Change fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans
    • 2.5% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma
  • Invasive aspergillosis:
    • Uncommon and primarily occurs in immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis individuals 
    • 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: 1–2 cases in 100,000 individuals in the United States
      • Higher in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who have undergone a transplant
      • Associated with approximately 15,000 hospitalizations

Host risk factors

Humans inhale spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax daily, but generally do not develop the disease if they have a competent immune system Immune system The body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs. Aspergillosis often occurs in people with underlying conditions such as:

  • Immunosuppression: 
  • Lung disease:
    • 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 
    • Asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma
    • Cystic Cystic Fibrocystic Change fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans
    • Chronic obstructive pulmonary disease Pulmonary disease Diseases involving the respiratory system. Blastomyces/Blastomycosis ( COPD COPD Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD))
    • 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
    • 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

Transmission

  • Inhalation of spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax (most common)
  • Invasion through damaged 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

Pathophysiology

The pathogenesis of each type of aspergillosis is not completely understood.

In immunocompetent patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship:

  • Inhalation of conidia Conidia Mycology → taken up 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 
  • Germination into hyphae Hyphae Microscopic threadlike filaments in fungi that are filled with a layer of protoplasm. Collectively, the hyphae make up the mycelium. Mycology immune recognition Immune Recognition Yaws, Bejel, and Pinta by 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 components
  • Neutrophil recruitment Recruitment Skeletal Muscle Contraction hyphae Hyphae Microscopic threadlike filaments in fungi that are filled with a layer of protoplasm. Collectively, the hyphae make up the mycelium. Mycology destruction

In immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship:

  • Hyphae Hyphae Microscopic threadlike filaments in fungi that are filled with a layer of protoplasm. Collectively, the hyphae make up the mycelium. Mycology invade tissues and walls of blood vessels → invasive aspergillosis
  • The invasion results in the following conditions in organs (most commonly the lung):
    • Tissue infarction
    • Hemorrhage
    • Necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage 

In patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with underlying lung disease:

  • Tissue invasion is not as common unless concurrent immunodeficiency Immunodeficiency Chédiak-Higashi Syndrome is present.
  • Aspergillus Aspergillus A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family trichocomaceae. Echinocandins may inhabit pulmonary cavities → a tangled mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast of hyphae Hyphae Microscopic threadlike filaments in fungi that are filled with a layer of protoplasm. Collectively, the hyphae make up the mycelium. Mycology, fibrin Fibrin A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. Rapidly Progressive Glomerulonephritis, and inflammatory cells can develop → aspergilloma (fungus ball)
  • The presence of Aspergillus Aspergillus A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family trichocomaceae. Echinocandins can trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation a hypersensitivity reaction → ABPA

Clinical Presentation

The 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 based on the form of aspergillosis.

Common constitutional symptoms Constitutional Symptoms Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis

The following symptoms may be seen with any form of aspergillosis:

Allergic bronchopulmonary aspergillosis

Allergic bronchopulmonary aspergillosis should be suspected in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma or cystic Cystic Fibrocystic Change fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans who present with recurrent exacerbations. Symptoms include:

  • 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
  • Cough:
    • Productive
    • Green or brown mucous plugs
  • 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
  • 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

Aspergillus Aspergillus A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family trichocomaceae. Echinocandins sinusitis Sinusitis Sinusitis refers to inflammation of the mucosal lining of the paranasal sinuses. The condition usually occurs concurrently with inflammation of the nasal mucosa (rhinitis), a condition known as rhinosinusitis. Acute sinusitis is due to an upper respiratory infection caused by a viral, bacterial, or fungal agent. Sinusitis

Aspergillus Aspergillus A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family trichocomaceae. Echinocandins sinusitis Sinusitis Sinusitis refers to inflammation of the mucosal lining of the paranasal sinuses. The condition usually occurs concurrently with inflammation of the nasal mucosa (rhinitis), a condition known as rhinosinusitis. Acute sinusitis is due to an upper respiratory infection caused by a viral, bacterial, or fungal agent. Sinusitis may be allergic or invasive. Symptoms include:

  • Nasal congestion
  • Purulent nasal discharge
  • Decreased sense of smell Smell The sense of smell, or olfaction, begins in a small area on the roof of the nasal cavity, which is covered in specialized mucosa. From there, the olfactory nerve transmits the sensory perception of smell via the olfactory pathway. This pathway is composed of the olfactory cells and bulb, the tractus and striae olfactoriae, and the primary olfactory cortex and amygdala. Olfaction: Anatomy
  • Facial discomfort and/or sinus tenderness
  • 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

Chronic pulmonary aspergillosis and aspergilloma

Some patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with chronic pulmonary aspergillosis and aspergilloma are asymptomatic. Symptomatic individuals may present with:

  • 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
  • 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
  • Cough (dry or productive)
  • 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
  • Note: Constitutional symptoms Constitutional Symptoms Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis often occur with chronic pulmonary aspergillosis but not with aspergilloma.

Invasive aspergillosis

Pulmonary:

  • 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
  • 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 
  • 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
  • Respiratory distress

Disseminated infection:

  • Endophthalmitis Endophthalmitis Endophthalmitis is an inflammatory process of the inner layers of the eye, which may be either infectious or sterile. Infectious endophthalmitis can lead to irreversible vision loss if not treated quickly. Based on the entry mode of the infectious source, endophthalmitis is divided into endogenous and exogenous types. Endophthalmitis
  • 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
  • CNS aspergillosis:
    • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
    • Focal neurologic deficits Neurologic Deficits High-Risk Headaches
    • Mycotic aneurysms → subarachnoid hemorrhage Subarachnoid Hemorrhage Subarachnoid hemorrhage (SAH) is a type of cerebrovascular accident (stroke) resulting from intracranial hemorrhage into the subarachnoid space between the arachnoid and the pia mater layers of the meninges surrounding the brain. Most SAHs originate from a saccular aneurysm in the circle of Willis but may also occur as a result of trauma, uncontrolled hypertension, vasculitis, anticoagulant use, or stimulant use. Subarachnoid Hemorrhage

Cutaneous aspergillosis

Cutaneous aspergillosis may occur from direct inoculation or disseminated infection. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may present with:

  • Erythematous lesions with red or violet hardened plaques
  • Indurated or umbilicated papules and nodules
  • An overlying black eschar may occur.
Cutaneous aspergillosis

Cutaneous aspergillosis lesions:
A and B: Nodular lesions
C: Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion and necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage of a toe
D: A large necrotic plaque Plaque Primary Skin Lesions with surrounding erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion on a patient’s chest

Image: “Cutaneous aspergillosis” by Dermatology Department, UPEC (CB, SI-H-O, OC), Paris, France. License: CC BY 4.0

Diagnosis

Imaging

Chest imaging with X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests or CT are commonly ordered. Findings may include:

Laboratory evaluation

  • Tests for invasive aspergillosis:
    • Galactomannan antigen detection Antigen detection Respiratory Syncytial Virus:
    • 1,3 beta-D-glucan:
      • A 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 component of many fungi Fungi A kingdom of eukaryotic, heterotrophic organisms that live parasitically as saprobes, including mushrooms; yeasts; smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi, commonly known as molds, refer to those that grow as multicellular colonies. Mycology
      • Less sensitive than the test to detect galactomannan
  • Evaluation for ABPA may demonstrate: 
    • Eosinophilia Eosinophilia Abnormal increase of eosinophils in the blood, tissues or organs. Autosomal Dominant Hyperimmunoglobulin E Syndrome
    • Elevated serum IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions levels against Aspergillus Aspergillus A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family trichocomaceae. Echinocandins
    • Positive 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 reactivity to Aspergillus Aspergillus A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family trichocomaceae. Echinocandins antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination testing
  • Testing for chronic pulmonary aspergillosis: Aspergillus Aspergillus A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family trichocomaceae. Echinocandins IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis antibody

Culture and histopathology

Histopathology of aspergillosis

Methenamine silver Methenamine silver Pneumocystis jirovecii/Pneumocystis Pneumonia (PCP)-stained tissue section showing septate hyphae Hyphae Microscopic threadlike filaments in fungi that are filled with a layer of protoplasm. Collectively, the hyphae make up the mycelium. Mycology of Aspergillus Aspergillus A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family trichocomaceae. Echinocandins species

Image: “Histopathology and growth on culture medium” by Department of Orthopaedics, All India Institute of Medical Sciences, New Delhi 110029, India. License: CC BY 4.0

Management and Prevention

Management of ABPA

  • Oral steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors 
  • Itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles is reserved for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who cannot tolerate steroid tapers.
  • Optimize therapy for cystic Cystic Fibrocystic Change fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans or asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma.

Chronic pulmonary aspergillosis and aspergilloma

  • Aspergilloma does not require therapy if asymptomatic and does not respond to antifungal Antifungal Azoles therapy.
  • Antifungal Antifungal Azoles therapy for chronic pulmonary aspergillosis:
    • Itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles
    • Voriconazole Voriconazole A triazole antifungal agent that specifically inhibits sterol 14-alpha-demethylase and cytochrome p-450 cyp3a. Azoles
  • Bronchial artery embolization Embolization A method of hemostasis utilizing various agents such as gelfoam, silastic, metal, glass, or plastic pellets, autologous clot, fat, and muscle as emboli. It has been used in the treatment of spinal cord and intracranial arteriovenous malformations, renal arteriovenous fistulas, gastrointestinal bleeding, epistaxis, hypersplenism, certain highly vascular tumors, traumatic rupture of blood vessels, and control of operative hemorrhage. Gastrointestinal Bleeding for massive hemoptysis Massive hemoptysis Hemoptysis
  • Surgical resection for severe disease

Management of invasive aspergillosis

The following options may be used in invasive disease, including invasive sinusitis Sinusitis Sinusitis refers to inflammation of the mucosal lining of the paranasal sinuses. The condition usually occurs concurrently with inflammation of the nasal mucosa (rhinitis), a condition known as rhinosinusitis. Acute sinusitis is due to an upper respiratory infection caused by a viral, bacterial, or fungal agent. Sinusitis, cutaneous disease, and disseminated disease:

  • Antifungal Antifungal Azoles therapy:
    • Voriconazole Voriconazole A triazole antifungal agent that specifically inhibits sterol 14-alpha-demethylase and cytochrome p-450 cyp3a. Azoles (preferred)
    • Amphotericin B Amphotericin B Macrolide antifungal antibiotic produced by streptomyces nodosus obtained from soil of the orinoco river region of venezuela. Polyenes
    • Caspofungin Caspofungin A cyclic lipopeptide echinocandin and beta-(1, 3)-d-glucan synthase inhibitor that is used to treat internal or systemic mycoses. Echinocandins
  • Management of immunosuppression:
    • Discontinuation of corticosteroids Corticosteroids Chorioretinitis
    • 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 for HIV HIV Anti-HIV Drugs
  • Surgical: 
    • Debridement Debridement The removal of foreign material and devitalized or contaminated tissue from or adjacent to a traumatic or infected lesion until surrounding healthy tissue is exposed. Stevens-Johnson Syndrome of necrotic tissue
    • Valve replacement for 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

Prevention

Differential Diagnosis

  • 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: an infection 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 fungi Fungi A kingdom of eukaryotic, heterotrophic organisms that live parasitically as saprobes, including mushrooms; yeasts; smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi, commonly known as molds, refer to those that grow as multicellular colonies. Mycology that can present in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who are immunocompetent or 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. 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 is known to cause both pulmonary and extrapulmonary disease Extrapulmonary disease Blastomyces/Blastomycosis. 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 diagnosed using serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus, microscopic examination of specimens, and fungal cultures Fungal cultures Dermatophytes/Tinea Infections. Medical treatment is primarily with fluconazole Fluconazole Triazole antifungal agent that is used to treat oropharyngeal candidiasis and cryptococcal meningitis in aids. Azoles, itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles, or amphotericin B Amphotericin B Macrolide antifungal antibiotic produced by streptomyces nodosus obtained from soil of the orinoco river region of venezuela. Polyenes (for severe disease).
  • Paracoccidioidomycosis Paracoccidioidomycosis Paracoccidioidomycosis (PCM) is an endemic fungal infection caused by Paracoccidioides brasiliensis and P. lutzii. The fungus is geographically distributed across Mexico and South and Central America. Transmission is by inhalation, and most infections are asymptomatic. Paracoccidioides/Paracoccidioidomycosis: an opportunistic infection caused by Paracoccidioides Paracoccidioides Paracoccidioidomycosis (PCM) is an endemic fungal infection caused by Paracoccidioides brasiliensis and P. lutzii. The fungus is geographically distributed across Mexico and South and Central America. Transmission is by inhalation, and most infections are asymptomatic. Paracoccidioides/Paracoccidioidomycosis. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may present with mucocutaneous, lymphatic, or visceral disease. Paracoccidioidomycosis Paracoccidioidomycosis Paracoccidioidomycosis (PCM) is an endemic fungal infection caused by Paracoccidioides brasiliensis and P. lutzii. The fungus is geographically distributed across Mexico and South and Central America. Transmission is by inhalation, and most infections are asymptomatic. Paracoccidioides/Paracoccidioidomycosis is diagnosed based on microscopic evaluation of specimens and culture. Medical treatment is primarily with itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles or amphotericin B Amphotericin B Macrolide antifungal antibiotic produced by streptomyces nodosus obtained from soil of the orinoco river region of venezuela. Polyenes (for severe cases).
  • 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. The diagnosis is made with imaging and cultures Cultures Klebsiella. If patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship do not spontaneously improve, itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles may be given. Medical treatment includes fluconazole Fluconazole Triazole antifungal agent that is used to treat oropharyngeal candidiasis and cryptococcal meningitis in aids. Azoles, itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles, or amphotericin B Amphotericin B Macrolide antifungal antibiotic produced by streptomyces nodosus obtained from soil of the orinoco river region of venezuela. Polyenes (in severe cases). 
  • 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 Histoplasma capsulatum Histoplasma capsulatum Histoplasma/Histoplasmosis. Symptoms may be nonspecific or consistent with those 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. 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 is diagnosed based on fungal cultures Fungal cultures Dermatophytes/Tinea Infections or urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat and serum antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination testing. Itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles may be given if patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship do not show improvement in symptoms.
  • 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: an opportunistic infection caused by the yeasts, Cryptococcus Cryptococcus Cryptococcosis is an opportunistic, fungal infection caused by the Cryptococcus species. The principal pathogens in humans are C. neoformans (primary) and C. gattii. Cryptococcus neoformans is typically found in pigeon droppings and acquired by inhaling dust from contaminated soil. The majority of affected patients are immunocompromised. Cryptococcus/Cryptococcosis neoformans or C. gattii C. gattii A species of the fungus cryptococcus. Its teleomorph is filobasidiella bacillispora. Cryptococcus/Cryptococcosis. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may 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, 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, or cutaneous disease.  Fungal cultures Fungal cultures Dermatophytes/Tinea Infections and cryptococcal antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination testing can provide the diagnosis. Management depends on the 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 but can include fluconazole Fluconazole Triazole antifungal agent that is used to treat oropharyngeal candidiasis and cryptococcal meningitis in aids. Azoles and amphotericin B Amphotericin B Macrolide antifungal antibiotic produced by streptomyces nodosus obtained from soil of the orinoco river region of venezuela. Polyenes (for 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).

References

  1. Akuthota, P. (2021). Treatment of allergic bronchopulmonary aspergillosis. UpToDate. Retrieved April 19, 2021, from https://www.uptodate.com/contents/treatment-of-allergic-bronchopulmonary-aspergillosis
  2. Aspergillosis. (2020). Retrieved April 19, 2021, from https://www.cdc.gov/fungal/diseases/aspergillosis/index.html
  3. Gaillard, F. (n.d.). Pulmonary aspergillosis: Radiology reference article. Retrieved April 19, 2021, from https://radiopaedia.org/articles/pulmonary-aspergillosis?lang=us
  4. Kauffman, C. (2021). Diagnosis of invasive aspergillosis. UpToDate. Retrieved April 19, 2021, from https://www.uptodate.com/contents/diagnosis-of-invasive-aspergillosis
  5. Patterson, T. (2021). Treat and prevention of invasive aspergillosis. UpToDate. Retrieved April 19, 2021, from https://www.uptodate.com/contents/treatment-and-prevention-of-invasive-aspergillosis
  6. Kauffman, C.A. (2019). Epidemiology and clinical manifestations of invasive aspergillosis. In Bond, S. (Ed.). UpToDate. Retrieved April 23, 2021, from https://www.uptodate.com/contents/epidemiology-and-clinical-manifestations-of-invasive-aspergillosis
  7. Denning, D.W. (2020). Clinical manifestations and diagnosis of chronic pulmonary aspergillosis. In Bond, S. (Ed.). UpToDate. Retrieved April 23, 2021, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-chronic-pulmonary-aspergillosis
  8. Akuthota, P., Weller, P.F. (2020). Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis. In Hollingsworth, H. (Ed.). UpToDate. Retrieved April 23, 2021, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-allergic-bronchopulmonary-aspergillosis
  9. Vuong, M.F., Waymack, J.R. (2020). Aspergillosis. [online] StatPearls. Retrieved April 23, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK482241/
  10. Ortega, V.E., and Genese, F. (2019). Allergic bronchopulmonary aspergillosis (ABPA). [online] MSD Manual Professional Version. Retrieved April 23, 2021, from https://www.msdmanuals.com/professional/pulmonary-disorders/asthma-and-related-disorders/allergic-bronchopulmonary-aspergillosis-abp
  11. Revankar, S.G. (2019). Aspergillosis. [online] MSD Manual Professional Version. Retrieved April 23, 2021, from https://www.msdmanuals.com/professional/infectious-diseases/fungi/aspergillosis

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