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Paracoccidioides/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 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. The fungus 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 and then spreads to 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, mucous membranes, and other parts of the body. Primary infection Primary infection Herpes Simplex Virus 1 and 2 is typically self-limited. However, if infection is not contained by the host, and/or the patient is not treated, life-threatening complications can ensue. Acute 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 typically affect Affect The feeling-tone accompaniment of an idea or mental representation. It is the most direct psychic derivative of instinct and the psychic representative of the various bodily changes by means of which instincts manifest themselves. Psychiatric Assessment younger populations, with findings of 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, hepatosplenomegaly Hepatosplenomegaly Cytomegalovirus, 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, and signs of bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis dysfunction. More commonly, chronic paracoccidioidomycosis is seen, especially in men. Chronic paracoccidioidomycosis represents reactivation Reactivation Herpes Simplex Virus 1 and 2 of the infection, presenting with lung disease or disseminated infection. Diagnosis is by microscopy, histopathology, culture, and serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus. Itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles is typically used for mild to moderate disease and amphotericin B Amphotericin B Macrolide antifungal antibiotic produced by streptomyces nodosus obtained from soil of the orinoco river region of venezuela. Polyenes for severe and/or CNS disease.

Last updated: 30 Nov, 2021

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

General Characteristics of Paracoccidioides

Features

Morphology:

  • Thermally dimorphic fungus
    • Mold forms at 22°C–26°C
    • Yeast forms at 37°C
  • Mold form: thin, septated hyphae
  • Yeast form: 
    • Oval/round budding yeast
    • “Pilot’s wheel” or “Captain’s wheel” appearance: large cell surrounded by budding Budding Mycology cells
Paracoccidioidomycosis

Histopathology of Paracoccidioides:
Cells with budding Budding Mycology daughter cells (blastoconidia) seen in tissue, like a ship’s steering wheel (captain’s or pilot’s wheel)

Image: “Histopathology of paracoccidiodomycoisis” by CDC/Dr. Lucille K. Georg. License: Public Domain

Clinically relevant species

  • P. brasiliensis
  • P. lutzii

Forms of disease

  • Asymptomatic lung infection Lung infection 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
  • Acute/subacute
  • Chronic

Epidemiology

  • Endemic in rural areas in the following regions:
    • Southern Mexico to Argentina
    • Brazil
    • Colombia
    • Venezuela
    • Ecuador
    • Paraguay
  • 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 in endemic areas:
    • As high as 75% among adults
    • Estimated that only 2% of people develop active infection
  • Chronic form:
    • Most prevalent among men ages 30 to 60 years
    • Estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins may have a protective effect for women.
  • 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 are dependent on socioeconomic background.

Pathophysiology

Transmission and infectious Infectious Febrile Infant process

  • Route of entry: inhalation
  • Habitat: unknown, but likely in the soil
  • Animal reservoir Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli: armadillos
  • Rising cases are linked to the following factors:
    • Deforestation (seen in Brazil)
    • Urbanization in peripheral city areas with poor infrastructure
    • Increased soil and air humidity

Pathogenesis

  • Conidia Conidia Mycology inhaled through the respiratory tract → phagocytized by 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)
  • 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 within 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 → rapid fungal multiplication
  • Typically, infection is limited by nonspecific inflammatory response.
  • Most infected patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship have T helper cell type 1 Type 1 Spinal Muscular Atrophy ( Th1 Th1 A subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2; interferon-gamma; and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, th1 cells are associated with vigorous delayed-type hypersensitivity reactions. T cells: Types and Functions)–mediated immune response:
    • Alveolitis
    • Compact granuloma formation
    • Latent or asymptomatic infection
  • A deficient Th1 Th1 A subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2; interferon-gamma; and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, th1 cells are associated with vigorous delayed-type hypersensitivity reactions. T cells: Types and Functions response results in severe disease:
    • Granulomas Granulomas A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. Sarcoidosis do not form.
    • Development of Th2 Th2 A subset of helper-inducer T-lymphocytes which synthesize and secrete the interleukins il-4; il-5; il-6; and il-10. These cytokines influence b-cell development and antibody production as well as augmenting humoral responses. T cells: Types and Functions and Th9 responses, leading to the following:
      • B-lymphocyte activation
      • High levels of circulating antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions
      • Eosinophilia Eosinophilia Abnormal increase of eosinophils in the blood, tissues or organs. Autosomal Dominant Hyperimmunoglobulin E Syndrome
      • Hypergammaglobulinemia Hypergammaglobulinemia An excess of gamma-globulins in the serum due to chronic infections or paraproteinemias. Autoimmune Hepatitis
  • If unresolved → fungus can disseminate via venous and lymphatic system Lymphatic system A system of organs and tissues that process and transport immune cells and lymph. Primary Lymphatic Organs

Host risk factors

  • Agricultural work (especially coffee Coffee A beverage made from ground coffee beans (seeds) infused in hot water. It generally contains caffeine and theophylline unless it is decaffeinated. Constipation growers in endemic regions)
  • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
  • Alcohol use
  • HIV HIV Anti-HIV Drugs and 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
  • Immunosuppression

Clinical Presentation

General findings

  • Asymptomatic lung infection Lung infection Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia is common.
  • < 5% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship develop clinical disease.
  • 2 patterns of clinical disease:

Acute/subacute (juvenile) paracoccidioidomycosis

  • Typically observed in:
    • Children
    • Adolescents
    • Adults < 30 years of age
  • Represents < 10% of total cases
  • Signs and symptoms:
    • Constitutional:
      • 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
      • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
      • 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
    • 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
    • Hepatosplenomegaly Hepatosplenomegaly Cytomegalovirus
    • Manifestations of bone marrow failure Bone marrow failure Inherited or acquired diseases characterized by insufficient and/or dysplastic blood cells. Paroxysmal Nocturnal Hemoglobinuria (e.g., aplastic anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types)
    • 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 and mucous membrane Mucous membrane An epithelium with mucus-secreting cells, such as goblet cells. It forms the lining of many body cavities, such as the digestive tract, the respiratory tract, and the reproductive tract. Mucosa, rich in blood and lymph vessels, comprises an inner epithelium, a middle layer (lamina propria) of loose connective tissue, and an outer layer (muscularis mucosae) of smooth muscle cells that separates the mucosa from submucosa. Barrett’s Esophagus lesions
    • 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 involvement (less common)
Paracoccidioidomycosis lesions

Paracoccidioidomycosis-caused facial lesions in a Brazilian child.

Image: “Paracoccidioidomycosis lesions” by CDC/Dr. Martins Castro. License: Public Domain

Chronic paracoccidioidomycosis

  • Represents > 90% of cases
  • Presents months to years after initial infection
  • Primary lung infection Lung infection 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:
    • Cough (+/– 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 (less common)
    • 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
    • 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
  • Oropharyngeal and laryngeal mucous membrane Mucous membrane An epithelium with mucus-secreting cells, such as goblet cells. It forms the lining of many body cavities, such as the digestive tract, the respiratory tract, and the reproductive tract. Mucosa, rich in blood and lymph vessels, comprises an inner epithelium, a middle layer (lamina propria) of loose connective tissue, and an outer layer (muscularis mucosae) of smooth muscle cells that separates the mucosa from submucosa. Barrett’s Esophagus lesions:
    • Painful ulcers
    • Odynophagia Odynophagia Epiglottitis
    • Dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia
    • Dysphonia Dysphonia Difficulty and/or pain in phonation or speaking. Epiglottitis
    • Stridor Stridor Laryngomalacia and Tracheomalacia
    • Sialorrhea
  • Disseminated disease:
    • Can affect Affect The feeling-tone accompaniment of an idea or mental representation. It is the most direct psychic derivative of instinct and the psychic representative of the various bodily changes by means of which instincts manifest themselves. Psychiatric Assessment any body site
    • 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 (25% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship):
      • Crusted papules
      • Ulcers
      • Nodules
      • Plaques
      • Verrucous lesions
    • 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: cervical lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy most common
    • 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: commonly involved but typically asymptomatic
    • CNS:
      • Most common symptom: 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 (10%–25% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship)
      • 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
      • 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 lesion(s)
    • Less common:
      • Bones
      • Joints
      • Genitals
      • Eyes

Diagnosis

Laboratory tests

  • Microscopic visualization of culture growth is required for diagnosis.
  • Direct histologic examination of tissue:
    • Pilot’s wheel: large 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 cell with translucent cell walls and multiple buds
    • Sources:
      • Sputum
      • Bronchial lavage fluid
      • Exudates, 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
      • Biopsies of other tissues
    • Preparation:
    • May find granulomatous reaction: giant and epithelioid cells
  • Culture: 
    • Sabouraud dextrose Dextrose Intravenous Fluids agar or 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 extract agar
    • Can require up to 4 weeks for growth
  • Serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus:
    • Quantitative immunodiffusion (preferred)
    • Antibody titers monitored to check response to treatment
    • Limitations Limitations Conflict of Interest:
      • Cross reactivity Cross reactivity Reagent antibodies bind to molecules that are similar to the analyte → false positive/falsely elevated results) Immunoassays with other 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
      • Sensitivity Sensitivity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Blotting Techniques can be lower 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.
  • Additional evaluation:
    • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy function tests: 
      • Mild elevation of liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy function
      • Low albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests (correlated with poor prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas)
    • CBC: anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types
    • Adrenal dysfunction:
      • Morning cortisol Cortisol Glucocorticoids
      • Adrenocorticotropic hormone Adrenocorticotropic hormone An anterior pituitary hormone that stimulates the adrenal cortex and its production of corticosteroids. Acth is a 39-amino acid polypeptide of which the n-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotropic activity. Upon further tissue-specific processing, acth can yield alpha-msh and corticotropin-like intermediate lobe peptide (clip). Adrenal Hormones (ACTH) stimulation test

Radiographic findings

  • Chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests: mixed interstitial and alveolar infiltrates:
    • Usually perihilar, bilateral, and symmetrical Symmetrical Dermatologic Examination
    • Predominantly involve the lower 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
  • Chest CT:
    • Ground glass attenuations
    • Consolidations
    • Nodules
    • Masses
    • Cavities
    • Septal or interlobular thickening
    • Chronic disease:
  • Neuroimaging Neuroimaging Non-invasive methods of visualizing the central nervous system, especially the brain, by various imaging modalities. Febrile Infant:
    • Ring-enhancing lesions in 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 and/or 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
    • Findings may be nonspecific (i.e., solitary or multifocal Multifocal Retinoblastoma parenchymal lesions).

Management

  • Sensitive to antifungal Antifungal Azoles agents
  • Itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles:
    • Preferred agent for mild to moderate disease
    • Duration of 6–12 months
  • Amphotericin B Amphotericin B Macrolide antifungal antibiotic produced by streptomyces nodosus obtained from soil of the orinoco river region of venezuela. Polyenes:
    • Used for severe disease and CNS involvement
    • Duration of 3–6 weeks then → oral agent for prolonged course (> 2 years)
  • Trimethoprim Trimethoprim The sulfonamides are a class of antimicrobial drugs inhibiting folic acid synthesize in pathogens. The prototypical drug in the class is sulfamethoxazole. Although not technically sulfonamides, trimethoprim, dapsone, and pyrimethamine are also important antimicrobial agents inhibiting folic acid synthesis. The agents are often combined with sulfonamides, resulting in a synergistic effect. Sulfonamides and Trimethoprim sulfamethoxazole Sulfamethoxazole A bacteriostatic antibacterial agent that interferes with folic acid synthesis in susceptible bacteria. Its broad spectrum of activity has been limited by the development of resistance. Sulfonamides and Trimethoprim (TMP-SMX):
    • May be used alternatively for severe and/or CNS disease
    • Requires longer course than itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles on average (≥ 2 years)

Differential Diagnosis

  • 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: 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. Although 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 and paracoccidioidomycosis are both endemic to Central and South America, Paracoccidioides is not endemic to the Great Lakes and the Ohio and Mississippi River valleys. Diagnosis is made by cultures Cultures Klebsiella and imaging. The 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 of Paracoccidioides are typically smaller with thinner cell walls.
  • Tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis ( TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis): 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 Mycobacterium Mycobacterium Mycobacterium is a genus of the family Mycobacteriaceae in the phylum Actinobacteria. Mycobacteria comprise more than 150 species of facultative intracellular bacilli that are mostly obligate aerobes. Mycobacteria are responsible for multiple human infections including serious diseases, such as tuberculosis (M. tuberculosis), leprosy (M. leprae), and M. avium complex infections. Mycobacterium tuberculosis 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 Paracoccidioides, the 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 usually infect 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 are also 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 shelter, 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).). CD4 count < 300/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 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.
  • 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 ( aspergillosis Aspergillosis Aspergillosis is an opportunistic fungal infection caused by Aspergillus species, which are common spore-forming molds found in our environment. As Aspergillus species are opportunistic, they cause disease primarily in patients who are immunocompromised. The organs that are most commonly involved are the lungs and sinuses. Aspergillus/Aspergillosis, candidiasis Candidiasis Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis, pneumocystis pneumonia Pneumocystis Pneumonia Pneumocystis jiroveci is a yeast-like fungus causing pneumocystis pneumonia (PCP) in immunocompromised patients. Pneumocystis pneumonia is spread through airborne transmission and classically affects patients with AIDS, functioning as an AIDS-defining illness. Patients may present with insidious onset of fever, chills, dry cough, chest pain, and shortness of breath. Pneumocystis jirovecii/Pneumocystis Pneumonia (PCP), mucormycosis Mucormycosis Mucormycosis is an angioinvasive fungal infection caused by multiple fungi within the order, Mucorales. The fungi are ubiquitous in the environment, but mucormycosis is very rare and almost always occurs in patients who are immunocompromised. Inhalation of fungal spores can cause rhinocerebral or pulmonary mucormycosis, direct inoculation can cause cutaneous mucormycosis, and ingestion can cause gastrointestinal mucormycosis. Mucorales/Mucormycosis): 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 those with CD4 counts < 200/μL) and typically do not cause disease in healthy patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with normal 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 function. General signs and symptoms can be similar to those of paracoccidioidomycosis. Microscopy and culture of sputum 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 with identification Identification Defense Mechanisms of specific organism can help differentiate.
  • Leishmaniasis Leishmaniasis Leishmania species are obligate intracellular parasites that are transmitted by an infected sandfly. The mildest form is cutaneous leishmaniasis (CL), characterized by painless skin ulcers. The mucocutaneous type involves more tissue destruction, causing deformities. Visceral leishmaniasis (VL), the most severe form, presents with hepatosplenomegaly, anemia, thrombocytopenia, and fever. Leishmania/Leishmaniasis: parasitic disease found in tropical, subtropical, and southern Europe regions. The most common findings in leishmaniasis Leishmaniasis Leishmania species are obligate intracellular parasites that are transmitted by an infected sandfly. The mildest form is cutaneous leishmaniasis (CL), characterized by painless skin ulcers. The mucocutaneous type involves more tissue destruction, causing deformities. Visceral leishmaniasis (VL), the most severe form, presents with hepatosplenomegaly, anemia, thrombocytopenia, and fever. Leishmania/Leishmaniasis are cutaneous lesions causing 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 sores; however, the disease can also involve visceral organs (often the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen: Anatomy, liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, and bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis). 
  • Multiple carcinomas ( lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum, leukemia, 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, maxillofacial malignancies): have overlapping signs and symptoms with paracoccidioidomycosis (e.g., 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, hepatosplenomegaly Hepatosplenomegaly Cytomegalovirus, 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, oropharyngeal lesions). Diagnosis is made by histopathology.

References

  1. Centers for Disease Control and Prevention Resources for Health Professionals. (2021). Parasites—leishmaniasis. https://www.cdc.gov/parasites/leishmaniasis/health_professionals
  2. Nucci, M., Colombo, A. L. (2021). Clinical manifestations and diagnosis of acute/subacute paracoccidioidomycosis. UpToDate. Retrieved June 21, 2021, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-acute-subacute-paracoccidioidomycosis
  3. Nucci, M., Colombo, A. L. (2021). Clinical manifestations and diagnosis of chronic paracoccidioidomycosis. UpToDate. Retrieved June 21, 2021, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-chronic-paracoccidioidomycosis
  4. Nucci, M., Colombo, A. L. (2021). Mycology and epidemiology of paracoccidioidomycosis. UpToDate. Retrieved June 21, 2021, from https://www.uptodate.com/contents/mycology-and-epidemiology-of-paracoccidioidomycosis
  5. Nucci, M., Colombo, A. L. (2021). Treatment of paracoccidioidomycosis. UpToDate. Retrieved June 21, 2021, from https://www.uptodate.com/contents/treatment-of-paracoccidioidomycosis

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