Infection caused by fungus is known as mycosis.

Fungi are placed in the phylum Thallophyta. It is divisible into two groups, algae and fungi.

  1. Algae: Algae produce their own food by means of chlorophyll possessed by them.
  2. Fungi:

Fungi do not possess chlorophyll and are, therefore, saprophytes or parasites.

  1. Morphological classification.
  2. Systematic classification.

On the basis of morphology, there are four groups of fungi:

  1. Yeasts:
  • Yeasts are round, oval or elongated unicellular fungi.
  • Most reproduce by an asexual process called budding in which the cell develops a protuberance, which enlarges and eventually separates from the parent cell.
  • Some reproduce by fission.
  • On culture, they form smooth, creamy colonies.
  • Examples: Saccharomyces cerevisiae—nonpathogenic, yeast and Cryptococcus neoformans—pathogenic yeast.
  1. Yeast-like fungi:
  • Yeast-like fungi grow partly as yeast and partly as elongated cells resembling hyphae.
  • The latter form a pseudomycelium.
  • Example: Candida albicans is a pathogenic yeast-like fungus.
  1. Molds or filamentous fungi:
  • Molds or filamentous fungi form true mycelia and reproduce by the formation of different types of spores.
  • Examples: Dermatophytes, Aspegillus, Penicillium, Mucor and Rhizopus.
  1. Dimorphic fungi:
  • Many fungi pathogenic to man have a yeast form in the host tissue and in vitro at 37°C on enriched media and hyphal (mycelial) form in vitro at 25°C.
  • Examples: Histoplasma capsulatum, Sporothrix schenckii, Blastomyces dermatitidis, Coccidioides immitis, Paracoccidioides brasiliensis, and Penicillium marneffei.

On the basis of formation of sexual spores, fungi have been divided into 4 classes:

  1. Zygomycetes:
  • Zygomycetes are lower fungi which have nonseptate hyphae and form asexual spores called sporangiospores contained within swollen oospores.
  • Examples: Rhizopus, Absidia, Mucor, Pilobolus.
  1. Ascomycetes:

The Ascomycetes form sexual spores (ascospores) within a sac or ascus. Ascomycetes include both yeasts and filamentous fungi.

  1. Basidiomycetes:
  • The Basidiomycetes form sexual spores (basidiospores) on a basidium or base.
  • Examples: Mushrooms, Filobasidiella neoformans (anamorph), Cryptococcus neoformans.
  1. Deuteromycetes (Fungi Imperfecti):
  • Fungi that lack a known sexual state are placed in the class Deuteromycetes (Fungi Imperfecti).
  • Most fungi of medical importance belong to this class.
  • Examples: Coccidioides immitis, Paracoccidioides brasiliensis, Candida albicans.

Classification of fungal disease according to primary sites of infections:

Type of mycosis

Mycosis

Causative Fungal Agents

Superficial

Pityriasis versicolor

Tinea nigra

White piedra

Black piedra

Malassezia species Trichosporon species

Hortaea werneckii

Piedraia hortae

Cutaneous

Dermatophytosis

Microsporum species, Trichophyton species, and Epidermophyton floccosum

Candidiasis of skin, mucosa, or nails

Candida albicans and other candida species

Subcutaneous

Sporotrichosis

Sporothrix schencki

Chromoblastomycosis

Phialophora verrucosa, Fonsecaea pedrosoi, others

Mycetoma

Pseudallescheria boydii, Madurella mycetomatis,

others

Phaeohyphomycosis

Exophiala, bipolaris, exserohilum, and others

Systemic (prlmary, endemic)

Coccidioidomycosis

Coccidioides immitis, C. posadasii

Histoplasmosis

Histoplasma capsulatum

Blastomycosis

Blastomyces dermatitidis

Paracoccidioidomycosis

Paracoccidioides brasiliensis

Opportunistic

Systemic candidiasis

Candida albicans and other candida species

Cryptococcosis

Cryptococcus neoformans

Aspergillosis

Aspergillus fumigatus and other aspergillus species

Mucormycosis (zygomycosis)

Species of Rhizopus, Absidia, Mucor, and other zygomycetes

Penicilliosis

Penicillium marneffei

All fungi are eukaryotic protista that differ from bacteria and other prokaryotes in following ways:

  • They possess rigid cell walls containing chitin, mannan and other polysaccharides.
  • The cytoplasmic membrane contains sterols.
  • Cytoplasmic contents include mitochondria and endoplasmic reticulum.
  • They possess true nuclei with nuclear membrane and paired chromosomes.
  • They may be unicellular or multicellular.
  • They divide asexually, sexually or by both processes.
  • Most fungi are obligate or facultative aerobes.
  • They are chemotrophic, secreting enzymes that degrade a wide variety of organic substrates into soluble nutrients which are then passively absorbed
  • or taken into the cell by active transport.
  • The cells show various degrees of specialization.

Refer to Red and White Lesions of oral cavity.

  • Also k/a valley fever,san Joaquin valley fever.
  • Coccidioidomycosis was first discovered in Argentina in 1892 by a medical student.
  • Caused by infection by either Coccidioides immitis or C. posadasii.
  • Inhalation of the organism or inoculation through the skin.
  • Condition is endemic in the southwest USA, northern Mexico, and parts of Central and South America.
  • Usually C. immitis grows 5–30 cm under the ground, especially around burrows of rodents and reptiles.

Risk factors:

  • Activities that expose the subject to contaminated dust such as:
  • Archaeologist
  • Military personnel.
  • Construction workers.
  • Hunters
  • Earthquakes victims.
  • Immunocompromised patients.

Occurs in two basic forms:

  • Primary non disseminated disease.
  • Progressive disseminated disease.

Development of respiratory symptoms:

  • Cough
  • Pleural pain.
  • Headache
  • Anorexia
  • Fever
  • Fatigue
  • Night-sweats.
  • Weight-loss.

Rare:

  • Persistent pneumonia,
  • Hemoptysis
  • Fibrocavitary infection.
  • cavitary complication. 
  • 20% of the cases develop skin lesions, either erythema nodosum or erythema multiforme.
  • This form is self-limiting and runs its course within 10-14 days.
  • This form of the disease occurs in only about 1% of the cases.
  • Mortality rate of approximately 50%.
  • Runs a rapid course and the dissemination extends from the lung to various viscera, bones, joints, skin, and to the central nervous system.
  • Meningitis is frequent cause of death.
  • The dissemination to bone results in osteomyelitis.
  • Site of involvement is head and neck, oral cavity.
  • The most affected areas are the nasolabial groove and sternoclavicular area. Proliferative granulomatous and ulcerated lesions.
  • These lesions tend to heal by hyalinization and scar.
  • Lytic lesions of the jaws.
  • Coccidioidomycosis is typically a granulomatous infection involving the lungs, rarely presenting in the mouth.

The diagnosis is based on histopathological demonstration of fungal structures, culture (Biosafety level 3), skin tests, demonstration of humoral antibodies (withenzyme immune assay (EIA) and immunodiffusion (available for both early IgM and late IgG) and complement fixation (IgG), a quantitative antigen detection EIA and newer molecular methods such as polymerase chain reaction for coccidioidal DNA.

 Histoplasmosis, aspergillosis, cryptococcosis, paracoccidioidomycosis

  • Posaconazole (second-generation triazole): 300 mg/day.
  • Alternative to azole antifungal therapy, Amphotericin B (0.5–0.7 mg/kg/d IV) may also be prescribed.
  • Also k/a torulosis, European blastomycosis.
  • Cryptococcal infections are fungal infections most commonly seen in immunocompromised patients.
  • The majority of disseminated cryptococcal infections occur in patients with acquired immunodeficiency syndrome (AIDS).
  • Two species of Cryptococcuscommonly cause disease in humans: Cryptococcus neoformans and Cryptococcus gattii
  • Cryptococci and their spores are found in the soil and are primarily acquired by inhalation. Once acquired, further dissemination occurs by the haematogenous route, especially in the immunocompromised.
  • neoformansis the most common fungus to cause meningitis. The CSF is an ideal site for infection as it lacks complements and immunoglobulins.

Pulmonary Infection

  • Acute symptoms of pneumonia.
  • Asymptomatic colonization of the airways.
  • Simple pulmonary nodule on a chest radiograph.
  • Life-threatening pneumonia.
  • Acute respiratory distress syndrome.
  • Abnormal chest radiograph.
  • Well-defined single or multiple noncalcified nodules.
  • Pulmonary infiltrates.
  • Pleural effusions.
  • Hilar lymphadenopathy.
  • Lung cavitation. 

Central Nervous System Infection

Symptoms usually develop over a period of several weeks.

  • Headache
  • Fever
  • Cranial neuropathies.
  • Altered mentation.
  • Lethargy
  • Memory loss.
  • Signs of meningeal irritation.

In severely immunocompromised, HIV-infected patients with CNS cryptococcosis, the burden of fungal organisms is usually high and can reach levels of more than 1 million yeasts per milliliter of cerebrospinal fluid (CSF).

Skin Infection

  • Cutaneous infections are the third most common clinical manifestations.
  • Skin lesions appear as multiple brown papules which ultimately ulcerate; the clinical picture is not specific.

Eye Infection

  • Ocular palsies.
  • Papilledema
  • Extensive retinal disease with or without vitritis, which can lead to irreversible blindness.

Visual loss due to optic nerve infiltration by yeasts or vascular compromise from intracranial hypertension.

Infection at Other Body Sites

Bone involvement:

  • Circumscribed osteolytic lesions in any bone of the body.
  • Most commonly the vertebrae.
  • cryptococcal osteomyelitis.
  • Bone marrow infiltration.
  • Fungal peritonitis.
  • Cryptococcuria

Restoration of pathogen-specific immunity can result in a phenomenon known as the immune reconstitution inflammatory syndrome (IRIS), an entity that can occur before (“unmasking IRIS”) or during (“paradoxic IRIS”) antifungal therapy. Cryptococcal IRIS is best characterized in HIV-infected patients with CNS infection and is associated with significant morbidity and mortality.

  • Oral lesions are encountered rarely.
  • Oral Cryptococcosis can manifest as superficial ulcers, violaceous nodules, granuloma,
  • Cancerous looking lesions or draining sinuses.

·         Direct Examination/India Ink

The most rapid method for diagnosis of cryptococcal meningitis is direct microscopic examination for encapsulated yeasts by India ink preparation of CSF. Cryptococcus can be visualized as a globular, encapsulated yeast cell with or without budding, ranging in size from 5 to 20 μm in diameter.

·         Culture and Identification

Cryptococcus can be cultured readily from biologic samples such as CSF, sputum, and skin biopsy on routine fungal and bacterial culture media. In adults with HIV-associated cryptococcal meningitis, CSF and blood cultures are positive.

·         Cytology and Histopathology

Cryptococcus can be identified by histologic staining of tissues from the lung, skin, bone marrow, brain, and other organs.

Histopathologic staining and cytology of centrifuged CSF sediment and other bodily fluids are more sensitive than the India ink staining method.

·         Serology

The diagnosis of cryptococcosis improved significantly with the development of serologic tests for the cryptococcal polysaccharide capsular antigen (CrAg), which is shed during infection.

  • Therapeutic options are typically guided by immune status and extent of disease. Patients with significant disease, initial therapy usually includes amphotericin B with or without the addition of flucytosine and fluconazole.
  • Initiation or resumption of highly active antiretroviral therapy (HAART) in the presence of AIDS-defining disease is essential to successful long-term therapy, and life-long maintenance with fluconazole is usually indicated.
  • Mucormycosis is a rare opportunistic fungal infection caused by mucorales.
  • It was first reported in humans by Paultaufin in 1885.
  • It is also known as zygomycosis or phycomycosis.
  • Three common genera of mucorale which cause this disease in human include rhizopus, rhizomucor and absidia. 
  • The organism implicated to cause mucormycosis is a saprophytic fungus, mainly rhizopus or mucor.
  • It is the most deadly and rapidly progressive form of fungal infection affecting humans.

Oral mucormycosis is usually caused by inhalation of spores or direct contamination of open oral wound.

Predisposing factors:

  • Diabetes mellitus.
  • Leukemia on chemotherapy
  • Chronic obstructive pulmonary disease treated with steroid therapy
  • Diabetes mellitus along with leukemia. 
  • Clinical presentation of mucormycosis depends upon the site of entry of micro-organism and the organ systems involved.
  • The most common form includes rhinocerebral, which involve the nose, paranasal sinuses, orbits and central nervous system.
  • Other forms of mucormycosis are cutaneous, gastrointestinal, pulmonary and disseminated.
  • Mucormycosis of the oral cavity can be of two different origins:
  1. One is from disseminated infection where the gateway of entry is inhalation (through the nose).
  2. Other is through direct wound contamination with dissemination to other viscera as a common complication.

Clinical features:

  • Non-healing extraction site.
  • Edema of face
  • Alveolar bone necrosis with palatal ulcer
  • Nasal discharge/blockage
  • Paresthesia of lower lip
  • Facial paresthesia
  • Trismus
  • Headache

Further spread of infection result in orbital involvement causing:

  • Chemosis (edema of conjunctiva).
  • Epiphora (excessive watering of eye).
  • Diplopia (double/blur vision).
  • Ptosis (drooping of upper eyelid).
  • Proptosis (protrusion of eye ball).
  • Ophthalmoplegia (paralysis of eye muscles).
  • Vision loss.

Radiograph:

  • Opacification of sinuses may be noticed in conjunction with patchy effacement of bony walls of sinuses.
  • CT with contrast or magnetic resonance image scan can demonstrate erosion or destruction of bone.
  • Histopathologically, the lesion demonstrates broad aseptate fungal hyphae that show branching at right angles.

squamous cell carcinoma, chronic granulomatous infection such as tuberculosis, tertiary syphilis, midline lethal granuloma, and other deep fungal infections.

  • Combination of surgical debridement of the infected area and systemic administration of Amphotericin B for 3 months.
  • Proper management of the underlying condition is also an essential aspect affecting the outcome of the treatment.
  • Caused by Geotrichum candidium which is a component of the normal microflora of the skin and the mucosa of the respiratory and digestive tracts.
  • It can also be isolated from vegetables, fruits, soil and plants.
  • Oral lesions are caused by  candidum and G. capitatum.

The infection caused by Geotrichum species of fungi is known as geotrichosis.

Predisposing factors:

  • Diabetes mellitus.
  • Acquired immunodeficiency syndrome.
  • Patients with organ transplantation.
  • Hematolymphoid malignancies.

Three clinical varieties:

  1. Pseudomembranous
  2. Hyperplastic
  3. Ulcerative
  • Geotrichosis can present as pseudomembranes, mucosal ulcerations, edematous and erythematous gingivae.
  • Easily scrapable creamy-white pseudomembranous plaques with an erythematous background seen on the tongue, resulting in glossitis and on the cheeks.
  • The most common symptoms are burning pain and impaired swallowing.
  • Angular cheilitis and palatal ulcers.
  • Palatal ulcers can result in a very aggressive palatine- cerebral condition with poor prognosis.
  • Direct examination and staining will reveal multiple septate hyphae with rectangular arthroconidia.
  • Some arthroconidia may have rounded appearance (clavata cells) and may be easily mistaken for Candida. Hence culture is recommended for the accurate diagnosis.
  • In culture G. candidum and G. capitatum are seen as white, membranous, villous, wet colonies.
  • In chromogenic culture media their villous wet growth with slight pink pigmentation distinguishes them from the major Candida species.
  • Molecular biology is the most accurate technique for species identification by internal transcriber spacer (rDNA).
  1. What is treatment of Geotrichosis?

Use of intravenous liposomal amphotericin B (3 mg/kg) sequentially with an oral azole, e.g., voriconazole(400 mg/day) may be a promising strategy for the long-term treatment of invasive cutaneous geotrichosis.

  • It is a subacute or chronic implantation (formerly subcutaneous) fungal infection, related to dimorphic fungi included within the Sporothrix schenckii
  • The infection is commonly caused by inoculation of the fungus that lives in the soil, plants, and decaying material; therefore, disease is known as “rose gardener’s disease”
  • The largest number of infections occurs in the autumn and winter, where the relative humidity is higher in most endemic countries.
  • Sporothrix schenckii(sl) lives in soil and environments high in cellulose, grasses, organic matter, wood, sphagnum moss, leaves and branches.
  • HIV-AIDS.
  • Chronic alcoholism.
  • Hematologic cancer (leukemia and lymphomas).
  • Diabetes mellitus.
  • Steroid treatment.
  • Transplanted patients.
  • Malnutrition
  • Slight male predominance.
  • Cutaneous sporotrichosis comprises three distinct clinical forms:
  1. Cutaneous-lymphatic sporotrichosis: It is usually located in upper limbs, lower limbs and the face. It is formed by linearly distributed, painful or pruriginous ulcerated nodules that in chronic stages may develop verrucous plaques.
  2. Cutaneous-fixed sporotrichosis: which occurs in the same inoculation site (called sporotrichoid chancre), usually consisting of an asymptomatic, sole, vegetative, or slow-growing verrucous lesion, and a squamous, erythematous or violaceous halo.
  3. Cutaneous-disseminated sporotrichosis: Also called hematogenous sporotrichosis that usually seen in immunocompromised patients. Appear as ulcerated nodules and verrucous plaques found affecting any part of the body surface and even mucous membranes. It may affect bones and joints, producing small granulomatous lesions or even extensive lytic lesions and osteomyelitis. Most affected bones are tibia, carp and metacarpus, ulna, knee and ankle.

Extracutaneous Sporotrichosis

Classified into two clinical types

  1. Types 1: The chronic type (most common), usually asymptomatic (98%), it presents with limited cavitary zones, indistinguishable from tuberculosis; symptomatic cases manifest as pneumonia, with little cough and expectoration. The radiographs show areas of condensation, or infiltrated milliard.
  2. Type 2: The acute and progressive type, involves tracheobronchial lymph nodes, developing massive adenopathies, which may derive into bronchial obstruction; common symptoms are cough with abundant expectoration, dyspnea and fatigue. Chest X ray shows parahilar lymphadenopathy and, less commonly, mediastinal enlargement. 

Central nervous system involvement manifests as meningoencephalitis and hydrocephalus, clinical symptoms include headache, fever, neck stiffness, mental confusion and vomiting.

  • Occurs secondary to disseminated disease from the skin or lung.
  • Oral lesions can manifest in various forms such as erythematous, ulcerative, suppurative, granulomatous, vegetative or papillomatous.
  • The oral lesions are usually painful and heal without scarring.
  • Regional lymphadenopathy.
  • Direct examinations and staining are not useful in cutaneous-lymphatic and cutaneous-fixed sporotrichosis, since yeasts are observed only in a low percentage (5%–10%),
  • In cases of cutaneous-disseminated, disseminated and pulmonary sporotrichosis, Gram, Giemsa, Periodic Acid–Schiff (PAS) and Gomori-Grocott stains are useful as well as immunofluorescence techniques.
  • Yeast forms are usually round, oval or lengthened, described as “cigar-shaped” in immunocompromised patients, large clusters of yeast are observed.
  • Cultures from exudative lesions, scale, tissue fragment, sputum and blood are the gold standard for diagnosis.
  • Sabouraud dextrose agar with and without antibiotics, incubated at 28 °C is often useful.
  • Histopathology is useful for cutaneous-lymphatic and cutaneous-fixed sporotrichosis diagnosis.
  • Other useful tests are precipitins, agglutinins and complement fixation; the intradermal reaction with sporotrichin 
  • To identify the fungus in tissues, exudates and culture, PCR and PCR-RFLP (chitin-synthetase gene, ChS1, 26S rDNA gene and topoisomerase II gene) are helpful.
  • For cutaneous-lymphatic and cutaneous-fixed sporotrichosis, potassium iodide can be administered in diluted solutions or in drops of saturated solution. Itraconazole at 200 mg/day for 3–6 months.
  • For cutaneous-disseminated, disseminated, pulmonary and osteoarticular sporotrichosis, the drug of choice is amphotericin B, preferably lipidic at 3–5 mg/kg/day and if the deoxycholate form is used, recommended doses are 0.7 to 1 mg/kg/day; the treatment duration varies depending on the response and side effects (mainly renal damage).
  • After intensive and aggressive treatment, the maintenance therapy is itraconazole at 400 mg/day (divided in two doses).
  • In HIV-AIDS or immunosuppressed patients, itraconazole can be administered at 200 mg/day for a long time to avoid relapses.
  • For fungemia and central nervous system involvement, high doses of amphotericin B (lipid 5 mg/kg/day and deoxycholate 1 mg/kg/day) are used, continuing with itraconazole between 200 and 400 mg/day for at least one year.
  • It is a systemic disease caused by Histoplasma capsulatum, a dimorphic fungus.
  • It was first identified by Samuel Darling in 1905, hence known as Darling’s disease.
  • Disease is acquired by inhalation of dust particles from the soil, contaminated with bat or bird feces, which contain fungal spores, the infectious form of the microorganism.
  • It can be found in hot and humid environments, with a predilection for areas with acid soils.
  • After contagion of the airways, the microconidia are phagocytosed by macrophages and start to replicate intracellularly.
  • Histoplasmosis has been reported in all continents, particularly in temperate regions.
  • It is an endemic disease in some areas such as Ohio, Mississippi River Valley, Central and South America and Africa.

Organisms have a special predilection for the reticuloendothelial system

  • Chronic low-grade fever.
  • Productive cough.
  • Splenomegaly
  • Hepatomegaly
  • Lymphadenopathy
  • Anemia and leucopenia.
  • Calcified pulmonary nodules.
  • Oral lesions occur as granular ulcerations, multiple painful ulcers and verrucous growths, deep ulcers surrounded by infiltrative edges with erythematous or white areas with irregular surfaces, as hardened and irregular nodular lesions accompanied by local lymphadenopathy, mimicking other infectious diseases or malignant tumors.
  • The sites commonly involved in the oral cavity are the tongue, the palate, the oral mucosa, the gingivae, and the pharynx.
  • Sore throat, hoarseness of voice, and dysphagia.
  • Histoplasmosis can be diagnosed based on clinical signs and symptoms, histopathology, cultures, serologic test, including compliment fixation test, immunodiffusion, and histoplasmin skin test.

Histologic findings:

  • Diffuse lymphohistiocytic infiltrates with fungal elements about 2–4 µm in size detected within the cytoplasm of histiocytes.
  • Special stains, such as GMS and PAS methods will highlight the fungal organisms’ cell wall.
  • A classic “halo” appearance caused by the cytoplasm retracting from the thick cell wall is helpful in identifying the fungi.

Squamous cell carcinoma, hematologic malignancies, tuberculosis, other deep fungal infections, oral lesions observed with Crohn’s disease, necrotizing sialometaplasia of the palate, and chronic traumatic ulcers.

  • The disease is self-limiting in immunocompetent patients.
  • Amphotercin B, at a dose of 2 gms IV for 10 weeks, is used in the management of pulmonary histoplasmosis, in HIV patients.
  • Immunocompetent patients without AIDS, amphotercin B is effective by 68-92%, itraconozole by 100%, and ketaconozole by 56-70%, whereas, in patients with AIDS, amphotercin B is effective by 74-88% and itraconozole by 85%.
  • Itraconozole has rapid action and is effective in preventing a relapse.
  • First case of Rhinosporidiosis was reported by Malbron of Buenas Aires in 1892.
  • Seeber in 1990 first described in detail about the microorganism causing Rhinosporidiosis.
  • The life cycle of the microorganism causing Rhinosporidiosis was given by Ashworth in 1923.
  • Rhinosporidiosis (RS) is a chronic, noncontagious sporadic disease caused by Rhinosporidium seeberi.
  • It is a cosmopolitan disease of human and domestic animals, prevalent in hot tropical climate of endemic zones like India, Sri Lanka, East Africa, parts of America and also encountered among expatriate population in the West.
  • Water and soil are the main reservoirs of infection and the endospores are transmitted through water and dust into the nasal mucosa by traumatic inoculation where they mature subepithelially and after maturation burst with release of sporangia into the tissues.
  • Males are commonly affected compared to females (4:1 ratio).
  • Occur at any age but frequently encountered between 20 and 35 years. Predominantly affects the mucus membranes of nose and nasopharynx.
  • Cutaneous lesions appear as pedunculated or sessile growths, verruca vulgaris like lesions, friable nodular lesions, subcutaneous swellings, furunculoid lesions, cutaneous horn, shiny globular swellings, cutaneous ulceration and cystic swellings.
  • It also involves lips, palate, uvula, maxillary antrum, conjunctiva, lacrimal sac, epiglottis, larynx, trachea, bronchus, ear, scalp, skin, penis, vulva, and vagina.
  • RS is characterized by a reddish, friable, polypoidal, hyperplastic mass mostly occurring in the nasal cavity and nasopharynx.
  • Rhinosporidiosis involving parotid duct manifests itself as a facial swelling.
  • Oronasopharyngeal lesions appear as soft, red (vascular) polypoid growth.

Nasopharyngeal angiofibroma, is a vascular tumor-like lesion occurring in the nasopharynx may extend into the oral cavity.

  • Diagnosis can be made by histopathology.
  • Microscopically, the organisms appear as sporangia containing large numbers of round or ovoid endospores, each measure approximately 5-7 µ in diameter. The surrounding connective tissue shows vascular granulation tissue and mixed inflammatory cells.
  • Contrast computed tomography (CT) scan to delineate extent of the lesion.
  • Contrast MRI to demarcate the extent and it appeared as an intensely enhancing lesion in the respective area.
  • Complete excision with wide surgical margins to reduce recurrence is the treatment of choice.
  • Antifungal agents such as griseofulvin and amphotericin B.
  • Treatment with the drug dapsone (diaminodiphenylsulphone, 100 mg, OD).
  • Paracoccidioidomycosis (PCM), also known as South American blastomycosis,Lutz’s disease is a chronic mycosis caused by Paracoccidiooides brasiliensis.
  • PCM more commonly affects farm workers and/or people who live in rural areas.
  • Affects between 30 and 50 years of age, particularly males.
  • The disease is more prevalent in South and Central Americas, especially in regions with wet climate, high rainfall, and acid soils.

PCM manifests firstly in lungs, and later may spread systemically, affecting:

  • Lymph nodes.
  • Skin
  • Oral and nasal mucosae.
  • Adrenal glands.
  • Gastrointestinal tract.
  • Central nervous system through lymphatic and blood vessels.
  • Expectoration, cold, dyspnea, thoracic pain, fever, hemoptysis, anorexia, and weight loss. 
  • Regional lymphadenopathy.
  • Oral lesions commonly affect gums, palate, and labial and buccal mucosae.
  • The oral lesions had a characteristic appearance with a granular purpuric surface.
  • The upper gingiva is typical site, but lesions were also seen in the palate, tongue, and buccal mucosa.
  • Exfoliative cytology.
  • Serological investigation.
  • Molecular assays, like enzyme-linked immunosorbent assay and polymerase chain reaction.
  • Difference between North American and South American blastomycosis is in the size of the causative organisms.
  • The fungus in the South American form of the disease varies between approximately 10µand 60µ in diameter, being considerably larger than that of the North American disease.
  • Also K/a Gilchrist disease.
  • First observed in Baltimore in 1894 by Gilchrist.
  • Infection caused by the hypomcete, Blastomyces dermatitidis, and is characterized by suppurating and granulomatous lesions of the skin, subcutaneous tissues, lungs, bones (particularly the vertebrae and ribs), liver, spleen, kidneys, and the central nervous system.
  • More common in men than in women.
  • Occurs in middle age group.
  • Fever
  • Sudden weight loss.
  • Productive cough (lung involement).
  • Chest pain.
  • Fatigue (extreme tiredness).

Skin lesions:

  • Begin as small red papules which gradually increase in size and form tiny military abscesses or pustules which may ulcerate to discharge the pus through a tiny sinus.
  • Crateriform lesions are typical and these often exhibit indurated and elevated borders.
  • Oral lesions of North American blastomycosis may be more common than has been believed.
  • Oral lesions may be the first noticed manifestation of the disease.
  • Oral lesions of North American blastomycosis are secondary to primary pulmonary involvement.
  • Oral lesions occur most often as single or multiple ulcerations. They may, however, appear as verrucal lesions, as draining lesions, or as radiolucencies in the maxilla or mandible.
  • The clinical presentation, physical exam, and the radiographic manifestations are non-specific.
  • Sputum or tissue samples stained with 10% potassium hydroxide, calcofluor white, Gomori methenamine silver (GMS) or periodic acid-Schiff (PAS) can facilitate visualization of the characteristic Blastomyces
  • Culture of Blastomycesprovides a definitive diagnosis.
  • Classic antibody testing by complement fixation (CF) or immunodiffusion (ID) is not clinically useful for the diagnosis of blastomycosis due to poor sensitivity and specificity.
  • A newer enzyme immunoassay (EIA) that uses microplates coated with BAD1 protein has enhanced sensitivity.
  • As BAD1 is unique to Blastomyces, BAD1 assays can distinguish between histoplasmosis and blastomycosis.
  • Antigen assay that detects a galactomannan component in the cell wall of Blastomyces has supplanted CF and ID, and can be used to test urine, serum, BAL fluid, and CSF specimens.

Histopathological features:

  • The inflamed connective tissue shows occasional giant cells and macrophages and the typical round organisms, often budding, which appear to have a doubly refractile capsule.
  • Organisms, usually measuring between 5µ and 15µ in diameter, are common within giant cells.
  • Microabscesses are frequently found.
  • If the lesions are not ulcerated, overlying pseudoepitheliomatous hyperplasia may be prominent.

Site of Infection

Disease severity

Initial therapy

Step-down therapy

Pulmonary blastomycosis

Mild to moderate

Oral itraconazole 200mg 3× daily for 3 days and then 1× or 2× daily for 6–12 months.

Not applicable

Moderately severe to severe

Lipid formulation of AmB 3–5mg/kg daily or AmB deoxycholate 0.7–1 mg/kg daily for 1–2 wks or until improvement is noted

Oral itraconazole 200mg 3× daily for 3 days and then 2× daily for 6–12 months

Disseminated or extrapulmonary blastomycosis

Mild to moderate

Oral itraconazole 200mg 3× daily for 3 days and then 1× or 2× daily for 6–12 months.

Not applicable

Moderately severe to severe

Lipid formulation of AmB 3–5mg/kg daily or AmB deoxycholate 0.7–1 mg/kg daily for 1–2 wks or until improvement is noted

Oral itraconazole 200mg 3× daily for 3 days and then 2× daily for at least 12 monthsa,b

Central nervous system disease

 

Lipid formulation AmB 5 mg/kg per day for 4–6 wks

Options include:

1) Oral fluconazole 800mg daily

2) Oral itraconazole 200mg 2× or 3× daily

3) Voriconazole (200–400 mg 2× daily)

Treatment should continue for at least 12 months and until resolution of CSF abnormalities

Immunocompromised patients

 

Lipid formulation of AmB 3–5mg/kg daily or AmB deoxycholate 0.7–1 mg/kg daily for 1–2 wks or until improvement is noted

Oral itraconazole 200mg 3× daily for 3 days and then 2× daily for at least 12 months.

Pregnant women

All disease

Lipid formulation of AmB 3–5 mg/kg per day

Azoles should be avoided due to risks of teratogenicity and spontaneous abortion

Newborn

All disease

AmB deoxycholate 1.0 mg/kg per day

Not applicable

Children

Mild to moderate (non-meningeal)

Oral itraconazole 10 mg/kg per day (max of 400 mg/d) for 6–12 months.

Not applicable

Severe

AmB deoxycholate 0.7–1.0 mg/kg daily or lipid AmB at 3–5 mg/kg daily until improvement

Oral itraconazole 10 mg/kg per day (max of 400 mg/d) for 12 months.

  • Aspergillosis is second most prevalent opportunistic fungal infection.
  • Aspergillus species are universally found in humid areas, damp soil, grain, cereal, mouldy flour and organic decaying or decomposing matter.
  • In India, the most common species encountered is A. flavus followed by Aspergillus fumigatus and A. niger.

Three chief variants:

  • Invasive
  • Non-invasive.
  • Non-invasive destructive type.

Invasive type: represents true fungal tissue invasion that can be either slow progressive and destructive (non-fulminant) or highly aggressive and lethal (fulminant).

Non-invasive type: Further classified into Aspergilloma, Fungal ball, Mycetoma (usually affecting one sinus) or allergic Aspergillus sinusitis (involving more than one sinus).

Destructive non-invasive: Variant is locally destructive but shows no tissue invasion.

  • Occurs after inhalation of spores, that can result in both upper and lower respiratory tract infection- bronchopulmonary aspergillosis.
  • From lungs, infections may spread to the brain, bone or endocardium.
  • Paranasal sinuses, larynx, eyes, ears and the oral cavity may be involved in primary aspergillosis.
  • Fumigatus is the usual agent of sinus aspergillosis, whereas A. flavus is more common in invasive lesions in immunosuppressed individuals.
  • Orofacial aspergillosis is relatively common in patients undergoing treatment for malignancies of the blood and blood-forming organs.
  • Aspergillus does not contain chlorophyll, thus light is not required for growth.
  • Aspergillus exhibits a centrifugal linear growth unless inhibited by natural or artificial barriers. This is why Aspergillus in the paranasal sinus eventually develops into a ball-shaped mass.
  • The centre of the mass contains calcium phosphate and therefore mimics a foreign body on radiography.
  • Oral aspergillosis lesions are yellow or black in color, with a necrotic ulcerated base, classically located on the palate or posterior tongue.
  • Aspergillus hyphae invade host tissues through the release of various toxins. These include various proteases, phospholipases, hemolysins, gliotoxin, aflatoxin, phthioic acid and other toxins.
  • The hyphal elements of the fungus may invade the oral mucosa and penetrate the walls of small to medium-sized blood vessels, producing thrombosis, infarction and necrosis, finally leading to systemic spread.
  • Histopathologically, invasive lesions show chronic granulomatous reactions.
  • In hematoxylin and eosin-stained sections hyphal forms can be seen faintly in the center of an area of necrosis.
  • The fungi appear as septate hyphae, showing branching at 45° angles and are about 2-4 mm in diameter.
  • Conidiospores and fruiting bodies are also seen.
  • This fungus should be differentiated from mucor which shows broader non-septate hyphae with branching at 90°.
  • Vericonazole:

IV 6 mg/kg q 12h on day 1, then 4 md/kg q 12 h.

Oral  form: 200mg q12h.

  • L-AmB (Liposomal Amphotricin B): 3-5mg/kg/day IV.
  • ABLC (Amphotericin B lipoid complex): 5 mg/kg/day IV.
  • Caspofungin: 70 mg IV day 1, then 50 mg/day.
  • Micafungin: 100-150 mg/day IV.
  • Posaconazole: 200 mg 4 times/day po; after stablilization, 400 mg BID po.
  • Itraconazole:

 I V – 200 mg q 12h for 2 days then 200 mg/day.

Oral form: 600 mg/day for 3 days, then 400 mg/day. 

  1. LABORATORY DIAGNOSIS

Specimens for the diagnosis of mycoses include: skin scrapings, oral scrapings, vaginal scrapings, corneal scrapings, hair and nails, blood, cerebrospinal fluid, urine, sputum, bronchial lavage specimens, pus and tissues.

Causative agents of mycoses can be identified by following methods:

A. Direct Microscopy

  1. Potassium hydroxide (KOH) preparation: Specimens can be examined satisfactorily in wet mounts after partial digestion of the tissue with 10-20% potassium hydroxide. The alkali digests cells and other tissue materials, enabling the fungus elements to be seen clearly.
  2. Newer preparations for the KOH test may provide easier and more reliable results. These preparations incorporate dimethyl sulfoxide (DMSO) and a stain into the KOH solution. The DMSO facilitates more rapid breakdown of cellular debris without requiring heat while the stain is taken up by fungal elements, making them readily visible upon microscopic examination of the slide preparation.
  3. Potassium hydroxide (KOH) with Calcofluor white: Addition of Calcofluor white and subsequent examination by fluorescence microscopy enhances the detection of most fungi since the fluorescent hydroxide-calcofluor binds to the fungal cell walls.
  4. Gram staining: Gram films may also be used for the diagnosis of yeast infections of mucous membranes.
  5. India ink preparations: Used for detecting encapsulated yeast Cryptococcus neoformans in cerebrospinal fluid (CSF).
  6. Histology: Common tissue stains used for detection of fungal elements are the periodic acid-Schiff (PAS), Grocott-Gomori methenamine-silver (GMS), hematoxylin and eosin (H and E), Giemsa, and the Fontana-Masson stains, are based on the presence of chitin and polysaccharides in their cell wall.

B. Culture

  1. Culture media: The commonest culture media used in mycology, Sabouraud’s dextrose agar (SDA, pH 5.4), SDA with antibiotics, potato dextrose or the slightly modified potato flakes agar (PFA), and brain heart infusion (BHI) agar with blood and antibiotics.
  2. Incubation: Cultures are routinely incubated in parallel at room temperature 25°C (room temperature for weeks) and at 37°C for days. Many fungi develop relatively slowly and cultures should be retained for at least 2-3 weeks (in some cases up to 6 weeks) before being discarded. Yeasts usually grow within 1-5 days.

2. IDENTIFICATION OF FUNGI

Once an organism has grown, it is examined for characteristic gross and microscopic structures, so that identification can be made.

A. Gross or macroscopic examination of cultures: Growth characteristics useful for identification are the rapidity of growth, color and morphology of

the colony on the obverse and pigmentation on the reverse. Molds are identified by their macroscopic and microscopic morphology.

B. Microscopic examination: Microscopic characteristics that should be observed are the following:

  • Septate versus sparsely septate hyphae
  • The types, size, shape, and arrangement of conidia.
  • Hyaline or dematiaceous hyphae.
  • Fruiting structures.
  1. MISCELLANEOUS TESTS FOR THE IDENTIFICATION OF YEASTS:
  • Germ tube production, carbohydrate assimilation, chromogenic substrates, corneal agar, potassium nitrate assimilation, temperature studies, and urease.
  • Both Candida albicans and Candida dubliniensis are identified by germ-tube production.
  1. SEROLOGIC TESTS

The most common tests for:

A. Fungal antibodies:

  1. Immunodiffusion.
  2. Countercurrent immuno-electrophoresis (CIE).
  3. Whole cell agglutination.
  4. Complement fixation.
  5. Enzyme-linked immunosorbent assay (ELISA).

B. Antigen detection:

  1. Latex particle agglutination;
  2. ELISA

5 .POLYMERASE CHAIN REACTION (PCR):

Detection of fungal DNA in clinical material, principally blood, serum, broncho-alveolar lavage fluid and sputum, is increasingly used for diagnosis.

It is defined as the initiation of antifungal treatment in an individual at high risk for an invasive fungal infection and manifesting symptoms and/or signs of an infection but without microbiological documentation of the infection. Empiric therapy utilizes a broad-spectrum antifungal agent for 3 or more days until de-escalation is possible based upon the specific infection identified, its location, and the patient’s clinical status.

It is defined as the use of an antifungal agent with intent to prevent the likelihood of an invasive fungal infection in an individual at high risk for such an infection.

It is defined as the initiation of antifungal therapy based upon the results of an early diagnostic test.

  1. Antibiotics

A. Polyenes: Amphotericin B (AMB), Nystatin, Hamycin

B. Echinocandins: Caspofungin, Micafungin, Anidulafungin

C. Heterocyclic benzofuran: Griseofulvin

2. Antimetabolite Flucytosine (5-FC)

3. Azoles

A. Imidazoles:

Topical: Clotrimazole, Econazole, Miconazole, Oxiconazole.

Systemic: Ketoconazole

B. Triazoles(systemic):

 Fluconazole, Itraconazole, Voriconazole, Posaconazole

  1. Allylamine Terbinafine.
  2. Other topical agents

Tolnaftate, Undecylenic acid, Benzoic acid, Quiniodochlor, Ciclopirox olamine, Butenafine, Sod. thiosulfate.

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