Subcutaneous Mycoses

Subcutaneous Mycoses Dr. R. Tan

Subcutaneous Mycoses these are chronic, localized infections of the skin and subcutaneous tissue following the traumatic implantation of the etiologic agent The causative fungi are all soil saprophytes (grow in soil or in decaying vegetation) of regional epidemiology whose ability to adapt to the tissue environment and elicit disease is variable Should be introduced into subcutaneous tissue in order to produce disease Lesions spread slowly from the implantation area Pathology is frequently the result of the interaction between host and pathogen, with contributions both from fungal invasiveness and from host responses the pathogens of subcutaneous mycoses have only a few common characteristics and belong to very different taxonomic groups

Mode of Transmission :  Direct subcutaneous inoculation via: Traumatic implantation  rose thorn  stepping on a stick Exposure of subcutaneous tissue to air  Burn  motor vehicle accident  Inhalation of airborne fungal cells, followed by implantation in paranasal sinuses or lungs  Iatrogenic intravenous catheter contaminated dressings

Disease

Causative Organism

Incidenc e

Chromoblastomyco sis

Fonsecaea, Phialophora, Cladosporium

Rare

Mycotic mycetoma

Rare

Rhinosporidiosis

Pseudallescheria, Madurella,  Acremonium, Exophiala Rhinosporidium seeberi etc.

Lobomycosis

Loboa loboi

Very rare

Sporothricosis

Sporothrix schenckii 

Rare

Very rare

SPOROTRICHOSIS Common name: “Rose Gardener’s Disease” etiologic agent: Sporothrix schenckii is primarily a chronic mycotic granulomatous infection of the cutaneous or subcutaneous tissues and adjacent lymphatics characterized by nodular lesions which may suppurate and ulcerate infections are caused by the traumatic implantation of the fungus into the skin (usually due to puncture by contaminated plant material e.g. wood splinters,thorns, sphagnum moss) very rarely, dessimination to the bones, muscles, central nervous system, lungs or genitourinary tract

porothrix schenckii rarely seen in pus and tissues from human infections yeastlike cells are of various sizes and shapes: appear as small, round to cigar shaped, and often have elongated gram (+) “pipe-stem” budding cells budding is on a narrow base rate of growth: rapid (mature within 5 days) thermally dimorphic Sabouraud’s Agar  Filamentous (mold) when cultured at 2530°C  Yeast when cultured at 35-37°C

Filamentous appearance olony morphology: Cream-colored to black, moist, wrinkled, leathery or velvety colonies with narrow white border develop within 3 – 5 days

icroscopic morphology: yphae are narrow, branching, and septate, with slender , tapering conidiophores rising at right angles

Yeast-like appearance incubated at 35-37°C Macroscopic: colonies are cream or tan, smooth and yeastlike Microscopic: budding yeast cells appearing as short, round, oval or cigarshaped

Pathogens & Clinical Finding: Fungus

Trauma

skin of extremities

pustule, abscess or ulcer lymphatics become thickened, cordlike multiple subcutaneous nodules and abscess along the lymphatics but infection in debilitated patient

usually has little systemic illness dissemination of the sometimes occur

Clinical manifestations: Fixed cutaneous sporotrichosis:  Presence of only 1 lesion  Primary lesions develop at the site of implantation of the fungus  usually at more exposed sites mainly the limbs, hands and fingers  Lesions often start out as a painless nodule which soon become palpable and ulcerate often discharging a serous or purulent fluid  Importantly, lesions remain localized around the initial site of implantation and do not spread along the lymphatic channels

Lymphocutaneous sporotrichosis  75% of cases of Sporotrichosis  Primary lesions develop at the site of implantation of the fungus  secondary lesions also appear along the lymphatic channels which follow the same indolent course as the primary lesion  Initially, a small, movable, nontender, subcutaneous nodule develop which becomes discolored; the overlying skin darkens to a reddish color and eventually blackens and ulcerates  No systemic symptoms are

Pulmonary sporotrichosis  This is a rare entity usually caused by the inhalation of conidia but cases of hematogenous dissemination have been reported  Symptoms are nonspecific and include cough, sputum production, fever, weight loss and upperlobe lesion  Hemoptysis may occur and it can be massive and fatal  The natural course of the lung lesion is gradual progression to death Osteoarticular sporotrichosis  Most patients also have cutaneous lesions and present with stiffness and pain in a large joint, usually the knee, elbow, ankle or wrist  Osteomyelitis seldom occurs without arthritis 

Treatment: In most Cases: self – limited infection Potassium Iodide  4-6 ml three time a day for 2-4 months orally  has therapeutic benefits in the cutaneous manifestations Extracutaneous forms of sporotrichosis may need a combination of antifungal treatment with Amphotericin B or itraconazole together with surgical debridement Control: Prevention of trauma in the following occupations: - gardeners - miners -

Chromoblastomycosis Chromomycosis/Chromoblastomycosis is caused by traumatic implantation of any of the several dematiaceous fungus specie into the subcutaneous tissue dematiaceous fungus  fungi that produce varying degree of melanin-like pigments  These pigments are found in the conidia and/or hyphae and give the organism a green, brown or black color Specie causing chromoblastomycoses 1) Fonsecaea pedrosoi - most common 2) Phialophora verrucosa - second most common 3) Cladosporium carrionii

Natural reservoir of these fungi  Soil  plant debris World-wide distribution but more common in bare footed populations living in tropical regions A slowly progressive granulomatous mycotic infection of the cutaneous and subcutaneous tissues caused by the traumatic implantation of fungal elements into the skin characterized by the development of tissue proliferation usually occurs around the area of inoculation producing crusted, verrucose, wart-like lesions

Morphology & Identification: In exudates and tissues appear as “scleotic bodies”  round, dark brown, thick walled, septate cell 5 – 15µm in diameter usually with a single septum or 2 intersecting septa  colonies vary in pigmentation form olive gray to brown to black (dematiacious fungi) so name because they produce melanin-like pigments

Fonsecaea pedrosoi colony morphology: surface is dark green, gray, brown to black covered with fuzzy or velvety surface 

Usually undistinguishable with other dematiaceous fungi

Microscopic morphology: hyphae are septate, branched, and brown; conidia are dark 4 types of conidial forms:

Fonsecaea type Conidiophores are septate and erect, distal end of conidiophore develop swollen dentricles

Rhinocladiella type Conidiophores are septate, erect and swollen, denticle bears 1°conidia at the tip & side

Cladosporium type Conidiophores are erect and give rise to large 1° conidia that in turn produce short, branching oval 2° conidia

Phialophora type Phialides are vase shaped w/ terminal cuplike collaretes, conidia accumulate

Phialophora verrucosa colony morphology: surface is dark gray, greenish brown to black with a close matlike olive to gray velvety to wooly mycelium  some strains are heaped and granular  others are flat Microscopic morphology: hyphae are brown, branched and septate  phialides - vase-shaped with round to oval conidia at the apex giving a vase of flower appearance

Cladosporium carrionii colony morphology: surface is dark , flat

with slightly raised center, covered with velvety dull gray short-napped mycelium

Microscopic morphology: septate hyphae, dark colored with lateral and terminal conidiophores Conidiophores produce long branching chains of brown, smooth-walled, oval somewhat pointed conidia

Pathogenesis & Clinical Findings: fungi introduced by trauma into the skin Lesions of chromoblastomycosis are most often found on exposed parts of the body and usually start a small scaly papules or nodules which are painless but may be itchy most common site:  legs  Feet dissemination to other parts of the body is rare Other prominent features include epithelial hyperplasia, fibrosis and microabscess formation in the epidermis

Satellite lesions may gradually arise and as the disease develops rash-like areas, enlarge and become raised irregular plaques that are often scaly or verrucose (wartlike) growth that extend along the lymphatics of the affected area with crusting abscesses In long standing infections, lesions may become tumorous and even cauliflower-like in appearance

Diagnostic Laboratory Tests: Specimen: Scraping or biopsy from lesions Microscopic Examination (a) Skin scrapings should be examined using 10% KOH = presence of dark brown, round fungus cells (sclerotic bodies) inside leukocytes or giant cell

(b) Tissue sections should be stained using H&E, PAS digest and Grocott's methenamine silver = showing characteristic dark sclerotic bodies

Treatment: - Flucytosine = 150ml/k/ day P.O - has achieved the most success - Itraconazole 400 mg/day for 6 to 12 months terbinafine 500 mg/ day - Successful surgical excision requires the removal of a margin of uninfected tissue to prevent local dissemination - skin grafting may be required

Mycetoma A mycotic infection of humans and animals induced by inoculation by a number of different actinomycetes and fungi Fungal mycetoma Aka: Madura foot, Maduromycosis Mycetoma characteristics:  Suppuration and abscess formation  Tumefaction and deformation of the tissue  draining sinus tracts containing granules  cardinal sign of mycetoma is the so-called “granule” (sometimes called “sulfa granule”) or “sclerotia” • • •

Are microcolonies of the fungi packed with tissue debris Appear as variety of colors (white, brown, yellow, black) like a grain of sand and gritty to the touch

the disease results from the traumatic implantation of

• world-wide distribution but most common in bare-footed populations living in tropical or subtropical regions Etiologic agents of Mycetoma: Actinomycotic Mycetoma  caused by actinomycetes (filamentous bacteria)  differentiated by biochemical test and chromatographic analysis of cell wall component n n n

Nocardia spp. Actinomadura spp. Streptomyces spp.

Mycotic Mycetoma (caused by the TRUE fungi) a) b) c)

d)

e)

Madurella mycetomatis - most cases worldwide Exophiala jeanselmei most common Pseudallescheria boydii (sexual state) etio. agent in Scedosporium apiospermum (asexual state) US Madurella grisea - common etiologic agent in South America Acremonium sp.

Morphology & Identification Actinomycotic mycetoma  granules (white, yellow, red) are composed of narrow intertwined filaments that are radially oriented and most numerous at the edge of the granule Mycotic Mycetoma  Granules ( white, yellow, red or black) are extruded in pus  the granules contain septate, variously shaped hyphae and depending on the species, may have longer, thickwalled cells at the periphery; and are often accompanied by numerous chlamydoconidia and swollen cells Black grains are generally fungal small white grains bacterial (nocardial) large white grains either fungal or bacterial

Madurella mycetomatis colony morphology: Colonies are slow growing, flat and leathery at first, white to yellow to yellowish-brown, becoming brownish, folded and heaped with age and the formation of aerial mycelia A brown diffusable pigment is characteristically produced in primary cultures

Microscopic morphology:  two types of conidiation have been observed: 1) flask-shaped phialides that bear rounded conidia 2) simple or branched conidiophores bearing pyriform conidia (3-5 um) with truncated bases

Exophiala jeanselmei colony morphology: surface is brownish black, or greenish black and skin-like; it then becomes covered with short velvety, grayish hyphae Microscopic morphology:  young culture consist of many yeast-like budding cells  septate hyphae form with numerous conidiogenous cells (annellides) that are slender, tubular, sometimes branched, and characteristically tapered to a narrow, elongated tip 

Conidia are hyaline, smooth, thin-walled, broadly ellipsoidal held in slimy gel at

Pseudallescheria boydii (Sexual state) colony morphology: : surface has a spreading, white, cottony aerial mycelium w/c later turns gray or brown Microscopic morphology:  large brown to black, spherical cleistothecia are formed  mostly submerged in the agar and consist of irregularly interwoven brown hyphae  When crushed, cleistothecia release faintly brown, ellipsoidal ascospores

Scedosporium apiospermum (Asexual state) Microscopic morphology:  numerous, single-celled, pale-brown broadly clavate to ovoid conidia, borne singly or in small groups on elongate, simple or branched conidiophores laterally on hyphae

Graphium eumorphum  the Graphium type of asexual conidiation is seen occasionally characterized by long, erect, narrow conidiophores that are cemented together, diverge at the apex, and bear clusters of oval,

Pathogenic & Clinical Findings: Causative agent introduced into subcutaneous tissue by trauma (usually foot, hand, back , head, neck, chest, shoulder and arms) ↓ start out as a small hard painless nodule which over time begins to soften on the surface and ulcerate to discharge a viscous, purulent fluid containing granules abscess may extend to muscle and bones

within the abscess, the granule is often surrounded by eosinophilic matrix representing host materials and antigen antibody complexes untreated lesions persist for years and extend deeper and peripherally causing deformity and loss of function Histologically - lesions resemble actinomycosis with prominent abscess formation, granulation tissue, necrotic foci and fibrosis

Diagnostic Laboratory Test: Clinical specimens for diagnosis:  pus -  with granules  tissue -  for histological examination Direct Microscopy:  Serosanguinous fluid containing the granules should be examined using 10% KOH  tissue sections should be stained using H&E, PAS digest, and Grocott's methenamine silver (GMS) Culture: Sabouraud’s agar  With the exception of Pseudoallescheria boydii, most agents of eumycotic mycetoma grow well on media containing cyclohexamide  Pseudoallescheria boydii is inhibited by cyclohexamide but grows well on Emmons' modification of Sabouraud’s medium

Treatment: Surgical draining assist in healing No established therapy for fungal mycetoma since drugs frequently do not penetrate the infected tissue well enough to reach the fungal pathogens Until recently, only surgical removal of the whole affected area was successful recent study:  Itraconazole yields the best results for the treatment of fungal mycetomas  Ketoconazole is an alternative  Amphotericin B – for Madurella infections  Nystatin and Potassium iodide – for P. boydii infections Control:

RHINOSPORIDIOSIS A chronic infection characterized by the development of polypoid masses of the nasal mucosa Etiologic agent: Rhinosporidium seeberi  Produce large spherules in lesions and in epithelial cell tissue cultures  Has not grown in vitro in culture media  Habitat: water, fish, aquatic insects 90% of cases are found in India and Sri Lanka More common in children and young adults  Many patients are divers

Lesions:  Found on the mucosa of the nose, nasopharynx, or soft palate as well as other mucocutaneous sites (conjunctiva, larynx, skin, genitalia and rectum)  initially flat, but develop into discolored, cauliflower-like polypoid masses varying in size

Laboratory Diagnosis: 

Histologic exam of infected tissue reveals epithelial hyperplasia, and a cellular infiltrate of neutrophils, lymphocytes, plasma cells, and giant cells

Treatment:  

Surgical removal Topically or local injection of ethylstilbamidine

LOBOMYCOSIS A chronic subcutaneous infection of humans and dolphins Etiologic agent: Loboa loboi Patients have been men, mostly adults Natural infection has been discovered in Atlantic bottle-nose dolphins off the coast of Florida and South America Initial lesions are small, hard, painless subcutaneous nodules, usually appearing on the extremities, face or ear presumably as a result of traumatic inoculation of the etiologic agent  Lesions become verrucose or ulcerative and resemble chromomycosis, mycetoma or carcinoma Lymph nodes are not involved

Laboratory Diagnosis: Direct microscopic examination of skin scrappings, biopsies, or wet preparation of exudative lesions  Appears as large, spherical, or oval yeasts (10µm in dm) that exhibit multiple budding and characteristically form short chains of 3-6 or more yeast cells  are multinucleated and thick-walled  Tissue sections reveal granulomatous nodules and occasional asteroid bodies Treatment:  Surgical excision  Sulfa drugs

The End Thank You!