SUBCUTANEOUS MYCOSES SUBCUTANEOUS MYCOSES • The agents of subcutaneous mycoses usually inhabit the soil • They enter the skin by traumatic inoculation with contaminated material • Tend to produce granulomatous lesions in the subcutaneous tissue MYCETOMA • Chronic, slowly progressive granulomatous infection of the skin and subcutaneous tissues • Triad: Swelling, discharging sinuses and presence of granules in the discharge • A lso known as Maduramycosis or Madura foot, as it was first described in Madurai, South India, by John Gill (1842) Types of Mycetoma and Causative Agents • Eumycetoma – caused by fungi • Actinomycetoma – Caused by bacteria • Botryomycosis - mycetoma like condition caused by some bacteria such as Staphylococcus aureus. Organisms causing Mycetoma Eumycetoma Black granulesMadurella mycetomatis Madurella grisea Exophiala jeanselmei Curvularia species White granulesPseudallescheria boydii Aspergillus nidulans Acremonium species Fusarium species Actinomycetoma White to yellow granulesNocardia species- Most common agent Streptomyces somaliensis Actinomadura madurae Pink to red granulesActinomadura pelletieri Pathogenesis • Accidental trauma (thorn prick or splinter injury)  Organisms enter the skin or subcutaneous tissue from contaminated soil  micro abscesses by polymorphs  chronic granulomatous tissue in skin and subcutaneous tissues Clinical Manifestations • Clinical triad 1. Tumor like swelling (tumefaction) 2. Discharging sinuses 3. Discharge oozing from sinuses containing granules • Commonest site – Feet • Osteolytic or osteosclerotic bony lesions • Usually painless Eumycotoma v/s Actinomycotoma Features Tumor Sinuses Discharge Grains Bone Grains contain Eumycotoma Actinomycotoma Single, well defined margins Multiple tumour masses with ill defined margins Appear late, few in number Appear early, numerous with raised inflamed opening Serous Purulent Black/white White/ red Osteosclerotic lesions Osteolytic lesions fungal hyphae (>2um) Filamentous bacteria (< 2um) Epidemiology • Endemic in Africa, India, the Central and South America • Globally Actinomycetoma is more common (60%) than eumycetoma (40%) • Eumycetoma is more common in Africa • In India, Rajasthan reports the maximum cases of mycetoma per year followed by Tamil Nadu and West Bengal • Actinomycetoma predominates in India (65%), except in Rajasthan where eumycetoma is more common Laboratory Diagnosis • Specimen Collection • Grains collected on sterile gauze by pressing the sinuses from periphery or by using a loop • Direct Examination • Granules washed in sterile saline; crushed between the slides and examined • Macroscopic appearance of granules - color, size, shape, texture Laboratory Diagnosis • Suspected Eumycetoma : - KOH mount - hyphae of 2–6 μm width along with chlamydospores at margin • Suspected Actinomycetoma: - Gram staining - filamentous gram positive bacilli (0.5– 1 μm wide) - Modified acid fast stain – Nocardia is weekly acid fast Histopathological staining of the granules • Eumycetoma: granulomatous reaction with palisade arrangement of hyphae in the cement substance (A) • Actinomycetoma: granulomatous reaction with filamentous bacteria at the margin (B) A B Culture • Granules - best specimen for culture • Both fungal (SDA) and bacteriological media (Lowenstein Jensen medium, Blood agar) inoculated • Eumycetoma agents - growth rate, colony morphology, production of conidia and their sugar assimilation patterns • Agents of actinomycetoma - growth rate, colony morphology, urease test, acid fastness and decomposition of media containing casein, tyrosine, xanthine, etc Treatment • Surgical removal of the lesion followed by: Antifungal agents for eumycetoma (itraconazole or • amphotericin B for 8–24 months) • Antibiotics for actinomycetoma such as Welsh regimen (amikacin plus cotrimoxazole) SPOROTRICHOSIS • Also known a Rose Gardner’s disease • Subcutaneous noduloulcerative lesions • Caused by Sporothrix schenckii, thermally dimorphic fungus • Pathogenesis • Minor trauma by thorn prick or splinter injury  Spores of S.schenckii introduced into skin  Fungal Enzymes help in local invasion  spread along the lymphatics Clinical Manifestations • Chronic subcutaneous pyogranulomatous disease • Incubation period - about 3 weeks • Lymphocutaneous type: most common type (80%) - Painless noduloulcerative lesions (sporotrichoid pattern ) along the lymphatics - Enlarged Lymph nodes, indurated and have cord like feeling on palpation Other clinical types • Osteoarticular type: seen among alcoholics • Pulmonary type: following spore inhalation, seen in people with COPD • Disseminated sporotrichosis: in immunocompromised patients (AIDS) • Fixed cutaneous type: Single nodule is found, that is less progressive and does not spread by lymphatics Sporotrichoid lymphocutaneous infection • Syndrome characterized by the development of superficial cutaneous lesions that progress along dermal and subcutaneous lymphatics • Common causes: Sporothrix schenckii, Nocardia brasiliensis, Mycobacterium marinum or Leishmania brasiliensis • Rare causes: Coccidioidomycosis, cryptococcosis, blastomycosis, histoplasmosis, anthrax, Burkholderia pseudomallei, lepromatous leprosy, lupus vulgaris, Francisella tularensis and cowpox virus Epidemiology • Tropical countries with high humidity • World: Central South America, South Africa and India • India: Sub Himalayan hilly areas of northeast states ranging from Himachal Pradesh to Assam - Other endemic foci - northern Karnataka and southern Maharashtra • Source: Decaying vegetations (wood, bark, leaves), and soil • Risk factors - people walking bare foot, certain occupations such as farmers and gardeners Laboratory Diagnosis • Specimens - pus, aspirate from nodules, curettage or swabbing from ulcers • Direct microscopy: KOH mount or calcofluor staining  elongated yeast cells of 3–5 μm in diameter • Histopathological staining of tissue sections - cigar-shaped asteroid bodies • Asteroid body - central basophilic yeast cell surrounded by radiating extensions of eosinophilic mass, composed of antigen-antibody complexes (Splendore-Hoeppli phenomenon) Laboratory Diagnosis • • • • • • • • • • Culture: It is the most definitive tool for diagnosis. Specimens are inoculated onto SDA and blood agar in duplicate and incubated at 25°C and 37°C simultaneously, because S. schenckii is a dimorphic fungus . At 25°C: It produces mycelial form, consisting of slender delicate hyphae with conidia arranged in flower-like pattern (Fig. 52.11B) . At 37°C: It produces yeast form, characterized by moist creamy white colonies which turn brown black in 10–14 days. Sporothrix schenckii Yeast form (asteroid body) Mold form showing thin septate hyphae with flower-like sporulation Sporotrichosis • Serology: Latex agglutination test detects serum antibodies in patients with extracutaneous form of the disease • Skin test: delayed type of hypersensitivity reaction against sporotrichin antigen • Treatment Sporotrichosis • Itraconazole - drug of choice for all forms of sporotrichosis; except for disseminated form where amphotericin B is recommended • Duration: 2–4 weeks after the lesions resolve CHROMOBLASTOMYCOSIS • Slow growing chronic subcutaneous lesions caused by group of dematiaceous or phaeoid fungi (i.e. darkly pigmented fungi) that produce a characteristic morphology called sclerotic body • Agents of chromoblastomycosis: - Fonsecaea pedrosoi and F. compacta - Phialophora verrucosa - Cladosporium carrionii - Rhinocladiella aquaspersa. CHROMOBLASTOMYCOSIS • Lesions - slow growing and polymorphic - verrucose (most common type), crusted, ulcerative and nodular or tumor-like • Sclerotic bodies: brown thick walled round cells (5–12 μm size) with multiple internal transverse septa - also called Medlar bodies or muriform cells or “copper pennies.” CHROMOBLASTOMYCOSIS • Tropical or subtropical climates, often in rural areas • Treatment: - Surgical removal (cryosurgery or laser therapy) of the lesion followed by antifungals (itraconazole) PHAEOHYPHOMYCOSIS • Chronic subcutaneous lesions, caused by dematiaceous or phaeoid fungi other than that are described in chromoblastomycosis (i.e. they do not produce sclerotic bodies) • They exist in mycelial form • Caused by: - Alternaria species - Bipolaris species - Curvularia species - Exophiala jeanselmei - Cladophialophora bantiana (it is neurotropic, produces brain abscess) RHINOSPORIDIOSIS • Chronic granulomatous disease, characterized by large friable polyps in the nose conjunctiva and occasionally in ears, larynx, bronchus and genitalia • Agent: Rhinosporidium seeberi, an aquatic protistan parasite • Source: Stagnant water • Distribution: tropical countries, especially in Sri Lanka and India (Tamil Nadu, Kerala, Odisha and Andhra Pradesh) RHINOSPORIDIOSIS • D iagnosis - histopathology of the polyps  spherules (large sporangia up to 350 μm size, that contain numerous endospores, each 6–9 μm in size) • Stained better with mucicarmine stain • R.seeberi has not been cultivated yet RHINOSPORIDIOSIS • Treatment: • Radical surgery with cauterization is the mainstay of treatment • Dapsone • Recurrence is common