Chromoblastomycosis
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Chromoblastomycosis is a chronic fungal infection caused by several soil fungi that are acquired through traumatic skin inoculation. It is characterized by the development of warty or tumor-like skin lesions, usually on the legs or feet, that resemble cauliflower. Diagnosis involves microscopic identification of sclerotic bodies in skin scrapings or biopsy specimens. Treatment can include antifungal drugs like itraconazole or terbinafine for 6-18 months, sometimes combined with surgery, cryotherapy or heat therapy. The infection is difficult to treat and cure rates are variable.
Chromoblastomycosis
- 1. Name: Purshotam Kumar Sah Kanu Roll No.: MB 1318/075 Level: M.Sc Microbiology (3rd Sem) Central Department of Microbiology Tribhuvan University, Kirtipur Kathmandu, Nepal MB 609 Systemic and Diagnostic Mycology
- 2. Introduction Chromoblastomycosis is a chronic fungal infection acquired through traumatic inoculation of an organism, primarily into the skin and subcutaneous tissue. The infection is characterized by the development of a papule at the site of the traumatic insult that slowly enlarges to form warty or tumorlike lesions characterized as resembling cauliflower capable of spreading through the lymphatic system. Secondary infection and ulceration may occur. The lesionsusually are confined to the feet and legs but may involve the head, face, neck, and other body surfaces.
- 3. The term chromomycosis includes chromoblastomycosis and phaeohyphomycosis caused by dematiaceous fungi.
- 4. Chromoblastomycosis • This disease, also known as chromomycosis,is a chronic, localized disease of the skin and subcutaneous tissues, characterized by crusted, warty lesions usually involving the limbs. • The disease is mainly encountered in the tropics. • Like mycetoma, the disease is seen most often among males in rural areas. Chromoblastomycosis is a slowly progressing granulomatous infection caused by several soil fungi. These are Fonsecaea pedrosoi, Fonsecaea compactum, Cladosporium carrionii, and Phialophora verrucosa.
- 5. Cont.. These fungi are collectively called dematiaceous fungi because they have brown to black melanin pigment in their cell wall, and their conidia or hyphae are dark colored, either gray or black. All the fungi causing chromoblastomycosis appear morphologically similar in tissues stained by hematoxylin and eosin (H and E) or other stains. The infection occurs following introduction of any of the dematiaceous fungi into the skin through trauma. The development of warty nodules that appear at site of inoculation characterizes chromoblastomycosis.
- 6. Cont.. During the course of infection, these lesions vegetate and develop to a cauliflowerlike lesion. The disease is more common in tropical and subtropical countries.
- 7. Etiological Agents The etiological agents are soil inhabiting fungi of the family Dematiaceae. All are dematiaceous fungi, having melaninized cell walls. These include: Phialophora verrucosa,Fonsecaea pedrosoi, Rhinocladiella aquaspersa,Fonsecaea compacta and Cladophialophora carrionii. They enter the skin by traumatic implantation. The lesion develops slowly around the site of implantation. The infection is chronic and characterized by the slow development of progressive granulomatous lesions that in time induce hyperplasia of the epidermal tissue.
- 8. Table: Important causative agents and colour of the grains of various types of mycetoma Causative agent Color of the grains A. Eumycetoma • Madurella mycetomatis Black • M.grisea Black • Exophiala jeanselmei Black • Curvularia geniculata Black • Pseudallescheria boydii White-yellow • Acremonium kifiense White-yellow • Aspergillus nidulans White • Fusarium species White B.Actinomycetoma • Actinomadura madurae White-yellow •A. pellitieri RedYellow
- 9. Causative agent Color of the grains • Nocardia asteroids White-yellow • N.brasiliensis White • Nocardiopsis dassonvillei Cream • Streptomyces somaliensis Yellow C. Botryomycosis • Staphylococcus species White • Streptococcus species White • Escherichia coli White • Proteus species White • Pseudomonas aeruginosa. White • Actinobacillus lignieresi Yellow
- 10. Epidemiology Chromoblastomycosis is reported worldwide mainly in tropical and subtropical regions includingWest Indies, Brazil, NewVenezuela, Madagascar, China, Japan,Philippines, Malaysia, and India. Sub-Himalayan, eastern and western coastal areas in India have endured the most of the disease. In Mexico, chromoblastomycosis is mostly found in the southeastern states having tropical/subtropical climatic conditions. Chromomycosis occurs secularly in all races including European,Asian, LatinAmerican, andAfrican population. They are 10 times more likely to possess human leukocyte antigen serotype (HLA-A29) histocompatibility antigen.
- 11. Pathogenesis F.pedrosoi is the commonest pathogen (90% of cases) in humid and tropical regions. The Rhytidhysteron species has been implicated in causing chromoblastomycosis in a renal transplant patient. Although most individuals have no underlying disease or debility, the infection has been noted in conjunction with malignancy,leprosy, immunosuppression, organ transplant or corticosteroids use.
- 12. Clinical Features The initial lesion is a small, painless, papule at the site of inoculation. The exposed body parts are commonly involved. After a long incubation period; this enlarges to form warty nodules or plaques (Fig. 7). Multiple, nodular, tumoral, hyperkeratotic verrucous plaques, usually unilateral and seldom associated with pruritus or pain, are common (Fig. 8). Autoinoculation or superficial lymphatic spread can lead to satellite lesions. Rare extracutaneous spread to lymph nodes, brain, ileocecal region, tonsils, tracheobronchial tree, lungs, pleural cavity, and bone has been reported. Development of squamous cell carcinoma in a chronic lesion is well- known.
- 13. Figs 7A and B: Chromoblastomycosis:Verrucous plaques over heel. Lesions of long-standing duration result in large, verrucous or cauliflower-like plaque formation
- 14. Figs 8A and B: Chromoblastomycosis. (A) Large, hyperkeratotic, superficial, scaly, verrucous plaque over elbow, and (B) Over dorsal hand. Small, dark aggregations of clotted blood and fungal cells are characteristic and likely to yield fungal cells in smears or histologic sections Figs 8A and B: Chromoblastomycosis. (A) Large, hyperkeratotic, superficial, scaly, verrucous plaque over elbow, and (B) Over dorsal hand. Small, dark aggregations of clotted blood and fungal cells are characteristic and likely to yield fungal cells in smears or histologic sections Fig. 9: Chromoblastomycosis. Sclerotic bodies, as seen in potassium hydroxide mounts, are 5–13 μm, round, thick-walled, brown muriform cells, having longitudinal and transverse septa
- 15. Box 1: Differential diagnoses for chromoblastomycosis Tuberculosis verrucosa cutis Fixed cutaneous sporotrichosis Foreign body granuloma Lupus vulgaris Leprosy Cutaneous leishmaniasis Common warts Malignancy including squamous cell carcinoma and keratoacanthoma
- 16. Laboratory Diagnosis A. Microscopic Examination: The dark-colored fungal elements are relatively easy to see on microscopical examination of skin scrapings, crusts and pus. The agents of chromoblastomycosis are identified by their modes of conidiation. Histologically, the lesions show the presence of the fungus as round or irregular, dark brown, yeastlike bodies with septae, called sclerotic cells (Fig 73.7). Diagnosis can be established by demonstration of these sclerotic bodies in KOH mounts or in sections and by culture on Sabouraud’s agar.
- 17. Cont.. Fig. 73.7: Chromblastomycosis: KOH mount of lesion large septate „scierotic bodies‟
- 18. • Figure 60-1 Sclerotic bodies from the tissue of a patient with chromoblastomycosis (3400). (FromVelasques LF, Restrepo A: Chromomycosis in the toad (Bufo marinus) and a comparison of the etiologic agent with fungi causing human chromomycosis, Sabouraudia 13:1,1975.)
- 19. B. Histopathology Histological features include pseudoepitheliomatous epidermal hyperplasia, granulomatous inflammation with foreign body giant cells, and areas of microabscess formation. Fibrosis occurs in longstanding cases. The muriform cells (sclerotic or copper penny bodies) are often seen in the deeper sections, whereas hypha and budding cells are present near the lesion surface. Nevertheless, the presence of fungal cells or the copper penny bodies, singly or in clusters, found within giant cells is pathognomic (Fig. 10).
- 20. A B Figs 10A and B: Chromoblastomycosis: Histopathology - pseudoepitheliomatous hyperplasia, granulomatous inflammation with foreign body giant cells, and areas of microabscess formation. Demonstartion (arrows) of “sclerotic or copper penny bodies” (A) especially within the giant cells (B) is pathognomic (H & E × 40)
- 21. C. Culture: Culture from skin scraping/biopsy tissue of the causative fungus in SDA is attempted. Culture is important for species differentiation. Lesional biopsy material, crusts or pus is incubated at room temperature for at least 4-6 weeks. Colonies on SDA, vary greatly in morphology though they are deeply pigmented, gray, dark olive gray, dark brown or nearly black (Fig. 11). The causative fungus can be identified by colony morphology, characteristic sporulation, arrangement of conidia and morphology of the conidiogenous cell (Fig. 12).
- 22. Fig. 12. Chromoblastomycosis: Fonsecaea pedrosoi, seen as broad, septate hyphae. Conidia are one celled and broadly clavate with flat base and arise from the swollen apex of the conidiophore. Each conidium form several conidia in repeating process and form complexly branched head termed as “Fonsecaea synanamorph” that is considered as most distinct (arrow). (Lactophenol cotton blue × 40) Fig. 11: Chromoblastomycosis: Colonies of Fonsecaea pedrosoi, the commonest pathogen, in Sabouraud‟s glucose agar are olivaceous-black and velvety in texture. However, clinically the lesions of chromoblastomycosis appear morphologically similar regardless of the implicated organism
- 23. D.Serodiagnosis/Molecular Diagnosis Serological tests are not used routinely. The available methods are based on identification or amplification of specific deoxyribonucleic acid (DNA) from ribosomal or internal transcribed spacer (ITS)-1and ITS-2 regions of the ribosomal deoxyribonucleic acid (rDNA) and the 5.8S sequence. There are no diagnostic serological tests available commercially.
- 24. Treatment The drug of choice for treatment of chromoblastomycosis is 5-fluorocytosine. Cautery and surgical removal of early lesion is also useful.
- 25. Treatment Spontaneous resolution is very rare and treatment is difficult as response to drugs is limited. Infections caused by F.pedrosoi tend to be more resistant. Untreated, the risk of complications like recurrent secondary infections, distant/extracutaneous spread, malignant change, and risk of chronicity needs to be kept in mind. Small lesions of shorter duration are at best amenable to local destruction by surgical excision, cryotherapy, CO2 laser or local heat therapy.Treatment with SSKI alone or in combination with other antifungal agents is widely used for more extensive lesions.
- 26. Cont… Currently, itraconazole, and terbinafine are recommended drugs. Itraconazole (200–400 mg/day) or terbinafine (500 mg/day) is given over a period of 6–18 months or longer. Itraconazole monotherapy for 18–30 months has shown good response even in pulse schedules. Addition of 5-flucytosine (5-fluorocytosine) (50–150 mg/kg/day divided in four equal doses) may also improve therapeutic outcome. Amphotericin B is administered intravenously (0.5–1.0 mg/kg/day not exceeding 1.5 mg/kg/day). It is rarely effective when given alone and is best used in combination with intralesional injections.
- 27. Cont…. Poirriez et al. observed using two or more treatment modalities, yield better results. Sequentially, combination of intravenous amphotericin B and oral 5-flucytosine (4 g/day) for first 1 month, followed by oral itraconazole (200 mg/day) and 5-flucytosine for next 12 months yielded successful cure. As there are no well-defined clinical or experimental criteria for stopping systemic antifungal treatment or achieving cure, recurrences may occur after partial treatment.
- 28. Cont…. Ketoconazole has not been found effective and results have been variable with thiabendazole. Voriconazole and posaconazole have shown a broad spectrum in vitro and in vivo antifungal activity against dematiaceous fungi. Posaconazole (400 mg twice daily), in combination with topical heat therapy or surgical excision has demonstrated efficacy. Voriconazole alone, 200 mg twice daily for 12 months, showed only partial response.
- 29. Cont…. Topical heat therapy using chemical or electric pocket warmers at 42–46°C is another effective option. It is safe, does not cause discomfort and results are seen in relatively short time of 2–6 months, combined with CO2 laser, it produces better results.