Review article

Orofacial manifestations of the systemic mycoses

Crispian Scully^ and Oslei Paes de Almeida^ 'Centre for the Study ol Oral Disease. University of Bristol. England and -Faculty of Odontology. University of Campinas. Brasil

Scully C, Paes dc Almeida O: Orofacial manifestations of the systemic mycoses. J Oral Pathol Med 1992; 21: 289-94. Aspergillosis, cryptococcosis and zygomycosis (mucormycosis) are overall the most common systemic mycoses but histoplasmosis is particularly endemic in parts of central USA and other areas worldwide. Orofacial lesions caused by systemic mycoses have rarely been reported in the past though they have been recorded particularly in outdoor workers from geographic areas with a high prevalence of infection and occasionally in immunocompromised individuals. Increasing worldwide travel, and the dramatic increase in numbers of immunocompromised persons, especially those with human immunodeficiency virus (HIV) disease, have been responsible for an increase in reports and other studies of orofacial disease in systemic mycoses and new opportunists are now being recognized. Those in Oral Medicine and Pathology must now be aware of the possibility of a systemic mycosis as the cause of chronic oral ulceration, chronic maxillary sinus infection, or bizarre mouth lesions, especially in patients with HIV disease, lymphoproliferative disorders, or diabetes mellitus. or in those who have been in endemic areas. Diagnosis and management should be undertaken in consultation with a physician with appropriate expertise, as pulmonary and other systemic infection may well be present. This paper reviews the eight main systemic mycoses.

Accepted for publication January 26. 1992.

There are some 100,000 species of fungi but lew are pathogenic to man. Systemic fungal infections, apart from candidosis, are usually only seen in the Western world in immunocompromised or debilitated patients, including those with HIV disea.se. However, these systemic and subcutaneous mycoses (deep mycoses) occasionally may be seen in otherwise healthy persons from the tropics or certain other geographical areas where the infections are endemic. Fortunately direct human lo liuman spread is very rare: airborne transmission is the predominant mode of spread. This paper discusses the more common of the systemic mycoses where orofacial lesions have been reported: some of the less common mycoses are outlined in Table 1 to indicate the range of infections that may now be seen, albeit rarely particularly in immunocompromised patients (I, 2). Oral lesions have rarely been recorded in these cutaneous and other less common myco.ses, though antral involvement may occur. Orofacial lesions caused by any of the main systemic mycoses may occasionally be seen in isolation but in several they are typically associated with systemic

ehest radiograph. A sp)ecialist physician should be consulted. In most systemic mycoses, treatment is predominantly using systemic amphotericin (5). Aniphotericin is given slowly intravenously in 5% dextrose over 2 to 4 h, in doses of 0.3 to I.O mg/kg/day. It penetrates CSF and is excreted mainly via the liver. Potential adverse effects include thrombophlebitis (heparin may prevent this), renal impairment (usually reversible), ehills. nausea, anemia and hypokalemia. Ketoconazole penetrates CSF^ poorly and thus is regarded as second line treattnent for most mycoses except the blastomyeoses. Ketoeonazole is given orally in doses of 200 to 600 mg/day. Adverse effects include nausea. g\'necomastia atid liver datnage. Other antifungals that may be employed include miconazole. given intravenously over 2 to ? h in doses of 600 to 10(10 mg tds. Thrombophlebitis or ventricular tachycardia are the tnainly adverse elTects and its penetrates CSF poorly. Flucytositie is sometimes used, usually to completnent amphotoericin, in a dose of 150 tng/kg/day orally or intravenously in divided doses. Diar-

lesions, often in the respiratory tract (Table 2). Infection of healthy individuals with these fungi is not uncommon (especially in endemic areas) but is often asymptomatic and. perhaps surprisingly, resolves spontaneously. Even aeute pultnonary disease, which typically presents with fever and cough, and primary mucocutaneous forms, in otherwise healthy persons may resolve without treatment. However, chronie pulmonary infection tends to progress and can. as is often the case in disseminated infections, lead to death. Immunoeompromised persons, including those with HIV disease, are at particular risk from any infection with these tnycoses. Surveillance cultures have been tried in such individuals in order to detect and thus prevent tnyeoses. but the efTieaey and cost-effectiveness has not been proven {}). Most of these mycoses therefore are potentially serious infeetions. sometimes lelhal. usually diagnosed mainly on the basis of history of foreign travel or an itntnunocotnpromising state, and investigations include smear, biopsy and particularly culture of the alTected tissues (4). physical examination and

Key words: aspergillosis: cryptococcosis; HIV: immunocompromised: mucormycosis: mycoses: zygomycosis. Crispian Scully. Centre tor the Study of Oral Disease. Bristol Dental Hospital and School. Lower Maudlin Street. Bristol. BS1 2LY. England

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Table I. Cutaneous and other less common mycoses: increasingly reported immunocompromised patients.

mainly in

rogenically following dental procedures such as endodontics or itnplants in the maxilla (8 10). Though A. fumigdtus is the usual cause of sinus aspergillosis (II), A. flavus appears to predominate in immunocompromised individuals (12). Rarely, other species such as A. rcpens are encountered, sometimes with other myco-

Predominantly cutaneous mycoses Dermatophytes Epidermophyton Microsporum Trichophyton Others Malassezia (Pityrosporum or Pityrosporan) Trichosporon ses such as Microascus cincreiis (13). PaHyalohyphomycoses Fusarium species-especially tients with leukemias. lymphomas, HIV F. solani. F oxysporum. disease, or those iatrogenically immunoF moniliforme and F. ro.seum suppressed such as when undergoing Penicillium species-especially bone marrow transplantation, are at P. cru.staceum. P. cummune and P. marneffei particular risk from such invasive sinus Paecilomyces species-especially P. lilacinm and P marquandii aspergillosis (12, 14-18). Other species eg: Chronic sinus aspergillosis presents Acremonium. Anxiopsi.s. Chryosporium. Cylindrocarpon. Geolrichum. Oilhcrella. Gymnascella. Lecythophora. Microascus. Myrtodontium. P.svudoalle.scheria. Scedospurium. Schopuhirioas chronic unilateral sinusitis unresponpu.i. Scytaliium. Tritrachium. Volutclta. sive to conventional therapy. There is a

diffusely opaque antrutn on radiography, sometimes with dense punctate raA altcrnata. dio-opacities. Allergic fungal sinusitis is Exophiala jeanselmei (Phialophora gougerotii) usually due to other fungi. In invasive Wangiella dermatitidis sinus aspcrgillosis there is destruction of Bipolaris (Dreehsclera) spicifera Other species eg: the antral wall which may be characterExserophitum. Cladosporium. Curvularia. Fon.secaeae. Phialophora. Phoma. Xylohypha.ised by antral pain, swelling, or sequelae from orbital invasion (impaired ocular motility. exophthalmos. or itrtpaired virhoea. hepatitis and bone marrow de- sinuses. Allergic bronchopulmonary as- sion) or intracranial extension (headpression are dose-related. Itraconazole pergillosis is the most common resultant aches, meningism). Oral lesions of aspergillosis, seen preand fluconazole are now being used in chronic respiratory disease, typically some trials. Unfortunately, the cost of caused by A. fumigalus. Invasive asper- dominantly in some immunocompromsuch drugs is prohibitive where they are gillosis is less common: it affects the ised patients, are yellow or black, nelungs mainly but may spread to brain, crotic ulcers, typically in the palate or needed in the developing world. Though the above generalizations are bone or endocardium and either A. fum- occasionally the posterior tongue (16. true for most mycoses, each has individ- igatm or A. flavus may be responsible. 18). The main differential diagnoses are ual characteristics and therefore, the Aspergillomas are fungus balls that from mucor and pseudomonas infecmycoses arc described separately below. grow in pre-existing cavities such as tu- tions. berculous lung cavities. Aspergillosis Diagnosis is confirmed by smear and may also occur in the external ear, cor- lesional microscopy, staining with perAspergillosis nea or endocardium. iodic acid Schiff (PAS) or methenamine Orofacial lesions caused by Aspergil- silver, to show narrow (4 |.im) regular Aspergillosis is second only to candidosis as the most prevalent opportu- lus include antral aspergilloma. indolent width, branching, septate hyphae. In nistic mycosis. Aspergillus species are chronic sinusitis, allergic sinusitis, inva- contrast, mucor hyphae are wider (6 to the most common fungi in the environ- sive aspergillosis of the antrum (6) and 50 (im) and invade blood vessels. Culment, being prolific saprophytes in soil oral lesions. Aspergillosis of the maxil- ture of tissue or fluids on Sabouraud's and decaying vegetation. Inhalation of lary antrum is uncommon, presenting or mycoscl agar may be positive but this the conidiosporcs must be extremely typically in a healthy host as a hyphal is not invariable and. in view of the common but. unless there is massive in- ball in a chronically obstructed sinus ubiquitous nature of the organistn. isohalation or the host is immunocom- (aspergilloma, or non-invasive sinus as- lation of aspergillus is not /)ro«/of disease. Estimations of serum precipitins promised, overt disease is rare. Never- pergillosis). theless, asfjergillosis is the most comInvasive sinus aspergillosis is ob- and IgE specific antibody may help dimon of the systemic mycoses, is found served mainly in the immunocomprom- agnosis (6). worldwide, and is increasing (6). ised host, though also in some apparAntifungals alone are not of proven ently healthy individuals, predomi- efficacy in the treatment of sinus asperAspergillu.s fumigatu.i is the most common pathogen but A. Jlavus, A. nantly in subtropical countries with a gillosis. Non-invasive forms arc treated warm climate, such as Sudan, Saudi by antral dcbridement and restoration glaucwi. A. nidulan.s. A. terreus, A. reof drainage though corticosteroids may pens. A. para.siticu.s and A. niger are also Arabia or India. Interestingly, subcliniencountered. Of these, /4.y7avMi appears cal defects in cell-mediated immune re- also be indicated in allergic sinusitis (6). spon.ses to A.spergillus have recently In invasive aspergillosis a course of amto be the most virulent. Aspergillus spores have a proclivity been shown in patients with sinus as- photcricin should be tried but since a to germinate in mucus and. since they pergillosis (7). Occasional cases of sinus prolonged conservative approach may are inhaled, they may colonize the respi- aspergillosis arise as a result of metasta- worsen the prognosis, treatment is again ratory tract including the paranasal air sis from pulmonary aspcrgillosis or iat- by surgical dcbridement together with.

Phaeohyphomycoses Alternaria species especially

Orofacial lesion.t in sy.ftemic mvcoxe.'; 291 some suggest, .supplementation with hyperbaric oxygen. Treatment of oral lesions of aspergillosis is with amphotcricin syslemically. Flucytosinc and rifampin increase the activity of amphotericin against Aspcrgillii.s. at least in vitro (19) but niiconazole is not active against Aspcrgillus.

Blastomycosis

Coccidioidomycosis

Coccidioitk's immitis is found in soil, mainly in arid parts of the New World such as South West USA. Mexico. Central America and parts of South America. Inhalation of spores produces subclinical infection in up to 90% of the population in such areas. Clinical illness can produce acute pulmonary disease (San Joaquin valley fever) sometimes with erythema nodosum or erythema multiforme. Chronic pulmonary disease is less common. Rarely, disseminated or meningeal coccidioidomycosis are seen. Pregnant women, blacks. Philipinos and Mexicans are prone to disseminated infection. Immunocompromised persons, such as those with HIV disease are also prone to disseminated coccidioidomycosis (22, 23). Oral lesions of coccidioidomycosis have rarely been reported but are typically verrucous lesions, sometimes with underlying infection of the jaw (24, 25). Diagnosis is confirmed mainly by histology showing granulomas with spherules containing endospores. and serology. and rarely by the eoccidioidin skin test. Culture is useful but is potentially hazardous to laboratory staff. Chest radiography is indicated. Management is with systemic amphoteriein. sometimes supplemented with ketoconazole. itraconazole or fluconazole (23).

The term blastomycosis has sometimes been taken to include a range of granulomatous systemic mycoses, including South American blastomycosis (paracoccidioidomycosis or Lutz" disease). North American blastomycosis (Gilchrist's disease), coccidioidomycosis, and cryptococcosis but is now generally restricted to the South American and North American forms. The latter form of blastomycosis arc fungus infection of viscera, lymph nodes and mucocutaneous tissues: Blastomvcc.i (lcri)tatili(li.s causes the North American form; Particoccitlioidcs hrasilien.si.s causes the South American form described later as paracoccidioidomycosis. North American blastomycosis is seen predominantly in the Mississippi. Missouri and Ohio River valleys and Southern Canada and is restricted to that continent, or travellers to North America. B. dcrmatiticli.s is found in soil and spores may be inhaled to produce respiratory and sometimes disseminated disease. Cutaneous blastomycosis is oc- Cryptococcosis casionally seen. Outdoor workers are Cryptocoicu.s ncofornuins is a ubiquiparticularly affected by blastomycosis. tous yeast found especially in pigeon Extension of cutaneous blastomyco- feces and present in soil. The disease sis may alTect the lips, or disseminated occurs worldwide and is mainly caused blastomycosis may produce ulcerating by capsular serotype A. sometimes D. lesions affecting the oral mucosa (20. Aspiration of spores may lead to pul21). Mandibular involvement is rare. monary infection and subsequent disDifferential diagnosis includes carcino- semination via the bloodstream particma, other mycoses, tuberculosis and ularly to CNS. heart, spleen, pancreas, other causes of chronic uleeration. adrenals, ovaries, muscles, liver and gasDefinitive diagnosis is based on trointestinal tract. Dissemination is essmear or culture: histology may show pecially liable to occur in imnuinocomblastomyces-like lesions in the lesional promised persons. Most patients with tissue with granulomas and yeast forms cryptococcosis have cryptococcal mewith single buds, though the organism ningoencephalitis at the time of diagnocan be mistaken lor lli.stoplasiiui capsu- sis and untreated disseminated cryptolaium. Staining with periodic-acid SchitT coccosis is fatal in over 70"/'o of cases. or methenamine silver nitrate helps However, in healthy persons, infection identifieation but direct immunostain- with cryptococcus is typically subcliniing is the most useful confirmation. Skin cal (26). tests and serology are. unfortunately, At least three cases have now been unreliable. recorded of oral lesions due to C. ncoKetoconazole is highly effective treat- fornuut.s in i-)ersons infected with HIV ment as are amphotericin, mieonazole (27 29) and there have previously been and itraconazole. rare cases reported in leuketnics. Oral

cryptococeus infection has presented mainly with non-healing extraction wotmds. or chronic uleeration on the palate or tongue (27-29). The main differential diagnoses are from histoplasmosis. tuberculosis, syphilis and chronic herpesvirus infections. Diagnosis is confirmed by microscopy, staining with periodic aeid-Sehiff. mucicarmine or methenamine silver, showing granulomas. Smears may be stained with India ink or nigrosin. The yeast cell is round or elliptical. 4 to 6 nm in diameter, clear and capsulated. and fluoresces in ultraviolet light. Culture, and assay of serum or CSF for capsular antigen and antibody (latex agglutination test) may be helpful in the diagnosis. Amphotericin systetnically is eflective therapy but is best supplemented with flucytosine. Ketoconazole is regarded by some as the treatment of choice for non-meningeal eryptocoecosis but may be less effective than amphotericin in meningeal cryptococcosis (30). Histopiasmosis

Histopld.inui copsulatum is a soil saprophyte found particularly in north eastem and central USA (mainly in the Ohio and Mississippi valleys), in Central and South America. Africa. India, the Far East and in Australia. Histoplasmosis is the most frequently diagnosed systemic mycosis in the USA and has now been recorded in about 30 countries. H. capsulatum var. duhoisii is the type mainly found in equatorial Africa and particularly cau.ses skin lesions. The fungus is found especially in bird and bat feces. and inhaled spores produce mainly respiratory infection. Over 70"i) of adults from endemic areas appear to have been infected, typically subclinically. Clinical presentations include acute and chronic pulmonary forms and. rarely, disseminated and potentially lethal histoplasmosis typically in immunocompromised persons. Oral lesions of histoplasmosis have been recorded in persons with pulmonary histoplasmosis (31. 32). and in up to 50", I. of those with disseminated histoplasmosis (33 36) particularly in HIV infection (37 39) and in Hodgkin's lymphoma (40\ Occasionally, isolated lesions have been recorded in apparently healthy persons with no obvious systemic histoplasmosis (41). Oral lesions typically afteet the tongue, palate, buccal mucosa or gingiva and gen-

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Table 2. The more common pathogenic members of the mucorales Synonyms

Family

Species

Cunninghamellaceae

Cwininghamcllu elegans C herllwlk'liae

Mortiercllaceae

Morlierella wolfii

Mucoraceae

Ahsidia corymhifera

A. ramosa

Mucor circint'lloides M. miehei M. pusillus

Rhizomucormiehei Rm.

Rhizopus microsporus R. oryzae R. rhizopoiliformis

R. cirrhizus R. cohnii. R. equlnus

Saksenaeaceae

Sak.semicci vasiformis

Syncephalaslraceae

S\ncephaluslrum

sp.

A d a p t e d from LI;IIRKR CI UI. (51).

myeosis. Most eases have been recorded from the Caribbean, Latin America, and Central and West Africa (47-49). Zygomyeosis is found worldwide. Infection with most Mucoraceae however, is virtually unheard of in otherwise healthy individuals. Immunocompromising conditions usually underlie zygomyeosis: leukemia, lymphoma, diabetes with ketoaeidosis. burns, malnutrition, cancer chemotherapy and immunosuppressive therapy may be responsible (50-52). Rhinocerebral zygomyeosis is especially predisposed to by diabetes mellitus (52, 53) but case are now appearing in HIV disease (54). Rhinoeerebral and pulmonary zygomyeosis are most eommon, but cutaneous, gastrointestinal, and disseminated zygomyeosis may be seen (55). Rhinocerebral zygomyeosis is usually caused by Rhizopus oryzae or R. arrhizus, and typically commences in the nasal cavity or paranasal sinuses with pain and nasal discharge, and invades the palate to produce a black neerotic oral ulcer. ZygoZygomyeosis (mucormycosis: myeosis occasionally commences in the phycomycosis) palate (52, 53, 56). Orbital invasion may Fungi of the family Mucoraceae of the produce orbital eellulitis, impaired ocuclass Zygomycetes (Table 2). which are lar movements, proptosis, and ptosis. responsible, are ubiquitous, being found lntracranial invasion follows penetrain soil, manure and decaying organic tion of ophthalmic vessels or the cribrimatter. However, similar disease can be form plate. Though rhinocerebral zygomyeosis caused by other Zygomyeetes such as Rhizopus, and also Ahsidia. Apophyso- typically affects ill adults, eases have myces, Saksenaca. Rhizomucor. Cunnin- recently been recorded in African chilghamello and other species and. there- dren with malnutrition (56). One patient fore, zygomyeosis is the preferred term presented with pain and radiographic (46). Mucoraceae ean commonly be cul- features suggestive of fibrous dysplasis tured from the nose, throat, mouth and in the maxilla, possibly a consequence faeces. In some warmer regions, some of chronic selerosing osteomyelitis. Zyzygomycetes, notably Conidioholus co- gomyeosis of the mandible has also been ronatus, affeet a range of animals and reported (57). can cause human rhinofaeial zygoDiagnosis is confirmed by smear, or

erally present as indurated ulcers or exophytic lesions which must be difTercntiated from careinoma. sarcoidosis, tuberculosis, and other mycoses. Rare cases have been recorded with antral involvement (42) and invasion of the mandible (43). Diagnosis is confirmed by microscopy showing granulomas with periodic acid-Schiff positive spores with a narrow halo in macrophages, microabscesses and necrosis. Culture on Sabouraud's agar is confirmatory. In non-endemic areas, the histoplasmin skin test is of little importance diagnostically but serology is more useful; complement fixation tests may be of value: a titer greater than 1:32 being indicative of infection. Ketoconazole and/or amphotericin ean be used for the treatment of histoplasmosis (44): it is recommended that amphotericin be given first, followed by ketoeonazole (45).

histologie demonstration of tissue invasion by broad (5 to 50 |im) irregular width, nonseptate, branching, hyphae invading blood vessels and causing thrombosis, ischemia and necrosis. MeIhenamine silver or PAS staining is best to show the fungi. The organism is difficult to culture from a swab. Radiography typically shows nodular or diffuse thickening of the antral mucosa with patchy destruction of the walls. Computerized axial tomography may help demonstrate the extent of the lesion. Zygomyeosis was almost uniformly fatal in the past. Control of underlying disease is essential, together with systemic amphoteriein, and surgical debridement (55). Paracoccidioidomycosis

South American blastomycosis (paracoccidioidomycosis) is caused by P. brasilien.sis and is found in Columbia, Venezuela, Uruguay, Argentina and particularly Brasil, where it can be endemic in certain areas, especially the states of Sao Paulo, Rio de Janiero, and Minas Gerasis. Although symptomatic cases are uncommon subclinieal infection is not uncommon. Disseminated paracoccidioidomycosis is rare. Aeute pulmonary paracoeeidioidomycosis is also rare but chronic pulmonary disease is common and presents with cough, dyspnoea, fever, weight loss and haemoptysis. Pulmonary disease is often found with other lesions, especially oral ulcers (57). Oral ulcers are chronic and often granular or exophytic (57). Anlral lesions are rare (58). Oral lesions have yet to be reported in HIV disease though cases of paracoceidioidomyeosis are now being seen in HIV disease and submandibular lymph node involvement has been reported (59). The differential diagnosis of paracoeeidioidomycosis is mainly from careinoma, tuberculosis, lupus erythematosus, sareoiclosis, syphilis, Wegener's granulomatosis. granuloma inguinale, actinomycosis, leishmaniasis, and other mycoses. Pus or scrapings examined in potassium hydroxide may show rounded refractile cells of P. hrasiliensis which can be distinguished from B. dermatitidis only when the characteristic multiple budding of the former is evident. Biopsy is required for definitive diagnosis and shows a suppurative granulorna with giant cells and blastospores which are double-contoured eyst-like structures

Orofacial

approximately 30 |.im diameter, often References surrounded by daughter spores. Methenamine silver nitrate or PAS are partic1. WAL.SH T J . PIZZO P A . Nosoeomial fungal infeetions: a classification for hospiularly useful to show the organisms: dital-acquired fungal infections and mycorect immunostaining with Blastomyces ses arising from endogenous flora or reantiserum is less frequently used. Smear activation. Aim Rev Mkrohiol 1988; 42: or culture can also be diagnostically use517-45. ful, but R brcLsiliensis grows only ex2. DRUTZ D J . Fungal infeetions. Current tremely slowly. Serologic examination Opinion in Infectious Diseases 1989; 2; by immunodiffusion or particularly the 227-33. complement fixation is useful mainly in 3. WALSH TJ. Role of surveillance cultures epidemiologic studies. Skin tests are not in prevention and treatment of fungal available. infeetions. NCI Monogr 1990; 9: 43-5. Amphotericin intravenously can be 4. WKITZMAN 1. Saprophytic molds as agents of cutaneous and subcutaneous curative. Amphotericin plus a sulfoninfection in the imtnunoeompromised amide such as sulfamethoxypyridazine host. Arch Dermatol 1986; 122: 1161-8. is a more effective therapy. Sulfadiazine 5. TOMKKI KJ. DlJKSTRA JWE, HALL G S . or sulfisoxazole alone can also arrest STKCK W D . Systemic mycoses. J Am the disease but it relapses. Ketoconazole Acad Dermatol 1989; 21: 1285-93. is now regarded as superior to ampho6. HARTWtcK RW. BATSAKIS J G . Sinus astericin since it is effective and can be pergillosis and allergic fungal sinusitis. given orally, though it is sometimes used Ann Olol Rlunol Laryngol 1991; 100: together with a sullbnamide. Paracoc427 30. cidioidomycosis also responds well to 7. LoiDOLi- D. MANGGE H W M . BhAuroRr intravenous mieonazole. though this is F. SrHAUENSTKtN K. In vivo and in vitro suppression der Lymphozytenfunktion far less convenient than oral ketoconabei Nebenhohlenmykosen. Ltiryngorhizole. Oral itraconazole also produces a nootologie 1989; 68: 407-10. clinical cure in most patients. 8. BAt:)KR G. Sinusites aspergillaires d'origine dentaire. Rev Odonloslomalol 1989; 18: 345 53.

Sporotrichosis

Sporothrix schcnckii is found throughout the world particularly as a saprophyte on various plants and shrubs (61). Disease is seen almost exclusively in tropical and subtropical countries. Infection usually occurs via an injury lo the epithelium. Skin infection follows and progresses in some to the lymphatic form. The primary lesion is a sporotrichotic chancre which may ulcerate if in the mouth. Lesions may also be superficial and diffuse (62). Pulmonary and disseminated sporotrichosis are rare and of uncertain origin. Diagnosis is confirmed by histology showing granulomas and occasionally bud-shaped organisms, and by culture. Potassium iodide is elTective for trealment of superficial sporolrichosis: itraconazole or intravenous amphotericin are used for other forms (61).

9. LKGKNT

F . Btt.t.ET J, BhADVILLAIN C .

Candidiasis is classically regarded as a superficial mycosis and therefore not discussed here. Nevertheless, it is now a common nosocomial pathogen and increasingly frequently causes invasion of deep organs: this is reviewed elsewhere (63, 64).

mycoses

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Candidiasis (candidosis)

lesioits in systemic

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