Postgraduate Medical Journal (September 1979) 55, 598-602

Imported mycoses: some diagnostic problems

W. ST C. SYMMERSM.D.

Charing Cross Hospital and Medical School, The Reynolds Building, St Dunstan's Road,London W6 8RP

SummaryInfections by actinomycetes or by true fungi may causediagnostic difficulties in countries where they are notfamiliar. Illustrative cases from a series of 353instances are given together with rare indigenousexamples of the same infections. Early, accuratediagnosis is essential for rational and effectivetreatment.

IntroductionThe first, and in many cases the greatest, problem

in the correct clinical management of mycoses is theirrecognition. In general, delay in the diagnosis ofmycoses results primarily from failure to considerthat a fungal or actinomycetous infection may be thecause of a patient's symptoms. In this respect theproblem is a commonplace one, not confined tomycoses: its solution lies in greater knowledge andgreater awareness of diagnostic possibilities. Amongthe 353 cases of 'imported mycoses' in the accom-panying table, the possibility of a mycosis was amongthe initial diagnostic considerations in just under15%.

Mycoses in north-western EuropeIn north-western Europe (the area covered by

Belgium, Denmark, France, the German FederalRepublic, the Irish Republic, Luxemburg, TheNetherlands, Norway, Sweden, and the UnitedKingdom), the indigenous mycoses (excluding super-ficial mycoses of the skin, ocular mycoses andotomycoses) that are liable to cause serious andprogressive disease, or that are potentially disablingor potentially life-threatening, include the following:actinomycosis; adiaspiromycosis; aspergillosis; basi-diobolomycosis; candidiasis; chromomycosis (cutan-eous and subcutaneous; cerebral and meningocere-bral; other visceral infections); cryptococcosis;geotrichosis; mycetoma (caused by Acremonium spp.,Aspergillus nidulans and Petriellidium boydii); nocar-diosis (caused by Nocardia asteroides); penicilliosis;petriellidiosis (pulmonary, see also mycetoma,above); phycomycosis (caused by Absidia spp.,Rhizopus spp. and probably other genera); sporo-trichosis.

It should also be remembered that species of

Trichophyton and possibly of other fungi that causedermatophytosis may invade the subcutaneoustissues and eventually give rise to distant lesions as aresult of spread by the lymphatics or in the bloodstream.

In any case of the infections listed above, andparticularly in any case of those infections that occurless frequently in Europe than in other parts of theworld, the possibility that infection took place whilethe patient was resident or travelling outside Europeought to be considered. None of the infections isconfined to Europe. In contrast, some importantmycoses do not occur naturally in north-westernEurope.

Mycoses not indigenous in north-western EuropeBlastomycosis (caused by Blastomyces dermati-

tidis); coccidioidomycosis; histoplasmosis, includingAfrican histoplasmosis; lobomycosis; mycetomas(except those caused by the fungi named in the listof indigenous mycoses of north-western Europe,above); paracoccidioidomycosis; rhinoentomoph-thoromycosis; rhinosporidiosis.However, instances of all these diseases have been

seen in patients in north-western Europe whoseinfection originated while they were in parts of theworld where the condition is indigenous. Further, inexceptional circumstances, blastomycosis, coccidio-idomycosis, histoplasmosis and lobomycosis havebeen acquired in north-western Europe (Table 1)either through inadvertent exposure to infectiveforms of the causative organism in laboratories or asa result of contact with imported goods contamin-ated with the fungus (or, in the case of lobomycosis,in consequence of a needle prick while excising abiopsy specimen from an infected dolphin).

Diagnostic awarenessAlthough in comparison with the situation 10-20

years ago there is now much more awareness amongclinicians and in laboratories of the occurrence ofmycoses, their recognition is still frequently delayed.This is a world-wide shortcoming; even in NorthAmerica, where we in Europe expect familiarity withmycoses to be general, the diagnosis of those infec-tions that are endemic in parts of the continent is

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Imported mycoses

very liable to be as much delayed, or almost so,through failure to consider the possibility of amycosis. A basic knowledge of some of the exoticmycoses including histoplasmosis, and less often ofcoccidioidomycosis, is quite usual among youngBritish doctors. Yet the same doctors, and theirseniors, tend to be at best only vaguely and insuffi-ciently informed about such infrequent indigenous

TABLE 1. Three hundred and fifty-three cases of non-indigenous and rarely indigenous mycoses seen personally inBritain from 1946 to 1977 (figures in parentheses indicate thenumber of cases with firm evidence or good circumstantialevidence that infection was acquired in Britain or elsewhere

in north-western Europe)

Number ofMycosis cases

BasidiobolomycosisBlastomycosis ('North American') causedby Blastomyces dermatitidis

Blastomycosis, South American; seepapacoccidioidomycosis.

Chromomycosiscutaneoussubcutaneous (phaeosporotrichosis)

caused or presumptively caused byPhialophora gourgerotii

central nervous system, caused orpresumptively caused by Cladosporiumtrichoides in most cases

other visceral infections (heart and/orlungs

CoccidioidomycosisHistoplasmosis, caused by Histoplasma

capsulatumHistoplasmosis, African, caused byH. duboisii

Lobomycosis (occupational contact withnaturally infected dolphin that hadbeen captured in European waters)

Mycetoma:actinomycetous:

A. maduraeActinomadura pelletieriNocardia brasiliensisStreptomyces somaliensis

fungal:Acremonium falciformeAspergillus spp.Leptosphaeria senegalensisMadurella griseaM. mycetomatisMicrosporum ferrugineumPetriellidium boydiiPhialophora jeanselmeiZopfia rosatii

ParacoccidioidomycosisPenicilliosis presumptively caused by

Penicillium marneffeiRhinoentomophthoromycosisRhinosporidiosis

5 (2*)32 (2t)

63 (21)31 (6*)

18 (6*)

11 (7*)

3 (2*)41 (27-22t; 5t)

101 (3-1t; 2t)

14 (0)

71 (2)24 (0)6 (0)3 (0)10 (0)5 (0)

47 (2)2 (0)2 (0)4 (0)3 (0)

19 (0)4 (0)5 (2*)7 (0)1 (0)9 (0)

1 (0)2 (0)

13 (0)

mycoses as nocardiosis, the phycomycoses andsporotrichosis.

Geographical considerationsThe importance of enquiring about a patient's

geographical history and relating it to the presentingclinical problem cannot be stressed too strongly.Failure to do this may result in ignoring the possi-bility of an exotic fungal disease; this may leadto the patient's death.

Illustrative casesOnly a brief sketch of some causes of delayed

recognition of 'imported' mycoses can be includedhere. The cases are from the series summarized inTable 1.

(A) Diagnostic delay through failure to consider thepossibility of mycosis

Case 1. Madurella mycetomatis mycetoma of thetibia. A boy whose home was in India was struckover the tibial tuberosity by a cricket ball while atschool in England. The unexpectedly severe painthat this caused led to X-ray examination whichshowed a large osteolytic lesion with some new boneformation. The radiological diagnosis was 'probableosteosarcoma'. Radiotherapy and amputation wereadvised. The child's guardians refused permissionfor such treatment The lesion enlarged and showedsigns of extension into the skin, with imminentulceration. Biopsy was then undertaken and showedcolonies of M. mycetomatis in a chronic inflamma-tory mass. There was no neoplasm. For the first timea careful history was taken: this disclosed that thechild had accidentally run an acacia thorn into theleg at the site of the eventual mycetoma. The remainsof the thorn were found in tissue removed duringfurther conservative surgical treatment. Recoveryfollowed.

Case 2. Nocardia brasiliensis mycetoma of theshoulder region. A Mexican student in London wastreated over many months for 'chronic furunculosis'of the skin of the back of one shoulder. There waslittle effect from a wide range of antibacterial anti-biotics and fresh lesions continued to appear over anincreasingly wide area. Eventually, the patient con-sulted a fellow countryman who was on a post-graduate course in England: the latter made animmediate diagnosis of N. brasiliensis infection onclinical grounds; this was soon confirmed bothhistologically and by isolation of the organism.Treatment with a sulphone resulted in cure.

Case 3. N. brasiliensis mycetoma of foot. AnEnglish student gave a history of transfixion of onefoot by a thorn, which pierced it from the sole to thedorsum in the region of the head of the metatarsalbones of the fourth and fifth toes. The thorn was

* Naturally occurring indigenous infections.t Infections presumptively mediated by fomites.L$aboratory infections.

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immediately withdrawn intact. Some months later a'boil' appeared at the site of the former puncture onthe dorsum of the foot. By this time the student hadreturned to England from the region of CentralAmerica in which he had been working on anarchaeological site at the time of the injury. The'boil' persisted in spite of treatment with anti-bacterial drugs. After some months colonies of N.brasiliensis were recognized in the discharge. Theinfection subsided permanently on treatment withdapsone.

Case 4. N. brasiliensis mycetoma of the forearm.A Venezuelan, resident in London, developed aseries of ulcerating nodules in the subcutaneoustissue of one forearm. His case was demonstrated ata clinical meeting as a classic example of the ascend-ing lymphangitic type of sporotrichosis, althoughSporothrix had not been isolated. It was a youngMexican doctor in the audience who made thecorrect clinical diagnosis of N. brasiliensis mycetoma:he had been taught in his own country that sporo-trichosis is only one of several infections that maypresent with this picture. His diagnosis was con-firmed. The condition responded to treatment withdapsone.

Case 5. Verrucose chromomycosis of the arm.An Englishman who had recently retired to Germanyafter many years' residence in Jamaica sought treat-ment for a chronic verrucose eruption that extendedfrom the dorsum of one hand to above the elbow.A clinical and histological diagnosis of chronicverrucose tuberculosis was made and intensivetreatment with a range of anti-tuberculosis drugs,supplemented by excision of the larger of the lesions,was undertaken. It was not until one year later thata review of the histological specimens in anothercountry disclosed the presence in every lesionexamined of typical pigmented fungal cells ofPhialophora sp.

Case 6. Psoriasiform chromomycosis of theelbow. A lesion, variously regarded as pustularpsoriasis, lichen, traumatic keratosis and dermatitisartefacta, proved after many months of study invarious hospitals to be chromomycotic. The fungalcells had been overlooked in biopsy specimens. Thepatient had never been outside the British Isles. Hisoccupation was agricultural.

Case 7. Subcutaneous chromomycosis (phaeo-sporotrichosis) (Symmers, 1971b). A large 'coldabscess' in the upper part of a thigh was assumed tobe tuberculous. It was repeatedly aspirated but itregularly re-formed. Anti-tuberculosis drugs had noeffect. The patient was a Pakistani immigrant inBritain. He moved to Germany, where biopsy of thewall of the abscess showed pigmented fungalelements. P. gougerotii was isolated.

Case 8. Sporotrichosis of the face. An Iranian girl

at school in Europe was looked after by a successionof doctors over a period of 9 months during whichextensive ulceration of the skin of one cheek de-veloped; the accompanying cervical and submentallymphadenitis became complicated by sinus forma-tion. Although no Leishmania could be shown in thelesions she was repeatedly treated for leishmaniasis.Eventually the possibility of a fungal infection wassuggested and Sporothrix schenckii was isolated.Treatment with iodide led to healing. Gross scarringwas left.

Case 9. Generalized coccidioidomycosis. AnItalian man, living in Britain, developed what wasregarded as a classic gummatous ulcer in the skinover the sternum. Medical students were summonedto see what was demonstrated to them as thatcontemporary rarity, clinical evidence of tertiarysyphilis. When serological tests for syphilis provedto be negative a biopsy was undertaken and showedCoccidioides immitis; the fungus was isolated inculture (and a number of members of the laboratorystaff acquired the infection). The patient's conditionhad deteriorated seriously during the weeks betweenthe initial diagnosis of syphilis and the eventualdiagnosis of coccidioidomycosis; he died in spite ofintensive treatment with amphotericin and flucy-tosine. He had worked as an agricultural labourer inCalifornia, U.S.A.

Case 10. Coccidioidal pneumonia complicatingHodgkin's disease (Symmers, 1967- Case 1). Amedical student from California died in Britain ofpneumonia that did not respond to antibacterialantibiotics. The post-mortem showed the pneumoniato be coccidioidal. Review of the clinical case notesshowed that although the patient's statement that hehad once had 'valley fever' had been recorded,apparently no steps had been taken to discover what'valley fever' was. Had it been realized that 'valleyfever' was the vernacular term for the illness accom-panying the initial infection by Coccidioides,acquired in the San Joaquin Valley, in California, itmight have been realized that the patient's pneu-monia could be a manifestation of the fungalinfection, reactivated by the coincident developmentof Hodgkin's disease and the immunosuppressiveeffects of the treatment that was given for the latter.

Case 11. Bilateral apical cavitating pulmonary his-toplasmosis complicated by Histoplasma meningitis.Haemoptysis led to the radiological demonstrationof cavities in both lungs of a European businessmanwho had spent many years in Kentucky and Ohio,U.S.A. He was treated with anti-tuberculosis drugs,in spite of failure to demonstrate mycobacteria in hissputum; the treatment was ineffectual and he died.Histoplasmosis was found at post-mortem to havebeen the cause of the pulmonary disease; the

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infection had spread to the meninges in the terminalstages of the illness.

Case 12. Oral ulceration and Addison's diseasedue to histoplasmosis (Symmers, 1972). A Dutchmanwho had spent many years as a public works con-tractor in south-eastern Asia developed Addison'sdisease during his retirement in Europe. He also hadextensive ulceration of the tongue, lips and throat.Hormone therapy and anti-tuberculosis drugs hadlittle effect. Post-mortem showed destruction of bothadrenals by caseous tissue that contained greatnumbers of H. capsulatum. The oral ulcers were alsoa manifestation of histoplasmosis. There had beenno biopsy or other laboratory examination of theselesions at any time during his illness.

Case 13. African histoplasmosis. A surgeon's armwas amputated because his colleagues failed to seeH. duboisii in the foreign-body giant cells in thebiopsy of an osteolytic lesion in one radius. The giantcells were interpreted as sarcomatous.

Case 14. Paracoccidioidomycosis of the face. APortuguese man, working in a London hospital as aporter, developed a chronic ulcer of the skin of onecheek. The clinical likeness of the lesion to that inCase 8 (above) led to a diagnosis of sporotrichosis.When treatment with iodide had no effect on thecondition the possibility of carcinoma was con-sidered. Biopsy showed no evidence of a tumour. Itwas a further 7 months before the sections werereviewed and the presence in them of typical formsof Paracoccidioides brasiliensis demonstrated. Mean-time, the ulcer had almost doubled its extent. Uglyscarring accompanied the eventual cure. The patienthad worked in Brazil some years earlier.

(B) Double infectionsCase 15. Rhinosporidiosis of the nasal septum

with accompanying leprosy (Symmers, 1966 b - Case34). The pathologist's excitement at seeing his firstcase of rhinosporidiosis caused him to examine thebiopsy specimen inadequately. The presence ofMycobacterium leprae in the tissue was not demon-strated until a chance review of the sections someyears later.

Case 16. Entamoeba histolytica infection of acoccidioidal cavity in a lung. A physician acquiredcoccidioidomycosis while studying in California.The disease failed to subside spontaneously and acavity formed and, following inadequate response toamphotericin, was excised. Three years later arecurrent cavity was also excised. The sectionsshowed the presence of both E. histolytica andC. immitis in the wall of the cavity. The patient hadsubclinical amoebic colitis. There has been norecurrence of either infection following appropriatetreatment. Another case of coexistent pulmonarycoccidioidomycosis and pulmonary amoebiasis has

been mentioned elsewhere (Symmers, 1973a, Figs7 and 8).

(C) Misidentification offungiCase 17. Blastomycosis of bone (Sissons, 1979). A

solitary skeletal focus of infection by Blastomycesdermatitidis was discovered in consequence of thepathological fracture that its presence had caused.Initially, the nature of the lesion was overlookedbecause only haematoxylin-eosin (HE) preparationsof the biopsy specimen were examined. At this timethe clinical investigation was oriented toward findinga primary carcinoma as the bone lesion was pre-sumed to be a metastatic deposit. No tumour wasfound. The sections were reviewed: many buddingyeast-like fungal cells were shown by special stainingprocedures; more careful study made it clear that theorganisms were visible in the HE preparations buthad been overlooked. Because of their size theorganisms were first taken for cryptococci. Later,because the patient had come from South Africa,they were interpreted as African histoplasmas (H.duboisii which, in fact, is not known to occur insouthern Africa). Finally, they were recognized to beB. dermatitidis; this was confirmed by specificimmunofluorescent staining. Meantime, the lesionhad healed with no treatment other than straight-forward orthopaedic measures. There has been nofurther evident infection.

ConclusionThe infections exemplified above, even if their

recognition was belated, were all eventually identifiedas being caused by known specific organisms. Duringthe same period when these cases were seen therewas also a very small number of cases of unidentifiedbut probably fungal infection. The appearances ofthe fungus (or presumed fungus) could not be identi-fied as belonging to any known genus. Two wereexamples of a peculiar infection (the so-called'Wewak disease') which to date has been observedonly in patients returning from Papua New Guinea.The lesions are verrucose or superficially ulceratednodules and areas of induration in the skin of alimb. The histological sections show histiocytosis ofthe dermis and great numbers of organisms in amucoid matrix that seems to be a product of theirgrowth (Fig. 1) (unpublished personal observations).The disease appears to be confined to the skin.Other infections of unidentified nature include a

form of widespread verrucose granulomatosis of theskin caused by a morphologically peculiar myceliatefungus and contracted in central or southern Africa(unpublished personal observations). Such casesindicate that the limits of knowledge of the variety oforganisms that may cause mycoses or related infec-tions in man have not yet been reached.

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602 W. St C. Symmers

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FIG 1. Histological sections of the lesions of 'Wewak' disease showing histiocytosis of the dermisand great numbers of organisms in a mucoid matrix which seems to be a product of their growth.

Algal infections seem now to be considered mostconveniently along with the mycoses (Baker et al.,1971). Infection by an alga (probably Proto-theca sp.) has been seen in an American visitingLondon. The organisms were first mistaken forspherules of Coccidioides immitis (Symmers, 1973a,Fig. 6).

ReferencesReferences prefixed with an asterisk relate to cases in

Table 1.BAKER, R.D. and 27 co-authors (1971) Human Infection with

Fungi, Actinomycetes and Algae. Springer-Verlag, NewYork.

SISSONS, H.A. (1979) In: Systemic Pathology, 2nd edn, vol. 5,p. 2420, Figs 37.35F and 37.35G. Churchill Livingstone,Edinburgh.

*SYMMERS, W.ST C. (1960) Histological examination in thediagnosis of deep-seated fungal infections. In: RecentAdvances in Clinical Pathology, Series 3 (Ed. by Dyke,S.C.), Section 4 (Ed. by Robb-Smith, A.H.T.), p. 304.J. &. A. Churchill, London.

*SYMMERS, W.ST C. (1963) Les infections mycosiques dusysteme nerveux central dues aux champignons d6mati6s-la cladosporiose c6r6brale et les infections semblables.Revue lyonnaise de medecine, 12, 979.

*SYMMERS, W.ST C. (1964) The tissue reactions in deep-seatedfungal infections. The role of histological examination inmycological diagnosis. Annales de la Societe' belge demJdecine tropicale, 44, 869.

*SYMMERS, W.ST C. (1966a) Les mycoses du systeme nerveuxcentral. Vie medicale, 47, 353.

*SYMMERS, W.ST C. (1966b) Deep-seated fungal infectionscurrently seen in the histopathologic service of a medical

school laboratory in Britain. American Journal of ClinicalPathology, 46, 514.

*SYMMERS, W.ST C. (1967) Cases of coccidioidomycosis seenin Britain. In: Coccidioidomycosis - Proceedings of SecondCoccidioidomycosis Symposium, Phoenix, Arizona (Ed. byAjello, L., p. 301. University of Arizona Press, Tucson.

*SYMMERS, W.ST C. (1968a) Aspects of contributions of histo-pathology to the study of deep-seated fungal infections. In:Systemic Mycoses - A Ciba Foundation Symposium inCommemoration of William Balfour Baikie (Ed. byWolstenholme, R.E.W. and Porter, Ruth), p. 26. J. & A.Churchill, London.

*SYMMERS, W.ST C. (1968b) Sporotrichosis in Ireland - areview. Ulster Medical Journal, 37, 85.

*SYMMERS, W.ST C. (1969) Fungal infections of the liver. Actahepatologica japonica, 10, 373.

*SYMMERS, W.ST C. (1971a) Die Histopathologie der tiefenMykosen unter besonderer Berucksichtigung der Lungen-mykosen (mit 29 erlauternden Fallen). Zentralblatt furBakteriologie, Parasitenkunde, Infektionskrankheiten undHygiene, L Abteilung, Originale, 217, 368.

SYMMERS, W.ST C. (1971b) New-style cold abscesses. BritishMedical Journal, 2, 337.

*SYMMERS, W.ST C. (1972a) Histopathology of phycomycoses.Annales de la Societj belge de midecine tropicale, 52, 365.

SYMMFRS, W.ST C. (1972b) Histoplasmosis in southern andsouth-eastern Asia - a syndrome associated with a peculiartissue form of histoplasma: a study of 48 cases. Annales dela Societe belge de medecine tropicale, 52, 435.

SYMMERS, W.ST C. (1973a) Histological diagnosis of fungalinfections. In: Anatomic and Clinical Pathology-Proceed-ings of the VIII World Congress of Anatomic and ClinicalPathology, Munich, 12-16 September 1972 (Ed. byNordmann, M., Merten, R. & Lommel, H.), p. 255.Excerpta Medica, Amsterdam.

*SYMMERS, W.ST C. (1973b) Fungal infections of the spine.British Medical Journal, 2, 423.

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