Postgrad Med J: first published as 10.1136/pgmj.55.647.598 on 1 September 1979. Downloaded from Postgraduate Medical Journal (September 1979) 55, 598-602

Imported mycoses: some diagnostic problems W. ST C. SYMMERS M.D. Charing Cross Hospital and Medical School, The Reynolds Building, St Dunstan's Road, London W6 8RP

Summary and possibly of other fungi that cause Infections by actinomycetes or by true fungi may cause may invade the subcutaneous diagnostic difficulties in countries where they are not tissues and eventually give rise to distant lesions as a familiar. Illustrative cases from a series of 353 result of spread by the lymphatics or in the blood instances are given together with rare indigenous stream. examples of the same infections. Early, accurate In any case of the infections listed above, and diagnosis is essential for rational and effective particularly in any case of those infections that occur treatment. less frequently in Europe than in other parts of the world, the possibility that infection took place while Introduction the patient was resident or travelling outside Europe The first, and in many cases the greatest, problem ought to be considered. None of the infections is in the correct clinical management of mycoses is their confined to Europe. In contrast, some important recognition. In general, delay in the diagnosis of mycoses do not occur naturally in north-westernProtected by copyright. mycoses results primarily from failure to consider Europe. that a fungal or actinomycetous infection may be the cause of a patient's symptoms. In this respect the Mycoses not indigenous in north-western Europe problem is a commonplace one, not confined to (caused by Blastomyces dermati- mycoses: its solution lies in greater knowledge and tidis); ; , including greater awareness of diagnostic possibilities. Among ; ; mycetomas the 353 cases of 'imported mycoses' in the accom- (except those caused by the fungi named in the list panying table, the possibility ofa was among of indigenous mycoses of north-western Europe, the initial diagnostic considerations in just under above); ; rhinoentomoph- 15%. thoromycosis; . However, instances of all these diseases have been Mycoses in north-western Europe seen in patients in north-western Europe whose In north-western Europe (the area covered by infection originated while they were in parts of the Belgium, Denmark, France, the German Federal world where the condition is indigenous. Further, in Republic, the Irish Republic, Luxemburg, The exceptional circumstances, blastomycosis, coccidio- http://pmj.bmj.com/ Netherlands, Norway, Sweden, and the United idomycosis, histoplasmosis and lobomycosis have Kingdom), the indigenous mycoses (excluding super- been acquired in north-western Europe (Table 1) ficial mycoses of the , ocular mycoses and either through inadvertent exposure to infective otomycoses) that are liable to cause serious and forms of the causative organism in laboratories or as progressive disease, or that are potentially disabling a result of contact with imported goods contamin- or potentially life-threatening, include the following: ated with the (or, in the case of lobomycosis, actinomycosis; adiaspiromycosis; ; basi- in consequence of a needle prick while excising a on September 25, 2021 by guest. diobolomycosis; ; chromomycosis (cutan- specimen from an infected dolphin). eous and subcutaneous; cerebral and meningocere- bral; other visceral infections); ; Diagnostic awareness ; mycetoma (caused by Acremonium spp., Although in comparison with the situation 10-20 nidulans and Petriellidium boydii); nocar- years ago there is now much more awareness among diosis (caused by Nocardia asteroides); penicilliosis; clinicians and in laboratories of the occurrence of petriellidiosis (pulmonary, see also mycetoma, mycoses, their recognition is still frequently delayed. above); (caused by Absidia spp., This is a world-wide shortcoming; even in North spp. and probably other genera); sporo- America, where we in Europe expect familiarity with trichosis. mycoses to be general, the diagnosis of those infec- It should also be remembered that species of tions that are endemic in parts of the continent is 0032-5473/79/0900-0598$02.00 © 1979 The Fellowship of Postgraduate Medicine Postgrad Med J: first published as 10.1136/pgmj.55.647.598 on 1 September 1979. Downloaded from Imported mycoses 599

very liable to be as much delayed, or almost so, mycoses as nocardiosis, the phycomycoses and through failure to consider the possibility of a . mycosis. A basic knowledge of some of the exotic mycoses including histoplasmosis, and less often of Geographical considerations coccidioidomycosis, is quite usual among young The importance of enquiring about a patient's British doctors. Yet the same doctors, and their geographical history and relating it to the presenting seniors, tend to be at best only vaguely and insuffi- clinical problem cannot be stressed too strongly. ciently informed about such infrequent indigenous Failure to do this may result in ignoring the possi- bility of an exotic fungal disease; this may lead to the patient's death. TABLE 1. Three hundred and fifty-three cases of non- Illustrative cases indigenous and rarely indigenous mycoses seen personally in Britain from 1946 to 1977 (figures in parentheses indicate the Only a brief sketch of some causes of delayed number of cases with firm evidence or good circumstantial recognition of 'imported' mycoses can be included evidence that infection was acquired in Britain or elsewhere here. The cases are from the series summarized in in north-western Europe) Table 1. Number of Mycosis cases (A) Diagnostic delay through failure to consider the 5 (2*) possibility of mycosis Blastomycosis ('North American') caused Case 1. Madurella mycetomatis mycetoma of the by 32 (2t) tibia. A boy whose home was in India was struck Blastomycosis, South American; see over the tibial tuberosity by a cricket ball while at papacoccidioidomycosis. school in England. The unexpectedly severe pain Chromomycosis 63 (21) Protected by copyright. cutaneous 31 (6*) that this caused led to X-ray examination which subcutaneous (phaeosporotrichosis) showed a large osteolytic lesion with some new bone caused or presumptively caused by formation. The radiological diagnosis was 'probable Phialophora gourgerotii 18 (6*) osteosarcoma'. and central nervous system, caused or Radiotherapy amputation were presumptively caused by Cladosporium advised. The child's guardians refused permission trichoides in most cases 11 (7*) for such treatment The lesion enlarged and showed other visceral infections (heart and/or signs of extension into the skin, with imminent lungs 3 (2*) ulceration. was then undertaken and Coccidioidomycosis 41 (27-22t; 5t) Biopsy showed Histoplasmosis, caused by Histoplasma colonies of M. mycetomatis in a chronic inflamma- capsulatum 101 (3-1t; 2t) tory mass. There was no . For the first time Histoplasmosis, African, caused by a careful history was taken: this disclosed that the H. duboisii 14 (0) Lobomycosis (occupational contact with child had accidentally run an acacia thorn into the naturally infected dolphin that had leg at the site of the eventual mycetoma. The remains been captured in European waters) of the thorn were found in tissue removed during Mycetoma: 71 (2) further conservative surgical treatment. Recovery http://pmj.bmj.com/ actinomycetous: 24 (0) followed. A. madurae 6 (0) Actinomadura pelletieri 3 (0) Case 2. Nocardia brasiliensis mycetoma of the Nocardia brasiliensis 10 (0) shoulder region. A Mexican student in London was Streptomyces somaliensis 5 (0) treated over many months for 'chronic furunculosis' fungal: 47 (2) of the skin of the back of one There was Acremonium falciforme 2 (0) shoulder. Aspergillus spp. 2 (0) little effect from a wide range of antibacterial anti- Leptosphaeria senegalensis 4 (0) biotics and fresh lesions continued to appear over an Madurella grisea 3 (0) increasingly wide area. Eventually, the patient con- on September 25, 2021 by guest. M. mycetomatis 19 (0) sulted a fellow was on Microsporum ferrugineum 4 (0) countryman who a post- Petriellidium boydii 5 (2*) graduate course in England: the latter made an Phialophora jeanselmei 7 (0) immediate diagnosis of N. brasiliensis infection on Zopfia rosatii 1 (0) clinical grounds; this was soon confirmed both Paracoccidioidomycosis 9 (0) Penicilliosis presumptively caused by histologically and by isolation of the organism. Penicillium marneffei 1 (0) Treatment with a sulphone resulted in cure. Rhinoentomophthoromycosis 2 (0) Case 3. N. brasiliensis mycetoma of foot. An Rhinosporidiosis 13 (0) English student gave a history of transfixion of one * Naturally occurring indigenous infections. foot by a thorn, which pierced it from the sole to the t Infections presumptively mediated by fomites. dorsum in the region of the head of the metatarsal L$aboratory infections. bones of the fourth and fifth toes. The thorn was Postgrad Med J: first published as 10.1136/pgmj.55.647.598 on 1 September 1979. Downloaded from 600 W. St C. Symmers immediately withdrawn intact. Some months later a at school in Europe was looked after by a succession 'boil' appeared at the site of the former puncture on of doctors over a period of 9 months during which the dorsum of the foot. By this time the student had extensive ulceration of the skin of one cheek de- returned to England from the region of Central veloped; the accompanying cervical and submental America in which he had been working on an lymphadenitis became complicated by sinus forma- archaeological site at the time of the injury. The tion. Although no Leishmania could be shown in the 'boil' persisted in spite of treatment with anti- lesions she was repeatedly treated for leishmaniasis. bacterial drugs. After some months colonies of N. Eventually the possibility of a fungal infection was brasiliensis were recognized in the discharge. The suggested and was isolated. infection subsided permanently on treatment with Treatment with iodide led to healing. Gross scarring dapsone. was left. Case 4. N. brasiliensis mycetoma of the forearm. Case 9. Generalized coccidioidomycosis. An A Venezuelan, resident in London, developed a Italian man, living in Britain, developed what was series of ulcerating nodules in the subcutaneous regarded as a classic gummatous ulcer in the skin tissue of one forearm. His case was demonstrated at over the sternum. Medical students were summoned a clinical meeting as a classic example of the ascend- to see what was demonstrated to them as that ing lymphangitic type of sporotrichosis, although contemporary rarity, clinical evidence of tertiary Sporothrix had not been isolated. It was a young syphilis. When serological tests for syphilis proved Mexican doctor in the audience who made the to be negative a biopsy was undertaken and showed correct clinical diagnosis ofN. brasiliensis mycetoma: immitis; the fungus was isolated in he had been taught in his own country that sporo- culture (and a number of members of the laboratory trichosis is only one of several infections that may staff the The condition present with this picture. His diagnosis was con- acquired infection). patient's had deteriorated seriously during the weeks betweenProtected by copyright. firmed. The condition responded to treatment with the initial diagnosis of syphilis and the eventual dapsone. diagnosis of coccidioidomycosis; he died in spite of Case 5. Verrucose chromomycosis of the arm. intensive treatment with amphotericin and flucy- An Englishman who had recently retired to Germany tosine. He had worked as an agricultural labourer in after many years' residence in Jamaica sought treat- U.S.A. ment for a chronic verrucose eruption that extended California, from the dorsum of one hand to above the elbow. Case 10. Coccidioidal pneumonia complicating A clinical and histological diagnosis of chronic Hodgkin's disease (Symmers, 1967- Case 1). A verrucose was made and intensive medical student from California died in Britain of treatment with a range of anti-tuberculosis drugs, pneumonia that did not respond to antibacterial supplemented by excision of the larger of the lesions, antibiotics. The post-mortem showed the pneumonia was undertaken. It was not until one year later that to be coccidioidal. Review of the clinical case notes a review of the histological specimens in another showed that although the patient's statement that he country disclosed the presence in every lesion had once had 'valley fever' had been recorded, apparently no steps had been taken to discover what examined of typical pigmented fungal cells of http://pmj.bmj.com/ Phialophora sp. 'valley fever' was. Had it been realized that 'valley Case 6. Psoriasiform chromomycosis of the fever' was the vernacular term for the illness accom- elbow. A lesion, variously regarded as pustular panying the initial infection by Coccidioides, psoriasis, lichen, traumatic keratosis and dermatitis acquired in the San Joaquin Valley, in California, it artefacta, proved after many months of study in might have been realized that the patient's pneu- various hospitals to be chromomycotic. The fungal monia could be a manifestation of the fungal cells had been overlooked in biopsy specimens. The infection, reactivated by the coincident development patient had never been outside the British Isles. His of Hodgkin's disease and the immunosuppressive on September 25, 2021 by guest. occupation was agricultural. effects of the treatment that was given for the latter. Case 7. Subcutaneous chromomycosis (phaeo- Case 11. Bilateral apical cavitating pulmonary his- sporotrichosis) (Symmers, 1971b). A large 'cold toplasmosis complicated by Histoplasma meningitis. abscess' in the upper part of a thigh was assumed to Haemoptysis led to the radiological demonstration be tuberculous. It was repeatedly aspirated but it of cavities in both lungs of a European businessman regularly re-formed. Anti-tuberculosis drugs had no who had spent many years in Kentucky and Ohio, effect. The patient was a Pakistani immigrant in U.S.A. He was treated with anti-tuberculosis drugs, Britain. He moved to Germany, where biopsy of the in spite of failure to demonstrate mycobacteria in his wall of the abscess showed pigmented fungal sputum; the treatment was ineffectual and he died. elements. P. gougerotii was isolated. Histoplasmosis was found at post-mortem to have Case 8. Sporotrichosis of the . An Iranian girl been the cause of the pulmonary disease; the Postgrad Med J: first published as 10.1136/pgmj.55.647.598 on 1 September 1979. Downloaded from Imported mycoses 601 infection had spread to the meninges in the terminal been mentioned elsewhere (Symmers, 1973a, Figs stages of the illness. 7 and 8). Case 12. Oral ulceration and Addison's disease due to histoplasmosis (Symmers, 1972). A Dutchman (C) Misidentification offungi who had spent many years as a public works con- Case 17. Blastomycosis of bone (Sissons, 1979). A tractor in south-eastern Asia developed Addison's solitary skeletal focus of infection by Blastomyces disease during his retirement in Europe. He also had dermatitidis was discovered in consequence of the extensive ulceration of the tongue, lips and throat. pathological fracture that its presence had caused. Hormone therapy and anti-tuberculosis drugs had Initially, the nature of the lesion was overlooked little effect. Post-mortem showed destruction of both because only haematoxylin-eosin (HE) preparations adrenals by caseous tissue that contained great of the biopsy specimen were examined. At this time numbers of H. capsulatum. The oral ulcers were also the clinical investigation was oriented toward finding a manifestation of histoplasmosis. There had been a primary carcinoma as the bone lesion was pre- no biopsy or other laboratory examination of these sumed to be a metastatic deposit. No tumour was lesions at any time during his illness. found. The sections were reviewed: many budding Case 13. African histoplasmosis. A surgeon's arm -like fungal cells were shown by special staining was amputated because his colleagues failed to see procedures; more careful study made it clear that the H. duboisii in the foreign-body giant cells in the organisms were visible in the HE preparations but biopsy of an osteolytic lesion in one radius. The giant had been overlooked. Because of their size the cells were interpreted as sarcomatous. organisms were first taken for cryptococci. Later, Case 14. Paracoccidioidomycosis of the face. A because the patient had come from South , Portuguese man, working in a London hospital as a they were interpreted as African histoplasmas (H. porter, developed a chronic ulcer of the skin of one duboisii which, in fact, is not known to occur in cheek. The clinical likeness of the lesion to that in southern Africa). Finally, they were recognized to be Protected by copyright. Case 8 (above) led to a diagnosis of sporotrichosis. B. dermatitidis; this was confirmed by specific When treatment with iodide had no effect on the immunofluorescent staining. Meantime, the lesion condition the possibility of carcinoma was con- had healed with no treatment other than straight- sidered. Biopsy showed no evidence of a tumour. It forward orthopaedic measures. There has been no was a further 7 months before the sections were further evident infection. reviewed and the presence in them of typical forms of Paracoccidioides brasiliensis demonstrated. Mean- Conclusion time, the ulcer had almost doubled its extent. Ugly The infections exemplified above, even if their scarring accompanied the eventual cure. The patient recognition was belated, were all eventually identified had worked in Brazil some years earlier. as being caused by known specific organisms. During the same period when these cases were seen there (B) Double infections was also a very small number of cases of unidentified Case 15. Rhinosporidiosis of the nasal septum but probably fungal infection. The appearances of with accompanying (Symmers, 1966 b - Case the fungus (or presumed fungus) could not be identi- http://pmj.bmj.com/ 34). The pathologist's excitement at seeing his first fied as belonging to any known genus. Two were case of rhinosporidiosis caused him to examine the examples of a peculiar infection (the so-called biopsy specimen inadequately. The presence of 'Wewak disease') which to date has been observed Mycobacterium leprae in the tissue was not demon- only in patients returning from Papua New Guinea. strated until a chance review of the sections some The lesions are verrucose or superficially ulcerated years later. nodules and areas of induration in the skin of a Case 16. Entamoeba histolytica infection of a limb. The histological sections show histiocytosis of coccidioidal cavity in a lung. A physician acquired the dermis and great numbers of organisms in a on September 25, 2021 by guest. coccidioidomycosis while studying in California. mucoid matrix that seems to be a product of their The disease failed to subside spontaneously and a growth (Fig. 1) (unpublished personal observations). cavity formed and, following inadequate response to The disease appears to be confined to the skin. amphotericin, was excised. Three years later a Other infections of unidentified nature include a recurrent cavity was also excised. The sections form of widespread verrucose granulomatosis of the showed the presence of both E. histolytica and skin caused by a morphologically peculiar myceliate C. immitis in the wall of the cavity. The patient had fungus and contracted in central or southern Africa subclinical amoebic colitis. There has been no (unpublished personal observations). Such cases recurrence of either infection following appropriate indicate that the limits of knowledge of the variety of treatment. Another case of coexistent pulmonary organisms that may cause mycoses or related infec- coccidioidomycosis and pulmonary amoebiasis has tions in man have not yet been reached. Postgrad Med J: first published as 10.1136/pgmj.55.647.598 on 1 September 1979. Downloaded from 602 W. St C. Symmers

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

Algal infections seem now to be considered most school laboratory in Britain. American Journal of Clinical conveniently along with the mycoses (Baker et al., Pathology, 46, 514. *SYMMERS, W.ST C. (1967) Cases of coccidioidomycosis seen 1971). Infection by an alga (probably Proto- in Britain. In: Coccidioidomycosis - Proceedings of Second theca sp.) has been seen in an American visiting Coccidioidomycosis Symposium, Phoenix, Arizona (Ed. by London. The organisms were first mistaken for Ajello, L., p. 301. University of Arizona Press, Tucson. spherules of (Symmers, 1973a, *SYMMERS, W.ST C. (1968a) Aspects of contributions ofhisto- pathology to the study of deep-seated fungal infections. In: Fig. 6). Systemic Mycoses - A Ciba Foundation Symposium in Commemoration of William Balfour Baikie (Ed. by Wolstenholme, R.E.W. and Porter, Ruth), p. 26. J. & A. http://pmj.bmj.com/ References Churchill, London. References prefixed with an asterisk relate to cases in *SYMMERS, W.ST C. (1968b) Sporotrichosis in Ireland - a Table 1. review. Ulster Medical Journal, 37, 85. BAKER, R.D. and 27 co-authors (1971) Human Infection with *SYMMERS, W.ST C. (1969) Fungal infections of the liver. Acta Fungi, Actinomycetes and Algae. Springer-Verlag, New hepatologica japonica, 10, 373. York. *SYMMERS, W.ST C. (1971a) Die Histopathologie der tiefen SISSONS, H.A. (1979) In: Systemic Pathology, 2nd edn, vol. 5, Mykosen unter besonderer Berucksichtigung der Lungen- p. 2420, Figs 37.35F and 37.35G. Churchill Livingstone, mykosen (mit 29 erlauternden Fallen). Zentralblatt fur

Edinburgh. Bakteriologie, Parasitenkunde, Infektionskrankheiten und on September 25, 2021 by guest. *SYMMERS, W.ST C. (1960) Histological examination in the Hygiene, L Abteilung, Originale, 217, 368. diagnosis of deep-seated fungal infections. In: Recent SYMMERS, W.ST C. (1971b) New-style cold abscesses. British Advances in Clinical Pathology, Series 3 (Ed. by Dyke, Medical Journal, 2, 337. S.C.), Section 4 (Ed. by Robb-Smith, A.H.T.), p. 304. *SYMMERS, W.ST C. (1972a) Histopathology of phycomycoses. J. &. A. Churchill, London. Annales de la Societj belge de midecine tropicale, 52, 365. *SYMMERS, W.ST C. (1963) Les infections mycosiques du SYMMFRS, W.ST C. (1972b) Histoplasmosis in southern and systeme nerveux central dues aux champignons d6mati6s- south-eastern Asia - a syndrome associated with a peculiar la cladosporiose c6r6brale et les infections semblables. tissue form of histoplasma: a study of 48 cases. Annales de Revue lyonnaise de medecine, 12, 979. la Societe belge de medecine tropicale, 52, 435. *SYMMERS, W.ST C. (1964) The tissue reactions in deep-seated SYMMERS, W.ST C. (1973a) Histological diagnosis of fungal fungal infections. The role of histological examination in infections. In: Anatomic and Clinical Pathology-Proceed- mycological diagnosis. Annales de la Societe' belge de ings of the VIII World Congress of Anatomic and Clinical mJdecine tropicale, 44, 869. Pathology, Munich, 12-16 September 1972 (Ed. by *SYMMERS, W.ST C. (1966a) Les mycoses du systeme nerveux Nordmann, M., Merten, R. & Lommel, H.), p. 255. central. Vie medicale, 47, 353. Excerpta Medica, Amsterdam. *SYMMERS, W.ST C. (1966b) Deep-seated fungal infections *SYMMERS, W.ST C. (1973b) Fungal infections of the spine. currently seen in the histopathologic service of a medical British Medical Journal, 2, 423.