INTRODUCTION

Primary cutaneous zygomycosis results from the direct inoculation of fungi belonging to the class Zygomycetes intotissue following disruption of the barrier function of the skineither from burns or other trauma. Two types have beendescribed. One is a subacute superficial form in which vesicles or pustules progress to eschar formation in an other-wise normal host. The second is a rapidly progressive gan-grenous form in patients with altered immunity, which ischaracterized by a central black necrotic area with a marginof erythematous to violaceous cellulitis, with the potential todisseminate if untreated.1 In the hospital setting, intravascu-lar catheterization,2 the use of contaminated adhesive elasticbandages,3 and wooden spatulas used as splints in neonates4

have been associated with this primary cutaneous zygo-mycosis.

Secondary cutaneous zygomycosis follows the haematoge-nous dissemination of the infection from pre-existing lesions2

and appears to be the less common form. Cutaneous infec-tions resulting from disseminated infection usually present asnodular subcutaneous lesions that may ulcerate.5 The muco-ralean zygomycetes invade blood vessels causing ischaemia,thrombosis and tissue necrosis, with minimal inflammatoryresponse. In the skin, this results in necrotic ulcers with blackeschars which expand to produce severe mucormycotic gangrenous cellulitis.2 In some infections, extension into thesubcutaneous fascia results in necrotizing fasciitis which israpidly progressive. Invasion of the blood vessels carries therisk of disseminated infection. Of the zygomycetes, Apophyso-myces elegans, Saksenaea vasiformis and Mucor spp. are morecommonly associated with cutaneous or wound zygomycosis.5

Mucor species have rarely been implicated as causing cuta-neous zygomycosis.

We describe the diagnosis and treatment of a cutaneous M. circinelloides infection on the forearm of a 62-year-oldwoman with myelodysplastic syndrome.

CASE REPORT

A 62-year-old woman with myelodysplastic syndrome pres-ented with a 4-week history of a non-healing ulcer on the volar aspect of her left forearm. On examination the ulcer was 4 cm by 6 cm with a central black eschar and had an erythematous edge (Fig. 1). Further history revealed that she had grazed her left forearm on a door 2 weeks before presentation and that the ulcer had developed from the abra-sion. The patient was afebrile. There were no other skinlesions and she had no palpable axillary lymph nodes. Apartfrom regular transfusions of packed cells and platelets, shehad received no treatment for her myelodysplastic syndrome.

A punch biopsy of the lesion showed features characteristicof a necrotizing fungal fasciitis/cellulitis consistent withzygomycosis. The subcutaneous fat and the deep dermis werecompletely necrotic and contained broad, irregular, sparselyseptate fungal hyphae which showed right-angled branchingconsistent with a zygomycete on haematoxylin and eosin(H&E) (Fig. 2) and periodic acid-Schiff (PAS) stains. Fungalhyphae were also present in the non-necrotic deep dermis andthere was an intense chronic inflammatory infiltrate. Theoverlying epidermis was mildly hyperplastic but otherwiseunremarkable. Endoscopic examination revealed a normal

Australasian Journal of Dermatology (2002) 43, 39–42

CASE REPORT

Primary cutaneous zygomycosis due to Mucor circinelloides

Suresh Chandra1 and Alan Woodgyer2

1Skin and Cancer Foundation and 2Microbiological Diagnostic Unit, The University of Melbourne, Melbourne, Victoria, Australia

SUMMARY

A 62-year-old woman with myelodysplastic syndromepresented with a 4-week history of a large induratedulcer with a black eschar on the forearm followingtrauma. On biopsy a diagnosis of zygomycosis wasmade as broad, sparsely septate, thin-walled hyphaewere seen in the deep dermis and subcutaneous fat.The zygomycete fungus Mucor circinelloides was cul-tured from tissue. Further investigation confirmed thatthe infection was localized to the skin. The 6 × 4 cmlesion was excised and the defect closed with a neuro-vascular island flap. No other treatment was under-taken. The patient died 6 months later from herhaematological disease without recurrence of the fungal infection.

Key words: myelodysplastic syndrome, oppor-tunistic.

Correspondence: Dr Suresh Chandra, Skin and Cancer Foundation,95 Rathdowne Street, Carlton, Vic. 3053, Australia. Email: chandrapete@hotmail.com

Suresh Chandra, MB BS. Alan Woodgyer, BSc (Hons).Submitted 26 March 1998; accepted 19 July 2001.

nasopharynx and nasal cavity. Sputum cultures were negativefor fungal elements and a chest X-ray was normal. There wereno significant findings on gastroscopy and a computerizedtomography (CT) scan of the abdomen was normal.

The lesion was surgically excised with a 1 cm margin andthe defect closed with a neurovascular island flap. Histo-pathology of the specimen confirmed the biopsy findings andthe ulcer was well clear of the margins. Six months after thesurgery, the patient died from her haematological illness.During this time, she suffered no recurrence of the fungalinfection.

MYCOLOGY

Culture of the specimen at 30°C on Sabouraud glucose agaryielded a fast-growing fungus that formed white cottonycolonies up to 6 mm in height and which became greyishbrown as sporulation occurred. The fungus grew well at 37°Cbut failed to grow at 40°C. The following description is basedon the morphology on malt extract and Czapek (Pitt modifi-cation6) agars incubated at 28°C for 9 days.

Microscopic examination showed the absence of stolons,apophyses and rhizoids. The hyphae contained yellow-brownoil-like droplets which were particularly notable on maltextract agar. Chlamydospores were produced in small num-bers. The sporangiophores were either tall or short and mostwere sympodially branched. The longer branches tended tobe erect whereas the shorter ones were sometimes circinate.The sporangia were globose, brownish grey, with spinulosewalls and ranged in size from 16 to 80 �m. The walls of thelarger sporangia readily broke down releasing their contentswhilst those of the smaller sporangia were more persistent.The columellae were variable in shape, globose in the smallersporangia but becoming more elongate in the larger sporangia.The walls of the larger sporangia left collars at the base of thecollumellae when they broke down. The sporangiosporeswere 4–6 �m in size, ellipsoidal and smooth. On the basis of the macro- and micromorphology and the temperature studies, the isolate was identified as M. circinelloides.7–9

DISCUSSION

Cutaneous zygomycosis is rare but has a sufficiently distinc-tive clinical presentation to prompt consideration of the diag-nosis. The diagnosis needs to be considered in patients whopresent with ecthyma gangrenosum-like lesions that appearnecrotic with marginal erythema and in burn patients with a secondary change in the appearance of the burn with associated fever.10 Necrotizing bacterial infections such asanaerobic cellulitis and fasciitis need to be excluded as partof the differential diagnosis.2

The diagnosis of zygomycosis is made on the basis of a full-thickness skin biopsy and on culture. In histology sections thediagnosis is confirmed by the finding of broad, thin-walled,irregular, sparsely septate hyphae ranging from 3 to 25 �m indiameter (average 12 �m) which show right-angled branch-ing. The zygomycetes stain well in H&E sections and althoughspecial stains such as PAS can be helpful, they tend to stainthe zygomycetes less intensely compared with other fungi.Blood vessels present in sections are usually invaded by fungal hyphae.11

Culture is essential to identify the aetiologic agents. Negativecultures may result from the use of tissue grinders to processspecimens as these are known to reduce the viability of zygo-mycetes. The growth of the zygomycetes is inhibited by cyclo-heximide and specimens from suspected cases of zygomycosisshould not be cultured onto media containing this chemical.A number of reports in the literature are incomplete. Eitherno culture was undertaken12 because at the time of specimencollection the diagnosis was not suspected, or the identifica-tion only goes as far as the genus.1,2,13–16 Although all too com-mon in the recent literature, the latter is unacceptable, assignificant fungal isolates should be referred to a reference laboratory for full identification. Negative cultures might alsobe reported if the resulting isolates were dismissed as conta-minants, or have failed to either grow on subculture or tosporulate.

Mucor circinelloides was the fungus responsible for primarycutaneous zygomycosis in our patient. According to the avail-able literature, there have been only three previous reports of

40 S Chandra and A Woodgyer

Figure 1 Zygomycotic lesion on the volar aspect of the left forearm.Note the central black eschar.

Figure 2 Section of the lesion in Fig. 1 showing the typical large,broad and non-septate hyphae (H&E).

cutaneous zygomycosis caused by this fungus.17–19 The first ofthese was a cutaneous lesion at an injection site in an intra-venous drug abuser with no underlying immunodeficiency.17

The infection was successfully treated by wide surgicaldebridement and amphotericin B. The second case occurredin a Chinese farmer with a lesion on the dorsum of the righthand which had been present for 17 years. There was nounderlying disease and treatment was not discussed in thereport.18 In neither of these patients was there evidence of inva-sion of blood vessels. The third case was in a 23-year-oldwoman receiving chemotherapy for acute myelogenousleukaemia who had necrotic lesions on her left shin, left calf,left patella and chest. Biopsy specimens from the shin andchest showed fungal hyphae in the deep and superficial dermis and in small blood vessels resulting in epidermalnecrosis. Culture of a biopsy from her chest lesion yielded apure growth of M. circinelloides. Culture of a nasal swab also yielded a pure growth of M. circinelloides. The lesionsresponded to amphotericin B and surgery was not required.19

In our patient, the lesion was excised and the skin defect thenclosed with a neurovascular island flap. Subsequent investi-gations showed no evidence of M. circinelloides infection else-where, which was consistent with a diagnosis of primarycutaneous zygomycosis. There was no evidence of recurrenceof the infection in the 6 months prior to her death.

Extensive surgical debridement is considered by someauthorities to be the key to the successful management of primary cutaneous zygomycosis and that antifungal chemo-therapy be used in patients with either underlying disease orprogressive disease zygomycosis.20,21 In the present case sur-gical excision with a 1 cm margin gave a good result with noevidence of residual infection up until the patient’s death some6 months later. Other reports in the literature favour the com-bination of extensive surgical debridement, the prompt admin-istration of high doses of amphotericin B and the treatment ofpredisposing conditions.2 Mucor circinelloides is highly sus-ceptible to amphotericin B.19 Some authors consider there tobe some potential marginal benefit in using an additional anti-fungal such as itraconazole in the treatment of cutaneouszygomycosis.16 In one recent case, hyperbaric oxygen was usedas an adjunctive treatment to surgery and amphotericin B,which resulted in almost complete healing of the ulcer after2 months.13 Granulocyte colony-stimulating factor (G-CSF)was used together with liposomal amphotericin B to treat anAbsidia corymbifera infection in a 12-year-old boy who hadundergone an allogenic bone marrow transplant. The authorsconsidered that the G-CSF may have contributed to the suc-cessful outcome by shortening the neutropenic period.22

The prognosis of cutaneous zygomycosis depends on thelocation and extent of the infection, whether the patient isimmunocompromised and on how quickly the diagnosis ismade. The prognosis is poor and death usually results if infec-tion extends into the vital organs.23 One study concluded thatcutaneous zygomycosis has a much more favourable prog-nosis than the other forms of zygomycosis but was still asso-ciated with significant fatality and long-term morbidity rates.The mortality rate is 16% for cutaneous zygomycosis com-pared with 100% for disseminated and gastrointestinal forms.21

In cases of cutaneous zygomycosis, appropriate investigations

should be conducted to exclude rhinocerebral, pulmonary andgastrointestinal involvement.

Cutaneous zygomycosis is a rare condition but should beconsidered in the differential diagnosis of a non-healing ulcer,especially in an immunocompromised patient. Because of theability of the fungal hyphae to invade blood vessels and dis-seminate haematogenously, patients with cutaneous lesionsare at risk of secondary generalized and life threatening infec-tions.1 Thus early diagnosis is important.

REFERENCES

1. Wirth F, Perry R, Eskenazi A, Schwalbe R, Kao E. Cutaneousmucormycosis with subsequent visceral dissemination in a childwith neutropenia: A case report and review of pediatric literature.J. Am. Acad. Dermatol. 1997; 36: 336–41.

2. Baraia J, Munoz P, Bernaldo de Quiros JCL, Bouza E. Cutaneousmucormycosis in a heart transplant patient associated with aperipheral catheter. Eur. J. Clin. Microbiol. Infect. Dis. 1995; 14:813–15.

3. Gartenberg G, Bottone EJ, Keusch GT, Weitzman I. Hospital-acquired mucormycosis (Rhizophus rhizopodiformis) of skin andsubcutaneous tissue. N. Engl. J. Med. 1978; 299: 1115–18.

4. Michell SJ, Gray J, Morgan MEI, Hocking MD, Durbin GM.Nosocomial infection with Rhizopus microsporus in preterminfants: An association with wooden tongue depressors. Lancet1996; 348: 441–3.

5. Ribes JA, Vanover-Sams CL, Baker DJ. Zygomycetes in human disease. Clin. Microbiol. Rev. 2000; 13: 236–301.

6. Klich MA, Pitt JI. Identification media and methods. In: ALaboratory Guide to the Common Aspergillus Species and TheirTeleomorphs. North Ryde: Commonwealth Scientific and IndustrialResearch Organisation, 1988; 6.

7. de Hoog GS, Guarro J, Tan CS, Wintermans RGF, Gene J. Part 1.Pathogenic fungi and common opportunists. In: Atlas of ClinicalFungi. Baarn: Centraalbureau voor Schimmelcultures | UniversitatRovira i Virgili: Reus, 1995; 49–50.

8. Samson RA, Hoekstra ES, Van Oorschot CAN. Zygomycetes. In:Introduction to Food-Borne Fungi, 2nd edn. Baarn: Centraalbureauvoor Schimmelcultures, 1984; 4–23.

9. Scholer HJ, Muller E, Schipper MAA. Mucorales. In: Howard DH,Howard LF (eds) Fungi Pathogenic for Humans and Animals (in Three Parts) Part A Biology. New York: Marcel Dekker, 1983;9–59.

10. Hata TR, Johnson RA, Barnhill R, Dover JS. Ecthyma-like lesionson the leg of an immunocompromised patient. Arch. Dermatol.1995; 131: 836–7.

11. Chandler FW, Kaplan W, Ajello L. Zygomycetes. In: A Colour Atlasand Text Book of the Histopathology of Mycotic Diseases. London:Wolfe Medical Publications Ltd, 1980; 122–7.

12. Geller JD, Peters MS, Su WPD. Cutaneous mucormycosis resem-bling superficial granulomatous pyoderma in an immuno-compromised host. J. Am. Acad. Dermatol. 1993; 29: 462–5.

13. Bentur Y, Shupak A, Raman Y, Abramovich A, Wolfin G, Stein H,Krivoi N. Hyperbaric oxygen therapy for cutaneous/soft-tissuezygomycosis complicating diabetes mellitus. Plast. Reconst. Surg.1998; 102: 822–4.

14. Umbert IJ. Su WPD. Cutaneous mucormycosis. J. Am. Acad.Dermatol. 1989; 21: 1232–4.

15. Penas PF, Rios L, de la Camara R, Fraga J, Daudan E. Cutaneouslesions as the first sign of disseminated mucormycosis. Arch. Derm.Venereol. 1995; 75: 166–7.

16. Trigg ME, Comito MA, Rumelhart SL. Cutaneous mucor infectiontreated with wide excision in two children who underwent marrow transplantation. J. Pediatr. Surg. 1996; 31: 976–7.

Cutaneous zygomycosis 41

17. Fetchick RJ, Rinaldi MG, Sun SH. Zygomycosis due to Mucorcircinelloides, a rare agent of human fungal diseases [abstract no.F42]. In: Proceedings of the Annual Meeting of the American Societyfor Microbiology. Washington DC: American Society for Micro-biology, 1986; 404.

18. Wang JJ, Satoh H, Takahashi H, Hasegawa A. A case of cutaneous mucormycosis in Shanghai, China. Mycoses 1990; 33:311–15.

19. Fingeroth JD, Roth RS, Talcott JA, Rinaldi MG. Zygomycosis dueto Mucor circinelloides in a neutropenic patient receivingchemotherapy for acute myelogenous leukemia. Clin. Infect. Dis.1994; 19: 135–7.

20. Chakrabarti A, Kumar P, Padhye AA, Chatha L, Singh SK, Das A,

Wig JD, Kataria RN. Primary cutaneous mucormycosis due toSaksenaea vasiformis and Apophysomyces elegans. Clin. Infect. Dis.1997; 24: 580–3.

21. Adam RD, Hunter G, DiTomasso J, Comerci G Jr. Mucormycosis:Emerging prominence of cutaneous infections. Clin. Infect. Dis.1994; 19: 67–76.

22. Leong K, Crowley B, White B, Crotty GM, O’Brian DS, Keane C,McCainn SR. Cutaneous mucormycosis due to Absidia corymbiferaoccurring after bone marrow transplantation. Bone MarrowTransplant. 1997; 19: 513–15.

23. Hurle A, Campos-Herrero MI, Rodriguez H, Elcuaz R, Arroyo J,Floriano P, Arbad C. Cutaneous mucormycosis of the thoracic wall.Clin. Infect. Dis. 1996; 22: 373–4.

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