Conidiobolomycosis, one of the forms of subcutaneous zygomycosis, also known as rhinoentomophthoromycosis,1Ribes J.A. Vanover-Sams C.L. Baker D.J. Zygomycetes in human disease.Clin Microbiol Rev. 2000; 13: 236-301Crossref PubMed Scopus (1218) Google Scholar, 2Sharma N.L. Mahajan V.K. Singh P. Orofacial conidiobolomycosis due to Conidiobolus incongruus.Mycoses. 2003; 46: 137-140Crossref PubMed Scopus (16) Google Scholar is a granulomatous infection usually caused by Conidiobolus coronatus.1Ribes J.A. Vanover-Sams C.L. Baker D.J. Zygomycetes in human disease.Clin Microbiol Rev. 2000; 13: 236-301Crossref PubMed Scopus (1218) Google Scholar, 2Sharma N.L. Mahajan V.K. Singh P. Orofacial conidiobolomycosis due to Conidiobolus incongruus.Mycoses. 2003; 46: 137-140Crossref PubMed Scopus (16) Google Scholar, 3Bras G. Gordon C.C. Emmons C.W. Prendegast K.M. Sugar M. A case of phycomycosis observed in Jamaica; infection with Entomophthora coronata.Am J Trop Med Hyg. 1965; 14: 141-145PubMed Google Scholar, 4Fromentin H. Ravisse P. Tropical entomophthoromycoses (in French).Acta Trop. 1977; 34: 375-394PubMed Google Scholar The first case of conidiobolomycosis in humans was reported in 1965.3Bras G. Gordon C.C. Emmons C.W. Prendegast K.M. Sugar M. A case of phycomycosis observed in Jamaica; infection with Entomophthora coronata.Am J Trop Med Hyg. 1965; 14: 141-145PubMed Google Scholar Most cases have been reported from Africa, Asia and the Americas, i.e., tropical or subtropical regions, and few cases have been caused by Conidiobolus incongruus.5Busapakum R. Youngchaiyud U. Sriumpai S. Segretain G. Fromentin H. Disseminated infection with Conidiobolus incongruus.Sabouraudia. 1983; 21: 323-330Crossref PubMed Scopus (29) Google Scholar, 6Walsh T.J. Renshaw G. Andrews J. Kwon-Chung J. Cunnion R.C. Pass H.I. et al.Invasive zygomycosis due to Conidiobolus incongruus.Clin Infect Dis. 1994; 19: 423-430Crossref PubMed Scopus (61) Google Scholar, 7Temple M.E. Brady M.T. Koranyi K.I. Nahata M.C. Periorbital cellulitis secondary to Conidiobolus incongruus.Pharmacotherapy. 2001; 21: 351-354Crossref PubMed Scopus (22) Google Scholar, 8Hay R.J. Fungal infections.in: Cook G.C. Zumla A.I. Manson's tropical diseases. 21st ed. Saunders, London2003: 1173-1194Google Scholar, 9Al-Hajjar S. Perfect J. Hashem F. Tufenkeji H. Kayes S. Orbitofascial conidiobolomycosis in a child.Pediatr Infect Dis J. 1996; 15: 1130-1132Crossref PubMed Scopus (14) Google Scholar We describe herein a case of an atypically localized conidiobolomycosis due to C. incongruus in a patient with type 2 diabetes, in which multiple complications led to the patient's death. A 49-year-old female, born and living in Ciudad Bolivar (a southern dry weather city, median temperature of 27.5 °C), Venezuela, presented with a complaint of pain in her right foot; she had a one-week history of ulcers on both heels, and had had intense pain in that foot the day before she was admitted. Violaceous lesions and secretions in that region were evident in the previous 12 hours. She related a history of 30 years of type 2 diabetes and 14 years of hypertension, with irregular control of these diseases. She had chronic renal failure as a result of diabetic nephropathy and was currently undergoing dialysis. Her condition at presentation was normal with a suspected diagnosis of erysipelas. Initial empirical treatment consisted of amikacin, clindamycin and vancomycin, but zygomycosis was also suggested as a diagnosis, and therefore further investigations were made. Smears with different stains prepared from the secretions showed large strap-like hyphae. Culture on Sabouraud glucose agar at 37 °C showed a glabrous growth on the third day and was cottony on the fifth day, with the opposite surface wall of the slant culture hazy and covered with discharged spores. Zygospores were not visualized in the preparations and the lactophenol cotton blue preparation showed globose, non-villose conidia, with pointed basal papillae in several of them. Based on the colony and spore morphology, the fungus was identified as C. incongruus. Treatment with amphotericin B (1.5 mg/kg/day IV) was then commenced. The patient also underwent surgical debridement. However, Doppler ultrasound of the right lower limb revealed the development of a complete occlusion of the tibioperoneal trunk in the infected and surrounding area, with severe hypoperfusion and tissular compromise; a supracondylar amputation was performed. A Doppler ultrasound evaluation from the previous year showed no evidence of any significant vascular alterations. Pathological study of a hematoxylin and eosin-stained tissue section showed hyphal encasement by eosinophilic material (Splendore–Hoeppli phenomenon), and Sabouraud culture resulted in growth of C. incongruus. There were no signs of infection in any other location; no disseminated fungal infection was evidenced. Shortly after this, her clinical condition became complicated with severe metabolic alterations, including hyponatremia, hyperkalemia, hypocalcemia and hyperglycemia, among others, leading to multiple organ dysfunction and subsequently death, despite intensive care treatment. Unfortunately, the patient's relatives refused a necropsy procedure. Conidiobolomycosis is a chronic subcutaneous inflammatory disease.1Ribes J.A. Vanover-Sams C.L. Baker D.J. Zygomycetes in human disease.Clin Microbiol Rev. 2000; 13: 236-301Crossref PubMed Scopus (1218) Google Scholar, 2Sharma N.L. Mahajan V.K. Singh P. Orofacial conidiobolomycosis due to Conidiobolus incongruus.Mycoses. 2003; 46: 137-140Crossref PubMed Scopus (16) Google Scholar The usual focus of infection is the nasal or adjacent tissue,3Bras G. Gordon C.C. Emmons C.W. Prendegast K.M. Sugar M. A case of phycomycosis observed in Jamaica; infection with Entomophthora coronata.Am J Trop Med Hyg. 1965; 14: 141-145PubMed Google Scholar and it only infrequently affects the lower extremities as occurred in this case caused by C. incongruus. This fungus rarely produces infections in humans, and this species rarely causes vascular compromise during infection;10Bittencourt A.L. Marback R. Nossa L.M. Mucocutaneous entomophthoramycosis acquired by conjunctival inoculation of the fungus.Am J Trop Med Hyg. 2006; 75: 936-938PubMed Google Scholar, 11Thomas M.M. Bai S.M. Jayaprakash C. Jose P. Ebenezer R. Rhinoentomophthoromycosis.Indian J Dermatol Venereol Leprol. 2006; 72: 296-299Crossref PubMed Scopus (29) Google Scholar, 12Receveur M.C. Roussin C. Mienniel B. Gasnier O. Riviere J.P. Malvy D. et al.Rhinofacial entomophthoromycosis. About two new cases in Mayotte (in French).Bull Soc Pathol Exot. 2005; 98: 350-353PubMed Google Scholar, 13Tadano T. Paim N.P. Hueb M. Fontes C.J. Entomophthoromycosis (zygomycosis) caused by Conidiobolus coronatus in Mato Grosso (Brazil): case report (in Portuguese).Rev Soc Bras Med Trop. 2005; 38: 188-190Crossref PubMed Google Scholar, 14Perez J.A. Correa A. Fuentes J. Melendez E. Conidiobolomycosis: a case report with histopathologic findings (in Spanish).Biomedica. 2004; 24: 350-355PubMed Google Scholar, 15Prabhu R.M. Patel R. Mucormycosis and entomophthoramycosis: a review of the clinical manifestations, diagnosis and treatment.Clin Microbiol Infect. 2004; 10: 31-47Crossref PubMed Scopus (389) Google Scholar however, as occurs in other species, occasional angioinvasion can occur as a result of the fungal infection.15Prabhu R.M. Patel R. Mucormycosis and entomophthoramycosis: a review of the clinical manifestations, diagnosis and treatment.Clin Microbiol Infect. 2004; 10: 31-47Crossref PubMed Scopus (389) Google Scholar, 16Jain D. Kumar Y. Vasishta R.K. Rajesh L. Pattari S.K. Chakrabarti A. Zygomycotic necrotizing fasciitis in immunocompetent patients: a series of 18 cases.Mod Pathol. 2006; 19: 1221-1226Crossref PubMed Scopus (57) Google Scholar Reported cases have involved deep structures such as lung, mediastinum, heart, liver and gastrointestinal tract.4Fromentin H. Ravisse P. Tropical entomophthoromycoses (in French).Acta Trop. 1977; 34: 375-394PubMed Google Scholar, 5Busapakum R. Youngchaiyud U. Sriumpai S. Segretain G. Fromentin H. Disseminated infection with Conidiobolus incongruus.Sabouraudia. 1983; 21: 323-330Crossref PubMed Scopus (29) Google Scholar Although these infections could have been serious, the first fatal case of disseminated entomophthoromycosis caused by C. incongruus was reported in 1983.6Walsh T.J. Renshaw G. Andrews J. Kwon-Chung J. Cunnion R.C. Pass H.I. et al.Invasive zygomycosis due to Conidiobolus incongruus.Clin Infect Dis. 1994; 19: 423-430Crossref PubMed Scopus (61) Google Scholar The current case was an unusual presentation of an aggressive subcutaneous infection with regional vascular compromise in a diabetic patient. Unfortunately, despite the medical and surgical management, she died due to metabolic complications. The diagnosis of infection by Conidiobolus is generally based on histological examination because cultures of the causative organism are negative in more than 85% of cases, although these should always be performed.1Ribes J.A. Vanover-Sams C.L. Baker D.J. Zygomycetes in human disease.Clin Microbiol Rev. 2000; 13: 236-301Crossref PubMed Scopus (1218) Google Scholar, 10Bittencourt A.L. Marback R. Nossa L.M. Mucocutaneous entomophthoramycosis acquired by conjunctival inoculation of the fungus.Am J Trop Med Hyg. 2006; 75: 936-938PubMed Google Scholar, 12Receveur M.C. Roussin C. Mienniel B. Gasnier O. Riviere J.P. Malvy D. et al.Rhinofacial entomophthoromycosis. About two new cases in Mayotte (in French).Bull Soc Pathol Exot. 2005; 98: 350-353PubMed Google Scholar, 13Tadano T. Paim N.P. Hueb M. Fontes C.J. Entomophthoromycosis (zygomycosis) caused by Conidiobolus coronatus in Mato Grosso (Brazil): case report (in Portuguese).Rev Soc Bras Med Trop. 2005; 38: 188-190Crossref PubMed Google Scholar, 14Perez J.A. Correa A. Fuentes J. Melendez E. Conidiobolomycosis: a case report with histopathologic findings (in Spanish).Biomedica. 2004; 24: 350-355PubMed Google Scholar If one considers the predominance of eosinophils in the infiltrate and the exuberant Splendore–Hoeppli phenomenon around the hyphae,10Bittencourt A.L. Marback R. Nossa L.M. Mucocutaneous entomophthoramycosis acquired by conjunctival inoculation of the fungus.Am J Trop Med Hyg. 2006; 75: 936-938PubMed Google Scholar, 14Perez J.A. Correa A. Fuentes J. Melendez E. Conidiobolomycosis: a case report with histopathologic findings (in Spanish).Biomedica. 2004; 24: 350-355PubMed Google Scholar the histopathology of the case is characteristic of entomophthoromycosis and different from that of other subcutaneous mycoses. Although the diagnosis could be obvious from the clinical appearance, mycological and histological examinations are essential for confirmation and a better therapeutic approach to the clinical management of these cases. In histological examination, the periodic acid-Schiff's (PAS) stain is useful to demonstrate the fungal hyphae.11Thomas M.M. Bai S.M. Jayaprakash C. Jose P. Ebenezer R. Rhinoentomophthoromycosis.Indian J Dermatol Venereol Leprol. 2006; 72: 296-299Crossref PubMed Scopus (29) Google Scholar, 14Perez J.A. Correa A. Fuentes J. Melendez E. Conidiobolomycosis: a case report with histopathologic findings (in Spanish).Biomedica. 2004; 24: 350-355PubMed Google Scholar There is no standard treatment for all forms of this fungal disease. There have been suggestions that trimethoprim–sulfamethoxazole, amphotericin B and fluconazole are useful in the treatment of C. incongruus infection,2Sharma N.L. Mahajan V.K. Singh P. Orofacial conidiobolomycosis due to Conidiobolus incongruus.Mycoses. 2003; 46: 137-140Crossref PubMed Scopus (16) Google Scholar but clinical failure has been reported during treatment with amphotericin B and flucytosine. Surgical resection of infected tissues has brought temporary relief at best. Additionally, hyperbaric oxygen has been used as adjunctive treatment in some cases of maxillofacial infection due to C. coronatus as well as in rhinocerebral mucormycosis.1Ribes J.A. Vanover-Sams C.L. Baker D.J. Zygomycetes in human disease.Clin Microbiol Rev. 2000; 13: 236-301Crossref PubMed Scopus (1218) Google Scholar, 2Sharma N.L. Mahajan V.K. Singh P. Orofacial conidiobolomycosis due to Conidiobolus incongruus.Mycoses. 2003; 46: 137-140Crossref PubMed Scopus (16) Google Scholar, 3Bras G. Gordon C.C. Emmons C.W. Prendegast K.M. Sugar M. A case of phycomycosis observed in Jamaica; infection with Entomophthora coronata.Am J Trop Med Hyg. 1965; 14: 141-145PubMed Google Scholar, 4Fromentin H. Ravisse P. Tropical entomophthoromycoses (in French).Acta Trop. 1977; 34: 375-394PubMed Google Scholar, 5Busapakum R. Youngchaiyud U. Sriumpai S. Segretain G. Fromentin H. Disseminated infection with Conidiobolus incongruus.Sabouraudia. 1983; 21: 323-330Crossref PubMed Scopus (29) Google Scholar, 6Walsh T.J. Renshaw G. Andrews J. Kwon-Chung J. Cunnion R.C. Pass H.I. et al.Invasive zygomycosis due to Conidiobolus incongruus.Clin Infect Dis. 1994; 19: 423-430Crossref PubMed Scopus (61) Google Scholar These therapeutic issues and the clinical evolution of this case illustrate the seriousness of subcutaneous zygomycosis in immunocompromised hosts, in which this infection can be life-threatening. This work was presented in part as a poster at the 12th International Congress on Infectious Diseases, Lisbon, Portugal, June 2006 (Abstract 14.009). Conflict of interest: No conflict of interest to declare.