Zigomicosis y síndrome hemofagocítico en un paciente inmunocompetente: informe de caso / Zygomycosis and hemophagocytic lymphohistiocytosis in an immunocompetent patient: a case report

Introducción: la zigomicosis es una infección fúngica poco frecuente, con alta tasa de mortalidad y de mal pronóstico. Afecta principalmente a pacientes inmunocomprometidos. La asociación con el síndrome hemofagocítico es extremadamente inusual, más aún en pacientes inmunocompetentes, con pocos ejemplos registrados en la literatura. Caso clínico: se presenta el caso de un paciente masculino inmunocompetente de 40 años con diagnóstico de mucormicosis y síndrome hemofagocítico que evoluciona desfavorablemente, con fallo multiorgánico, a pesar de los esfuerzos médicos. Conclusión: la asociación de mucormicosis con síndrome hemofagocítico en un paciente inmunocompetente es extremadamente rara; existen pocos casos informados en Latinoamérica. Debemos tener presente esta asociación, ya que requiere un tratamiento agresivo y soporte vital avanzado. (AU)

Introduction: zygomycosis is a rare fungal infection that carries with high mortality rates. This poor prognosis, rapidly progressive infection mainly affects immunocompromised patients. The association with hemophagocytic lymphohistiocytosis is extremely unusual, even more in immunocompetent patients, with few cases reported. Case: we present the case of an immunocompetent male patient who was diagnosed with zygomycosis and hemophagocytic lymphohistiocytosis. Despite medical efforts he developed multiorganic failure. Conclusion: the association of mucormycosis with hemophagocytic lymphohistiocytosis in an immunocompetent patient is exceptional with few cases reported in Latin America. We must always suspect this association considering they require aggressive treatment and advanced life support. (AU)

[Fatal zygomycosis caused by Mucor indicus after haplo-identical stem cell transplantation].

A 62-year-old woman with acute lymphoblastic leukemia in first complete remission was treated with unrelated cord blood transplantation, but exhibited primary graft failure. She then underwent HLA-haploidentical peripheral blood stem cell transplantation from her daughter. The conditioning regimen consisted of fludarabine 30 mg/m(2)/day for 6 days, intravenous busulfan 3.2 mg/kg/day for 2 days, and thymoglobulin 1 mg/kg/day for 2 days. Voriconazole was administered to prevent fungal infections. The patient achieved prompt hematopoietic recovery. Fever was observed 21 days after the second transplant, followed by sigmoid colon perforation and a liver space occupying lesion (SOL). A filamentous fungus was detected in a percutaneous biopsy of the liver SOL. In spite of changing the antifungal drug from voriconazole to liposomal amphotericin B, the patient died on day 41. The fungus was identified as Mucor indicus, a type of zygomycete. Although Mucor indicus inhabits soil, an infectious disease is extremely rare, and breakthrough infection after voriconazole prophylaxis had not been reported until now. It is mandatory to consider preventive antifungal treatment for drug-resistant fungal infectious diseases in patients after neutrophilic recovery with a strongly immunocompromised state after a HLA-haploidentical transplant.

Disseminated zygomycosis due to Mycocladus corymbifera with cutaneous and cerebral involvement.

Fungal infections caused by zygomycetes are important and potentially life threatening infections. These opportunistic moulds have been increasingly implicated in human disease and are most frequently seen in immune compromised patients. We report a case of disseminated infection with Mycocladus corymbifera involving the brain, lungs, kidneys and skin in a 16-year-old patient with acute lymphoblastic leukaemia. The skin lesions played a significant role in the diagnosis of mucormycosis. These infections have an exceedingly high mortality rate and early recognition of cutaneous lesions is essential to successful management.

[Epidural abscess in the spine extended from pulmonary zygomycosis during consolidation chemotherapy for acute lymphoblastic leukemia].

A 37-year-old woman with acute lymphoblastic leukemia developed fever and pneumonia during persistent neutropenia after consolidation chemotherapy. Pneumonia was rapidly followed by the formation of abscess in adjacent subcutaneous tissues, muscles and bones. She subsequently developed sudden onset of paraplegia and loss of all sensation below Th4. Epidural abscess was detected by MRI. Emergency drainage was performed, but the patient died 4 days after the operation. Rhizopus oryzae grew from culture of the epidural abscess. Since the incidence of zygomycosis appears to have increased over the recent years, clinicians should be aware of the possibility of zygomycosis in case of any infection that is resistant to antibiotics.

Rhino-cerebral zygomycosis after allogeneic transplant: case report and literature review.

The proportion of patients with hematological malignancies (HM) who develop rare invasive fungal infections (IFI) has increased worldwide over the past few decades. Zygomycosis is an opportunistic fungal infection, which begins in the nose and paranasal sinuses due to inhalation of fungal spores. Rhino-cerebral zygomycosis is the most common form of the disease, it typically develops in diabetic or immunocompromised patients and presents as an acute fulminate infection, which is often lethal. We report a case of rhino-cerebral zygomycosis in an allotransplanted patient to emphasize early diagnosis and treatment of this potentially fatal fungal infection. We discuss different risk factors, specific diagnosis procedures and review the current concepts in management of zygomycosis.

[Multiple myeloma complicated with disseminated zygomycosis after bortezomib therapy].

A 67-year-old man was diagnosed with multiple myeloma IgA-lambda type, Durie-Salmon classification stage IIIA in October 2001. He received five courses of induction chemotherapy consisting of vincristine, doxorubicin and dexamethasone and then underwent high dose chemotherapy followed by autologous stem cell transplantation in March 2003. He achieved partial response, but then relapsed after treatment with thalidomide and was admitted to our hospital in June 2007. The patient was complicated by tumor lysis syndrome (TLS) after receiving bortezomib therapy twice. Computed tomography after bortezomib therapy showed the rapid appearance of tumors in the right upper lobe of the lung, tail of the pancreas and the spleen. Though he was treated with antifungal agents, micafungin and voriconazole, he died eighty-five days after admission. Autopsy specimen showed fungal clumps and hemorrhagic infarction in the lung and spleen, and vegetation at the mitral valve was the same fungus as found in the lung. We diagnosed disseminated zygomycosis based on the pathological fungal morphology. This case suggested that metabolic acidosis was caused by TLS, while poorly controlled diabetes, secondary hemochromatosis due to transfusion, and breakthrough zygomycosis during antifungal therapy were thought to be factors contributing to the development of zygomycosis.

Rhino-orbital-cerebral zygomycosis in solid organ transplant recipients.

BACKGROUND: Rhino-orbital-cerebral disease is a significant manifestation of zygomycosis in solid organ transplant (SOT) recipients. However, its characteristics and outcome are not well addressed. METHODS: SOT recipients with zygomycosis as per the European Organization for Research and Treatment in Cancer and the Mycoses Study Group criteria in a cohort study at our centers published previously and those identified with a PubMed search from the 1950s to November 2009 were studied. Patients with mycosis involving the sinuses, orbits, or central nervous system (CNS) were included. RESULTS: Patients comprised a total of 90 SOT recipients with rhino-orbital-cerebral zygomycosis, including 13 in our cohort and 77 in the literature. CNS disease occurred in 57% (51 of 90). Overall mortality was 52.3% (46 of 88), and the mortality in patients with CNS disease was 73.5% (36 of 49). In logistic regression analysis, older age (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.04-1.21, P=0.002) was associated with a higher mortality rate, whereas lipid formulations of amphotericin B compared with amphotericin B deoxycholate (OR 0.09, 95% CI 0.02-0.50, P=0.006) and surgery (OR 0.12, 95% CI 0.01-0.94, P=0.043) were independently associated with an improved survival even when controlled for CNS involvement and the era of diagnosis of disease. CONCLUSIONS: Rhino-orbital-cerebral zygomycosis, particularly CNS disease, is associated with substantial mortality rate in SOT recipients. Older age is a significant risk factor for mortality, whereas lipid formulations of amphotericin B and surgery improved outcomes.

Zygomycotic invasion of the central nervous system.

Zygomycosis is an opportunistic fungal infection that affects the central nervous system (CNS). In this report, we present three cases of zygomycosis with CNS involvement. In two patients zygomycosis developed after neurosurgery, and in the third patient zygomycosis developed after bone marrow transplantation for leukemia. All patients developed persistent fever and neurological deficits. They presented with progressive cerebral infarction accompanied by hemorrhage. Intraoperative findings and histopathological examinations revealed that zygomycotic hyphae caused mycotic aneurysm, vasculitis, and venous occlusion.

Primary cutaneous zygomycosis from a tertiary care centre in north-west India.

BACKGROUND & OBJECTIVES: Zygomycosis is highly invasive fungal infection, with high mortality rate. In most of patients, diabetes mellitus is an underlying factor but in primary cutaneous zygomycosis, presentation may be different. Here we present the description of clinical presentation, fungi isolated and management of cases with cutaneous zygomycosis seen in a tertiary care hospital in north India during 2001-2007. METHODS: All patients diagnosed with primary cutaneous zygomycosis between November 2001 and September 2007 presenting with clinical diagnosis of necrotizing fasciitis were included. Detailed history of each patient was taken, clinical presentation, site of involvement, underlying illness and risk factor, if any were noted. The diagnosis was established by direct microscopic evidence of broad, aseptate or sparsely septate ribbon-like hyphae with right angle branching in KOH wet mount and histopathological examination of stained sections. Cultures were put up for fungal isolation and species identification. Outcome of the therapy was analysed. RESULTS: Of the nine patients reviewed, only one had diabetes mellitus. Commonest risk factor was injection abscess (33.3%). Apophysomyces elegans was isolated in four cases, Saksenaea vasiformis and Absidia corymbifera in one each. The fungal culture was sterile in three cases. Mortality rate was high with only four patients responded well to surgical and/or medical therapy. INTERPRETATION & CONCLUSION: Primary cutaneous zygomycosis appears to be on rise in India that calls for high index of clinical suspicion and an early biopsy of the affected area for timely diagnosis. The standard treatment is a combination of amphotericin B therapy, surgical debridement, and reversal of the underlying disease or immunosuppression.

Emerging invasive zygomycosis in a tertiary care center: epidemiology and associated risk factors.

OBJECTIVES: Invasive zygomycosis is a rare fungal opportunistic disease with a high morbidity and mortality rate, predominantly affecting immunosuppressed patients. Presented herein is our investigation of the epidemiological factors associated with an increasing incidence of the disease at the University of Geneva Hospitals, Geneva, Switzerland, over the past five years. METHODS: This was a retrospective study of the clinical charts and microbiology records of patients with a positive culture for zygomycetes, to evaluate predisposing factors and epidemiological characteristics. RESULTS: Three of 19 proven/probable invasive infections were diagnosed during 1989-2003, and 16 during 2003-2008. While the number of positive isolates for zygomycetes remained mainly stable, the ratio between invasive infections and colonized patients increased after the introduction of voriconazole and caspofungin in 2003 at our institution (p<0.001). All cases were unrelated and no nosocomial source of exposure or seasonal aggregation was identified. The increase in cases was coincident with an incremented use of voriconazole and caspofungin, and with an increased number of immunosuppressed patients, especially allogeneic bone marrow transplant recipients. CONCLUSIONS: Invasive zygomycosis is an emerging infection at our center and is probably related to an increase in immunosuppressed patients and the wide use of newer antifungals. Changes in antifungal drug prophylaxis and treatment prescription may help to control this emergence.

Organising pneumonia mimicking invasive fungal disease in patients with leukaemia.

Clinical charts from 63 consecutive highly immunocompromised haematologic patients presenting with pulmonary nodular lesions on CT scan, classified as either probable or possible invasive fungal disease (IFD) according to the revised EORTC/MSG classification, were retrospectively studied. Histopathological analysis of lung tissues, available for 23 patients, demonstrated proven IFD in 17 cases (14 invasive aspergillosis and 3 invasive zygomycosis), diffuse alveolar damage in one and organising pneumonia (OP) in five cases. In the OP cases, three of which have been defined as probable IFD according to EORTC/MSG classification, extensive immunohistochemical, molecular and immunological analyses for fungi were negative. Our case descriptions extend the notion that OP may be encountered as a distinct histopathological entity in pulmonary nodular lesions in patients with leukaemia with probable/possible IFD.

Meningoencefalitis zigomicótica piogranulomatosa en un puercoespín de cola pren sil (Coendou prehensilis) / Piogranulomatous zygomycotic meningoencephalitisb in a prehensile tailed porcupine (Coendou prehensilis)

Con el término de zigomicosis (ZM) se designa un grupo de enfermedades causadas por hongos de la clase Zygomicetes, de los órdenes Mucorales y Entomophthorales, de varios géneros y especies. La presentación de ZM en animales ocurre esporádicamente en numerosas especies tanto en animales domésticos como silvestres (incluso en mamíferos marinos) y son pocos los casos comprobados de aislamiento e identificación del agente causal. Pocos hongos son considerados como neurotrópicos ya que tienden a localizarse en el SNC después de invadir el hospedador; sin embargo, la mayoría de los casos de meningitis o meningoencefalomielitis son parte de micosis sistémicas como la Candidiasis, la Criptococosis, la Aspergilosis o la ZM. El presente trabajo documenta el hallazgo de una meningoencefalitis zigomicotica secundaria a un trauma craneoencefálico en un puercoespín de cola prensil (Coendou prehensilis), siendo una enfermedad rara infrecuente en el sistema nervioso central tanto en humanos como en animales y adicionalmente sin reportes previos en esta especie.

With the word Zygomycosis (ZM) are designating a group of diseases caused by fungi of the class Zygomicetes, the orders Mucorales and Entomophthorales, of several genera and species. The presentation of ZM in animals occurs sporadically in many species both in domestic and wild animals (including marine mammals), and are checked few cases of isolation and identification of the causative agent. Few fungi are considered to be neurotropic because they tend to be located in the CNS after invading the host; however, most cases of meningitis or meningoencephalomyelitis are part of systemic fungal infection such as Candidiasis, Cryptococcosis, Aspergillosis or ZM. This paper documents the discovery of a zigomicotic meningoencephalomyelitis secondary to a head trauma in a prehensile-tailed porcupine (Coendou prehensilis), being a rare disease infrequent in the central nervous system both in human and animals and additionally without previous reports in this specie.

[Forefront of diagnosis and treatment of deep-steam mycology in Korea--rhinoorbitocerebral zygomycosis].

Mucor is a mold which exists in nature, but mucor infections of humans, even in immunocompromised hosts, are rare. Clinical manifestations of mucormycosis are nonspecific and diagnosis is based on microscopic examination and culture of biopsy specimens. Serologic test or molecular methods of speciation are used only as research tools. We investigated medical records especially for underlying diseases, clinical findings, treatment, and prognosis of patients diagnosed with rhinocerebral mucormycosis retrospectively in the Asan Medical Center. The underlying diseases were diabetes mellitus in 8 patients, acute leukemia in 2, kidney transplantation in 2, and myelodysplastic syndrome in 1 of the total 13 patients. Six patients complained of nasal symptoms including stuffy nose, rhinorrhea, 5 patients complained of ophthalmic symptoms such as decreased visual acuity, diplopia, and ophthalmic pain and 2 of hard palate ulcer. The mortality was 23%(3/13; the two patients with kidney transplant, and one patient with acute leukemia). In summary, mucormycosis should be considered in an uncontrolled DM and an immunocompromised host. The combined modality of early surgical debridement and antifungal agents was used for better treatment of rhinocerebral mucormycosis.

Rare mycoses of the oral cavity: a literature epidemiologic review.

Stomatologic fungal infections display different etiologies, pathogenesis, and clinical presentations. The incidence of rare mycoses of oral cavity is very low. These infections can involve both immunocompromised and immmunocompetent patients with common predisposing factors, such as diabetes or suffering from diseases causing immune system impairment. Oral mycoses can cause acute, chronic, and mucocutaneous lesions. Candidiasis is the most common mouth mycosis. Although occasionally primary mouth pathogens, Cryptococcus spp. or filamentous fungi (Aspergillus spp. and zygomycetes) can cause oral mycoses, with the oral localization more commonly secondary to a more serious systemic infection. The diagnosis of oral mycoses is based on clinical examination; for yeasts, culture is necessary to identify the etiologic agents; for filamentous fungi, in particular for zygomycetes and dimorphic, a definitive diagnosis can be made by histologic examination and pertinent stains with or without isolation of the fungus from the same site.

Conidiobolomycosis in relapsed acute lymphoblastic leukemia.

Invasive fungal infections in immunocompromised children suffering from hematological malignancies have been a major cause of morbidity and mortality. In recent years fungi other than aspergillus and candida are gaining importance. These emerging fungal infections have distinct epidemiological features and management issues especially in immunocompromised patients. Here we report the isolation of Conidiobolus coronatus, a rarely reported zygomycetes infection in a patient suffering from acute lymphoblastic leukemia. Conidiobolus generally causes indolent infection in the sino-respiratory tract. They are known to be angioinvasive and can disseminate. There is no consensus regarding appropriate antifungal treatment for Conidiobolus infection.

Zygomycosis in Italy: a survey of FIMUA-ECMM (Federazione Italiana di Micopatologia Umana ed Animale and European Confederation of Medical Mycology).

The aims of the study were to analyze the clinical and epidemiological characteristics and treatments for patients who developed zygomycosis enrolled in Italy during the European Confederation of Medical Mycology of medical mycology survey. This prospective multicenter study was performed between 2004 and 2007 at 49 italian Departments. 60 cases of zygomycosis were enrolled: the median age was 59.5 years (range 1-87), with a prevalence of males (70%). The majority of cases were immunocompromised patients (42 cases, 70%), mainly hematological malignancies (37). Among non-immunocompromised (18 cases, 30%), the main category was represented by patients with penetrating trauma (7/18, 39%). The most common sites of infection were sinus (35%) with/without CNS involvement, lung alone (25%), skin (20%), but in 11 cases (18%) dissemination was observed. According to EORTC criteria, the diagnosis of zygomycosis was proven in 46 patients (77%) and in most of them it was made in vivo (40/46 patients, 87%); in the remaining 14 cases (23%) the diagnosis was probable. 51 patients received antifungal therapy and in 30 of them surgical debridement was also performed. The most commonly used antifungal drug was liposomal amphotericin B (L-AmB), administered in 44 patients: 36 of these patients (82%) responded to therapy. Altogether an attributable mortality rate of 32% (19/60) was registered, which was reduced to 18% in patients treated with L-AmB (8/44). Zygomycosis is a rare and aggressive filamentous fungal infection, still associated with a high mortality rate. This study indicates an inversion of this trend, with a better prognosis and significantly lower mortality than that reported in the literature. It is possible that new extensive, aggressive diagnostic and therapeutic procedures, such as the use of L-AmB and surgery, have improved the prognosis of these patients.

[Zygomycosis].

Zygomycosis is an invasive fungal infection with extremely high mortality caused by filamentous fungi which belong to Class Zygomycetes (Rhizopus spp., Mucor spp., Cunninghamella spp., etc). Despite of the similarities of the ecological characteristics and of the patients' backgrounds, zygomycosis is much rarer than invasive aspergillosis. In addition to well known immunosuppressive risk factors (hematological malignancy, hematopoietic stem cell or solid organ transplant, prolonged neutropenia, corticosteroid, etc), diabetic ketoacidosis, iron overload, and administration of deferoxamine are specific factors predisposing zygomycosis. Rhinocerebral, pulmonary and disseminated disease is characteristic forms. The mainstay of the treatment is surgical resection, reversal of immunosuppressive factors, and administration of high-dose amphotericin B or its liposomal formulation. Because of the difficulty of culture detection and the absence of reliable serological diagnostic methods, premortem diagnosis and no delaying of effective treatment remain a challenge to physicians.

Zigomicosis cutánea primaria por Rhyzopus oryzae en una niña con leucemia linfoblástica aguda tipo B / Primary cutaneous zygomycosis by Rhyzopus oryzae in a girl diagnosed with an acute lymphoblastic leukemia B type

La Zigomicosis es una infección infrecuente causada por hongos oportunistas integrantes del orden Mucorales, que se presenta en pacientes de alto riego como en: leucemia, linfomas con neutropenia prolongada, cetoacidosis diabética, malnutrición severa, ruptura de la integridad de la barrera cutánea y terapia inmunosupresora. Se presenta un caso de Zigomicosis cutánea en una paciente pediátrica con leucemia linfoblástica aguda de tipo B, con severa neutropenia y tratamiento con corticoides. A los cinco días de su hospitalización desarrolló en el antebrazo (zona de punción venosa), una lesión indurada, eritematosa, que progresó y ulceró. A partir de exudados y biopsias del tejido subcutáneo se realizaron exámenes microscópicos directos con KOH, cultivos en agar Sabouraud y estudio histológico a través de técnicas convencionales de hematoxilinaeosina y PAS. Los análisis de los materiales clínicos revelaron la presencia de hifas hialinas, no tabicadas, gruesas, compatibles con un Zygomycete. En todos los tubos se obtuvo abundante desarrollo de un hongo filamentoso, identificado como Rhizopus oryzae. Posteriormente a la escisión quirúrgica y tratamiento con anfotericina B se obtuvo una evolución favorable del paciente hasta el presente.

Zygomycosis is an infrequent infection caused by opportunistic fungi which belong to the order Mucorales and which is present in high risk patients diagnosed with : leukemia, lymphomas with prolonged neutropenia, diabetic cetoacidosis, severe malnutrition, rupture of the entire cutaneous barrier and immunesuppressing therapy. This paper deals with a case of cutaneous Zygomycosis in a pediatric patient diagnosed with acute lymphoblastic leukemia B type, suffering a severe neutropenia and corticosteroid treatment. On the fifth day of hospitalization, her forearm (venous puncture zone) showed an indured, erimatose lesion which progressed and ulcerated. Collection of exudates and biopsies of subcutaneous tissue served to carry out direct microsco-pic examinations with KOH, cultures in Sabouraud Agar and a histologic study through conventional hematoxilin-eosin and PAS techniques. Analyses of the clinical materials revealed the presence of hyaline, not septated and broad hyphae suitable to a Zygomycete. In all the tubes there was an abundant development of filamentous fungus identified as Rhizopus oryzae. After the surgical scission and treatment with anfotericine B, the patient showed a favorable evolution up to now.