Mucormycosis in Iran: a systematic review

Fungi in the order Mucorales cause acute, invasive and frequently fatal infections in susceptible patients. This study aimed to perform a systematic review of all reported mucormycosis cases during the last 25 years in Iran. After a comprehensive literature search, we identified 98 cases in Iran from 1990–2015. The mean patient age was 39.8 ± 19.2 years. Diabetes was the most common underlying condition (47.9%), and 22.4% of the patients underwent solid organ or bone marrow transplantation. The most common clinical forms of mucormycosis were rhinocerebral (48.9%), pulmonary (9.2%) and cutaneous (9.2%). Eight cases of disseminated disease were identified. Overall mortality in the identified cases was 40.8%, with the highest mortality rate in patients diagnosed with disseminated infection (75%). The mortality rate in rhinocerebral infection patients was significantly lower (45.8%). Rhinocerebral infection was the most common clinical manifestation in diabetes patients (72.9%). Patients were diagnosed using various methods including histopathology (85.7%), microscopy (12.3%) and culture (2.0%). Rhizopus species were the most prevalent (51.7%), followed by Mucor species (17.2%). Sixty‐nine patients were treated with a combination of surgery and antifungal therapy (resulting survival rate, 66.7%). Owing to the high mortality rate of advanced mucormycosis, early diagnosis and treatment may significantly improve survival rates. Therefore, increased monitoring and awareness of this life‐threatening disease is critical.     

Evaluation of 28 cases of mucormycosis

Mucormycosis is a rare but invasive fungal disease with high mortality. The present study aimed to retrospectively investigate the demographic characteristics, as well as the clinical, radiological and laboratory features and the results of treatment, in the patients followed in our hospital because of mucormycosis. The present study retrospectively evaluated 28 cases, which were followed in our hospital because of mucormycosis between January 2002 and July 2013. The clinical form was rhinocerebral in 27 cases (rhinoorbital in 12, nasal in 8 and rhinoorbitocerebral in 7) and disseminated in one case. With regard to predisposing factors, diabetes mellitus (n = 20), haematological malignancy (n = 6) and chronic renal insufficiency (n = 5) were the leading concomitant diseases. Seventeen (61%) of 28 cases showed atypical clinical picture. With regard to the therapeutic outcomes; it was found that 14 (50%) cases died and six cases recovered with sequel. Today, when particularly the prevalence of immunosuppressive diseases and conditions are gradually increasing, the incidence of mucormycosis is also increased. Considering that the majority of our cases had atypical clinical involvement and complications, being familiar with the characteristics of this disease could be life‐saving together with early diagnosis and treatment.     

Gastrointestinal mucormycosis in immunocompromised hosts

Invasive mucormycosis is a rare fungal infection in immunocompromised hosts, but it carries a high mortality rate. Primary gastrointestinal disease is the least frequent form of presentation. Early diagnosis and treatment are critical in the management; however, symptoms are typically non‐specific in gastrointestinal disease, leading to delayed therapy. To describe the clinical presentation, diagnosis, treatment and outcomes of gastrointestinal mucormycosis in immunocompromised hosts, we reviewed all cases of primary gastrointestinal mucormycosis in immunocompromised hosts reported in English literature as well as in our Institution from January 1st 1991 to December 31st 2013 for a total of 31 patients. About 52% of patients underwent solid organ transplant (SOT), while the rest had an underlying haematologic malignancy. Abdominal pain was the most common presenting symptom, followed by gastrointestinal bleeding and fever. Gastric disease was more common in SOT, whereas those with haematologic malignancy presented with intestinal disease (P = 0.002). Although gastrointestinal mucormycosis remains an uncommon condition in immunocompromised hosts, it carries significant morbidity and mortality, particularly in cases with intestinal involvement. A high index of suspicion is of utmost importance to institute early and appropriate therapy and improve outcomes.     

Delaying diagnostic procedure significantly increases mortality in patients with invasive mucormycosis

Invasive mucormycosis is an uncommon but increasing life‐threatening fungal infection. The present study investigated clinical characteristics and mortality among patients diagnosed as invasive mucormycosis infection. We retrospectively reviewed a total of 24 histologically proven cases of invasive mucormycosis at two tertiary care referral hospitals between November 2005 and February 2014. Overall survival was 50% (n = 12). The time between onset of symptom and diagnostic procedure proved to be associated with mortality (P = 0.009). In addition, preexisting renal failure and thrombocytopenia demonstrated trends toward a poor outcome in our study (P = 0.089 and 0.065, respectively). On multivariate regression analysis, delayed diagnostic procedure (more than 16 days after the onset of symptoms) was an independent predictor of mortality (OR= 12.34, 95% CI, 1.43–10.64; P = 0.022). Mucormycosis is a destructive fungal infection that is associated with high mortality rates, ranging from 40% to 100% depending on the form of disease. When a clinician suspects invasive mucormycosis infection, an early diagnostic procedure performed within 16 days from the onset of symptom and early initiation of antifungal therapy will lead to successful management of this highly fatal disease.     

Evaluation of 30 cases of mucormycosis at a university hospital in Iran

Mucormycosis is a deadly invasive fungal infection and mainly affects immunocompromised patients. To investigate the clinical features of patients who developed mucormycosis and to determine the parameters, which influenced the outcome following mycotic infection. The current investigation retrospectively evaluated the demographic characteristics, clinical features, therapeutic data, as well as the outcomes of treatment in all cases of proven and probable mucormycosis diagnosed from 2002 until 2016 in our hospital. A total of thirty cases were recorded. Rhizopus spp. was the predominant pathogen among the identified Mucorales (26.7%). Diabetes mellitus (46.7%) and haematological malignancy (40%), were the most common underlying diseases. With regard to predisposing factors, neutropenia (43.3%) and chemotherapy (40%) were the leading concomitant parameters. The most frequent sites of infection were lung (30%) and sinus (26.7%), whereas disseminated infection was also found in nine of 30 patients (30%). Neutropenia remained the only independent factor associated with mortality (Relative Risk=3.557, 95% CI=1.365‐9.271, P=.009). Diagnostic delay ‐either due to delayed presentation of patients to our centre or insufficient awareness about invasive fungal infection among our clinicians‐ is a likely explanation for such a high mortality rate in our series.     

Mucormycosis in paediatric patients: demographics, risk factors and outcome of 12 contemporary cases

Mucormycosis is associated with high morbidity and mortality and is perceived as an emerging fungal infection. However, contemporary paediatric data are limited. We present a series of paediatric cases of mucormycosis reported from Germany and Austria collected within a voluntary epidemiological survey through standardised, anonymized case report forms. Twelve cases were reported between January 2004 and December 2008 (six men; mean age: 12.6 years, range: 0.1-17 years). Mucormycosis was proven in nine, and probable in three cases. Isolates included Lichtheimia (syn. Absidia pro parte, Mycocladus) (five), Rhizopus (three) and Mucor (one) species. Infection was limited to soft tissue in three cases, the lung in two cases, and an infected thrombus in one case; rhinocerebral disease was found in three cases, and pulmonary-mediastinal, pulmonary-cerebral and soft tissue-cerebral involvement in one case each. All three patients with isolated soft tissue infection were cured, whereas seven of the remaining patients died (one patient without follow-up). The overall mortality rate was 67%. While these data cannot provide conclusive data on incidence and disease burden of mucormycosis in paediatric patients, they reflect the continuing threat of these infections to immunocompromised patients and the need for improved diagnosis and management.     

Rhinocerebral Mucormycosis: A Retrospective Study

Mucormycosis is an acute often fatal infection caused by fungi of family mucoracea (Kauffman and Malani Curr Infect Dis Rep 9(6):435–440). The principal pathogens in this family are rhizopus, mucor and absidia species. Mucoracea are found in soil, decaying vegetation and other organic matter. Mucormycosis is a polymorphic disease with diverse clinical manifestation. It is divided into rhinocerebral, pulmonary, cutaneous, cardiac, gastrointestinal and disseminated. Rhinocerebral mucormycosis the most commonest manifestation of mucormycosis is usually a fatal fulminant infection. Rhinocerebral mucormycosis can be further divided into rhino-maxillary and rhino-orbito-cerebral. The disease commonly occur in diabetics who have ketoacidosis but is also seen in severely debilitated or immunosuppressed patients. It has also been reported from otherwise normal individuals. Early diagnosis and treatment is mandatory for a successful management of this infection.     

Rhinocerebral mucormycosis,risk factors and the type of oral manifestations in patients referred to a University Hospital in Tabriz,Iran 2007‐2017

Inadequate data are available on the global epidemiology of mucormycosis, mainly derived from the evaluation of specific population groups. Rhinocerebral mucormycosis is an invading and fatal mycosis, particularly among diabetic patients. In the present study, patients hospitalised in Imam Reza Hospital in Tabriz, from 2007 to 2017, were evaluated. The hospital information system (HIS) was used to collect the records of the patients. A total of 42 patients with a diagnosis of mucormycosis were included in the study, 40 cases (95%) of which had a diagnosis of the rhinocerebral form. Of these 40 patients, 21 (52.5%) and 19 (47.5%) were male and female, respectively. Seven cases (17.5%) of rhinocerebral mucormycosis were due to dental procedures. The most predisposing factor in the patients was diabetes with 36 (90%) cases. In our study, the role of tooth extraction in patients with uncontrolled diabetes was identified as an important factor. It may show the important role of dentists in preventing of the disease in diabetic patients.     

Mucormycosis at a tertiary care centre in Gujarat,India

The prevalence of mucormycosis is reportedly high in India, although the studies are mainly from north and south India only. We analysed the mucormycosis cases at tertiary care centres of West India. We retrieved the clinical details of all the patients with probable and proven mucormycosis diagnosed at Sterling Hospital and ID clinic at Ahmedabad, Gujarat over the period from 1 January 2013 through 30 April 2015. The data were analysed to determine demography, risk factors, underlying diseases, site of infection and outcome of these patients. A total of 27 patients with the median age of 50 (16‐65) years were diagnosed with mucormycosis during the period. Rhino‐orbital‐cerebral mucormycosis was the most common (51.9%) presentation. Majority (55.6%) of the patients had uncontrolled diabetes with or without ketoacidosis; 25.9% patients had no underlying disease and most of them (85.7%) had cutaneous mucormycosis. In this group, the mortality was 25.9% and an equal percentage of patients were lost to follow up; 14 (51.9%) patients could complete 6 weeks of amphotericin B therapy. All patients who completed antifungal therapy survived except one. Like other parts of India, uncontrolled diabetes was the predominant risk factor for mucormycosis in our group. Patients completing 6 weeks of amphotericin B treatment were likely to survive.     

Oral mucormycosis in patients with haematologic malignancies in a bone marrow transplant unit

Mucormycosis is an aggressive and life‐threatening opportunistic fungal infection, which predominantly affects immunocompromised patients. It typically manifests in rhinocerebral, pulmonary or disseminated forms in patients with immunosuppressive conditions. Mucormycosis limited to the oral cavity is rare, and to the best of our knowledge only seven cases have previously been reported in English literature. We present five consecutive cases of oral mucormycosis in patients with leukaemia, and provide a literature review.     

Prevalence of the reversed halo sign in neutropenic patients compared with non‐neutropenic patients: Data from a single‐centre study involving 27 patients with pulmonary mucormycosis (2003‐2016)

Pulmonary mucormycosis (PM) is a life‐threatening infection and the diagnosis can be challenging. The objective was to retrospectively explore the value of the RHS in our cohort of 27 patients with mucormycosis and its relation to neutropenia. This was a retrospective study including all patients with a diagnosis of probable or proven invasive PM according to the 2008 EORTC/MSG criteria between September 2003 to April 2016. Fisher's exact test and Mann‐Whitney test, with a P‐value statistically significant under .05 (P<.05), were used to compare neutropenic and non‐neutropenic groups. 27 patients were eligible. The RHS could be identified in 78% of cases in the neutropenic group, and was less common in the non‐neutropenic group (31%) (P<.05). Reticulations inside ground‐glass opacity in case of RHS were present in 13 out of 15 patients (87%). Mucorales DNA detection by PCR on serum provided, a median time to the first PCR‐positive sample of 3 days (?33 to +60 days) before diagnosis was confirmed. Six patients had IPA co‐infection. In conclusion, RHS is more frequent in case of PM in neutropenic patients compare to non‐neutropenic patients. Its presence in immunocompromised patients should be sufficient to promptly start Mucorales‐active antifungal treatment, while its absence especially in non‐neutropenic cases should not be sufficient to exclude the diagnosis.     

Overview and outcome of mucormycosis among children with cancer: Report from the Children's Cancer Hospital Egypt

Mucormycosis represents a real challenge in immunocompromised patients. This study aimed to describe the clinical characteristics, treatment outcome and infection‐related mortality in our patients at the Children's Cancer Hospital 57357, Cairo, Egypt. This is a retrospective study during the period 2007‐2017. Data analysis included demographic data, risk factors, diagnostic workup, treatment and outcome. During the study period, 45 patients developed proven mucormycosis according to EORTC/MSG criteria (2008). Ninety percentof cases were of haematological malignancies. Liposomal amphotericin B was the mainstay of treatment. Posaconazole was used as secondary prophylaxis in 35% of cases. Combination antifungal was used in three cases with progressive mucormycosis. Surgical intervention was achievable in 50% of cases. Therapy was successful in 35 patients (66%). Complications related to mucormycosis were seen in five cases with disfigurement and perforated hard palate. Chemotherapy delay with subsequent relapse of primary malignancy was reported in one case. Mucormycosis‐related mortality was 33% (15 cases). Mucormycosis is a major cause of mortality among patients with haematological malignancies. Early diagnosis of Mucormycosis infection, with rapid initiation of appropriate antifungal therapy and surgical intervention, whenever feasible, is the backbone of mucormycosis treatment.     

Focus on invasive mucormycosis in paediatric haematology oncology patients: a series of 11 cases

Mucormycosis has emerged as an increasingly important infection in oncology centres with high mortality, especially in severely immunocompromised patients. We carried out a retrospective study of 11 children with mucormycosis treated in seven French oncology‐haematology paediatric wards during the period from 1991 to 2011. Lichtheimia corymbifera and Mucor spp. were the predominant pathogens. Treatment regimens included antifungal therapy, reversal of underlying predisposing risk factors and surgical debridement. Although mucormycosis is associated with high mortality, this infection could be cured in eight of our cases of severely immunocompromised paediatric cancer patients.     

Isolierte Cerebrale Mucormykose bei Leukämie: Isolated Cerebral Mucormycosis in a Patient with Leukemia

Zusammenfassung: Mucormykosen stellen seltene Infektionen dar. Bei Diabetikern findet man vor allem die rhinocerebrale, bei immungeschwächten Patienten dagegen die pulmonale und disseminierte Form. Wir berichten über eine Patientin im Stadium der Vollremission einer akuten lymphatischen Leukämie, die klinisch an einer Meningo-Encephalitis mit Hirnnervenbeteiligung ohne bekannte Ätiologie verstarb. Bei der Obduktion zeigte sich eine Thrombosierung der Arteria vertebralis links, die durch eine Mucorinfiltration bedingt war und zu einer hämorrhagischen Erweichung im Kleinhirn und in der Medulla oblongata führte. Außer dieser cerebralen Mucormykose wurden keine weiteren Infektionsherde gefunden.
Summary: Mucormycosis is a rare infection. In patients with diabetes mellitus a rhinocerebral form predominates, while in the immunocompromised host mucormycosis is mostly pulmonary or disseminated. We report on a patient in remission of an acute leukemia, who died clinically of a meningo-encephalitis with involvement of cranial nerves of unknown etiology. At autopsy a thrombosis of the left arteria vertebralis caused by mucor was found with hemorrhagic necrosis of the cerebellum and the medulla oblongata. Except of this cerebral mucormycosis no further foci of infection were detected.     

Successful treatment of rhinocerebral zygomycosis using liposomal nystatin.

We describe a case of successful treatment of rhinocerebral mucormycosis in a patient with multiple myeloma. Therapeutic strategies used included liposomal amphotericin, hyperbaric oxygen, GM-CSF and liposomal nystatin.     

Localized muscular mucormycosis in a child with acute leukemia

Mucormycosis is a rare fungal infection of childhood, occurring mainly in patients with chronic illnesses such as diabetes and malignancies. The fungus seldom grows in culture and confirmation of the diagnosis depends on histologic examination of infected tissues. To date, the reported natural history of the disease has been rapid progression and a fatal outcome. Therefore, the importance of early diagnosis by tissue biopsy and early treatment with surgical debridement and systemic antifungal therapy cannot be overemphasized. The pulmonary system is the most common site for mucormycosis in patients with leukemia. We report what we believe to be the first successfully treated case of isolated muscular mucormycosis occurring in a child with biphenotypic acute leukemia. The diagnosis was made promptly by tissue examination at the time of surgical debridement. The patient was also given systemic amphotericin-B therapy.      

Isolated palate ulcer due to mucormycosis

Mucormycosis is a rare but serious fungal infection that rapidly attacks and kills its untreated victims, who are often immunocompromised. It is one of the most fulminant and often fatal mycotic infections known to human beings. Rhinocerebral mucormycosis is the commonest presentation and its extension to the orbit and brain is quite usual but the palatal involvement is a rare and late occurrence. Isolated location of mucormycosis on the palate in an immunocompetent host is an unusual clinical entity. Here we report a case of deep hard palate ulcer due to mucormycosis in a 56-year-old man without any predisposing factor. He was successfully treated with a combination of surgical debridement and systemic liposomal amphotericin B administration for six weeks. By presenting this case report we would like to emphasis that mucormycosis should be included in the differential diagnosis of the hard palate ulcers even in immunocompetent patient.     

Transient response of cardiac angiosarcoma to paclitaxel

CASTILLA E., PASCUAL I., RONCALÉS F., AGUIRRE E. & RÍO A. DEL (2010) European Journal of Cancer Care 19 , 699–700 Transient response of cardiac angiosarcoma to paclitaxel Malignant tumours of the heart are a group of tumours with low incidence but very high mortality. Delays in diagnosis are common because of their multiple forms of presentation, and 80% present with metastases, further reducing the possibility for cure. We present here the case of a patient with primary cardiac angiosarcoma that highlights the misdiagnosis at clinical presentation, current diagnostic modalities and a possible new treatment using paclitaxel for cardiac angiosarcoma.     

Rhino-oculo Cerebral Mucormycosis with Multiple Cranial Nerve Palsy in Diabetic Patient: Review of Six Cases

AIM of the study is to evaluate etiopathogenesis role played by predisposing conditions (Diabetes, Immunosupression), precipitating factors (trauma/surgery/ketoacidosis) and possible role of occupational hazard is discussed briefly. Clinical presentation and management of patients presenting with rhinoorbitocerebral mucormycosis is discussed. The prospective study of patient undergoing treatment of mucormycosis] without control Setting was done in ENT Deptt. NSCB Medical College, Jabalpur (tertiary referral centre of mid India). Subject were patients presenting with invasive fungal rhino sinusitis presenting with orbital involvement and cranial nerve palsies undergoing treatment. The detailed history, clinical examination including cranial nerve examination, blood test, CTscan and biopsy. Nasal endoscopy, CWL surgery and medical management with 6 month follow up. All six patients were diabetic when evaluated on presentation. Two patients had ketoacidosis. Four had history of surgery in recent past. Blood stained nasal discharge and dysaesthesia of face are early warning signs. They had necrotic lesion in nose and infraorbital area with 2, 3, 4, 5, 6 and 7 cranial nerve involvement. Skin necrosis/Mucosal necrosis, facial palsy and diplopia signify advanced disease. Altered sensorium, panopthalmitis & diabetes complicated with ketoacidosis signify bad prognosis. In present study two patients with advanced disease, altered sensorium and ketoacidosis succumbed within 72 hours in spite of anti fungal medicine. Of the four surviving patients, all responded well to treatment but had residual sixth and seventh nerve palsy. One patient defaulted in diabetes control & had recurrence after 6 months. Early diagnosis, aggressive surgical debridement and proper management of underlying metabolic abnormality along with amphotericin B can avert the bad prognosis of rhinoorbitocerebral mucormycosis.     

Rhinocerebral zygomycosis in a patient with acute lymphoblastic leukemia

We report a case of a 28-year-old man with acute lymphoblastic leukemia whodeveloped rhinocerebral zygomycosis during induction chemotherapy. Thislife-threatening fungal infection is an infrequent cause of neutropenic fever,and is occasionally found in patients with leukemia and lymphoma, or patientswith severely compromised defence mechanisms due to other diseases. Itis caused by moulds belonging to theMucoraceaefamily, and ischaracterized by local destruction of the affected organ. In our patient, theinfection spread from the paranasal sinuses to the right orbit, destroyedintraorbital structures and resulted in blindness within days. Biopsy from theright maxillary sinus was performed and mucormycosis was suspected throughmicroscopic examination. Culture of the resected specimen identifiedRhizopus arrhizusas the causing agent.Treatment of zygomycosis should consist of radical surgical debridement ofthe infected tissue, together with intensive broad-spectrum antimycotictherapy with amphotericin B. What could be learned from this case is, thataggressive approaches to identify the cause of infection is necessary, andthat aggressive treatment strategies are inevitable to overcome the infection.Furthermore, treatment of the underlying disease should be continued as soonas possible.