Disseminated mucormycosis associated with invasive pulmonary aspergillosis in a patient treated for post-transplant high-grade non-Hodgkin's lymphoma

The incidence of mucormycosis, defined as systemic infection caused by fungi of the class Phycomycetes has been increasing over the past 2 decades, especially in profoundly immunocompromised hosts. We report a new case in a patient presenting with post-transplant high-grade non-Hodgkin's lymphoma who received a prolonged treatment with voriconazole and caspofungin for an invasive pulmonary aspergillosis. Definite diagnosis of mucormycosis was made by liver biopsy of nodules mimicking progressive lymphoma. The patient died 1 week after the diagnosis of mucormycosis despite the administration of liposomal amphotericin B. The role of voriconazole and caspofungin in the emergence of mucormycosis is discussed.     

Pulmonary mucormycosis with cervical lymph node involvement in a patient with acute myeloid leukaemia: a case report

Here we describe a rare case of pulmonary mucormycosis and simultaneous cervical lymphadenitis in a patient with acute myeloid leukaemia. The patient was successfully treated with liposomal amphotericin B. The diagnosis of Mucor is very difficult, especially in severely immunocompromised patients. This report seems to be the first case about documented lymph node involvement by mucormycosis in humans.     

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.     

The safety and efficacy of gi endoscopy in patients with acute-leukemia - a review of 27 cases

In the course of aggressive treatment for acute leukemia, the ensuing pancytopenia and intensive medical support may be accompanied by severe gastrointestinal (GI) complications. Therefore, to assess the safety and efficacy of GI endoscopy as a means of diagnosis, we analyzed the records of 16 patients undergoing 27 endoscopies a mean (+/-S.D.) of 18.4 +/- 11.9 days post chemotherapy. There were 6 procedures performed in patients with acute lymphocytic, 18 with acute myelogenous, including 3 with acute promyelocytic and 3 with blastic phase chronic myelogenous leukemia. 10/27 procedures were performed in patients with less than 1000 WBC/mm3 and 19/27 had less than 100,000 platelets. 15 patients had 25 upper endoscopies done for: bleeding (twenty-one), abdominal pain (two), and persistent vomiting (two). The principal bleeding sources were: esophagitis (eleven), Mallory Weiss tear (one), gastritis (three), gastric ulcer (one), duodenal ulcer (five). In the non-bleeding cases 2 exams were normal and the others had gastritis (one) and esophagitis (one). 15/25 procedures (64%) resulted in new diagnosis and 20/25 (80%) in additional therapies. 47% of patients undergoing upper GI endoscopy received specific new therapies as a result of that procedure. Nd: YAG laser photocoagulation was effective in stopping bleeding lesions in 4/6 cases. 10/12 bleeding patients had persistent or recurrent bleeding and 2 died from bleeding. None had surgery. Two patients underwent colonoscopy, both for colonic distention. One patient, who had been recently treated for Cl. difficile had submucosal petechiae. The other had non-specific colitis. No biopsies were done and both cases were successfully decompressed..No complications occurred from any GI endoscopy. We conclude that GI endoscopy can be safely performed in patients with acute leukemia, resulting in specific diagnoses and therapies. Esophagitis is a principal cause of GI bleeding in these patients. The role of therapeutic endoscopy in controlling bleeding is promising but requires further evaluation.     

Mucormycoses.

Over recent years the clinical importance of mucormycosis has significantly increased. Most frequently mucormycosis occurs in neutropenic patients with haematological diseases. It is caused by fungi of the order Mucorales. The clinical patterns of the disease produced by different genera or species of Mucorales are virtually identical. Rhizopus, Absidia, Rhizomucor and Mucor are the organisms most commonly isolated from patients who suffer from mucormycosis. Diagnosis of mucormycosis is difficult as it is based on culture methods or microscopy of clinical specimens. The diagnosis is often only made after a delay or even post-mortem. Therapy includes surgical intervention if possible and is based on systemic amphotericin B (conventional or liposomal).     

Successful management of hepatic mucormycosis in an acute lymphoblastic leukaemia patient: a case report and review of the literature

We present a case of hepatic mucormycosis in a 9‐year‐old boy with acute lymphoblastic leukaemia. Despite long‐term use of combined liposomal amphotericin B and posaconazole therapy, the lesion persisted and could only be treated by surgical excision. After surgery, antifungal treatment was continued with posaconazole. On follow‐up, the patient had two episodes of ascending cholangitis which were responsive to intravenous antibiotics. He is doing well at the moment in remission for 2.5 years. Mucormycosis was long regarded as a fatal infection with poor prognosis. With early medical and surgical management, survival rates increase. Isolated hepatic mucormycosis is rare and only seven cases were reported in the literature up to now. We wanted to emphasise the role of early surgery in patients with hepatic mucormycosis in view of the literature.     

Mucormycosis of nose and paranasal sinuses with orbital complication in young diabetic

A case report of mucormycosis of nose and paranasal sinuses with sudden loss of vision in a young diabetic with good recovery after endoscopic debridement, systemic and topical amphotericin B and control of Diabetes mellitus.     

Gastrointestinal Necrosis in Acute Leukemia: A Complication of Induction Therapy

Gastrointestinal complications in acute leukemia have been infrequently reported. Reported here is a review of all patients on the hematology teaching service with acute leukemia from 1974 to 1980 and those with intestinal complications. Of the 50 patients with acute leukemia, 14 (28%) developed an acute abdominal catastrophe. They presented with an acute surgical abdomen, diarrhea, gastrointestinal bleeding, and a paralytic ileus. All were granulocytopenic and thrombocytopenic. All but one episode was associated with the death of the patients; survival ranged from 4 to 26 days (median 9 days) after their last dose of chemotherapeutic drugs. Cytarabine was administered in 13 of the 14 patients. It is believed that bowel necrosis which causes death in acute leukemia occurs more frequently than previously thought. There is a close association of the clinical syndrome with chemotherapeutic drugs, especially cytarabine.     

Chronic systemic (hepatosplenic) candidiasis in a patient with granulocytic sarcoma

Chronic systemic (hepatosplenic) candidiasis (CSC) is a syndrome of invasive candidiasis characterized by fever without localizing signs or symptoms. It occurs predominantly in patients with acute leukemia, after prolonged severe neutropenia. We report a young woman who underwent extensive chemotherapy for granulocytic sarcoma of the ovary; CSC then developed in this patient. She was successfully treated with fluconazole and liposomal amphotericin B. Clinical presentation, diagnostic problems, and the current successful treatment with fluconazole and liposomal amphotericin B are discussed.     

Antifungal combinations in Mucorales: A microbiological perspective

Mucormycosis mostly affects immunocompromised patients and is associated with a high morbidity and mortality despite currently available treatments. In that context, combination therapy might be the key to a better outcome for these patients. Purpose of this review is to summarise and to discuss the current combination data obtained in vitro, in vivo in animal models of mucormycosis, and in patients. In vitro combination studies showed that most of the interactions between antifungal drugs were indifferent, even though that some synergistic interactions were achieved for the combination of echinocandins with either azoles or amphotericin B. Importantly, antagonism was never observed. Animal models of mucormycosis focused on infections caused by Rhizopus arrhizus, neglecting most other species responsible for human disease. In these experimental animal models, no strong interactions have been demonstrated, although a certain degree of synergism has been reported in some instances. Combinations of antifungals with non‐antifungal drugs have also been largely explored in vitro and in animal models and yielded interesting results. In patients with ketoacidosis and rhino‐orbito‐cerebral infection, combination of polyene with caspofungin was effective. In contrast, despite promising experimental data, adjunctive therapy with the iron chelator deferasirox was unfavourable and was associated with a higher mortality than monotherapy with liposomal amphotericin B. More combinations have to be tested in vitro and a much larger panel of Mucorales species has to be tested in vivo to give a valuable statement if antifungal combination therapy could be an effective treatment strategy in patients with 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.     

Pancreatic toxicity after liposomal amphotericin B

Though liposomal amphotericin B has been available in Germany since 1992, efficacy and safety of this formulation of amphotericin B are still not well-documented in children. As far as gastrointestinal side-effects are concerned, an elevated alkaline phosphatase and elevated transaminases have been reported. In our department, liposomal amphotericin B had been used since 1994 to treat patients with proven or suspected fungal infections in a daily dose of 1-3 mg kg-1. Additionally, patients with high-dose chemotherapy and autologous stem cell support received liposomal amphotericin B prophylactically in a dose of 1 mg kg(-1) three times per week. We performed a retrospective analysis of all 31 patients who had received liposomal amphotericin B by 1999. In five patients, an isolated transient elevation of the serum lipase level during, or shortly after, the therapy with liposomal amphotericin B was detected. Three of these patients showed clinical signs of pancreatitis, with one patient displaying slightly elevated transaminases. So far, elevated levels of serum lipase have not been described as a possible side-effect of a liposomal amphotericin B therapy. The pathogenesis of this elevation is unclear. As possible reasons, an enzyme induction due to fat overload or a toxic damage of the pancreatic tissue by the liposomes or amphotericin B itself are discussed.     

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.     

Typhlitis. An 18-year experience and postmortem review

A review of pediatric autopsy results at the Texas Children's Hospital, Baylor College of Medicine from 1970 through 1987 was conducted. Thirty-three cases of typhlitis were identified in patients with acute leukemia and two cases each in patients with lymphoblastic lymphoma and aplastic anemia. Patients ranged in age from 10 months to 17 years. Fifty-seven percent were male and 43% were female. All were myelosuppressed. A postmortem incidence rate of 24% was determined for patients with acute leukemia. Common symptoms included abdominal pain and distention in 78% of patients and acute lower gastrointestinal bleeding in 35%. Abdominal radiographs varied in spectrum from a nonspecific bowel gas pattern to frank right colonic pneumatosis intestinalis. Thirty-three patients received chemotherapy within 30 days before onset of abdominal symptoms. All patients were febrile (greater than 38.5 degrees C), and 33 received broad-spectrum antibiotics. Three patients received amphotericin B. Premortem, 84% of organisms cultured from blood were bacterial whereas 16% were fungal. Fungal pathogens accounted for 53% of new microorganisms seen at autopsy. Postmortem examination showed typhlitis in the following anatomic distributions: (1) confined to the cecum; (2) involving the cecum and ileum; (3) involving the cecum, ileum, and ascending colon; or (4) involving the cecum, with sporadic ulcers throughout the intestine. This review includes clinical and postmortem features of typhlitis and current strategies for diagnosis and management.     

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.     

The air crescent sign of invasive pulmonary mucormycosis in acute leukemia

An unusual radiographic sign of crescentic cavitation appeared in a case of invasive pulmonary mucormycosis complicating the treatment of a patient with acute myelogenous leukemia and having a normal admission chest radiograph. The first manifestation was a large, wedge-shaped pleural-based consolidation, which evolved about 10 days later into a fungus ball-like lesion, usually known as the air crescent sign. Amphotericin B and 5-fluorocytosine, which were initiated immediately after appearance of the sign, proved to be effective, probably in association with hematologic improvement. Transbronchial lung biopsy was not only helpful in establishing a definitive diagnosis, but also suggested that an intracavitary mass could have resulted from pulmonary infarction. This experience thus showed that the sign may appear in greater frequency in mucormycosis as well as in aspergillosis, and may be useful as a clinical index for initiating antifungal therapy in immunocompromised patients.     

Mucormycotic pseudoaneurysm of the common carotid artery with tracheal involvement

Mucormycosis is an emerging and fatal fungal infection. A high index of suspicion and the knowledge of its potential manifestations are essential for early diagnosis. We describe a patient with acute lymphoblastic leukaemia (L2 subtype) who developed a neck mass following a course of induction chemotherapy. Doppler ultrasonography and angiography of the neck revealed a pseudoaneurysm of the right common carotid artery. The patient then developed haemoptysis. Surgical exploration revealed a necrotic right common carotid artery with anteromedial pseudoaneurysm and adjacent tracheal wall perforation. Local debridement and tracheal repair were performed. Nonseptate hypheal invasion (mucormycosis) was found on the microscopic examination of the excised arterial wall. A subsequent recurrence of pseudoaneurysm was treated with local surgical debridement and intravenous amphotericin B (Fungizone) administration. Although rare, clinicians should be aware of these possible presenting features of mucormycosis as early diagnosis and treatment may potentially improve the survival.     

Mediastinal Mucormycosis: Case report,review of literature and treatment with continuous liposomal amphotericin B irrigation

Mediastinal mucormycosis is an uncommon but lethal infection associated with an 83% mortality. We describe a case of fatal Rhizopus microsporus mediastinitis despite three exploratory mediastinal surgeries and complementary systemic and mediastinal irrigation with liposomal amphotericin B. We further review the literature on surgical and antifungal management of mediastinal mucormycosis.     

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.      

Acute myelogenous leukemia complicated by acute necrotizing ulcerative gingivitis due to Aspergillus terreus

Infections caused by Aspergillus terreus are rare but have been associated with a poor outcome in immunocompromised patients due to frequent resistance to conventional antifungal therapy. This report describes a case of a woman who developed acute necrotizing ulcerative gingivitis (ANUG) due to A. terreus during induction chemotherapy for acute myelogenous leukemia. She initially failed to respond to treatment with amphotericin B but the infection resolved following the introduction of oral itraconazole. Opportunistic infections caused by A. terreus are an emerging problem and can be associated with a high mortality rate. Early microbiological diagnosis is critical since resistance to amphotericin B is likely and itraconazole appears to be an effective treatment for this infection.