Gastrointestinal mucormycosis complicated by arterio-enteric fistula in a patient with non-Hodgkin's lymphoma

Gastrointestinal mucormycosis is a rare, often fatal, systemic infection found predominantly in immunocompromised patients. We report a case of gastrointestinal mucormycosis in a 53-year-old female with non-Hodgkin's lymphoma. Following her first course of chemotherapy, bowel obstruction developed as a result of mucormycosis. Despite treatment with antifungal therapy, she required a laparotomy owing to severe haemorrhage caused by mucormycosal invasion of her iliac artery. With continued antifungal treatment and further chemotherapy, she ultimately underwent reversal of her Hartmann's procedure and remains disease-free.     

Reversal of cardiomyopathy with tocilizumab in a case of HIV‐negative Castleman's disease

The association between Castleman's disease (CD) and cardiomyopathy has been rarely reported and the optimal therapeutic approach remains unknown. We report a previously healthy 20‐year‐old African American female who presented with fever, dyspnea, anasarca, and generalized lymphadenopathy. Diagnostic workup, including an axillary lymph node biopsy, revealed that she had human immunodeficiency virus‐negative and human herpes virus‐8‐negative multicentric CD. She had a non‐anaphylactoid infusion reaction during her fourth rituximab infusion. A few weeks later, she developed new‐onset severe cardiomyopathy requiring inotropic therapy, warranting consideration for left ventricular assist device. Several clinical clues indicated her new‐onset heart failure was a manifestation of her CD. Interestingly, a trial of tocilizumab (an anti‐interleukin‐6 receptor monoclonal antibody) resulted in complete resolution of her cardiomyopathy and other manifestations of CD. Tocilizumab received orphan drug approval for the treatment of CD in Japan, but is not yet approved for this indication in the United States. Clinicians should be aware of its potential clinical utility in CD.     

Successful use of a humanized anti–interleukin‐6 receptor antibody,tocilizumab, to treat amyloid A amyloidosis complicating juvenile idiopathic arthritis

We report an excellent clinical response to treatment with a humanized anti–interleukin‐6 receptor antibody, tocilizumab, in a patient with progressive amyloid A (AA) amyloidosis complicating very active juvenile idiopathic arthritis. Treatment with tocilizumab immediately normalized the serum AA (SAA) level, and subsequently all of the clinical symptoms of AA amyloidosis disappeared. Serial gastrointestinal biopsy specimens showed marked lasting regression of AA protein deposits. The patient's functional ability score improved dramatically, she maintains her mobility, and she has regained her previous quality of life. Tocilizumab appears to have an excellent ability to suppress SAA levels and could therefore be an important therapeutic strategy in AA amyloidosis secondary to rheumatic diseases.     

Usefulness of 18F‐fluorodeoxyglucose positron emission tomography for diagnosis of asymptomatic giant cell arteritis in a patient with Alzheimer's disease

It is often difficult to diagnose disease in elderly patients, in particular those with dementia, who do not present with typical symptoms. This report describes our experience of an elderly patient (an 83‐year‐old woman) who presented with a chief complaint of memory loss, showed a marked inflammatory response, and was diagnosed with large‐vessel giant cell arteritis (GCA) on the basis of ¹⁸F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) findings. She had no symptoms typical of GCA including jaw claudication, visual field defect and heavy headed feeling. Corticosteroid therapy resulted in a trend toward improvement in the inflammatory response and then she first recognized that she might have experienced slight dull headache before treatment of GCA. This was probably because this patient had large‐vessel GCA, which produces a few symptoms in the head and neck, and because she had Alzheimer's disease and could not accurately describe her symptoms. Our experience suggests the usefulness of FDG‐PET for the diagnosis of GCA, particularly in elderly patients without typical symptoms. Geriatr Gerontol Int 2011; 11: 114–118.     

Accelerated hepatitis C virus replication with rituximab treatment in a non‐Hodgkin's lymphoma patient

The treatment of patients with non‐Hodgkin's lymphoma (NHL) may be complicated by concomitant chronic hepatitis C virus (HCV) infection. Recent data suggest that HCV may also be a contributing factor to the development of this disease. Although antiviral treatment has occasionally been reported to result in the regression of lymphoma in patients with HCV infection, the importance of the control of this infection on the prognosis of lymphoma needs to be defined. Here we report a patient with diffuse large B‐cell lymphoma who presented with a mass in her left breast. She had had HCV‐related liver cirrhosis for 6 years. She was given rituximab monotherapy for three consecutive weeks, but treatment had to be discontinued as a result of hematological toxicity. HCV viral load also increased, but then decreased gradually after rituximab was stopped. She could be given no further therapy. Six months later she presented with spinal involvement with infiltration of the cauda equina. Though cranial–spinal radiotherapy and steroids were started, she died shortly thereafter. Though rituximab is an invaluable drug in the treatment of B‐cell lymphomas, we believe that the use of such agents with potentially long‐lasting effects on B lymphocytes requires extended vigilance for accelerated replication of hepatitis B and C viruses.     

Low viral load post‐transplant lymphoproliferative disease localized within the tongue

Abstract: Post‐transplant lymphoproliferative disease (PTLD) can occur in different sites, such as lymph nodes, allograft, and central nervous system. We report a 6‐year‐old girl with end‐stage renal disease secondary to hypoplastic–dysplastic kidneys, who received a kidney transplant. Thirty months post transplant, she developed PTLD in the tongue, an area of muscular tissue only. At that time her peripheral blood Epstein–Barr viral (EBV) load was only 40 copies/10⁵ lymphocytes, though the tumor was EB early RNA (EBER) positive. Immunosuppression was reduced with initial improvement in her symptoms. One month later, she returned with abdominal complaints and a contained cecal abscess. The excised cecal tissue revealed CD20 and EBER‐positive lymphoid cells. At the same time, her peripheral blood EBV copy number rose to 400 copies/10⁵ lymphocytes. She was successfully treated for the progressive PTLD by complete cessation of immunosuppression and a modified reduced‐dose chemotherapy protocol plus rituximab. Partial immunosuppression was eventually re‐introduced with sirolimus and prednisone. She remains in remission 60 months post transplant, and 30 months post PTLD, with serum creatinine value maintained at 1.3 mg/dL. Unusual localization of PTLD to areas in non‐lymphoid tissue without regional lymphoid involvement may result in misleading low peripheral blood EBV viral loads.     

Mucormycosis in a liver allograft: salvage re‐transplantation and targeted immunosuppressive management

Zygomycetes infection is associated with a high mortality in transplant populations. We describe a child with liver allograft Rhizopus oryzae infection who was salvaged by liver re‐transplantation. A 10‐year‐old child presented with anastomotic bile leak that was repaired. A combined antibiotics and voriconazole regimen was introduced for Escherichia coli and Candida krusei growth in the peritoneal fluid. Despite broad antibiotic and antifungal coverage, the patient continued to have an ongoing infection. A follow‐up computed tomography scan 8 weeks later showed 2 liver abscesses infiltrating the stomach and the diaphragm, with splenic infarcts and pericardial effusion. Aspirated samples from the liver abscess and the pericardial fluid revealed R. oryzae. Immunosuppression was discontinued and an antifungal regimen combining amphotericin B, posaconazole, and caspofungin was introduced. After 3 weeks of treatment with control of the systemic signs of infection, a positron emission tomography showed the fluorescence stain limited to the liver. With infection confined to the liver, the child underwent liver re‐transplantation, splenectomy, and partial gastrectomy. Immunosuppression was reintroduced with recovery of the immune response observed by the CD4 cells adenosine triphophate release (Cylex^? ImmuKnow^® assay) and posaconazole was continued for another year. At 3‐year follow‐up, the child maintained normal graft function. We conclude that discontinuation of immunosuppression combined with a modern antifungal regimen may allow salvage re‐transplantation in patients with liver mucormycosis.     

Une opacité pulmonaire excavée chez un diabétique

Mucormycosis or zygomycosis is a group of infections caused by filamentous fungi of the mucorales order belonging to the zygomycetes family. They generally appear in patients with uncontrolled diabetes or immunodepression, especially neutropenic immunodepression. Incidence has increased with progress in immunosuppressive therapy and chemotherapy and the absence of the use of antifungal prophylactic agents effective against mucors.We report the case of a diabetic patient presenting with an excavated opacity in the right lung which failed to improve after receiving non-specific antibiotic treatment. Direct examination of the bronchial washing specimen led to the diagnosis of pulmonary mucormycosis. Prognosis depends mainly on early diagnosis, enabling appropriate treatment with amphotericin B. Mortality remains high, around 80%; diagnosis is commonly established post-mortem.     

Morbidly obese patient with non‐alcoholic steatohepatitis‐related cirrhosis who died from sepsis caused by dental infection of Porphyromonas gingivalis: A case report

Non‐alcoholic steatohepatitis (NASH) is associated with increased risks of developing lifestyle‐related diseases including type 2 diabetes, cardiovascular disease and cerebral vessel disease. While the two‐hit hypothesis and, recently, multiple parallel hits hypothesis of NASH pathogenesis were proposed, further details have not emerged. Recently, dental infection of Porphyromonas gingivalis (P. gingivalis) has been reported as a critical risk factor for NASH progression, which acts as multiple parallel hits to induce inflammation and fibrogenic responses in steatosis. We describe here a 54‐year‐old woman who died from sepsis and was diagnosed with NASH. Briefly, her body mass index (BMI) at the age of 35 years old had been 25.6 kg/m², but she became obese after withdrawing into her home at the age of 45 years. Severe obesity continued over 19 years without diabetes mellitus. She was admitted to our hospital due to a sudden disturbance of consciousness. On admission, her BMI was 48.5 kg/m². Computed tomography revealed cirrhotic liver with massive ascites, and laboratory data indicated increased inflammatory responses, renal failure and C grade Child–Pugh classification, suggesting the diagnosis of sepsis. Also, severe periodontal disease was present, because the patient's front teeth fell out easily during intubation. Although the focus of infection was not specified, the oral flora Parvimonas micra, a periodontal pathogen, was detected in venous blood. In spite of intensive care including artificial respiration management and continuous hemodiafiltration, she died on the 43rd day after admission. Surprisingly, P. gingivalis was detected in her hepatocytes. This case may represent the significance of P. gingivalis in the progress to cirrhosis in NASH patients.     

Treatment options for primary splenic low‐grade non‐Hodgkin's lymphomas

The purpose of this comparative study was to evaluate the response of primary splenic low‐grade non‐Hodgkin's lymphomas (NHL) to chemotherapy, splenectomy, and chemotherapy combined with splenectomy in order to elaborate the optimum treatment modality. A total of 104 patients (age range: 15–82 years) with primary low‐grade B‐cell NHL of the spleen were comprised by our study. Stage IV disease was determined in 102 (98.1%) cases. Regarding the treatment modality, splenectomy was performed in 14 patients, early splenectomy and single‐agent chemotherapy in 15, early splenectomy and combined chemotherapy in 19, single‐agent chemotherapy in 23, and combined chemotherapy in 33. In the above‐mentioned order, complete remission rate was following: none, 40.0, 31.6, 21.8, and 18.2%. Partial remissions were achieved in 85.7, 46.7, 57.9, 30.4, and 69.7% of cases, respectively. The median remission duration turned out to be longer (74.5 months) in the group of patients with complete remissions attained by means of splenectomy and combined chemotherapy. Local relapses in the spleen developed in 19 (72.7%) patients treated with combined chemotherapy and in 9 (90.0%), who had undergone single‐agent chemotherapy. The 5‐year overall survival was 54.4% after splenectomy, 39.4% after single‐agent chemotherapy, and 37.1% after combined chemotherapy, being significantly higher (P < 0.05) after splenectomy and single‐agent chemotherapy (67.2%), and splenectomy followed by combined chemotherapy (64.7%). Early splenectomy combined with chemotherapy is the optimum treatment option for primary low‐grade NHL of the spleen because of the superiority in complete remission rate, remission duration, and in overall survival rate. Splenectomy leads to somatic compensation of patients, makes impossible local relapsing in the spleen, prevents continuous dissemination from the primary tumor site, and mostly corrects cytopenias, creating better conditions for chemotherapy.     

A retrospective study of different treatments of limited‐stage small‐cell esophageal carcinoma and associated prognostic factor analysis

Primary, small‐cell esophageal carcinoma (SCEC) is a rare but highly malignant tumor. Due to lack of randomized, controlled, prospective studies, there are currently no unified treatment modalities for SCEC. This study retrospectively analyzed the outcomes of different treatments and prognostic factors that influence overall survival in patients with limited‐stage SCEC. The study included 106 patients pathologically diagnosed with limited‐stage SCEC at Huai'an First People's Hospital, Nanjing Medical University (Huai'an, China), between 1998 and 2007. There were 66 males and 40 females, with a median age of 58 years (range: 45–77 years). Fourteen patients received surgery alone, 42 received surgery and postoperative chemotherapy, 11 received radiotherapy alone, and 39 received concurrent chemoradiotherapy. Combined modality treatment with and without chemotherapy yielded 5‐year survival rates (5YSRs) of 27.2% and 0%, respectively. Associated median survival times were 22 months and 11 months, respectively, with a hazard ratio (HR) of 2.30 (95% confidence interval [CI]: 1.42–3.73, P = 0.001). Among patients treated with surgery plus postoperative chemotherapy or with concurrent chemoradiotherapy, the 5YSRs were 31.0% and 23.1%, respectively. Median survival times were 26 months and 18 months, with an HR of 1.25 (95% CI: 0.75–2.09, P = 0.725). Multivariate survival analysis using Cox regression model showed that chemotherapy was a positive independent prognostic factor for SCEC (HR 2.92, 95% CI: 1.25–6.80). Chemotherapy‐based combined modality treatment appears to increase the long‐term survival of patients with limited‐stage SCEC. Similar overall survival rates results are achieved with surgery combined with chemotherapy as with concurrent chemoradiotherapy, with chemotherapy being an independent prognostic factor. Randomized, controlled, prospective studies are needed to identify optimal chemotherapy regimens for treating SCEC.     

Therapeutic drug concentrations of isavuconazole following the administration of isavuconazonium sulfate capsules via gastro‐jejunum tube: A case report

Invasive fungal infections are a common complication in immunocompromised patients, such as organ transplant recipients. Isavuconazole is a broad‐spectrum azole antifungal for the treatment of aspergillosis and mucormycosis. The package insert for isavuconazole recommends against opening the capsule for administration through enteral feeding tubes. We describe the case of a 68‐year‐old man with a complex post‐lung transplant course receiving isavuconazole for presumed invasive aspergillosis (bronchial alveolar lavage galactomannan index of >3.75) therapy administered through a gastrostomy‐jejunostomy tube (G‐J tube). Therapeutic drug monitoring was performed to ensure appropriate absorption. Peak and trough concentrations were measured in the early and late phases of the treatment course and resulted in trough levels of 2.7 mcg/mL and 4.0 mcg/mL, which is consistent with previously published trough concentrations of isavuconazole when the capsule was administered intact. This case report suggests that opening isavuconazole capsules and administration through a G‐J tube results in appropriate absorption and serum drug levels comparable to intact capsules.     

Subacute hemolytic anemia after transcatheter edge‐to‐edge mitral valve repair: A case report

The MitraClip System is extensively used in high‐risk patients with symptomatic severe mitral regurgitation (MR). Some studies have identified complications associated with use of the MitraClip. We report the case of a 91‐year‐old woman with severe MR of a prolapsed posterior commissure. Two weeks after using the MitraClip, she developed hemolytic anemia. She was conservatively treated with blood transfusion and medical treatment; fortunately, her general condition did not deteriorate during the follow‐up period. To the best of our knowledge, this is the first report of hemolytic anemia after MitraClip implantation.     

Burkitt's lymphoma: single‐centre experience with modified BFM protocol

Burkitt's lymphoma is a rare aggressive lymphoma, which responds poorly to standard chemotherapy regimens used to treat high‐grade non‐Hodgkin's lymphoma (NHL). The use of intensive chemotherapy protocols using alkylating agents and intensive CNS prophylaxis has dramatically altered prognosis. We have treated eight patients with Burkitt's lymphoma with a modified BFM protocol. The dose of methotrexate was reduced from 5 g/m² to 1.5 g/m² with the aim of reducing toxicity. Seven patients received a total of six cycles of chemotherapy each and one patient received five cycles of chemotherapy. Each cycle included high‐dose methotrexate, an alkylating agent (ifosphamide or cyclophosphamide) and two triple intrathecal injections of chemotherapy. Two patients with bulky abdominal disease in addition received an autologous stem cell transplant. The regimen was well tolerated with minimal toxicity. At a median follow‐up of 16 months (range 10–28), six of the eight patients (75%) were alive and in complete remission. Two patients relapsed, one 24 months post‐BFM chemotherapy and the other 1‐month post‐autologous stem cell transplantation and 2 months post‐BFM chemotherapy.     

Treatment of allergic bronchopulmonary aspergillosis (ABPA) in CF with anti‐IgE antibody (omalizumab)

Allergic bronchopulmonary aspergillosis (ABPA) results from IgE induced pulmonary response to aspergillus species. Recognition and management of ABPA is challenging in cystic fibrosis (CF) patients because changes in symptoms, lung function and chest radiograph are similar to that seen in CF related pulmonary infection. Standard therapy for ABPA includes systemic steroids and adjunctive use of antifungal agents. Little has been published regarding the use of monoclonal anti‐IgE antibody in those with ABPA. We report a CF patient with her third exacerbation of ABPA who was treated with monoclonal anti‐IgE (omalizumab) antibody; she had unfavorable side effects with prednisone therapy. This therapy resulted in improvement of pulmonary symptoms and lung function not achieved with antibiotics or prednisone alone. Pediatr. Pulmonol. 2008; 43:1249–1251. © 2008 Wiley‐Liss, Inc.     

Skin lesion in a patient after hematopoietic stem cell transplant

We present a case of a 61‐year‐old Caucasian woman who was hospitalized with fever on day 176 after a matched unrelated stem cell transplant for acute myelogenous leukemia. She developed hemorrhagic bullae on the skin of her right thigh, and both blood cultures and skin biopsy confirmed Fusarium proliferatum. Despite antifungal therapy, her condition worsened and she died while on comfort‐only measures.     

High‐volume continuous venovenous hemodiafiltration plus resin hemoperfusion improves severe metformin‐associated toxicity

We present the case of a 42‐year‐old female patient who attempted suicide by taking approximately 100 tablets of metformin (500 mg). Laboratory tests revealed severe lactic acidosis with lactate levels of 24 mmol/L and pH of 7.09. The patient was treated with high‐volume continuous venovenous hemodiafiltration (CVVH) and resin‐sorbent hemoperfusion. Metformin concentrations were measured by high‐performance liquid chromatography during CVVH and hemoperfusion treatment. Before extracorporeal treatment, the plasma metformin concentration was 208.5 mg/L. After CVVH treatment for 24 h, the plasma metformin concentration had decreased to 13.9 mg/L. Resin‐based sorbent hemoperfusion plus CVVH treatment had reduced the metformin plasma concentration by 61.8% after 3 h. After 7 days, the patient's laboratory tests and clinical syndrome were improved, and she was discharged from hospital. We provide evidence that CVVH plus hemoperfusion is effective in eliminating metformins and metabolic products.     

Long‐term remission in idiopathic Castleman's disease with tocilizumab followed by consolidation with high‐dose melphalan—two case studies

Multicentric Castleman's disease (MCD) is an uncommon lymphoproliferative disorder, often associated with a clinically aggressive behavior. No standard treatment has been established, but patients are usually treated with lymphoma‐type regimens such as rituximab or combination chemotherapy. Recently, immunotherapies targeting IL‐6 have proven effective and have been approved for this indication. However, these agents require long‐term administration. Here, we describe the clinical course of two patients, refractory to rituximab and chemotherapy, showing long‐term remission (18 and 24 months), following an induction phase with tocilizumab (an anti‐IL‐6 receptor antibody) and a consolidative phase with high‐dose melphalan accompanied by autologous stem cell support. This may prove to be an effective option for this group of patients with an orphan disorder.     

Targeting of B‐cell receptor signalling in B‐cell malignancies

Pharmacological agents that inhibit enzymes of the B‐cell receptor (BCR) pathway are of increasing importance in the treatment of B‐cell malignancies. These include inhibitors of Bruton tyrosine kinase (BTK), phosphatidylinositol 3‐kinase (PI3K), splenic tyrosine kinase and protein kinase Cβ. Two agents are already approved in the USA and Europe: ibrutinib, a BTK inhibitor, for the treatment of chronic lymphatic leukaemia (CLL), mantle cell lymphoma (MCL) and Waldenström's macroglobulinemia; and idelalisib, a PI3Kδ inhibitor, for the treatment of CLL and follicular lymphoma. In addition, the role of these drugs in diffuse large B‐cell lymphoma and marginal zone lymphoma is under investigation, as single agents and in combination with chemotherapy. In CLL, both ibrutinib and idelalisib have an established role as first‐line therapy in patients with del(17p), and in MCL, ibrutinib is a standard option for patients relapsing after chemoimmunotherapy. Unexpected toxicities have been encountered when combining these potent new agents with other drugs, including chemotherapy and lenalidomide, and based on this experience the risks and benefits of novel combinations must be evaluated carefully. In this review, we summarize the efficacy and safety results with these inhibitors and discuss novel combinations that are under study and the future role of BCR inhibitors in these disorders.     

Successful treatment of mucormycosis infection after liver transplantation: report of a case and review of the literature

Mucormycosis (zygomycosis) is a rare opportunistic fungal infection mainly affecting patients with diabetes mellitus, immunodeficiency, malignancies and solid organ transplant. We present a 55-year-old female with a mucormycosis infection primarily affecting the paranasal sinuses after liver transplantation. The patient presented with a one-week history of right-sided occipital headache and gradual loss of vision in the right eye just 6 months after liver transplantation. Imaging studies revealed a right-sided sphenoiditis with orbital apex involvement. The patient underwent endoscopic sinus surgery and the histology confirmed the diagnosis of mucormycosis. Aggressive surgical ablation of the infected parts, along with antifungal treatment and adjustment of her immunosuppressive maintenance resulted in a good outcome and long-term survival.