Takotsubo (ampulla-shaped) cardiomyopathy associated with microscopic polyangiitis

Recently, a cardiac disorder characterized by ballooning and hypokinesis at the apex has been described as takotsubo (ampulla-shaped) cardiomyopathy. We encountered a patient with a rare case of takotsubo cardiomyopathy associated with microscopic polyangiitis. A 70-year-old woman suddenly presented with ventricular dysfunction during the active phase of microscopic polyangiitis. The findings on echocardiograms and electrocardiograms were consistent with those of takotsubo cardiomyopathy. The ventricular dysfunction completely resolved after treatment with 40 mg/day of prednisolone and methylprednisolone pulse therapy. This unique type of cardiomyopathy can be a complication of microscopic polyangiitis.     

Efficacy of granulocytapheresis and leukocytapheresis for the treatment of microscopic polyangiitis

We evaluated the efficacy of granulocytaperesis and leukocytapheresis for the treatment of rapidly progressive glomerulonephritis (RPGN) and lung hemorrhage caused by microscopic polyangiitis. Three patients with RPGN were treated by granulocytapheresis (GCAP) and five patients with RPGN were treated by leukocytapheresis (LCAP). The prednisolone dose was 0.4 +/- 0.2 g/kg/day (mean +/- SD; range 0.2-0.8 g/kg/day). Pre-treatment serum creatinine was 3.2 +/- 1.4 mg/dL (1.4-5.1 mg/dL). The patients were followed for a mean period of 15 +/- 6 months (6-23 months). Renal function improved in five of the eight RPGN patients. Three lung hemorrhage episodes in two different patients were treated with GCAP and one lung hemorrhage episode was treated with LCAP combined with various doses of corticosteroids. All four lung hemorrhage episodes were ameliorated. We concluded that combined therapy of GCAP or LCAP and corticosteroids is effective for the treatment of RPGN and lung hemorrhage due to microscopic polyangiitis.     

Sustained hypogammaglobulinemia under rituximab maintenance therapy could increase the risk for serious infections: a report of two cases

We report two patients with granulomatosis with polyangiitis in remission with rituximab maintenance therapy with sustained hypogammaglobulinemia. Both patients had serious infections and were admitted to the intensive therapy unit. The patients had at least low IgM levels prior to the initiation of rituximab. They received cyclophosphamide and prednisolone at induction and at maintenance. They had lung affection, low level of both IgM and IgG and a cumulative dose of rituximab over 7 g at the time of the severe infection. Our patients have features similar to common variable immunodeficiency patients, and therefore prolonged very low levels of immunoglobulins could heighten the risk for severe infections.     

Thrombocytopenia during avacopan administration: A case report

Avacopan is a novel C5a receptor antagonist recently approved for the treatment of microscopic polyangiitis and granulomatosis with polyangiitis. To our knowledge, thrombocytopenia induced by avacopan has not been reported. We report a case of a 78-year-old man with microscopic polyangiitis who developed rapidly progressive glomerulonephritis (RPGN) and vasculitis neuropathy. After developing RPGN, he was treated with prednisolone, which was ineffective. As the dosage of corticosteroids was decreased, he developed impaired dorsiflexion of the left ankle, tingling and numbness in his feet, consistent with vasculitis neuropathy. After a 3-day administration of methylprednisolone, we started avacopan and prednisolone 20 mg/d to reduce the corticosteroid dosage. One week after starting avacopan, platelet counts began to decrease, eventually leading to the cessation of the drug. The possibility of thrombotic microangiopathy and heparin-induced thrombocytopenia was considered unlikely given the clinical course and laboratory studies. After 3 weeks of avacopan cessation, platelet counts began to increase, suggesting avacopan as the most probable cause of thrombocytopenia. Our case highlights the importance of postmarketing surveillance of avacopan to identify its adverse events that were not reported in clinical trials to ensure its safe use. Clinicians should carefully monitor platelet counts when using avacopan.     

Microscopic polyangiitis complicated with bilateral brachial plexopathy: a case report and review of the literature

Microscopic polyangiitis is a small-vessel necrotizing vasculitis associated with anti-neutrophil cytoplasmic antibodies and presents itself with glomerulonephritis and hemorrhagic pulmonary capillaritis. Peripheral nervous system involvement is common in anti-neutrophil cytoplasmic antibodies-associated vasculitis, but brachial plexopathy is unusual. We present the case of a 22-year-old man with known microscopic polyangiitis who was under maintenance therapy with prednisolone and cyclophosphamide and developed cough, dyspnea, and hemoptysis which increased in 6 days accompanying pain and paresthesia in the upper limbs. His physical examination revealed hypoesthesia, absence of deep tendon reflexes, and decreased muscle strength in the upper limbs. His chest computed tomography scan showed ground glass pattern in the lower and middle lobes. Electromyography and nerve conduction study showed bilateral brachial plexopathy with involvement of all of the cervical roots that were more severe in the lower roots and left side.     

Usual interstitial pneumonia following resolution of cavitated pulmonary masses in a patient with ANCA‐associated vasculitis

A 72‐year‐old woman with slight pulmonary interstitial reticular markings was initially diagnosed with microscopic polyangiitis (MPA). Two years later, cavitated pulmonary masses appeared, and a biopsy specimen revealed granulomas. Granulomatosis with polyangiitis (GPA) was diagnosed. The masses resolved with treatment. Ten years later, the usual interstitial pneumonia (UIP) pattern appeared on chest computed tomography (CT). The diagnosis of lung toxicity from methotrexate (MTX) or cyclophosphamide (CYC) was precluded by the clinical course. Despite treatment with prednisolone (PSL), the UIP progressed. The change of pulmonary pathology from masses to UIP is rare in patients with GPA.     

Recovery of renal function in a dialysis-dependent patient with microscopic polyangiitis and both myeloperoxidase anti-neutrophil cytoplasmic antibodies and anti-glomerular basement membrane antibodies

A 40-year-old man with microscopic polyangiitis developed both myeloperoxidase anti-neutrophil cytoplasmic antibodies (90 EU) and anti-glomerular basement membrane antibodies (134 EU)-positive rapidly progressive glomerulonephritis and heparin-induced thrombocytopenia. Although the patient initially showed no signs of improvement, persistent therapy including 1 g/day intravenous methylprednisolone, 50 mg/day oral prednisolone, plasma exchange, and 900 mg/day intravenous cyclophosphamide resulted in the normalization of both titers, recovery of renal function, and discontinuation of dialysis. Though previous studies showed poor outcomes in such "double-positive" patients, aggressive immunosuppression in younger patients may result in the recovery of renal function, even in those with severe renal dysfunction.     

A case of microscopic polyangiitis in an elderly patient presenting predominantly with cholecystitis successfully treated with mizoribine

Abstract

An 82-year-old woman was previously diagnosed with cholecystitis and treated with antibiotics at another hospital. Because her fever and inflammation persisted, therapeutic cholecystectomy was performed. Histopathology of the gallbladder revealed periarterial vasculitis. After transfer to our hospital, an elevated titer of myeloperoxidase–antineutrophil cytoplasmic antibody (MPO–ANCA) was observed (47 U/mL). The patient’s renal dysfunction had previously been thought to be sequelae of her cholecystectomy. We diagnosed microscopic polyangiitis (MPA) and began treatment with 40 mg orally of prednisolone daily. The titer of MPO–ANCA decreased with the treatment, but fever recurred with prednisolone taper. We, therefore, added 50 mg orally of mizoribine (MZR) daily as an immunosuppressant and increased the MZR to 100 mg daily while monitoring its blood peak concentration. The peak level of MZR was 1.58 μg/mL at 6 h after administration. After adding MZR, we successfully tapered the orally dosed prednisolone without recurrent fever or complications. We describe this case of MPA in an elderly patient manifesting predominantly with cholecystitis and successfully treated with orally dosed prednisolone and MZR.     

Acute lymphoblastic leukemia: End-result analysis of treatment and prognostic factors in Indian patients

Acute Lymphatic Leukemia (ALL) patients seen during the period 1974–1978 at the Tata Memorial Hospital, Bombay, are analyzed retrospectively to evaluate the clinical features at presentation, results of sequential therapy, and prognostic factors. A total of 301 patients were registered during the study period. There were 153 evaluable patients. Of these 73 patients received induction therapy with vincristine and prednisolone (VP) followed by cranial prophylaxis (cranial radiotherapy, 2,400 rads, and 10 weekly intrathecal injections of methotrexate 7.5 mg/m²) and continuous oral maintenance with daily 6-mecrapatopurine and weekly methrotrexte (group A). Another 39 patients (group B) received pulse therapy with vincristine and prednisolone during maintenance therapy. Finally 41 patients (group C) received L-asparaginase during induction and pulse therapy in addition to drugs as in group A. Of the 153 patients, 88 (58%) achieved complete response after induction treatment. Induction remission was 53% with vincristine and prednisolone (group A and group B), whereas it was 70% in group C. The difference in complete response rate in group C was statistically significant (P<0.05). The 3-year survival in our series was 22%, with median survival of 11 months. Group C patients receiving L-asparaginase along with vincristine and prednisolone showed 41% 3-year survival compared to 16% for group B. The 3-year survival in group A patients was only 7%, probably owing to lack of pulse therapy during maintenance treatment. The prognostic factors such as age, sex, WBC count, and mediastinal node were compared for induction remission and total survival. Possible factors relating to poor results in our series as compared to developed countries are discussed.     

A case of non-specific interstitial pneumonia in patient with microscopic polyangiitis]

Non-specific interstitial pneumonia developed as an initial manifestation in a patient with microscopic polyangiitis. A 62-year-old man was admitted to our hospital in March 2001, because of fever and intermittent myalgia of lower extremities. Chest X-ray had revealed reticular shadows in the bilateral middle and lower lung fields since 1996. Just before admission, the patient had been diagnosed as having nonspecific interstitial pneumonia (NSIP) from the specimen obtained by video-assisted thoracoscopic surgery (VATS) in another hospital. Physical examination on admission revealed bilateral episcleritis. Laboratory data showed elevated levels of CRP and KL-6, polyclonal gammaglobulinemia, positive rheumatoid factor and myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA). Sensory and motor nerve conducting velocities were delayed in left peroneal nerve, but not other nerves, suggesting mononeuropathy. Biopsied specimens of the left quadriceps revealed vasculitis of arteioles. In spite of positive proteinuria and hematuria, no pathological lesion was found in the kidney. From all of these findings, the patient was diagnosed as having microscopic polyangiitis (MPA) without renal involvement. Methylprednisolone pulse therapy followed by intravenous cyclophosphamide pulse therapy improved his clinical conditions such as pyrexia, cough, myalgia, episcleritis and respiratory symptoms with decreased titer of serum MPO-ANCA. Thereafter, the dose of prednisolone was successfully tapered to 10 mg/day without clinical relapse. In the present patient who developed demonstrated non-specific interstitial pneumonia as an initial manifestation of MPA, VATS provided useful diagnostic and prognostic information, leading to an appropriate therapeutic choice.     

Mixed connective tissue disease associated with MPO-ANCA-positive polyangiitis

The patient was a 42-year-old woman diagnosed as having MCTD and Sj?gren's syndrome in 1989, and who was taking oral prednisolone. Proteinuria and microscopic hematuria were pointed out for the first time in December 2004. She was referred to our hospital because of massive hemoptysis. Advanced renal failure, anemia and pulmonary alveolar hemorrhage were diagnosed on admission. She was positive for serum MPO-ANCA. The patient was started on a therapy that included steroids, cyclophosphamide and plasmapheresis. However, her respiratory condition was untreatable and she died on the 16th day of hospitalization. The autopsy revealed alveolar hemorrhage in the lungs and crescentic glomerulonephritis. This patient was considered as a rare case of MCTD associated with MPO-ANCA-positive microscopic polyangiitis.     

Advances in Therapy for ANCA-Associated Vasculitis

The anti-neutrophil cytoplasmic antibody-associated vasculitides include granulomatosis with polyangiitis (Wegener??s granulomatosis) and microscopic polyangiitis. The introduction of therapy with cytotoxic agents such as cyclophosphamide transformed these diseases from fatal diagnoses to chronic conditions characterized by cycles of relapse and remission. Modern treatment strategies have focused on minimizing cyclophosphamide exposure or eliminating its use altogether. Two randomized clinical trials have shown that rituximab is not inferior to cyclophosphamide for induction of remission in patients with severe granulomatosis with polyangiitis (Wegener??s) or microscopic polyangiitis. For patients with non-life threatening disease, methotrexate may be used to induce and maintain remission, although some patients may have a higher long-term risk of relapse as a result. For patients with life-threatening disease, plasma exchange may be an effective adjuvant therapy. This article reviews seminal studies from the past decade that have contributed to the current standard of care.     

Ruptured arterial aneurysm of the kidney in a patient with microscopic polyangiitis

We present the case of a 55-year-old man with ruptured arterial aneurysm accompanied by microscopic polyangiitis in the kidney. He was admitted to our hospital because of general fatigue, fever and serious numbness of his extremities. Microscopic polyangiitis (MPA) was diagnosed on the basis of cardinal symptoms, including rapidly progressive glomerular nephritis, peripheral nerve disorder and the lung abnormality, as well as positive MPO-ANCA findings. Hemodialysis had to be started on admission because of renal failure. Renal biopsy demonstrated necrotizing glomeruli, crescent formation with interstitial infiltrates. There were no immune deposits on immunofluorescence study or electron micrographs. The pathological diagnosis was necrotizing glomerulonephritis involving small and medium-sized arteries. He was treated with intravenous semi-pulse methylprednisolone therapy because of the intensely pathological renal activation and the abnormal shadow on chest X-ray. The inflammatory reaction subsequently improved, MPO-ANCA decreased and the lung lesions diminished. He complained of sharp pain of sudden onset on his left side. His hemoglobin dropped from 9.8 g/dl to 6.0 g/dl developed in the subsequent hours, but there were no sign of hemorrhage. Abdominal CT scan showed a large left-sided perinephric, intracapsular hematoma. Selective arterial angiography showed multiple aneurysms in renal and hepatic arteries. No active bleeding was present and he recovered with transfusion, supportive therapy and monitoring alone. Multiple aneurysms detected by angiography in the renal and hepatic arteries showed improvement. He is currently stable on regular hemodialysis treatment with a low dose of oral prednisolone.     

Dexamethasone compared to prednisolone for adults with acute lymphoblastic leukemia or lymphoblastic lymphoma: final results of the ALL-4 randomized, phase III trial of the EORTC Leukemia Group

Background

Corticosteroids are a standard component of the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma. Our aim was to determine whether dexamethasone results in a better outcome than prednisolone.

Design and Methods

Adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma were randomized to receive, as part of their induction therapy on days 1–8 and 15–22, either dexamethasone 8 mg/m² or prednisolone 60 mg/m². Those who reached complete remission were given two courses of consolidation therapy with high-dose cytarabine and mitoxantrone and methotrexate and asparaginase. Subsequently patients younger than 50 years, with a suitable donor, were to undergo allogeneic stem cell transplantation, whereas the others were planned to receive either an autologous stem cell transplant or high-dose maintenance chemotherapy with prophylactic central nervous system irradiation. Randomization was done with a minimization technique. The primary endpoint was event-free survival and the analyses was conducted on an intention-to-treat basis.

Results

Between August 1995 and October 2003, 325 patients between 15 to 72 years of age were randomized to receive either dexamethasone (163 patients) or prednisolone (162 patients). After induction and the course of first consolidation therapy, 131 (80.4%) patients in the dexamethasone group and 124 (76.5%) in the prednisolone group achieved complete remission. No significant difference was observed between the two treatment groups with regards to 6-year event-free survival rates (±SE) which were 25.9% (3.6%) and 28.7% (3.5%) in the dexamethasone and prednisolone groups, respectively (P=0.82, hazard ratio 0.97; 95% confidence interval, 0.75–1.25). Disease-free survival after complete remission was also similar in the dexamethasone and prednisolone groups, the 6-year rates being 32.3% and 37.5%, respectively (hazard ratio 1.03; 95% confidence interval 0.76–1.40). The 6-year cumulative incidences of relapse were 49.8% and 53.5% (Gray’s test: P=0.30) while the 6-year cumulative incidences of death were 18% and 9% (Gray’s test: P=0.07).

Conclusions

In the ALL-4 trial in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma, treatment with dexamethasone did not show any advantage over treatment with prednisolone.     

Rituximab induction without maintenance for granulomatosis with polyangiitis and dialysis – Case report and literature review

ANCA-associated vasculitis (AAV) may lead to irreversible organ damage, particularly end-stage renal disease (ESRD) requiring dialysis. The chances of renal recovery diminish with prolonged dialysis. We describe a case of a 32-year-old woman admitted for pulmonary infiltrates and acute renal failure. Autoimmune workup revealed an elevated titer of proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA). The diagnosis of granulomatosis with polyangiitis (GPA) was confirmed by renal biopsy. The patient received induction therapy with IV rituximab (375 mg/m² per week for 4 weeks) along with systemic high-dose IV corticosteroids and one pulse of IV cyclophosphamide (1000 mg). Rapid deterioration of her kidney function led to pulmonary edema requiring intensive care (ICU) hospitalization. Dialysis and plasmapheresis were initiated. Significant clinical improvement ensued, but the patient remained dialysis dependent. No immunosuppressive maintenance therapy other than prednisone was given. Chronic dialysis was discontinued successfully after eight months. At a follow-up of 30 months since her hospitalization, the patient is in complete remission without relapses. We suggest that rituximab induction without maintenance therapy for GPA ESRD may be adequate.     

Microscopic polyangiitis initiated with liver dysfunction, calf pain and fever of unknown origin

We report herein a case of microscopic polyangiitis (MPA), presenting onset with a spiking fever, liver/biliary dysfunction without jaundice and calf pain without elevation of serum creatine phosphokinase. During 1 month of careful examinations for initial diagnosis, the patient developed renal dysfunction and pulmonary hemorrhage. Based on the results of positive MPO-ANCA, renal and pulmonary involvements, the patient was diagnosed with MPA and treated with high-dose prednisolone and oral cyclophosphamide. Soon after initiation of the treatment, symptoms such as fever, calf pain, liver/biliary dysfunction and renal dysfunction disappeared with decrease of MPO-ANCA titer to the normal level.     

A case of interstitial pneumonia preceding microscopic polyangiitis]

We encountered a case of interstitial pneumonia preceding microscopic polyangiitis (MPA). A 64-year-old asymptomatic woman was found to have interstitial pneumonia on a chest radiograph taken during a work-up before an operation for cataract. Six months later she presented with non-productive cough, low grade fever and renal dysfunction. Interstitial pneumonia worsened with new lesions. The test for MPO-ANCA was positive, though it had been negative six months previously. The histopathology of the lung by video-assisted lung biopsy showed the usual interstitial pneumonitis pattern and small vessel pulmonary vasculitis. Renal biopsy showed necrotizing glomerulonephritis. She was given a diagnosis of MPA and was immediately treated with methylprednisolone pulse therapy and a combination of prednisolone and cyclophosphamide. She has remained stable for two years. This positive inversion of MPO-ANCA, while interstitial pneumonia advanced, was of interest concerning the etiology of MPA. We discuss the important topic of the mechanism of the development of MPA.     

Cytomegalovirus infection in systemic necrotizing vasculitis: causative agent or opportunistic infection?

We report on a 69-year-old woman who presented with myalgia, hearing impairment, fever, night sweats, weight loss, muscular weakness, paresthesia, hypesthesia, and hypalgesia. Sural nerve biopsy showed demyelinative and axonal polyneuropathy due to necrotizing vasculitis with fibrinoid necrosis. A positive test for antineutrophil cytoplasmic antibodies (ANCA) with a perinuclear immunofluorescence pattern directed against myeloperoxidase was more suggestive of microscopic polyangiitis (MPA) than of polyarteritis nodosa (PAN), the possible differential diagnoses. In addition, positive tests for cytomegalovirus (CMV) antibodies (immunoglobulin (Ig)M and IgG) and the detection of CMV-DNA in sputum specimens by polymerase chain reaction (PCR) were indicative of active CMV infection. Treatment with ganciclovir and anti-CMV immunoglobulin in addition to prednisolone medication for 6 months resulted in rapid improvement of the clinical symptoms without relapse. CMV infection has been described to be related to ANCA-associated vasculitis in non-immunocompromized patients and may be either a causative agent or an opportunistic infection. Identification of a viral etiology in patients with atypical ANCA-associated vasculitides may lead to different, less aggressive treatment approaches, including antiviral therapy. Received: 5 April 2000 / Accepted: 16 June 2000     

Gastrointestinal involvement at the onset of granulomatosis with polyangiitis: A case report

A 30-year-old man had developed fever, bloody stools, and oral aphtha. Proteinase 3-antineutrophil cytoplasmic antibody level was 31 EU. Lower intestinal endoscopy revealed edematous mucosa with hemorrhage in the transverse colon. Biopsies of oral aphtha showed necrotizing angiitis with granuloma. Based on these findings, he was diagnosed with granulomatosis with polyangiitis (GPA). Digestive symptoms were remitted by treatment with prednisolone and azathioprine. GPA with digestive symptoms as the initial development is rare.     

Severe clinical rebound upon withdrawal of corticosteroid before interferon therapy: Incidence and risk factors

To analyse the incidence and risk factors of clinical rebound and hepatic decompensation during or upon withdrawal of prednisolone pretreatment before interferon (IFN) therapy, two series of Taiwanese patients with chronic viral hepatitis from two independent randomized controlled trials were compared. Group 1 included 41 patients with chronic hepatitis B who were pretreated with daily prednisolone (30 mg) for 3 weeks, 15 mg for 1 week and no prednisolone for 2 weeks prior to lymphoblastoid IFN therapy. Group 2 consisted of 59 patients with chronic hepatitis B who were pretreated with daily prednisolone (40 mg) for 2 weeks, 30 mg prednisolone for 2 weeks, 20 mg prednisolone for 2 weeks and no prednisolone for 2 weeks prior to IFNα-2a therapy. Clinical rebound developed more frequently in group 2 (67.8%) than in group 1 patients (41.5%; P <0.01). The peak serum transaminase levels of group 1 and 2 patients during clinical rebound were similar. Icteric and symptomatic clinical rebound occurred in four (one cirrhotic) group 2 patients. The incidence of hepatic decompensation was 3.4% in group 2 patients, or 5.0% in group 2 patients with clinical rebound. Patients pretreated with a higher dose (40 mg) of prednisolone (odds ratio 3.0; 95% CI 1.3–6.6; P <0.01) and non-cirrhotic patients (odds ratio 6.2; 95% CI 1.2–32.1; P < 0.02) tended to suffer from clinical rebound more frequently. However, once clinical rebound develops in cirrhotic patients, the relative risk of decompensation is 16 times that of non-cirrhotic patients. These results suggest that clinicians should be cautious in prescribing a short course of corticosteroids for patients with chronic viral hepatitis, because hepatic decompensation might occur in Oriental people with or without cirrhosis.