Substitution of methotrexate for cyclophosphamide in Wegener granulomatosis: a 12-year single-practice experience

We conducted a retrospective review to assess outcomes of therapy in patients with newly diagnosed Wegener granulomatosis (WG) using methotrexate (MTX) for mild to moderate disease and short-term treatment with cyclophosphamide (CYC) followed by MTX for severe disease. Patients with WG were included if their initial plan of therapy and subsequent care were directly supervised by the Cleveland Clinic Center for Vasculitis Care and Research. Severe disease (immediately life-threatening or involving critical organs) was initially treated with CYC and glucocorticoids. Mild to moderate disease was initially treated with MTX and glucocorticoids if serum creatinine was less than 2 mg/dL. Following initial improvement of severe disease, treatment was changed to MTX if serum creatinine was originally less than 2 mg/dL or had diminished to less than 2 mg/dL. Disease activity was determined at each visit and later converted to a Birmingham Vasculitis Activity Score, as modified for Wegener granulomatosis (BVAS/WG). Laboratory monitoring of disease and treatment toxicity was initially weekly and never less than monthly.Eighty-two (32%) of 253 patients with WG referred to the Center for Vasculitis Care and Research met eligibility criteria. Ineligible patients did not have new-onset disease or were not able to be followed principally in our center. Seventy percent of patients (57/82) initially had severe disease and received a short course of CYC for remission induction. In over half of these patients, illness was judged to be severe because of pulmonary hemorrhage; rapidly progressive glomerulonephritis, including need for dialysis; or neurologic abnormalities.All patients improved: remission was achieved in 50% (41/82) of patients within 6 months and in 72% (59/82) within 12 months. Sustained remission (BVAS/WG = 0 for at least 6 consecutive months) was ultimately achieved in 78% (64/82) of patients. Among the 75 (91%) patients who achieved remission of any duration, 45% relapsed within 1 year and 66% relapsed within 2 years following remission. Eighty-two percent of relapsed patients achieved subsequent remissions after additional treatment. About three-quarters of relapses were mild and promptly responded to treatment.Seventeen percent of patients developed serious infections. CYC-associated cystitis or bladder cancer did not occur in any patients. At least 1 form of permanent morbidity from WG alone was noted in 74.0% of patients. Three patients (3.7%) died over a median follow-up period of 4.5 years; no deaths were due to active disease.Although treatment was primarily directed toward achieving clinical improvement and not calculated to achieve marked lymphopenia, patients in whom treatment produced lymphocyte counts of 1000/mm was associated with a hazard ratio for relapse of 3.0, although the latter difference was not statistically significant.In patients with WG, a strategy that limits or avoids CYC therapy produced a frequency of remission comparable to that achieved with conventional CYC protocols, excellent survival, and avoidance of long-term CYC toxicity. However, relapses were common and incremental permanent morbidity occurred in most patients. While not a goal of therapy, when treatment produced marked lymphopenia, prolonged remissions were more likely.     

Wegener's granulomatosis in India: clinical features, treatment and outcome of twenty-five patients

OBJECTIVE: To report our clinical experience on Wegener's granulomatosis (WG). METHODS: A retrospective review of case records of all patients with WG in our Rheumatology Clinic during the period July 1988 to June 2000 was carried out and the details of demography, clinical and laboratory data, treatment and outcome were obtained and analysed. RESULTS: Twenty-five patients (16 females and 9 males) were found eligible for inclusion in the study. The mean age and duration of symptoms at presentation were 33.5 years and 5.5 months, respectively. Two patients had limited WG. Twenty-two patients with generalized WG were treated with standard regimen comprising oral prednisolone (1 mg/kg/day) and oral cyclophosphamide (2 mg/kg/day). Cyclophosphamide was continued for at least one year after the patient attained remission. One patient was treated with intravenous cyclophosphamide regimen. The two patients with limited WG were treated with oral prednisolone and methotrexate (10-12.5 mg as a single dose per week). Remission was achieved in 24 patients after a median time of six months. The median follow-up of patients was five years (range 4 months-11 years). Five patients were lost to follow-up. Eight patients suffered a relapse. The mean time for relapse was 34 months after the initial remission. Seven out of eight patients remitted again after reinstitution of the initial induction regimen. One patient died of diffuse pulmonary haemorrhage despite early institution of therapy. CONCLUSION: WG is being increasingly diagnosed in India now because of greater awareness and diagnostic aids. Although remissions are easy to achieve, relapses continue to pose a challenge to the treating physician.     

Staphylococcal toxic-shock-syndrome-toxin-1 as a risk factor for disease relapse in Wegener's granulomatosis

OBJECTIVES: Nasal carriage of Staphylococcus aureus constitutes a risk factor for disease exacerbation in Wegener's granulomatosis (WG). We hypothesized that staphylococcal superantigens (SAg) are a determinant of S. aureus-related risk for disease relapse in WG. METHODS: In a retrospective longitudinal cohort study in 62 WG patients, we investigated the presence of the staphylococcal SAg genes sea, seb, sec, sed, see, tsst-1 and eta in S. aureus strains isolated from WG patients during an observation period of seven years. Subsequently, we assessed whether relapses of WG were associated with the presence of SAg-positive staphylococci. RESULTS: Of 1718 swab cultures analysed, 709 (41.2%) were S. aureus-positive. Fifty-one patients carried S. aureus, of whom 37 (72.5%) patients carried at least one SAg-positive S. aureus strain. Of the 709 S. aureus-positive cultures, 326 (46%) contained at least one SAg gene. Except for see, all assessed SAg genes were detected. sea was found most frequently, followed by sec, tsst-1 and eta and finally, by sed and seb. Using a multivariate, time-dependent Cox regression analysis we found that the presence of S. aureus was associated with relapses of WG (RR 3.2; 95% CI 1.2-8.4). The risk for relapse was modulated by the presence and type of SAg, with tsst-1 being associated with an increased risk for relapse (RR 13.3, 95% CI 4.2-42.6). CONCLUSION: The risk for relapse of WG increases with the presence of tsst-1-positive S. aureus. Eradication of tsst-1-positive S. aureus in WG may show whether disease relapses can be prevented.     

Treatment of non-life threatening Wegener's granulomatosis with methotrexate and daily prednisone as the initial therapy of choice.

OBJECTIVE: To examine our experience with methotrexate (MTX) and daily prednisone (PRED) as the initial treatment of Wegener's granulomatosis (WG). METHODS: Between November 1992 and November 1997, we treated 19 patients with non-life threatening WG with the combination of oral weekly MTX (starting at 7.5-10.0 mg/week) and daily PRED (median starting dose 40 mg/day, range 20-60). The MTX dose was increased to 15 mg/week by the end of the first month, and then by 2.5 mg/week until the disease was controlled. We attempted to taper PRED to 20 mg/day by the end of the second month, but did not use alternate day corticosteroids. Before treatment with this regimen, no patient had received previous treatment for WG. RESULTS: At presentation, the average number of organ systems involved was 3.6. Nine of the 19 patients (47%) had glomerulonephritis, but none had a serum creatinine > 1.2 mg/dl at presentation. Only 37% of the patients were hospitalized at presentation. Seventeen of 19 patients (89%) improved with treatment, and 14 (74%) achieved remission. However, half those who achieved remission suffered relapses, and no patient achieved a durable, complete remission (disease-free status free of all medications). Fifteen patients (79%) were able to taper PRED to < 10 mg/day. Seven of 8 disease relapses responded to increases of MTX and/or PRED. Only one patient developed glomerulonephritis while receiving treatment and required a change of therapy to cyclophosphamide. There were no deaths among patients in this series. Treatment with MTX and PRED was well tolerated: only 2 (11%) of the patients stopped treatment because of side effects (major liver function test abnormalities in both cases). No patient suffered permanent morbidity from MTX treatment. CONCLUSION: In selected patients with WG, the combination of MTX and daily PRED effectively controls the disease. However, chronic disease courses are the rule with this treatment regimen, and the likelihood of disease relapse is high. In our experience, the use of MTX and PRED in WG was safer than previously described, despite the use of daily corticosteroids.     

Intravenous immunoglobulins for relapses of systemic vasculitides associated with antineutrophil cytoplasmic autoantibodies: Results of a multicenter,prospective, open‐label study of twenty‐two patients

Objective

To evaluate at 9 months and 24 months the safety and efficacy of intravenous immunoglobulins (IVIGs) administered for 6 months to treat relapses of Wegener's granulomatosis (WG) or microscopic polyangiitis (MPA) occurring either under treatment or during the year following discontinuation of corticosteroids and/or immunosuppressants.

Methods

Patients received IVIGs (0.5 gm/kg/day for 4 days) as additional therapy administered monthly for 6 months and were assessed every 3–6 months. Corticosteroids could be maintained or reintroduced at the time of relapse; immunosuppressants could be continued but could not be reintroduced. At months 9 (end point) and 24 (followup), the following information was collected: complete or partial remission, relapse as assessed with the Birmingham Vasculitis Activity Score (BVAS) 2005, and tolerance and safety of IVIG therapy.

Results

Twenty‐two Caucasian patients (7 men and 15 women) were studied: 19 had WG, and 3 had MPA. Their median age was 53 years (range 19–75 years), and their median duration of systemic vasculitis was 27 months (range 7–109 months). Their median BVAS 2005 score was 11 (range 3–25). At study entry, 21 patients were ANCA positive, and 21 patients were taking steroids and/or immunosuppressants. All patients experiencing relapse were treated with the same drug(s) plus IVIGs. All patients initially responded to IVIG therapy. By month 9, 13 patients had complete remission, 1 had partial remission, 7 had relapse, and 1 had treatment failure. In 8 of the 14 patients who had remission, the response persisted at month 24. Seven patients experienced minor side effects.

Conclusion

IVIGs induced complete remissions of relapsed ANCA‐associated vasculitides in 13 of 22 patients at month 9. Because of the good safety and tolerance profiles of IVIGs, these agents can be included in a therapeutic strategy with other drugs used to treat relapses of WG or MPA.

     

Mycophenolate mofetil for remission maintenance in the treatment of Wegener's granulomatosis

OBJECTIVE: To examine the safety of mycophenolate mofetil (MMF) for remission maintenance in patients with Wegener's granulomatosis (WG) who had been treated with daily cyclophosphamide (CYC) and glucocorticoids to induce remission. METHODS: Fourteen patients were treated for active WG using a standardized regimen of CYC and glucocorticoids for induction of remission and MMF for remission maintenance. Outcome was assessed using predetermined definitions based on clinical characteristics and pathologic, laboratory, and radiographic findings. RESULTS: Remission occurred in all 14 patients (100%) at a median time of 3 months. The median time to discontinuation of glucocorticoids was 8 months. No patients died during protocol treatment and 6 patients (43%) relapsed at a median of 10 months after achieving remission. MMF was well tolerated and no patients had to be withdrawn as a result of medication toxicity. CONCLUSION: The use of CYC and glucocorticoids for induction of remission and MMF for remission maintenance was well tolerated, but disease relapses were observed.     

An interdisciplinary approach to the care of patients with Wegener's granulomatosis: long-term outcome in 155 patients

OBJECTIVE: To examine the outcome in 155 consecutive patients with Wegener's granulomatosis (WG) followed up for a median of 7 years. METHODS: Treatment was adapted to the activity and extent of disease, with regular evaluation by an interdisciplinary team accompanied by group education about vasculitis. RESULTS: The estimated median survival time was 21.7 years (95% confidence interval [95% CI] 15.60-27.86). Twenty-two patients died; 19 deaths were attributable to WG and/or its treatment. Significant predictors of survival at diagnosis were age >50 years (hazard ratio [HR] 5.45, 95% CI 1.97-15.02), kidney involvement with impaired renal function (HR 5.42, 95% CI 1.76-16.68), and lung involvement (HR 3.75, 95% CI 1.26-11.16). At some stage, 142 patients received prednisone and cyclophosphamide (CYC), usually as daily CYC plus mesna as uroprotection, 50 patients received trimethoprim/sulfamethoxazole, and 45 received methotrexate. Complete remission was achieved in 83 of the 155 patients. One or more relapses occurred in 99 patients after either complete or partial remission. CYC-induced cystitis and myelodysplastic syndrome occurred in 17 and 11 patients, respectively. A cumulative dose of 100 gm or more of CYC resulted in a 2-fold greater risk of CYC-related morbidity than with lower CYC doses. Serious infections occurred in 41 patients. CONCLUSION: An interdisciplinary approach to the care of 155 WG patients resulted in a median survival of >21 years. Kidney or lung involvement at diagnosis was predictive of a >3-fold higher mortality. Although CYC remains essential in the treatment of WG, it was administered as briefly as possible and under close surveillance to avoid permanent CYC-related morbidity, which can lead to serious therapeutic problems in chronic relapsing WG.     

Pulse cyclophosphamide therapy in Wegener's granulomatosis: a pilot study.

Five patients with Wegener's granulomatosis (WG) have been treated with 6- to 8-monthly pulses of intravenous cyclophosphamide (CP) and glucocorticoids in an open pilot study. One patient achieved complete remission sustained during 30 months of follow-up; one patient had features of active disease after 28 months of remission; two patients after an initial remission had an exacerbation of the disease and received continuous oral administration of CP, and one patient required continuous oral CP to control the symptoms. These results suggest that this regimen may not achieve a high degree of sustained remission in patients with WG.     

Clinical features and outcome of pediatric Wegener's granulomatosis

OBJECTIVE: Wegener's granulomatosis (WG) is a predominantly small-vessel vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs). There are few reports describing its clinical features and outcome in children. We report on the experience at a single tertiary referral center over 21 years. METHODS: We conducted a retrospective chart review of all patients diagnosed with WG at The Hospital for Sick Children between 1984 and 2005. RESULTS: Twenty-five patients were identified. Median age at diagnosis and median followup were 14.5 years and 32.7 months, respectively. Male-to-female ratio was 1:4. Median duration of symptoms before diagnosis was 2 months. Of 22 patients, 21 were ANCA positive during their disease course (classic ANCA 78.9%). Constitutional symptoms were the most common clinical feature at presentation (24 of 25). Glomerulonephritis was present in 22 patients at presentation. Only 1 of 11 patients who presented with or developed renal impairment had normalization of serum creatinine. Upper airway involvement occurred in 21 patients at presentation and 24 over followup; only 1 had subglottic stenosis. Twenty patients had initial pulmonary involvement, most commonly nodules (44%) and pulmonary hemorrhage (44%). Five patients required ventilation for pulmonary hemorrhage. Four patients (16%) had venous thrombotic events (VTEs). Treatment included prednisone (100%), cyclophosphamide (76%), azathioprine (40%), and methotrexate (32%). CONCLUSION: Pediatric WG typically presents in adolescence and has a female predominance. Glomerulonephritis and pulmonary disease are common at diagnosis and frequently present as a pulmonary-renal syndrome. Loss of renal function is common and rarely completely reversible. As in adults, children with WG are at risk of VTEs.     

RENAL DISEASE IN DIABETICS—WHICH PATIENTS HAVE DIABETIC NEPHROPATHY AND WHAT IS THEIR OUTCOME?*

From August 1974 to January 1985, 53 patients (26 men; seven Maoris) mean age 45 (SD 15) years, with diabetes mellitus for a mean of 12 (SD nine) years had a renal biopsy and were followed. Indications for biopsy were nephrotic syndrome (24), proteinuria (23), renal impairment (five) and hematuria (one). Mean plasma creatinine concentration was 0.22 (SD 0.18) mmol/L and protein excretion 3.4 (SD 2.5) g/24 h. Diabetic nephropathy was demonstrated in 39 patients and significantly associated with retinopathy and insulin dependent diabetes mellitus (IDDM). Of the 39 patients followed for 25.7 (SD 22.8) months, 18 had died (nine myocardial infarction, six uremia, two sepsis, one stroke) and nine had begun dialysis. The five-year cumulative renal survival was 28%. The presence of the nephrotic syndrome and the plasma creatinine concentration at presentation were the best predictors of survival. Diabetics with IDDM of 20 years duration, retinopathy and heavy proteinuria, who survive the other complications of their disease, are likely to have diabetic nephropathy requiring renal replacement therapy.     

The continuous-DCMP therapy for acute nonlymphocytic leukemia in elderly patients--comparison with younger patients

Twenty seven previously untreated patients of acute nonlymphocytic leukemia with age ranging from 30 to 77 years, received a 7-day remission induction regimen consisting of daunorubicin, cytosine arabinoside, 6-mercaptopurine and prednisolone (continuous-DCMP). Patients who achieved complete remission were given ten courses of consolidation therapy and followed without any maintenance therapy. The complete remissions were obtained in 7 of 15 patients (46.6%) 60 years and older, and in 11 of 12 patients (91.7%) 30-59, years of age. Although a high mortality during periods of marrow hypoplasia after the intensive induction therapy, and early relapses in the 60 years and older patients remain major problems, our data suggest the elderly patients deserve a trial of intensive combination chemotherapy.     

Short remission durations in therapy-related leukemia despite cytogenetic complete responses to high-dose cytarabine

Seventeen patients with therapy-related myelodysplastic syndrome (t- MDS) or therapy-related acute nonlymphocytic leukemia (t-ANLL) were treated with single-agent high-dose cytarabine (HDAC; 1 to 3 g/m2 every 12 hours for 12 doses). The initial neoplasm was still present in eight patients when t-MDS/t-ANLL developed. Fifteen of the 16 patients with chromosomal abnormalities in bone marrow cells had loss or rearrangement of chromosomes 5 and/or 7. One patient had a t(15;17), and one had inadequate material for cytogenetic analysis. Twelve patients had normal metaphase cells (3% to 71%). Indications for HDAC therapy were progressive pancytopenia in 13 patients or rising blast count in four. Five patients died of marrow hypoplasia following therapy. Four others had refractory t-ANLL and died within the subsequent 5 months. Only one of ten patients with a poor performance status (PS greater than or equal to 2 using the ECOG scale) achieved a complete remission, but all seven patients with a good performance status (PS less than or equal to 1) had a complete remission. Hematologic remissions were achieved in 8 patients (47%) after one (6 patients) or two (2 patients) induction courses and were confirmed by recovery of a 100% normal marrow karyotype in six of the seven patients who were retested. Patients in remission received one to four consolidation courses with HDAC alternating with cytarabine/doxorubicin, but seven relapsed within 8 months (median remission duration, 5 months). In every case, the original chromosomal abnormality reappeared at relapse. HDAC has a high response rate for good-performance patients with t-MDS/t-ANLL, but complete remissions are short even when confirmed cytogenetically and consolidated intensively.     

The graft-versus-leukemia effect of nonmyeloablative stem cell allografts may not be sufficient to cure chronic myelogenous leukemia

We treated 12 patients with chronic myelogenous leukemia (CML) with a low-intensity preparative regimen followed by allogeneic stem cell transplantation in an attempt to confer a curative graft-versus-leukemia (GVL) effect with minimum morbidity. Seven patients in first chronic phase (CP1) and five in second chronic phase (CP2) (age 15-68 years) received a nonmyeloablative conditioning regimen of fludarabine and cyclophosphamide, followed by a G-CSF-mobilized peripheral blood stem cell (PBSC) transplant from an HLA-identical sibling. Cyclosporine (CsA) was used for graft-versus-host disease (GVHD) prophylaxis. Median follow-up was 384 days. Neutrophil recovery occurred at a median of 12 days. There was no transplant-related mortality. Of the seven CP1 patients transplanted, seven achieved a stable molecular remission; two with no post-transplant intervention, three after donor lymphocytes, imatinib and interferon, and two after a myeloablative stem cell transplant. Four of five CP2 patients died in blast crisis and one survived in molecular remission. Of the 12 patients with durable engraftment, six had Grades II-IV acute GVHD; six had limited chronic GVHD. These results suggest that cytoreduction is required to optimize the curative effect of allogeneic stem cell transplantation for CML.     

Rituximab for treatment-resistant extensive Wegener`s granulomatosis—additive effects of a maintenance treatment with leflunomide

Extensive Wegener’s granulomatosis (WG) is treated by glucocorticosteroids (GC) and cyclophosphamide (CYC). In some cases, the disease is refractory to CYC. For those patients the depletion of B-lymphocytes with rituximab is a promising new treatment modality. This is a retrospective study of six patients receiving rituximab (RTX) with 4 × 375 mg/m² body surface weekly because of inefficacy of CYC. Proteinase-3-antineutrophil cytoplasmic antibodies (PR3-ANCA) and c-ANCAs were assessed. For clinical follow-up the Birmingham Vasculitis Activity Score for WG (BVAS/WG) was used. In five of the six cases, leflunomide (LEF) was given as maintenance treatment. Mean follow up was 16 months (12–21 months). The median PR3-ANCA titer fell from 36.8 U/ml at baseline to 21.4 U/ml after 3 months, 8.3 after 6 months, and 4.3 at month 12. The median BVAS/WG at baseline was 5 and 0 after 1 month. Two minor relapses could be noticed at month 3. After 6 months, one patient still had a BVAS of 1, all the others had a BVAS of 0. At month 18, a major relapse occurred in one patient, which was successfully retreated with RTX. The RTX infusions were well tolerated. Rituximab is a well-tolerated, very effective medication for patients with Wegener’s granulomatosis. Leflunomide maintenance may increase the efficacy of rituximab and prolong the disease-free period.     

Predictive factors for renal sequelae in adults with Henoch-Schönlein purpura

OBJECTIVE: To examine the outcome and risk factors for renal sequelae in an unselected population of adults with Henoch-Schonlein Purpura (HSP). METHODS: Retrospective study of adult patients (> 20 years) with biopsy proved cutaneous vasculitis diagnosed as having HSP seen at a single center between 1984 and 1998. Patients were classified as having HSP according to proposed criteria. Only those patients with a followup of at least 1 year were included in this study of renal sequelae. RESULTS: Twenty-eight patients with a mean followup of 5.5 years fulfilled the inclusion criteria. When the study was concluded, 10 patients (36%) had renal sequelae and 2 (7%) had renal insufficiency. Men outnumbered women. However, neither a previous history of drugs, gender, nor age at disease onset was associated with a higher risk of permanent renal involvement. Patients with hematuria at disease onset or renal involvement during the course of the disease more commonly developed renal sequelae (p < 0.001). The presence of anemia (p = 0.05) at the time of diagnosis and the onset in summer (p < 0.05) were also more common in those with permanent renal involvement (renal sequelae). Patients with relapses had also a higher trend to develop renal sequelae (p = 0.07). All patients who fulfilled more than 2 of these 5 risk factors developed permanent renal involvement. With this model we were able to predict renal sequelae in 8 of the 10 patients who had this complication. The Goodman-Kruskal gamma test value was 0.92 (95% CI 0.78-1.00). CONCLUSION: In unselected adults with HSP, permanent renal involvement (renal sequelae) is not uncommon. Hematuria at disease onset and persistence of renal manifestations during the course of the disease are significant indicators of possible development of renal sequelae. These manifestations plus other features such as onset in summer, anemia at disease onset, or relapses of the disease may predict the development of renal sequelae in most patients.     

Relapses and recurrences in giant cell arteritis: a population-based study of patients with biopsy-proven disease from northwestern Spain

We conducted the present study to determine the incidence of disease flares (relapses and recurrences) in a series of patients with biopsy-proven giant cell arteritis (GCA). We assessed a series of 174 patients who were diagnosed with biopsy-proven GCA, uniformly treated, and followed at the rheumatology division of Hospital Xeral-Calde (Lugo, Spain), the single rheumatology division for a well-defined population. All of them were followed for at least 1 year after the disease diagnosis. Seventy-one (40.8%) experienced relapses or recurrences of the disease. Patients who had relapses or recurrences did not show clinical differences when compared with the remaining biopsy-proven GCA patients. However, the total duration of corticosteroid therapy was significantly longer in those patients who had relapses or recurrences of the disease. The median dose of prednisone and the median duration of corticosteroid treatment at the time of the first relapse were 5 mg/d and 16 months, respectively. Headache (52%) was the most common feature at the time of the first relapse. Polymyalgia rheumatica manifestations occurred in 30% of the patients at that time. However, none of them developed visual loss. Thirty-two patients experienced recurrences of the disease when prednisone dose had been discontinued. The median time from the disease diagnosis to the time of the recurrence was 23 months. The presence of anemia (hemoglobin <12 g/dL) at the time of disease diagnosis was the best predictor of relapses or recurrences of GCA (odds ratio, 2.17; 95% confidence interval, 1.02-4.62; p = 0.04). The results from the present study confirm that relapses and recurrences are frequent in homogenously treated patients with biopsy-proven GCA. A chronic inflammatory response manifested by anemia at the time of disease diagnosis may predict the development of disease flares.     

Long-term follow-up of microscopic polyangiitis, 17-year experience at a single center

BackgroundLong-term prognoses of Wegener granulomatosis (WG) and Churg–Strauss syndrome (CSS) are known; however, few data exist on long-term prognoses for microscopic polyangiitis (MPA). Our aim was to analyse the prognoses of MPA.MethodsCohort study with retrospective selection of patients. Twenty-two patients admitted to our Hospital (1990–2006) with biopsy-proven MPA were studied. The start date for entry into the study was the date of diagnosis. Statistical analysis was performed to look for prognostic factors for survival.ResultsMPA patients were followed-up for a median of 78 (5–131) months. MPA patients were treated with cyclophosphamide (Cy) plus corticosteroid (Cs) (59%) or Cs alone (41%). Seven MPA patients died. Cumulative MPA patient survival at 1, 5, and 10 years were 85% (75–95%), 85% (75–95%), and 74% (60–88%) in those treated with Cy plus Cs and 50% (32–68%), 36% (14–58%), and 0% (0–30%) in those treated with Cs alone, respectively (P = 0.04). Disease extent index < 5 (P = 0.02) and age < 65 years (P = 0.02) were associated with improved survival rates in MPA patients treated with Cy.Five MPA (23%) patients relapsed after a median of 54 months (35–93). No variables were related to relapses.Despite treatment, 11 MPA (50%) patients developed end-stage renal disease after a median of 9 months (0–53).ConclusionsMost MPA patients had life-threatening renal or lung involvement at diagnosis. Patients not treated with immunosuppressants had a poorer prognosis. The long-term prognosis of MPA patients who survived 6 months post diagnosis was good, although renal survival rates are low.     

Response to plasma exchange and splenectomy in thrombotic thrombocytopenic purpura. A 10-year experience at a single institution.

BACKGROUND--This study was designed to assess the response of patients with thrombotic thrombocytopenic purpura to plasma exchange and to evaluate the role of splenectomy after relapse. METHODS--The records of all patients with thrombotic thrombocytopenic purpura who had plasma exchange as primary treatment at a single center during a 10-year period were retrospectively reviewed. Response to the initial course of plasma exchange was determined, and the clinical outcome was evaluated in patients whose conditions were either refractory to exchange, responded without relapse, or relapsed after initial response. The outcome of patients treated during relapse with splenectomy was evaluated. A literature review was conducted to determine the clinical outcome in patients treated similarly. RESULTS--Twenty-seven patients for whom data could be evaluated had been treated in the 10-year period. Twenty-one (78%) responded to the plasma exchange, but the conditions of six (22%) were refractory and these patients died. Eight patients (30%) had one or multiple relapses after initial response but had prolonged remissions after additional plasma exchange alone (two patients) or splenectomy (six patients). A review of 19 reports, including 224 patients with thrombotic thrombocytopenic purpura initially treated with plasma exchange, revealed similar findings, with initial response in 81%, refractoriness in 19%, and relapse after initial response in 27% of patients. CONCLUSION--Response to plasma exchange in thrombotic thrombocytopenic purpura is associated with an excellent prognosis, and most deaths occur in patients whose conditions are refractory. Relapses after initial response are frequent but can be managed successfully with additional plasma exchange or with splenectomy, which often induces long-term remissions.     

Association between active Wegener's granulomatosis and anticytoplasmic antibodies

Autoantibodies reacting with the cytoplasm of granulocytes and monocytes (anticytoplasmic antibodies [ACPAs]) were found in 42 of 45 patients with active Wegener's granulomatosis (WG) (sensitivity, 93%). Specificity was tested in selected groups of patients with closely related diseases. Of 58 patients without a diagnosis of WG, 2 had ACPAs (specificity, 97%). The significance of ACPA titration for assessing or predicting disease activity was evaluated in a 16-month prospective study of 35 patients with WG. Seventeen relapses were observed and all were preceded by a significant rise of the ACPA titer. Anticytoplasmic antibodies are a specific and sensitive marker for active WG; a rising titer is a sensitive marker for the development of a relapse.     

Aggressive primary gastrointestinal lymphomas: review of 91 patients treated with the LNH-84 regimen. A study of the Groupe d'Etude des Lymphomes Agressifs.

PURPOSE: Patients with aggressive primary gastrointestinal lymphoma undergoing the LNH-84 chemotherapy regimen were analyzed to determine the efficacy of intensive combination chemotherapy, the role of surgical debulking in patients treated with combination chemotherapy, and the toxicity associated with each of these modalities. PATIENTS AND METHODS: Ninety-one patients with primary gastrointestinal lymphoma who participated in the prospective multicenter LNH-84 combination chemotherapy trial (total number of patients in trial, 737) were analyzed. These 91 patients included 69 (76%) with diffuse large cell, nine (10%) with diffuse mixed, and seven (8%) with small noncleaved cell lymphoma. Two patients (2%) had stage IE, 54 patients (59%) stage IIE, and 35 patients (38%) stage IV disease; all patients with stage IE, 22 with stage IIE, and 18 with stage IV disease had bulky (greater than or equal to 10 cm) tumors. Specific sites of gastrointestinal involvement included stomach (47%), small bowel (38%), ileocecum (14%), colon (11%), and rectum (7%). Although surgical resection was attempted in 71 patients (78%), only 28 (31%) had complete tumor excision. All patients received three or four cycles of ACVB (defined in text) induction therapy followed by sequential consolidation as previously described. RESULTS: Responses to treatment in the 91 patients included 71 (78%) complete remissions, six (7%) partial remissions, five (5%) nonresponses, and nine (10%) deaths. With a median follow-up of 3 years, 10 patients (14%) have had relapses; predicted 4-year disease-free survival of complete responders is 85% and predicted 4-year survival of the entire group is 62%. In patients with stage IE or IIE disease, the complete response, survival, and disease-free survival rates were similar in those who underwent complete surgical resection or incomplete or no surgical resection prior to the administration of combination chemotherapy. Prognostic factors predicting for survival in the 91 patients with primary gastrointestinal lymphoma were similar to those in the 646 other patients treated with the LNH-84 regimen. CONCLUSIONS: Patients with aggressive gastrointestinal lymphoma treated with intensive chemotherapy have outcomes and prognostic factors comparable to those of patients with similar-stage aggressive lymphoma without primary gastrointestinal involvement. Surgical resection prior to the administration of combination chemotherapy did not influence the complete response rate, survival rate, or disease-free survival rate in this small group of patients.