Parity in patients with chronic inflammatory arthritides childless at time of diagnosis.

OBJECTIVE: To assess parity in women with chronic inflammatory arthritides (CIA) childless at time of diagnosis. METHODS: Patients were selected from the Norwegian Disease-Modifying Anti-Rheumatic Drug (NOR-DMARD) registry. Each patient was matched by year of birth with 100 reference women from the Norwegian Population Registry. Data linkage for patients and references with the Medical Birth Registry of Norway (MBRN) identified all offspring until time of linkage (October 2007). Patients and corresponding references childless at the time of diagnosis were included in the analyses. Kaplan-Meier curves visualized the proportion of childless women and were compared by a log rank test. RESULTS: In all, 156 rheumatoid arthritis (RA), 107 other chronic arthritides (OCA), and 75 juvenile idiopathic arthritis (JIA) patients were childless at time of diagnosis. At the time of data linkage, the proportions (%) of childless RA/OCA/JIA patients versus references were 61.5/62.6/57.3 versus 46.9/42.9/41.0, respectively, all differences statistically significant. The log rank test showed lower parity in all diagnostic groups compared with references (p < 0.001 for RA and OCA and p = 0.002 for JIA). No difference in parity was observed between RA and OCA patients, but both diagnostic groups had lower parity than JIA patients (p = 0.001). Disease characteristics were similar between childless and fertile patients. CONCLUSIONS: Reduced parity was observed in all diagnostic groups compared with references. RA and OCA patients had lower parity than JIA patients, indicating that having the disease as a young adult may influence parity more than having the disease in childhood.

Characteristics of late onset neutropenia in rheumatologic patients treated with rituximab: a case review analysis from a single center.

BACKGROUND: Late onset neutropenia (LON) secondary to rituximab has been reported as an adverse event in the treatment of hematological malignancies but reports on autoimmune diseases are scarce. AIM: To review the characteristics of LON in rheumatologic patients from a single center. DESIGN: Retrospective case record study. METHODS: Clinical and laboratory data since the introduction of rituximab in our clinic in 2006 were collected and analyzed retrospectively. LON was defined as an absolute neutrophil count <1.0 × 10(9)/l occurring 4 weeks after the last rituximab infusion. RESULTS: LON was identified in eight patients (6% of all patients receiving rituximab). All patients had complicated and refractory disease and had been treated with a median of 4.5 different immunosuppressive drugs prior to rituximab. LON appeared after a median interval of 23 weeks with recovery of LON after a median of 6.5 days. Four patients had concomitant infection at the onset of neutropenia, when six patients had both low immunoglobulin M and immunoglobulin G. Six patients were rechallenged with rituximab without recurrence of LON. CONCLUSION: The characteristics of LON after rituximab treatment in patients with autoimmune disease are comparable with experiences from hematological malignancies. LON seems to precede B-cell recovery implying a perturbation of the granulocyte homeostasis. LON with its rapid recovery does not seem to increase the risk for serious infection in contrast to the sustained hypogammaglobulinemia that may follow rituximab. The risk of LON recurrence after rechallenge is low.

Effectiveness of switching between TNF inhibitors in ankylosing spondylitis: data from the NOR-DMARD register.

OBJECTIVE: To assess the effectiveness of switching to a second tumour necrosis factor inhibitor (TNFi) in patients with ankylosing spondylitis (AS). METHODS: Data were extracted from an ongoing longitudinal observational multicentre study in Norway. This study included anti-TNF naïve patients with AS starting treatment with a TNFi as well as treatment with a second TNFi in these same patients. Effectiveness data and 2-year drug survival were compared between switchers and non-switchers and within switchers (first and second TNFi). RESULTS: 514 anti-TNF naïve patients with AS were included; 77 patients switched to a second TNFi while 437 patients did not switch. The percentages of non-switchers using etanercept, infliximab or adalimumab were 53%, 32% and 15%, and the percentages of first and second TNFi in the switchers were 42%, 53% and 5% and 40%, 23% and 36%, respectively. The reason for switching was insufficient response (IR) in 30, adverse events (AEs) in 44 and not reported in 3 patients. Baseline disease activity was similar between the groups. Three-month BASDAI 50 and ASAS 40 responses were achieved by 49% and 38% of non-switchers, by 25% and 30% of switchers after the first TNFi and by 28% and 31% after the second TNFi. The 3-month disease activity level was higher for switchers on the second TNFi than for non-switchers. Drug withdrawal rate was higher during the second TNFi among switchers than for non-switchers (p=0.001). No difference was found in the effectiveness of the second TNFi between switchers due to IR and AE. CONCLUSION: This study confirms that switching to a second TNFi can be effective in AS and can be as useful as in rheumatoid arthritis, although overall effectiveness seems to be somewhat lower than in non-switchers.

Postpartum onset of rheumatoid arthritis and other chronic arthritides: results from a patient register linked to a medical birth registry.

BACKGROUND: It is known that onset of rheumatoid arthritis (RA) is increased post partum. OBJECTIVE: To compare incidence rates between RA and other chronic arthritides (OCA) 0-24 months after delivery, and to compare the incidence rates within each group 0-24 versus 25-48 months post partum. METHODS: Premenopausal women from a Norwegian patient register were linked with the Medical Birth Registry of Norway to study the interval between delivery and time of diagnosis. Cox regression analysis with adjustments for age at delivery and birth order was applied to compare proportions of incident cases of RA and OCA with onset 0-24 months post partum. Poisson regression analysis with adjustment for the population at risk was applied to estimate the incidence rate ratio (IRR) 0-24 versus 25-48 months post partum. RESULTS: Of 183 RA and 110 patients with OCA diagnosed after delivery, 69 (37.7%) had RA and 31 (28.2%) OCA during the first 24 months post partum (p = 0.09). The IRR (95% CI) for diagnosis during 0-24 months versus 25-48 months was 1.73 (1.11 to 2.70) (p = 0.01) for RA, 1.05 (0.59 to 1.84) (p = 0.86) for OCA. The IRR was 2.23 (1.06 to 4.70) and 1.87 (0.67 to 5.21), respectively, when only considering diagnoses after the first pregnancy. Clinical characteristics were similar within each diagnostic group. CONCLUSION: The proportions of incident cases with onset 0-24 months after delivery were not different between RA and OCA. A peak in incidence during 0-24 months was seen in the RA group, both when considering all pregnancies and only the first pregnancy.

Comparison of work disability and health-related quality of life between males and females with rheumatoid arthritis below the age of 45 years.

OBJECTIVES: To compare work disability (WD) and health status between males and females with rheumatoid arthritis (RA) in the age group 18-45 years, and to compare health status between patients with and without WD within each gender, and finally to identify factors independently associated with WD in this age group. METHODS: A cross-sectional study of RA patients at the time starting with disease-modifying antirheumatic drug (DMARD) therapy and/or biological treatment. Patients receiving a permanent, national WD pension corresponding to >or= 50% were defined as work disabled. We examined gender differences with regard to disease characteristics, health status and WD. The Mann-Whitney U-test and Pearson's chi(2)-test were applied for group comparisons. Multiple logistic regression analyses with adjustments for duration of education, disease duration, age, erosive disease, disability score [using the Modified Health Assessment Questionnaire (MHAQ)], Disease Activity Score-28 (DAS-28), the Short Form Health Survey (SF-36) mental health score and gender were used to identify variables associated with WD. RESULTS: Out of 474 (372 females) patients, the number (%) of work-disabled females/males was 91 (24.7)/8 (8.1) (p<0.001). WD was associated with worse health status in both genders. The odds ratio (95% confidence interval) [OR (95% CI)] for WD in females vs. males was 4.84 (1.85-12.65) in the multivariate analyses. Other factors independently associated with WD were worse mental health, disease duration and low level of education. CONCLUSION: Females with RA had a fourfold increased risk of WD compared to men. Low level of education, disease duration and worse mental health were also independently associated with WD.

Work disability and health-related quality of life in males and females with psoriatic arthritis.

OBJECTIVES: To compare health status, demographic variables and work disability (WD) between males and females with psoriatic arthritis (PsA) in the 18-45 age group, and further to compare health status between those with and without WD for each gender and to identify variables associated with WD. METHODS: A cross-sectional study was carried out of patients with PsA with peripheral arthritis at the time at which they started disease-modifying antirheumatic drug therapy (DMARD) and/or biological treatment. Patients receiving a permanent national WD pension corresponding to >or=50% were defined as work disabled. Gender differences were examined with regard to health status, demographic variables and WD. Mann-Whitney U test and Pearson chi(2) were applied for group comparisons between males and females and work disabled versus not work disabled for each gender. Multiple logistic regression analyses with adjustments for duration of education, disease duration, age, erosive disease, disability score (Modified Health Assessment Questionnaire; MHAQ), the short form-36 (SF-36) mental health score, and gender were used to identify variables associated with WD. RESULTS: Out of 271 (102 females) patients, the number (%) of work-disabled females/males was 33 (32.7%)/29 (17.4%) (p = 0.004). Work-disabled patients had generally worse health status than non-work-disabled patients, and these differences were generally more pronounced in males than in females. In the multiple logistic regression model, low educational level, increasing disability score (MHAQ), presence of erosive disease, female gender and disease duration were independently associated with WD. CONCLUSIONS: WD in patients with PsA below 45 years of age was independently associated with educational level, disability score, erosive disease, female gender and disease duration.

The comparative effectiveness of anti-TNF therapy and methotrexate in patients with psoriatic arthritis: 6 month results from a longitudinal, observational, multicentre study.

OBJECTIVES: To compare the response to treatment with tumour necrosis factor (TNF) inhibitors and methotrexate (MTX) monotherapy in patients with psoriatic arthritis (PsA) within a real-life clinical setting. METHODS: We analysed data from an ongoing longitudinal, observational multicentre study in Norway. Our data comprised 526 cases of patients with PsA who received either anti-TNF treatment (n = 146) or MTX monotherapy (n = 380) and were followed for at least 6 months with measures of disease activity, health status and utility scores. A propensity score was computed to adjust for channelling bias. The changes in measures of disease activity and health-related quality of life from baseline to 3- and 6-month follow-up were compared between the groups with adjustments for the baseline value of the dependent variable and the propensity score (analyses of covariance (ANCOVA)). RESULTS: The groups were significantly different at baseline with respect to demographic and disease activity measures. The variables included in the propensity score were age, sex, number of previous disease modifying anti-rheumatic drugs (DMARDs), presence of erosive disease, treatment centre and investigator's global assessment. The adjusted changes at 6 months were significantly larger in the anti-TNF group for ESR, DAS-28, M-HAQ, patient's assessments of pain, fatigue and global disease activity on a visual analogue scale (VAS) and 4 out of 8 SF-36 dimensions. CONCLUSIONS: Clinical improvement was superior with TNF inhibitors compared to MTX monotherapy in patients with PsA, when assessed in this setting of daily clinical practice.

Detection of cerebral embolic signals in patients with systemic lupus erythematosus.

BACKGROUND: Involvement of the CNS in systemic lupus erythematosus (SLE) is caused by several pathogenic mechanisms including cerebral embolism. AIM: To measure the frequency of microembolic signals (MES) by using transcranial Doppler (TCD) ultrasound and to assess their association with cerebral infarction, neuropsychological dysfunction, and biochemical, sonographic and clinical variables in an unselected group of patients with SLE. METHODS: A 1-h TCD recording from the middle cerebral artery was carried out in 55 patients with SLE having a mean age of 46 (SD 13) years. MRI of the brain, carotid artery ultrasonography with intima-media thickness and atherosclerotic plaque assessments were carried out in addition to a broad biochemical and clinical assessment. All patients underwent a neuropsychological assessment. RESULTS: Of the 55 patients, MES were detected in 5 (9%) and cerebral infarcts were found in 9 (18%). A significant association was found between MES and cerebral infarcts and considerably more neuropsychological deficits were found in MES-positive patients compared with the negative group. MES were not associated with other clinical, sonographic and biochemical factors believed to be associated with cerebral embolism. CONCLUSIONS: Cerebral embolism may be one of the important mechanisms responsible for the high prevalence of cerebrovascular events and the neuropsychological deficits observed in patients with SLE. Although the number of MES-positive patients was small, the lack of a significant association between MES and other known risk factors for MES suggests a complex pathogenesis for the embolisation in these patients.

Pulmonary function and high-resolution CT findings five years after disease onset in patients with Wegener's granulomatosis.

OBJECTIVE: Although pulmonary involvement is common in Wegener's granulomatosis (WG), little is known about the pulmonary outcome. We evaluated the relationship between clinical disease characteristics and pulmonary function and high-resolution computed tomography (HRCT) findings after disease duration of 5 years. METHODS: A pulmonary function test (PFT) and pulmonary HRCT were performed in 41 patients from a population-based register of WG. Clinical predictors for abnormal PFT and HRCT were tested by logistic regression. RESULTS: Previous WG-related lung involvement (PLI) had occurred in 80% of patients, but only 24% of patients still reported pulmonary symptoms at the research visit. One-third of patients had abnormal PFT findings, with reduced alveolar diffusion by KCO (transfer coefficient) being most common (24%). The number of PLI episodes was associated with reduced KCO and reduced FEV1% (forced expiratory volume in 1 s as a percentage of forced vital capacity) (overall presence 10%). Reduced KCO was also associated with disease duration. Reduced total lung capacity (TLC) (overall presence 8%) was only related to prior WG-related lung nodules. Pulmonary HRCT was abnormal in 80%, but with more severe abnormalities in only 30%. Pleural thickening and parenchymal bands were associated with PLI. None of the treatment variables was associated with the PFT or HRCT findings. CONCLUSION: Five years after disease onset a quarter of the WG patients reported pulmonary symptoms, had severe abnormalities on HRCT, and abnormal PFT. The correlation between these abnormalities was poor, but the number of pulmonary involvements was a risk factor for reduced gas diffusion, obstructive lung disease, parenchymal bands, and pleural thickening. Treatment variables had no discernible negative pulmonary effects.

Neuropsychiatric disturbances in SLE are associated with antibodies against NMDA receptors.

To determine whether neuropsychiatric manifestations in patients with systemic lupus erythematosus (SLE) are influenced by antibodies against the human N-methyl-D-aspartate (NMDA) receptor types NR2a or NR2b. A decapeptide was synthesized containing a sequence motif present in the extracellular ligand-binding domain of NMDA receptors NR2a and NR2b, bound by the monoclonal murine anti-DNA antibody R4A. In an ELISA with the murine monoclonal R4v as positive control, plasma samples of 57 patients with SLE were examined for the anti-peptide (anti-NR2) antibody after the patients had been subjected to comprehensive psychological and cognitive testing. Poor performance on the Visual Paired Associates test (immediate), the Grooved Pegboard test, as well as high scores on the Beck Depression Inventory, and scales D-2 (depression), Pd-4 (psychopathic deviate), Sc-8 (schizophrenia), and Ma-9 (hypomania) of the MMPI-2 were significantly associated with elevated levels of anti-NR2 antibodies. The findings in several domains indicate an association between anti-NR2 antibodies and depressed mood in addition to decreased short-time memory and learning. Antibodies to NMDA receptors thus may represent one of several mechanisms for cerebral dysfunction in patients with SLE.

Predictors of survival and organ damage in Wegener's granulomatosis.

OBJECTIVE: To determine survival, organ damage and predictors of these outcomes in a population-based, longitudinal cohort study of patients with Wegener's granulomatosis (WG). METHODS: In a retrospective study, 56 WG patients (median age 50 yr) were followed for 56.5 months. Clinical and laboratory data, disease activity, organ involvement and the Vasculitis Damage Index (VDI) were recorded at baseline (start of treatment) and at a research visit after 42.5 months. The Kaplan-Meier method was used to estimate survival and Cox proportional hazards and linear regression models were used to study predictors of outcome. RESULTS: Duration of symptoms before the start of treatment (baseline) was 6 months (1-102 months) and 21 patients (37.5%) had organ damage (VDI > or = 1) at baseline. Baseline organ damage was associated with delay in the start of treatment and an elevated serum creatinine concentration. Fifty-five patients received prednisolone (Pred) and 53 patients received cyclophosphamide by intravenous pulse (CYCiv) or as a daily oral dose (CYCpo). CYCiv patients received lower cumulative doses of CYC and spent less time on Pred >20 mg/day than CYCpo patients. Thirteen patients died during the study period. Ten-year patient survival was 75%. Baseline predictors of reduced survival were higher age, dialysis-dependence and the presence of organ damage. Chronic, end-stage renal failure developed in 10 patients overall and was associated with reduced renal function at baseline. Severe organ damage (VDI > or = 5) developed in 71% of the patients and new damage occurred mainly during the first 6 months. Increased time (months) on Pred >20 mg/day during follow-up increased the last VDI [beta=0.5, 95% confidence interval (CI) 0.3 to 0.8], P<0.001), whereas increased time on CYC during the first 6 months reduced the last VDI (beta=-0.6, 95% CI -1.1 to -0.02, P=0.04). CONCLUSION: Treatment with CYC and corticosteroid led to a 10-yr survival rate of 75% in WG but did not prevent severe organ damage. The presence of baseline organ damage was a marker of poor outcome. There was an association between damage and treatment given.

Neuropsychological dysfunction in systemic lupus erythematosus is not associated with changes in cerebral blood flow.

Cognitive dysfunction is found in a considerable proportion of patients with systemic lupus erythematosus (SLE). SPECT provides an estimate of regional cerebral blood flow (rCBF) which has been claimed to be sensitive to detect brain involvement in SLE. It is, however, uncertain if these perfusion defects are related to cognitive dysfunction. In the present study we investigated whether cerebral dysfunction assessed by neuropsychological measures was associated with changes in rCBE Fifty-two SLE patients were examined with a battery of neuropsychological tests and MRI of the brain. For each patient 99mTC-HMPAO-SPECT was performed with the visual cortex as reference, and a reduction in rCBF of > 15% was considered abnormal. Regional CBF was performed with an automated computer program quantitatively estimating blood perfusion in 16 symmetrical sectors of the brain. Several sectors of the brain showed varying areas of reduced rCBF with the temporal lobes most frequently involved. There were generally no associations between cognitive level of functioning and reduced rCBF. MRI demonstrated cerebral infarcts in 9 (17%) patients. In general rCBF was reduced in all sectors of the brain in patients with infarcts, although statistical significant difference in rCBF between patients with and without infarcts was only seen in the parietal lobe. Several neuropsychological functions were influenced by the presence of cerebral infarcts. There was no significant association between immunological measures and SPECT findings or neuropsychological measures. Neuropsychological dysfunction in SLE was associated with the presence of cerebral infarcts detected by MRI, but not by changes in rCBF. SPECT seems to add little if any information to that obtained by clinical examination, neuropsychological testing, and MRI. Since anticoagulation may prevent cerebral infarcts, such prophylactic intervention may be of importance in preventing cognitive deterioration.

Peripheral neuropathy in systemic lupus erythematosus--a longitudinal study.

OBJECTIVE: Peripheral neuropathy (PN) is reported to occur in 5-27% of patients with systemic lupus erythematosus (SLE) mostly as a length-dependent sensorimotor axonopathy. Studies over time have not been performed. Design - Longitudinal study. SUBJECTS AND METHODS: Thirty-three Caucasian SLE patients consented to participate in the study and were subjected to clinical examination, laboratory tests, and nerve conduction velocity (NCV) studies. At the follow-up 7 years later, 7 patients (21%) were dead, 4 refused to participate, and 2 did not want to perform NCV studies. Twenty patients were thus available for longitudinal study. RESULTS: When all SLE patients were considered on a group basis at follow-up, 8 (33%) out of 24 NCV parameters showed significant deterioration despite correction for time, while 16 (67%) were unchanged. Analysis of change from baseline showed that, except for F-responses, several NCV changes were highly dependent (negative regression coefficients) on baseline levels at start of study. No demographic, laboratory, or disease associated quantitative factor was associated with these changes in NCV parameters over time. Nor was a consistent effect on NCV parameters from any qualitative demographic or disease associated factor confirmed by Repeated Measures ANOVA analyses. CONCLUSIONS: A modest progressive neuropathic process exists in patients with SLE. Important is also the finding that, over time, the abnormalities of NCV parameters fluctuate in the individual patients, and the impairments are not necessarily irreversible. This study also shows no association to medication, demographic-, or other disease associated factors.

Somatic and psychological features of headache in systemic lupus erythematosus.

OBJECTIVE: Headaches--especially of migrainous type--have been considered part of the disease spectrum of systemic lupus erythematosus (SLE). We wished to characterize prevalence and types of headaches in SLE and find out if headache is associated with disease, personality traits, or other psychological factors. METHODS: Fifty-eight consecutive Caucasian patients with SLE were given a clinical examination. We recorded SLE disease activity according to the SLE Disease Activity Index, types of headache according to International Headache Society criteria, and personality traits and emotional status according to Minnesota Multiphasic Personality Inventory-2 and Beck Depression Inventory (BDI). RESULTS: Thirty-eight SLE patients (66%) were headache sufferers; of these, 22 patients (38%) had migraine and 21 (36%) had tension-type headache. Headaches were not associated with disease activity or any other disease associated variable, including tests for antiphospholipid antibodies. Migraine was associated only with a tendency to social isolation and anxiety, while tension-type headache was associated with psychological distress, such as anxiety, somatic complaints, reduced energy, mental tension, social discomfort and withdrawal, and depressive mood according to the BDI. CONCLUSION; Migraine and tension-type headaches occur frequently in patients with SLE. Migraine shows the same clinical presentation as in a non-SLE population, and may not be part of a neuropsychiatric disease spectrum. This also applies to tension-type headache, which in contrast to migraine shows some associations with emotional and personality traits, and could represent components of a chronic pain syndrome.

Epidemiology of Wegener's granulomatosis in northern Norway.

OBJECTIVE: To determine if changes in the incidence, prevalence, and clinical presentation of Wegener's granulomatosis (WG) have occurred in the stable population of northern Norway during a 15-year period. METHODS: We performed a retrospective cohort study using hospital discharge records from all 11 hospitals in the region and the databases of the 2 pathology departments in the area. Only patients fulfilling the American College of Rheumatology 1990 criteria for WG were included in the study, and demographic and clinical data at diagnosis were recorded. Incidence, point prevalence, and period prevalence rates were estimated for three 5-year periods. RESULTS: Fifty-five patients (62% male) with a median age at diagnosis of 50 years (range 10-84 years) fulfilled the inclusion criteria. The annual incidence/ million population increased from 5.2 (95% confidence interval [95% CI] 2.7-9.0) during 1984-1988 to 12.0 (95% CI 8.0-17.3) during 1994-1998. The point prevalence/million increased from 30.4 (95% CI 16.6-51.0) to 95.1 (95% CI 69.1-129.0). The highest incidence rate occurred in men ages 65-74 years. There were no significant period differences in age, first organ involved, delay of diagnosis, or disease activity, but fewer patients had malaise and renal insufficiency during the earliest time period. No seasonal variation in the onset of WG was present, although we noted a pattern of annual fluctuation. CONCLUSION: The prevalence of WG has tripled in northern Norway over the last 15 years. While more efficacious therapy may explain part of this increase, we also found a significant trend toward increased incidence over that period. The incidence rate over the last 5 years is the highest reported so far, while the clinical presentation has remained unchanged.

Long-term efficacy of azathioprine treatment for proliferative lupus nephritis.

BACKGROUND: Combination therapy with cytotoxic drugs and corticosteroids reduces the risk for renal failure in patients with proliferative lupus nephritis (PLN), but uncertainty remains about the best mode of immunosuppression and its long-term effects. We report long-term results of combined azathioprine-prednisolone treatment for PLN, which has been the therapy of choice for the treatment of PLN at our centre for 15 yr. PATIENTS AND METHODS: A retrospective cohort study was carried out of 26 lupus patients, seen between 1978 and 1993, with histological and/or clinical evidence of PLN. Therapy consisted of prednisolone 1 mg/kg daily, tapered after 4 weeks to the lowest possible maintenance dose combined with azathioprine up to 2.5 mg/kg. Median duration of azathioprine treatment was 53 months. Standard statistical lifetable analyses were performed. RESULTS: Median follow-up on 1 January 1998 was 119 months. Patient survival estimates after 5, 10 and 15 yr of follow-up were 96, 91 and 82%, respectively. Four patients (15%) developed end-stage renal failure and three received renal transplants after a mean period of 27 months on haemodialysis. Renal survival estimates after 5, 10 and 15 yr of follow-up were 92, 87 and 87%, respectively. No malignancies were seen during the study period. CONCLUSION: Azathioprine treatment for 4-1/2 yr was well tolerated in this cohort of Caucasian patients with PLN and was associated with outcomes similar to those reported for pulse cyclophosphamide therapy.

Wegener's granulomatosis: long-term follow-up of patients treated with pulse cyclophosphamide.

Treatment with daily oral cyclophosphamide (CY) has improved survival in Wegener's granulomatosis (WG), but is associated with severe and potentially lethal adverse effects. Less toxic treatment regimens, such as pulse CY, have been used, but the effect has been questioned. We have treated 11 patients with WG with pulse CY (15 mg/kg initially every second week, gradually increasing the pulse interval). After 4.5 yr follow-up and a total of 501 pulses of CY, one patient died and eight patients (73%) were in complete remission. Remission was induced in 91% of the patients after a median period of 3.5 months and relapses were seen in 60%. With the same treatment protocol, a new complete remission was induced in 75% of those relapsing. Except for one patient who died, no patient developed end-stage renal failure. Haemorrhagic cystitis was not observed and no malignancies recorded. Severe infections were seen in 36%, but none caused by Pneumocystis carinii. Nausea was the most frequent side-effect, seen in 64% of the patients. We conclude that treatment with pulse CY every second week is safe and effective in inducing remission and treating relapses in WG. The relapse rate seems to be higher than with low-dose oral CY, but the cumulative dose of CY is less.

Severe intestinal involvement in Wegener's granulomatosis: report of two cases and review of the literature.

The clinical and pathological manifestations of severe intestinal involvement in Wegener's granulomatosis were studied by a review of the literature and reports of two patients. Altogether, six cases, two females and four males, were studied. One patient developed two episodes of bowel manifestations necessitating immediate surgical interventions. The average age at onset of intestinal symptoms was 43.3 yr (26-55 yr) and, in all cases, the first signs of such manifestations developed within the first 2 yr of disease. Prior to the onset of intestinal symptoms, immunosuppressive therapy was administered in six of seven instances. Acute abdominal pain with signs of peritonitis or distention only constituted the main clinical picture in six of the seven events. The last episode was manifested clinically with profuse diarrhoea with blood and mucus. Of the seven instances of severe intestinal manifestations, the small bowel was involved in two, the large bowel in three, and both the small and large bowel were affected in two episodes. Histological evidence of vasculitis in the bowel was demonstrated in three of the seven biopsy specimens, while in four, ischaemia, inflammation and ulceration were the pathological findings. Intestinal perforation was seen four times and surgery was performed in six of seven episodes. Severe intestinal involvement is rare in Wegener's granulomatosis. The initial bowel manifestations occur within the first 2 yr of disease, and affect both the large and small bowel. Histologically, vasculitis, ischaemia, inflammation and ulceration are the prevailing findings. Death due to intestinal catastrophy occurred in one of the six patients reported. Most likely, the manifestations are associated with the disease process rather than related to the use of immunosuppressive agents.