Citations

Objective A very few studies describe the epidemiology of primary Sjögren's syndrome (pSS). The reported frequency of pulmonary involvement in pSS varies widely depending on the detection method employed, and consists mainly of various forms of airways disease. We aimed to evaluate the incidence and mortality of pSS and of lung disease in pSS, focusing on interstitial lung disease (ILD). Methods A population-based incidence cohort of patients diagnosed with pSS in 1976–2005 was assembled. Diagnosis was based on the 2002 American-European Consensus Group criteria for pSS. Cumulative incidence adjusted for the competing risk of death was estimated. A Cox model with a time-dependent covariate was used to determine the incidence and the standardised mortality HR of pSS. Results 85 patients with pSS were identified (mean age 59.9 years; 91% women). The annual incidence of pSS was 4.2, 95% CI (3.3 to 5.1)/100 000 population and it increased with higher age at pSS diagnosis (18–44 years: 2.1/100 000 vs ≥75 years: 12.3/100 000). Standardised mortality ratio in pSS compared with the general population was 0.92, 95% CI (0.57 to 1.41). A total of 105 patients with pSS and ILD were identified (mean age 58.1 years; 91% women). Among patients with pSS without prior ILD, the cumulative incidence of ILD in patients with pSS was 10% (±3%) at 1 year after diagnosis of pSS and increased to 20% (±4%) by 5 years after pSS. The development of lung disease in pSS was associated with poor survival (HR 2.16; 95% CI 0.99 to 4.74). Conclusions pSS incidence seems to be almost the same as was reported in a previous study conducted among Olmsted County Minnesota population. Survival among patients with pSS and general population does not differ substantially. However, patients with pSS who have ILD likely have increased premature mortality.

Abstract We report findings in 70 patients with both diffuse interstitial lung disease and either polymyositis (PM) or dermatomyositis (DM). Initial presentations were most commonly either musculoskeletal (arthralgias, myalgias, and weakness) or pulmonary (cough, dyspnea, and fever) symptoms alone; in only 15 patients (21.4%) did both occur simultaneously. Pulmonary disease usually took the form of acute to subacute antibiotic-resistant community-acquired pneumonia. Chest radiographs and computed tomography most commonly demonstrated bilateral irregular linear opacities involving the lung bases; occasionally consolidation was present. Jo-1 antibody was present in 19 (38%) of 50 patients tested. Synchronous associated malignancy was present in 4 of 70 patients (5.7%). Surgical lung biopsies disclosed nonspecific interstitial pneumonia (NSIP) in 18 of 22 patients (81.8%), organizing diffuse alveolar damage (DAD) in 2, bronchiolitis obliterans organizing pneumonia (BOOP) in 1, and usual interstitial pneumonia (UIP) in 1. Treatment usually included prednisone in 40–60 mg/d dosages for initial control, followed by lower dose prednisone plus an immunosuppressive agent such as azathioprine or methotrexate for disease suppression. Survival was significantly better than that observed for historical control subjects with idiopathic UIP, and was more consistent with survival previously reported in idiopathic NSIP. There was no difference in survival between Jo-1 positive and Jo-1 negative groups.

Abstract Lymphangiomyomatosis (LAM) is a progressive and often fatal interstitial lung disease characterized by a diffuse proliferation of abnormal smooth muscle cells in the lungs. LAM is of unusual interest biologically because it affects almost exclusively young women. LAM can occur as an isolated disorder (sporadic LAM) or in association with tuberous sclerosis complex (TSC). Because only a minority of women with TSC develops symptomatic LAM, we hypothesized that a relationship might exist between the type of germline TSC1 or TSC2 gene mutation and the risk of developing LAM. We examined all 41 exons of the TSC2 gene and 21 coding exons of the TSC1 gene for mutations in a group of 14 women with both TSC and LAM using single-strand conformation polymorphism analysis. Seven mutations were found in TSC2 and one in TSC1. Of the seven patients with TSC2 mutations, two had the same in-frame exon 40 deletion and one had an exon 41 missense change. We conclude that germline mutations in the extreme carboxy-terminus of tuberin can result in LAM. Further studies will be required to determine whether mutations in exons 40 and 41 are associated with an increased incidence and/or severity of LAM in women with TSC.

Abstract Pulmonary lymphangioleiomyomatosis (LAM) is an uncommon disease reported to occur exclusively in women. We describe a phenotypically normal man with pulmonary LAM. Fluorescence in situ hybridization (FISH) studies performed on the lung biopsy confirmed a normal XY genotype. Our patient also had stigmata of tuberous sclerosis complex (TSC), including facial angiofibromas and renal angiomyolipoma. Immunohistochemical stains of both LAM and renal angiomyolipoma showed positive immunoreactivity for hamartin (TSC1) and loss of immunoreactivity for tuberin (TSC2). Loss of heterozygosity (LOH) for TSC2 was further demonstrated in the renal angiomyolipoma. Coupled with the results of immunostains, these findings are consistent with TSC2 mutation.

Abstract The clinical records of 487 patients seen at Mayo Clinic Rochester (MCR) during 1994 through 1996 who were diagnosed as having idiopathic pulmonary fibrosis of the usual interstitial pneumonia type (IPF/UIP) were reviewed. Computed tomography (CT) had been done in 94.7% of patients and surgical open lung biopsy (OLB) in 20.3%. Median survival was 3.2 yr. We compared survival as a function of treatment program, based on intent to treat at the time of the initial contact within the study window. Treatment advised included colchicine alone in 167, no therapy in 157, prednisone at maintenance dosages alone in 54, colchicine plus prednisone in 71, and other programs in 38. Oxygen therapy was advised in 133 patients. By univariate analysis, worse survival was associated with prednisone therapy compared with no therapy, and with oxygen therapy compared with no oxygen therapy. However, on multivariate analysis, worse survival was associated with older age, male gender, lower diffusing capacity for carbon monoxide (DlCO), lower alveolar volume (Va), and a history of worsening pulmonary function. When adjustment was made for these factors, there was no significant difference in survival between those patients treated with colchicine or prednisone and those on no therapy, and no difference between those on oxygen therapy and those without oxygen.

Abstract Idiopathic pulmonary fibrosis (IPF) is a generally fatal disorder with a reported median survival of 3 to 6 yr. This has been based on relatively few studies with diagnoses inconsistently confirmed by adequate lung biopsy. Retrospective analysis of 104 patients with IPF who had open lung biopsy (OLB) at Mayo Medical Center from 1976 to 1985 was performed to establish the overall survival rate, the spectrum of histopathological subgroups and their associated prognostic significance. The study group consisted of 54 men and 50 women with a median age of 63 yr. Median survival was 3.8 yr after diagnosis by OLB with an estimated 10 yr survival of 27%. Current histopathologic review showed a heterogeneous group including usual interstitial pneumonia (UIP), desquamative interstitial pneumonia (DIP), nonspecific interstitial pneumonia/fibrosis (NSIP), acute interstitial pneumonia (AIP), bronchiolitis, bronchiolitis obliterans organizing pneumonia (BOOP), and others. Median survival of the UIP group was 2.8 yr which is significantly worse (p < 0.001) than for other subgroups of chronic interstitial pneumonias. IPF includes several histopathologic subgroups with significantly different survival rates. Patients with UIP have worse survival than patients with other types of idiopathic chronic interstitial pneumonias including NSIP. Accurate histopathologic classification is essential for prognostication in patients with IPF.

ObjectivePulmonary disease represents an important extraarticular manifestation of rheumatoid arthritis (RA). While the association of RA and interstitial lung disease is widely acknowledged, obstructive lung disease (OLD) in RA is less well understood. We therefore aimed to assess the incidence, risk factors, and mortality of OLD in patients with RA.MethodsWe examined a population‐based incident cohort of patients with RA and a comparison cohort of individuals without RA. OLD was defined using a strict composite criterion. Cox proportional hazards models were used to compare OLD incidence between the RA and comparator cohorts to investigate risk factors and to explore the impact of OLD on patient survival.ResultsA total of 594 patients with RA and 596 subjects without RA were followed for a mean of 16.3 and 19.4 years, respectively. The lifetime risk of developing OLD was 9.6% for RA patients and 6.2% for subjects without RA (hazard ratio [HR] 1.54, 95% confidence interval [95% CI] 1.01–2.34). The risk of developing OLD was higher among male patients, among current or former smokers, and for individuals with more severe RA. Survival of RA patients diagnosed with OLD was worse compared to those without OLD (HR 2.09, 95% CI 1.47–2.97).ConclusionPatients with RA are at higher risk of developing OLD, which is significantly associated with premature mortality. Effective diagnostic and therapeutic strategies to detect and manage OLD in patients with RA may help to improve survival in these patients.

Objective Autoimmune pancreatitis (AIP) is a treatable form of chronic pancreatitis that has been increasingly recognised over the last decade. We set out to better understand the current burden of AIP at several academic institutions diagnosed using the International Consensus Diagnostic Criteria, and to describe long-term outcomes, including organs involved, treatments, relapse frequency and long-term sequelae. Design 23 institutions from 10 different countries participated in this multinational analysis. A total of 1064 patients meeting the International Consensus Diagnostic Criteria for type 1 (n=978) or type 2 (n=86) AIP were included. Data regarding treatments, relapses and sequelae were obtained. Results The majority of patients with type 1 (99%) and type 2 (92%) AIP who were treated with steroids went into clinical remission. Most patients with jaundice required biliary stent placement (71% of type 1 and 77% of type 2 AIP). Relapses were more common in patients with type 1 (31%) versus type 2 AIP (9%, p<0.001), especially those with IgG4-related sclerosing cholangitis (56% vs 26%, p<0.001). Relapses typically occurred in the pancreas or biliary tree. Retreatment with steroids remained effective at inducing remission with or without alternative treatment, such as azathioprine. Pancreatic duct stones and cancer were uncommon sequelae in type 1 AIP and did not occur in type 2 AIP during the study period. Conclusions AIP is a global disease which uniformly displays a high response to steroid treatment and tendency to relapse in the pancreas and biliary tree. Potential long-term sequelae include pancreatic duct stones and malignancy, however they were uncommon during the study period and require additional follow-up. Additional studies investigating prevention and treatment of disease relapses are needed.