Screening for late-onset Pompe disease in western Denmark.

OBJECTIVE: Late-onset Pompe disease (LOPD) is a rare autosomal recessively inherited metabolic myopathy caused by reduced activity of the lysosomal enzyme alpha-glucosidase. In a previous screening study at two large neuromuscular university clinics in Denmark, three patients with LOPD were identified out of 103 patients screened. No systematic screening has been performed at the other neurological departments in the western part of Denmark. Thus, patients with a diagnosis of unspecified myopathy were screened for LOPD. MATERIALS AND METHODS: At seven neurological departments in the western part of Denmark, medical records were evaluated for all patients registered with myopathy diagnosis codes (ICD 10 codes: G 71.0-71.9 and G 72.0-72.9) during the period January 1, 2002, to December 31, 2012. If no specific diagnosis has been reached, patients were invited for screening. Dried blood spot (DBS) test was used to analyze the activity of the enzyme alpha-glucosidase. RESULT: A total of 654 patients were identified. From the medical records, information was obtained concerning symptoms, family history, electromyography, muscle biopsy results and creatine kinase levels. Eighty-seven patients (13.3%) (males 61%) at a mean age of 53.3 years (SD 16.5) fulfilled the criteria for screening. A DBS test was performed in 47 (54%) patients. In all patients, the enzyme activity was within reference values. CONCLUSION: None of the screened patients had a reduced activity of the enzyme alpha-glucosidase. Although the cohort studied was small, our findings do not suggest that LOPD is underdiagnosed in patients with unspecified myopathy in western Denmark.

Myasthenia and risk of cancer: a population-based case-control study.

BACKGROUND AND PURPOSE: To evaluate the association between having non-thymoma myasthenia and the risk of extra-thymic cancer in a population-based setting. METHODS: A nationwide case-control study was conducted in Denmark based on medical registries. The study included all cases with a first time diagnosis of cancer during 2000-2009. Each case was matched by birth year and gender with eight population controls using risk set sampling. Subjects with myasthenia were identified through a validated register-based algorithm. Conditional logistic regression was used to compute crude and adjusted odds ratios (ORs), with 95% confidence intervals (CIs), for cancer associated with a prior diagnosis of myasthenia. RESULTS: In all, 233 437 cases and 1 867 009 controls were identified. A total of 80 cases and 518 controls had a prior diagnosis of myasthenia. Myasthenia was not associated with an increased risk of overall cancer (OR 1.1; 95% CI 0.9-1.4). Adjusted ORs for major cancer sites were also close to unity, whereas an elevated risk of lymphomas was observed (OR 2.0; 95% CI 0.8-5.5). Early-onset myasthenia was associated with a slightly increased OR for overall cancer (1.5; 95% CI 1.0-2.3); however, this estimate was based on small numbers. CONCLUSIONS: Non-thymoma myasthenia was not associated with an increased risk of overall cancer. Larger studies are necessary to evaluate the association between myasthenia and risk of lymphoma and the potential effect modification by age of myasthenia onset in relation to cancer risk.

Risk of non-melanoma skin cancer in myasthenia patients treated with azathioprine.

BACKGROUND AND PURPOSE: The association between use of azathioprine and risk of non-melanoma skin cancer (NMSC) in patients with myasthenia was evaluated in a nationwide setting. Treatment of autoimmune myasthenia frequently involves long-term exposure to immunosuppressants, including azathioprine. Use of azathioprine increases the risk of NMSC in organ recipients and probably also in patients with other autoimmune disorders. No previous study has specifically investigated the risk of NMSC in myasthenia patients treated with azathioprine. METHODS: This is a case-control study based on Danish population-based registries. Cases were myasthenia patients with a first time diagnosis of NMSC during 2004-2009. Age- and sex-matched controls were selected amongst myasthenia patients with no history of cancer using incidence density sampling. Prior use of azathioprine in cases and controls was assessed through prescription records (1995-2009). Conditional logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI) for skin cancer associated with a high cumulative dose (≥150 g) or long-term use (≥5 years) of azathioprine, adjusted for confounders. RESULTS: Thirty NMSC cases and 360 matched controls were identified. Ever use of azathioprine was associated with a considerably increased risk of NMSC (OR 3.3, 95% CI 1.5-7.3) that was even more apparent in patients with high cumulative dose (OR 4.6, 95% CI 1.7-12.5) or long-term (OR 4.8; 95% CI 1.7-13.6) use of azathioprine. CONCLUSION: Azathioprine use in patients with myasthenia is associated with an increased risk of NMSC.

Late-onset myasthenia not on the increase: a nationwide register study in Denmark, 1996-2009.

BACKGROUND: An increase in late-onset myasthenia gravis (MG) has been reported. There are few large population-based studies over longer periods of time reflecting recent developments in MG incidence. METHODS: We identified a nationwide cohort of patients with incident myasthenia in Denmark in 1996-2009. We used a validated algorithm to track subjects based on a combination of diagnosis and prescription (pyridostigmine) data from nationwide registers. Patients with myasthenia were classified into early onset (<50 years old) and late onset (50+ years). We calculated incidence rates (IRs) and corresponding 95% confidence intervals. RESULTS: We identified 693 patients (362 women) with incident MG in the study period corresponding to an IR of 9.2 per million person-years (8.5-9.9). Overall, 207 (29.9%) were classified as early-onset and 486 (70.1%) as late-onset MG. Women predominated in the early-onset group (70.5%), but not in the late-onset group (44.4%). The incidence rate of early-onset MG was 4.2 (3.6-4.8) and late-onset MG 18.9 (17.3-20.7) per million person-years and it did not vary over time in the study period (P-values for trend 0.54 and 0.15, respectively). CONCLUSION: Late-onset MG comprised a large proportion of all incident cases in Denmark, was more common in men than women, and occurred with a stable incidence in the 14-year study period. Therefore, we speculate whether previous reports of a rise in late-onset MG reflect a non-biological phenomenon, that is, a gradual improvement in the diagnosis of MG in this age group in previous years.

Use of azathioprine for non-thymoma myasthenia and risk of cancer: a nationwide case-control study in Denmark.

BACKGROUND AND PURPOSE: To evaluate the association between the use of azathioprine and risk of cancer in patients with non-thymoma myasthenia gravis (MG) in a nationwide setting. METHODS: Case-control study based on population-based registries. Cases were patients with MG with a first time diagnosis of cancer (except non-melanoma skin cancer) registered during 2000-2009, and controls were patients with MG with no history of cancer. Prior use of azathioprine in cases and controls was assessed through prescription records (1995-2009). We used unconditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for cancer associated with a high cumulative dose [≥ 1000 defined daily doses (DDD)] or long-term use (≥ 5 years) of azathioprine, compared with never use of the drug and adjusted for potential confounders. RESULTS: We identified 89 cases and 873 controls. The prevalence of ever use of azathioprine was similar among cases (39.3%) and controls (39.4%). We observed a slightly elevated OR for cancer overall associated with long-term use of azathioprine (1.22; 95% CI: 0.62-2.40, P = 0.56). The highest ORs were observed for use of 2000 DDD or more of azathioprine; however, these risk estimates were based on small numbers. CONCLUSIONS: Use of azathioprine in patients with non-thymoma MG may be associated with a slightly increased risk of cancer overall. Larger studies are necessary to address the risk of site-specific cancers.