Development of Inflammatory Bowel Disease in Children With Juvenile Idiopathic Arthritis Treated With Biologics.

OBJECTIVE: The aim of our study was to describe the distinct features of inflammatory bowel disease (IBD) in juvenile idiopathic arthritis (JIA) patients and to identify risk factors for its development. METHODS: Data from the German biologics in pediatric rheumatology registry (Biologika in der Kinderrheumatologie) collected between 2001 and 2021 were analyzed retrospectively. RESULTS: In 5009 JIA patients, 28 developed confirmed IBD before the age of 18 years: 23 (82.1%) with Crohn disease (CD), 4 (14.3%) with ulcerative colitis (UC), and 1 (3.6%) with IBD-unclassified (IBD-U). The incident rate of IBD during 20 years of observation was 0.56% (0.46% for CD, 0.08% for UC, and 0.02% for IBD-U), of whom 20.3% were HLA-B27 positive, 25% had enthesitis-related arthritis, and 14.3% psoriatic arthritis. Within 90 days before IBD diagnosis, 82.1% (n = 23) received treatment with etanercept (ETA), 39.3% (n = 11) non-steroidal anti-inflammatory drugs, 17.9% (n = 5) systemic corticosteroids, 8 (28.6%) methotrexate (MTX), 14.3% (n = 4) sulfasalazine, 10.7% (n = 3) leflunomide, and 3.6% (n = 1) adalimumab and infliximab, respectively. The incidence of IBD was lower in patients treated with MTX, but higher in patients treated with ETA except if ETA was combined with MTX. Also in patients on leflunomide or sulfasalazine, the IBD incidence was higher. CONCLUSIONS: In our JIA cohort, an increased IBD incidence is observed compared to the general population, and the ratio of CD to UC is markedly higher hinting at a distinct phenotype of IBD. Pretreatment with MTX seems to be protective. Treatment with ETA does not prevent IBD development and JIA patients treated with leflunomide and sulfasalazine may be at an increased risk for IBD development.

Current and projected incidence trends of pediatric-onset inflammatory bowel disease in Germany based on the Saxon Pediatric IBD Registry 2000-2014 -a 15-year evaluation of trends.

AIMS: An increasing number of children and adolescents worldwide suffer from inflammatory bowel disease (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC). The present work aims to investigate the incidence, prevalence and future trends of IBD in children and adolescents in Saxony, Germany. METHODS: The Saxon Pediatric IBD Registry collected data on patients up to 15 years of age from all 31 pediatric hospitals and pediatric gastroenterologists in Saxony over a 15-year period (2000-2014). In 2019, an independent survey estimated a registry completeness of 95.7%. Age-standardized incidence rates (ASR) per 100,000 person-years (PY) and prevalence per 100,000 children and adolescents were calculated. Evaluation was also been performed in sex and age subgroups. Joinpoint and Poisson regression were used for trend analyses and projections. RESULTS: 532 patients with confirmed IBD during 2000-2014 were included in the epidemiological evaluation. 63.5% (n = 338) patients had CD, 33.1% (n = 176) had UC and 3.4% (n = 18) had unclassified IBD (IBD-U). The 15-year IBD prevalence was 111.8 [95%-CI: 102.3-121.3] per 100,000. The incidence ASR of IBD per 100,000 PY over the whole observation period was 7.5 [6.9-8.1]. ASR for the subtypes were 4.8 [4.3-5.3] for CD, 2.5 [2.1-2.9] for UC and 0.3 [0.1-0.4] for IBD-U. The trend analysis of ASR using the joinpoint regression confirmed a significant increase for incidence of IBD as well as CD. For IBD, the ASR per 100,000 PY increased from 4.6 [2.8-6.3] in 2000 to 8.2 [7.5-13.6] in 2014; projected incidence rates for IBD in Germany are 12.9 [6.5-25.5] in the year 2025 and 14.9 [6.7-32.8] in 2030, respectively. Thus, the number of new IBD diagnoses in Germany would more than triple (325%) in 2030 compared to 2000. The increase is expected to be faster in CD than UC, and be more in males than in females. The expected number of newly diagnosed children with IBD in Germany is projected to rise to about 1,584 [1,512-1,655] in 2025, and to about 1,918 [1,807-2,29] in 2030. CONCLUSION: The incidence of IBD in children and adolescents in Saxony increased at a similar rate as in other developed countries during the observation period. Given this trend, the health care system must provide adequate resources for the care of these young patients in the future.

Incidence trends of pediatric onset inflammatory bowel disease in the years 2000-2009 in Saxony, Germany-first results of the Saxon Pediatric IBD Registry.

AIMS: In developed countries, the incidence of inflammatory bowel disease (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC) is increasing. Therefore, we aimed to investigate the incidence rates and trends over time in the population of children and adolescents in one of the federal states of Germany, in Saxony. METHODS: Over the 10-year period 2000-2009 all 31 children's hospitals and pediatric gastroenterologists, respectively in Saxony reported all IBD patients up to 15 years of age to the Saxon Pediatric IBD Registry. The completeness of the registry was estimated as 96.7% by independent surveys in the years 2005-2009. Incidence rates were presented as age-standardized incidence rates (ASR) regarding New European Standard Population 1990 per 100,000 person-years (PY) with 95% confidence intervals [CI]. Joinpoint and linear regression was used for trend analyses. RESULTS: 344 patients with confirmed IBD between 2000-2009 were included in the epidemiological evaluation: 212 (61.6%) patients with CD, 122 (35.6%) with UC and 10 (2.9%) with unclassified IBD (IBD-U). The ASR per 100,000 PY over the whole observation period was 7.2 [6.4-7.9] for IBD, 4.4 [3.8-5.0] for CD, 2.6 [2.1-3.0] for UC and 0.2 [0.1-0.3] for IBD-U. For IBD, the ASR per 100,000 PY increased from 4.6 [2.8-6.3] in 2000 to 10.5 [7.5-13.6] in 2009. The incidence trend analysis of ASRs using the joinpoint regression confirmed a significant increase of IBD as well as UC. The mean age at first diagnosis decreased significantly during the observation period from 11.5 (11.0-13.4) in 2000 to 9.6 (5.1-13.5) years in 2009. The median of the diagnostic latency among IBD patients was 3 months. CONCLUSION: The incidence of IBD in children and adolescents in Saxony was slightly higher than the average of other countries in the same time period and followed the trend towards a general increase of IBD. The age at diagnosis was subject to a very unfavorable downward trend.

Chronic graft-versus-host-disease-like dermopathy in a child with CD4+ cell microchimerism.

We report the case of an 11-year-old boy suffering from a severe progressive chronic skin disease with clinical features of progressive systemic scleroderma, systemic lupus erythematosus and dermatomyositis. Skin biopsies revealed fibrosis and lichenoid changes and muscle biopsy a myositis. Immunohistology of the skin showed a lichen-ruber-like pattern. Despite repeated extensive investigations, no autoantibodies were detectable. Some of these findings looked like those described in juvenile dermatomyositis. Finally, it could be demonstrated that the boy showed microchimerism with approximately 1% maternal CD4+ lymphocytes in his peripheral blood leukocytes. Furthermore maternal cells could be demonstrated in inflamed muscle tissue. So a graft-versus-host-disease-like pathomechanism appears to be likely. Several systemic therapies have been used with limited success to improve the condition including corticosteroids, azathioprine, cyclosporine A and mycophenolate mofetil. A distinct improvement of erythemas and sclerosis could be achieved by means of low-dose UVA1 phototherapy which was applied with escalating single doses of 3-12 J/cm2 for 35 consecutive days.

Two German CINCA (NOMID) patients with different clinical severity and response to anti-inflammatory treatment.

Chronic infantile neurologic, cutaneous, articular (CINCA) syndrome is characterized by fever, chronic meningitis, uveitis, sensorineural hearing loss, urticarial skin rash, and a deforming arthritis. In the CIAS1 gene of many but not all CINCA patients, disease-associated mutations have been found recently. We here describe two such patients from Germany. One of them, a 3-yr-old boy, has a 1709A-->G, Y570C, mutation, which has previously been described to cause CINCA syndrome. His clinical course is very severe and no satisfying response has been achieved even with high doses of local and systemic steroids. The other patient has a somewhat milder clinical course and considerable improvement could be accomplished with moderate and low doses of steroids. In her CIAS1 gene we have found a 1043C-->T, T348M, mutation, which has only been detected in Muckle-Wells syndrome before. Our results suggest that the severity of symptoms in CINCA patients may be influenced by the underlying mutation in the CIAS1 gene. Furthermore, our observations support the view that CINCA syndrome and Muckle-Wells syndrome are essentially the same disease with different degrees of severity.