Paediatric reference ranges for plasma chromogranin A.

BACKGROUND: Neuroendocrine neoplasms (NENs) are a heterogeneous group of rare diseases with varied aggressiveness originating from endocrine cells belonging to the diffuse endocrine system and most often produce and secrete chromogranin A (CgA). CgA in plasma is therefore used to screen, diagnose, and monitor for NENs in both adults and children with sporadic or familial NENs. METHODS: Plasma CgA was measured using the Brahms Kryptor assay in 268 healthy children/adolescents; 85 children were tested as part of a familial cancer screening program and 183 additional children younger than 20 years of age underwent screening for allergies. Repeated measurements (month - years) was used to calculate the intra-individual variation. The dataset was analysed in R using the referenceInterval package. RESULTS: The plasma CgA concentration decreased with age and was 32-118 µg/L for children aged 0-3 years, 18-85 µg/L for children aged 4-13 years, and 6-79 µg/L for adolescents aged 14-19 years. Earlier reported CgA reference intervals for adults have upper limits from 88 to 102 µg/L while no lower limits have been reported. The median for the three groups were 78, 51, and 39 µg/L, respectively. The median intra-individual variation was 14% (25%-centile 9.4%/75%-centile 21%). CONCLUSIONS: The reference interval will be useful when screening, diagnosing, and monitoring children for NENs respecting the limitations plasma CgA has.

Identification of a Novel PLCD1 Variant in a Danish Family with Hereditary Leukonychia.

A 1-year-old girl presented with porcelain white fingernails, accidentally discovered when she was referred for an infantile hemangioma consultation. The family reported that the nails had been milky white since birth and her father had similar white finger and toenails. The father remembered that additional family members on his side of the family presented with white nails; however, he could not provide exact information about the number of other relatives affected by this nail abnormality. The girl and her father were the only available family members with white nails presented for this study (Figure 1). The girl presented with leukonychia totalis on all fingernails only, while the father had this abnormality on all finger and toenails (Figure 2). We were not aware of any association with other diseases or features in this family, except hemangioma in the girl. (SKINmed. 2023;21:44-46).

Early menarche is associated with increased risk of asthma: Prospective population-based study of twins.

AIM: To examine the association between early menarche and risk of post-menarcheal asthma. METHODS: Using data from two multidisciplinary questionnaire surveys, conducted eight years apart, we prospectively studied 10,648 female twins, 12-41 years of age, from the nationwide Danish Twin Registry. Early menarche was defined as menarche before 12 years of age. We performed a cohort analysis and a co-twin control analysis including twin pairs discordant for incident asthma. RESULTS: Early menarche was observed in 9.3% of the individuals. The eight-year cumulative incidence of asthma was higher in girls with early menarche compared to girls without early menarche (7.4 vs. 4.5%), OR = 1.71 (1.31-2.22), p < 0.001; also after adjustment for BMI, current age, physical activity, education, and smoking, OR = 1.53 (1.15-2.04), p = 0.003. The unadjusted risk of asthma was increased by 8% (1-15%), p = 0.041 per year earlier menarche occurred. Among 167 twin pairs discordant for incident asthma, there was a non-significant tendency towards early menarche being more common in the asthmatic than the non-asthmatic co-twin (12.0 vs. 9.6%), OR = 1.57 (0.61-4.05), p = 0.350. The risk of asthma was not uniform in discordant monozygotic and dizygotic twins. CONCLUSION: Early menarche is associated with increased risk of asthma among Danish female twins independently of BMI, age, physical activity, educational level and smoking. Results indicate a complex relationship possibly mediated through innate and non-genetic effects.

Cutaneous and gastrointestinal symptoms in two patients with systemic mastocytosis successfully treated with omalizumab.

The pathogenesis of mastocytosis is not well defined and thus treatment remains challenging and remains on a palliative basis. We present two cases (a 48-year-old woman and a 57-year-old man) with indolent systemic mastocytosis in whom omalizumab (anti-IgE) reduced gastrointestinal and cutaneous symptoms significantly. This observation provides additional insight into the effects of omalizumab on systemic mastocytosis.

Age at menarche and risk of asthma: systematic review and meta-analysis.

BACKGROUND: Several studies have suggested a relationship between the age at menarche and risk of asthma development. OBJECTIVE: To conduct a systematic review and meta-analysis of the relationship between the age at menarche and the risk of asthma. METHODS: This systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). A pre specified literature search strategy was used to identify studies of potential relevance and independent reviews were carried out by two authors. Raw data was pooled using the software package RevMan to calculate summary odds ratios. The risk of publication bias was assessed graphically by using a funnel plot and the robustness of the overall estimate obtained was assessed by using sensitivity analyses. RESULTS: The searches identified 61 potentially relevant articles of which seven articles, with a total of 22,859 subjects, matched the inclusion criteria for the meta-analysis. Pooling of the seven studies showed that girls with early menarche (<12 years) had an increased risk of asthma relative to girls with late menarche; random effects odds ratio = 1.37 (1.15-1.64), (p = 0.0005). Substantial heterogeneity was revealed (I(2) = 55%). Sensitivity analysis showed that the risk estimate was not markedly changed when excluding any of the studies. The funnel plot did not indicate publication bias. CONCLUSIONS: Early menarche appears to be associated with increased risk of asthma. Hormonal, immunological, genetic and environmental factors may act in a developmental context to explain this relationship. Future studies are warranted to further determine the mechanisms responsible for this observation.

Asthma affects time to pregnancy and fertility: a register-based twin study.

Coexistence of infertility and asthma has been observed clinically. Therefore, we investigated the association between asthma and delayed pregnancy in a nationwide population-based cohort of twins. A cohort of 15 250 twins living in Denmark (aged 12-41 years) participated in a questionnaire study including questions about the presence of asthma and fertility. Differences in time to pregnancy and pregnancy outcome were analysed in subjects with asthma, allergy and in healthy individuals using multiple regression analysis. Asthma was associated with an increased time to pregnancy, the percentage of asthmatics with a time to pregnancy >1 year was 27% versus 21.6% for non-asthmatics (OR (95% CI) 1.31 (1.1-1.6); p=0.009). The association remained significant after adjustment for age, age at menarche, body mass index and socioeconomic status (OR (95% CI) 1.25 (1.0-1.6); p=0.05), and was more pronounced in those >30 years of age (32.2% versus 24.9%, OR (95% CI) 1.44 (1.1-1.9); p=0.04). Untreated asthmatics had a significant increased risk of prolonged time to pregnancy compared to healthy individuals (OR (95% CI) 1.79 (1.20-2.66); p=0.004), while asthmatics receiving any kind of treatment for asthma tended to have a shorter time to pregnancy than untreated asthmatics (OR 1.40; p=0.134). Asthma prolongs time to pregnancy. The negative effect of asthma on fertility increases with age and with disease intensity, indicating that a systemic disease characterised by systemic inflammation also can involve reproductive processes.

Intake of alcohol and risk of adult-onset asthma.

AIM: To examine the association between intake of alcohol and risk of adult-onset asthma. METHODS: Using data from two multidisciplinary questionnaire surveys we prospectively studied 19,349 twins, 12-41 years of age, from the nationwide Danish Twin Registry. RESULTS: The eight-year incidence of asthma was 4.3%. After adjustment for sex, age, BMI, physical activity, educational level and smoking, the risk of new-onset asthma was significantly related to overall alcohol intake in a U-shaped manner with the lowest risk observed in the group with a moderate weekly intake of alcohol (1-6 units/week), p = 0.006. The highest risk of asthma was observed in rare/never drinkers (<1 unit/month), OR = 1.59 (1.25-2.02), p = 0.000, whereas the risk of asthma in heavy daily drinkers (≥4 units/day) was also increased, however not statistically significant, OR = 1.13 (0.54-2.36), p = 0.747. The risk of new-onset asthma was lower for subjects with wine preference (3.3%) compared with beer preference (4.3%) or no preference (4.4%). After multivariable adjustment, wine preference was inversely related to incident asthma compared with beer preference. However, this finding was not statistically significant, OR = 0.87 (0.51-1.46), p = 0.590. CONCLUSION: Alcohol intake is associated with new-onset asthma in adults with a U-shaped association between amount of alcohol intake and the risk of asthma.