Mannose-binding lectin deficiency is associated with early onset of polyarticular juvenile rheumatoid arthritis: a cohort study

BACKGROUND: Mannose-binding lectin (MBL) is an innate immune protein. The aim of our study was to determine whether genetically determined MBL deficiency is associated with susceptibility to juvenile rheumatoid arthritis (JRA) and whether MBL2 genotypes are associated with JRA severity. METHODS: In a retrospective cohort study of 218 patients with polyarthritis (n = 67) and oligoarthritis (n = 151), clinical and laboratory disease variables were obtained by clinical examination and chart reviews. Healthy Caucasian adults (n = 194) served as control individuals. MBL2 gene mutations were determined by Taqman analysis to identify genotypes with high, medium and low expression of MBL. Functional MBL plasma concentrations were measured using enzyme-linked immunosorbent assay. Associations between clinical and laboratory variables and MBL2 genotypes were determined by Kruskal-Wallis and χ(2 )tests. RESULTS: MBL2 genotype frequencies were similar in polyarthritis and oligoarthritis patients as compared with control individuals. MBL plasma concentrations were associated with the high, medium and low MBL genotype expression groups (P < 0.01). In polyarthritis patients, the presence of low-expressing (deficient) MBL2 genotypes was associated with early age at onset of disease (P = 0.03). In oligoarthritis patients, patients with low-expressing MBL2 genotypes were more often in remission (81%) than patients in the medium (54%) and high (56%) genotype groups (P = 0.02). The remaining clinical and laboratory variables, such as arthritis severity index, presence of radiographic erosions and antinuclear antibody positivity, were not associated with MBL2 genotypes. CONCLUSION: Genetically determined MBL deficiency does not increase susceptibility to JRA, but MBL deficiency is associated with a younger age at onset of juvenile polyarthritis. On the other hand, MBL-deficient children with juvenile oligoarthritis are more often in remission. Therefore, MBL appears to play a dual role in JRA

Nailfold capillary scleroderma pattern may be associated with disease damage in childhood-onset systemic lupus erythematosus:important lessons from longitudinal follow-up

OBJECTIVES: To observe if capillary patterns in childhood-onset SLE (cSLE) change over time and find associations between a capillary scleroderma pattern with disease activity, damage or scleroderma-like features. METHODS: Clinical and (yearly) capillaroscopy data from a longitudinal cohort of patients with cSLE (minimum of four Systemic Lupus International Collaborating Clinics (SLICC) criteria, onset <18 years) were analysed. Disease activity was measured by Systemic Lupus Erythematosus Activity Index (SLEDAI) and disease damage by SLICC Damage Index. A scleroderma pattern was defined according to the ‘fast track algorithm’ from the European League Against Rheumatism Study Group on Microcirculation in Rheumatic Diseases. An abnormal capillary pattern, not matching a scleroderma pattern, was defined as ‘microangiopathy’. RESULTS: Our cohort consisted of 53 patients with cSLE with a median disease onset of 14 years (IQR 12.5–15.5 years), median SLEDAI score at diagnosis was 11 (IQR 8–16), median SLEDAI at follow-up was 2 (IQR 1–6). A scleroderma pattern (ever) was seen in 18.9%, while only 13.2% of patients had a normal capillary pattern. Thirty-three patients had follow-up capillaroscopy of which 21.2% showed changes in type of capillary pattern over time. Type of capillary pattern was not associated with disease activity. Raynaud’s phenomenon (ever) was equally distributed among patients with different capillaroscopy patterns (p=0.26). Anti-ribonucleoprotein antibodies (ever) were significantly more detected (Χ(2), p=0.016) in the scleroderma pattern subgroup (n=7 of 10, 70%). Already 5 years after disease onset, more than 50% of patients with a scleroderma pattern had SLE-related disease damage (HR 4.5, 95% CI 1.1 to 18.8, p=0.034), but they did not develop clinical features of systemic sclerosis at follow-up. Number of detected fingers with a scleroderma pattern was similar between cSLE, juvenile systemic sclerosis and juvenile undifferentiated connective tissue disease. CONCLUSION: This longitudinal study shows that the majority of capillary patterns in cSLE are abnormal and they can change over time. Irrespective of disease activity, a capillary scleroderma pattern in cSLE may be associated with higher risk of SLE-related disease damage

Clinical practice: Protein-losing enteropathy in children

Protein-losing enteropathy (PLE) is a rare complication of a variety of intestinal disorders characterized by an excessive loss of proteins into the gastrointestinal tract due to impaired integrity of the mucosa. The clinical presentation of patients with PLE is highly variable, depending upon the underlying cause, but mainly consists of edema due to hypoproteinemia. While considering PLE, other causes of hypoproteinemia such as malnutrition, impaired synthesis, or protein loss through other organs like the kidney, liver, or skin, have to be excluded. The disorders causing PLE can be divided into those due to protein loss from intestinal lymphatics, like primary intestinal lymphangiectasia or congenital heart disease and those with protein loss due to an inflamed or abnormal mucosal surface. The diagnosis is confirmed by increased fecal concentrations of alpha-1-antitrypsin. After PLE is diagnosed, the underlying cause should be identified by stool cultures, serologic evaluation, cardiac screening, or radiographic imaging. Treatment of PLE consists of nutrition state maintenance by using a high protein diet with supplement of fat-soluble vitamins. In patients with lymphangiectasia, a low fat with medium chain triglycerides (MCT) diet should be prescribed. Besides dietary adjustments, appropriate treatment for the underlying etiology is necessary and supportive care to avoid complications of edema. PLE is a rare complication of various diseases, mostly gastrointestinal or cardiac conditions that result into loss of proteins in the gastrointestinal tract. Prognosis depends upon the severity and treatment options of the underlying disease

Use of antidepressants during pregnancy in the Netherlands: Observational study into postpartum interventions

Background: Psychiatric disorders and use of selective antidepressants during pregnancy can have negative effects on mother and infant postpartum. This study aimed to provide evidence-based recommendations on observation of antidepressant-exposed mother-infant dyads. Methods: In this observational study, mother-infant dyads were observed for possible consequences of either the maternal psychiatric disorder or fetal exposure to selective antidepressants during pregnancy. These possible complications can lead to medical interventions, including 1. adjustment of antidepressants 2. admission to the psychiatric department 3. additional investigations due to indistinctness about the origin of neonatal symptoms 4. treatment of poor neonatal adaptation and 5. consultation of an external organization for additional care. The type, number and time to medical interventions were analyzed. Results: In 61% of the 324 included mother-infant dyads one or more intrventions were performed. Adjustment of antidepressants and treatment of poor neonatal adaptation were most prevalent. In 75% of dyads the final intervention was performed within 48 h. Conclusions: The high prevalence and type of medical interventions requires professional observation of all mother-infant dyads exposed to selective antidepressants. In the absence of specialized home care, hospital admission is indicated whereby an observational period of 48 h seems sufficient for most dyads

Adapted Finnegan scoring list for observation of anti-depressant exposed infants

Objective: The Finnegan scoring list (FSL) is widely used to screen for poor neonatal adaptation in infants exposed to anti-depressants in utero. However, the large number of FSL-items and differential weighing of each item is time consuming. The aim of this study was to shorten and simplify the FSL yet preserving its clinimetric properties.Methods: This observational study examined infants exposed to an anti-depressant during pregnancy admitted for at least 72 h on a maternity ward. Trained nurses completed the FSL three times daily. Items for the adapted FSL were selected through forward analysis whereby the number of selected items was based on the area under the curve (AUC). Internal validity was assessed by cross-validation.Results: 183 infants met the inclusion criteria. By forward analysis eight equally-weighed items resulted in an AUC of 0.91. In cross-validation, the mean AUC was 0.89 for 8 items. This adapted FSL had a sensitivity of 97.7% and specificity of 37.0% and a sensitivity of 41.9% and specificity of 86.2% regarding a cut-off of, respectively, 1 and 2.Conclusions: An adapted FSL with eight equally-weighed items has acceptable clinimetric properties and can serve as an easy to apply screening tool in infants exposed to anti-depressants during pregnancy