Ultraviolet light exposure is not a requirement for the development of cutaneous neonatal lupus

Cutaneous neonatal lupus erythematosus (NLE) is a rare disorder, linked to the presence of transplacentally acquired maternal autoantibodies (anti-ENA). NLE skin lesions frequently appear in the second or third month of life, and ultraviolet exposure is thought to be an initiating factor since it can externalize intranuclear autoantigens at the cell surface. We report a baby who was born already with an extensive NLE rash, suggesting that sun exposure is not a requirement for the development of NLE skin lesions. A 31-year-old woman affected with mixed connective tissue disease gave birth to a female after 38 weeks of gestation. Pregnancy was uneventful and no perinatal complications were seen. The mother was positive for anti-RNP, but negative for anti-SSA/Ro and SSB/La autoantibodies. Already at birth, an extensive scarring rash with a few erythematosus lesions was present on the baby's face and scalp; this progressed over the following months, and subsequently stabilized. Anti-RNP were present in the baby's serum. Due to the unusual features of the disease expression, a skin biopsy was performed at age 5 months; results were consistent with the diagnosis of NLE, showing mononuclear cell infiltration and immunoglobulin deposition. No other features of NLE were detected. This observation is unusual for: (1) the presence of an NLE rash in the absence of anti-SSA/Ro; (2) the scarring and atrophic characteristics of the lesions; and (3) the development already in utero. This latter finding argues against sun exposure being necessary for lesion induction.     

Osteoporosis

Bone mass is determined primarily by genetic influences, but exogenous factors may also play a major role. The prevention of osteoporosis can start at childhood. Optimal achievement of peak bone mass during childhood and adolescence is important to minimize future fracture risk. Chronic inflammatory diseases can have a detrimental effect on bone mass through a variety of mechanisms. Different diagnostic methods for detecting osteoporosis (eg, dual x-ray absorptiometry, quantitative computed tomography, ultrasounds) are in use or under investigation. New treatment options are available; among these, the use of bisphosphonates seems to be the more promising approach.     

Response to tetanus vaccination in infants exposed in utero to immunosuppressants for maternal autoimmune disorders

Immunosuppressive drugs given during pregnancy to mothers suffering from a systemic autoimmune disease (AID) can cross the placenta, thus being potentially able to affect the offspring immune system. Aim of our study was to evaluate the in vivo immune function of a series of these newborns. Twenty-two babies born from mothers suffering from autoimmune diseases (AID) who had been taking immunosuppressive drugs during pregnancy were evaluated for their response to vaccination with C. Tetani toxoid. Six babies born from mothers receiving low-dose aspirin only were used as controls. The immune response to C. Tetani vaccination was evaluated with an ELISA to detect circulating antibodies. Five children out of 28 (17%) did not achieve a protective titer of anti C. Tetani toxoid IgG. No clear relationship was found between specific drug exposure and antibody response. Our findings suggest that maternal immunosuppressive treatment given for a systemic AID can affect the response to an active immunization, without specificities for drug types used.     

Transforming growth factor beta1 in the pathogenesis of autoimmune congenital complete heart block: lesson from twins and triplets discordant for the disease

OBJECTIVE: Clinical evidence and experimental evidence suggest that anti-Ro/La autoantibodies are necessary but not sufficient for the development of congenital complete heart block (CCHB). Maternal, fetal, and environmental factors may also contribute to heart damage in CCHB. The aim of our study was to investigate polymorphisms of transforming growth factor beta1 (TGFbeta1) and tumor necrosis factor alpha (TNFalpha) genes in twins and triplets discordant for CCHB whose mothers are anti-Ro/La positive. METHODS: We studied 2 families in which 1 of the mothers gave birth to triplets and the other gave birth to twins. Only 1 child in each family was affected by CCHB, although 1 of the triplets had incomplete heart block. We analyzed TNFalpha and TGFbeta1 polymorphisms in the 2 babies with CCHB and their siblings. TNFalpha polymorphisms at the promoter region and TGFbeta1 polymorphisms at codons 10 and 25 were determined using polymerase chain reaction-restriction fragment length polymorphism analysis. In addition, the production of TGFbeta1 and TNFalpha by resting or mitogen-stimulated peripheral blood mononuclear cells in cell culture supernatants was evaluated by enzyme-linked immunosorbent assay. RESULTS: The profibrotic TGFbeta1 genotype was detected in the twin with CCHB but not in the healthy twin, while all of the triplets displayed the same TGFbeta1 genotype at codon 10. Peripheral blood mononuclear cells from the children with CCHB displayed higher spontaneous and mitogen-stimulated TGFbeta1 secretion than was observed in their siblings. No differences regarding TNFalpha polymorphisms and secretion of TNFalpha were observed. CONCLUSION: The results of this study suggest that, besides anti-Ro/La autoantibodies, a fetal profibrotic response might contribute to the development of CCHB, but additional pathogenic mechanism(s) are also likely to play a role.     

Retention rate of a second line with a biologic DMARD after failure of a first-line therapy with abatacept,tocilizumab, or rituximab: results from the Italian GISEA registry

Clinical Rheumatology - EULAR recommendations do not suggest which biologic disease-modifying anti-rheumatic drug (bDMARD) should be preferred after failure of a first bDMARD in the treatment of...     

Mild cognitive impairment in psoriatic arthritis: Prevalence and associated factors

To assess the prevalence and factors associated with mild cognitive impairment (MCI) in patients suffering from psoriatic arthritis (PsA).A cross-sectional evaluation was conducted in consecutive PsA patients. Sociodemographic data and the clinimetric variables related to PsA and psoriasis were collected for each patient. MCI was assessed through the Montreal Cognitive Assessment (MoCA). The cognitive performance of PsA patients was compared to healthy subjects using one-way analysis of variance (ANOVA). The correlations among variables were studied by the Spearman rank correlation coefficient. A multivariate logistic regression analysis was carried out to establish the predictors of MCI.The study involved 96 PsA patients and 48 healthy subjects. MCI (defined as a MoCA score < 26/30) was detected in 47 (48.9%) PsA patients. Compared to healthy subjects, the MoCA score resulted significantly lower in PsA patients (P = .015). The main differences involved the denomination and language domains. MoCA was negatively correlated with age (r = −0.354; P < .0001), HAQ-DI (r = −0.227; P = .026), and fatigue (r = −0.222; P = .029), and positively correlated with psoriasis duration (r = 0.316; P = .001) and DLQI (r = 0.226; P = .008).The multivariate logistic regression analysis revealed the duration of psoriasis (P = .0005), age (P = .0038), PASI (P = .0050), and HAQ-DI (P = .0193) as predictors of the MoCA score.MCI is present in a significant proportion of PsA patients, and is mainly determined by age, cutaneous variables, and disability.     

Immune function in children born to mothers with autoimmune diseases and exposed in utero to immunosuppressants

The administration of immunosuppressive drugs during pregnancy is often necessary in women with autoimmune diseases. Teratogenicity of immunosuppressives during pregnancy has been evaluated, only few data exist about the effects on immune systems. We therefore performed a pilot study on the influence of foetal exposure to immunosuppressives on immune function of babies born to mothers with autoimmune disorders. We investigated serological and cellular parameters as indicators of immune system status. We included in the study 14 babies (mean age 11 months, range 1-24) born to mothers with autoimmune diseases and exposed in utero to different immunosuppressants and, as controls, 14 babies whose mothers had autoimmune manifestations but did not receive immunosuppressive therapy. We evaluated: (i) complete blood count, (ii) immunoglobulin levels and IgG subclasses, (iii) antibody response to hepatitis B vaccine, (iv) leukocyte subpopulations and (v) interleukin-2 and interferon gamma in vitro production by resting or activated peripheral blood mononuclear cells. We did not find statistically significant differences between exposed and not exposed babies or among treatments for the tested parameters. Immunosuppressive regimens currently in use for controlling maternal autoimmune disorders do not significantly affect the immune status of the offspring.     

Transforming growth factor β1 in the pathogenesis of autoimmune congenital complete heart block: Lesson from twins and triplets discordant for the disease

Objective

Clinical evidence and experimental evidence suggest that anti‐Ro/La autoantibodies are necessary but not sufficient for the development of congenital complete heart block (CCHB). Maternal, fetal, and environmental factors may also contribute to heart damage in CCHB. The aim of our study was to investigate polymorphisms of transforming growth factor β1 (TGFβ1) and tumor necrosis factor α (TNFα) genes in twins and triplets discordant for CCHB whose mothers are anti‐Ro/La positive.

Methods

We studied 2 families in which 1 of the mothers gave birth to triplets and the other gave birth to twins. Only 1 child in each family was affected by CCHB, although 1 of the triplets had incomplete heart block. We analyzed TNFα and TGFβ1 polymorphisms in the 2 babies with CCHB and their siblings. TNFα polymorphisms at the promoter region and TGFβ1 polymorphisms at codons 10 and 25 were determined using polymerase chain reaction–restriction fragment length polymorphism analysis. In addition, the production of TGFβ1 and TNFα by resting or mitogen‐stimulated peripheral blood mononuclear cells in cell culture supernatants was evaluated by enzyme‐linked immunosorbent assay.

Results

The profibrotic TGFβ1 genotype was detected in the twin with CCHB but not in the healthy twin, while all of the triplets displayed the same TGFβ1 genotype at codon 10. Peripheral blood mononuclear cells from the children with CCHB displayed higher spontaneous and mitogen‐stimulated TGFβ1 secretion than was observed in their siblings. No differences regarding TNFα polymorphisms and secretion of TNFα were observed.

Conclusion

The results of this study suggest that, besides anti‐Ro/La autoantibodies, a fetal profibrotic response might contribute to the development of CCHB, but additional pathogenic mechanism(s) are also likely to play a role.

     

The comparison of effects of biologic agents on rheumatoid arthritis damage progression is biased by period of enrolment: Data from a systematic review and meta-analysis

Objectives

To indirectly compare the 12-month effects of available biologic agents in slowing RA radiographic progression.

Methods

A systematic review of literature of randomised, double-blind, controlled trials (RCTs) evaluating RA radiographic progression as end point was conducted using a PubMed searching of MEDLINE from January 1995 to May 2012. For each trial, the mean change from baseline of the standardised annual radiographic progression score (weighted for estimated annual progression rate) was estimated, and the effect size was calculated as the difference between biologic and non-biologic-treated groups. In order to optimise data homogeneity and improve RCTs comparison, a mixed-effect model was applied including previous responsiveness to methotrexate (MTX-experienced or MTX-naïve populations) and period of study enrolment as moderators.

Results

The PubMed search resulted in 183 references, and 14 were eligible for the meta-analysis. The analysis of study distribution in forest plots showed a high correlation between the study period of enrolment and the impact of biological therapy in both MTX-naïve and MTX-experienced subgroups. In particular, effect size was the highest for older trials and progressively decreased in the most recent ones, suggesting a highest propensity to radiographic progression in populations enroled in older trials. Some statistically significant differences among RCTs were found in both subgroups but were significantly biased by the different propensity to radiographic progression due to period of enrolment.

Conclusions

Our meta-analysis demonstrated that period of enrolment deeply influence study population propensity to radiographic progression in each trial. This finding does not allow the indirect comparison of various biologic agents, despite our mixed-model significantly reducing heterogeneity among RCTs.