eLetters

51 e-Letters

published between 2018 and 2021

  • Correspondence on “Short-term dose and duration-dependent glucocorticoid risk for cardiovascular events in glucocorticoid-naïve patients with rheumatoid arthritis” by Ocon et al.

    We read with great interest the article by Ocon et al.,1 which reported that daily doses of ≥5 mg of prednisone-equivalents, elevated cumulative dose and extended duration of use of glucocorticoid (GC) over the preceding six-month and one-year intervals are associated with an increased risk for incident cardiovascular event (CVE) in steroid-naïve patients with rheumatoid arthritis (RA). Additionally, they also noted that no association with risk for CVE was found with daily prednisone of ≤4 mg or shorter cumulative doses and durations. This study is a valuable addition to the literature. However, some issues have not been addressed by the authors.
    First, metabolic syndrome and its components could mediate and may be causal in the association between CVE in RA and use of GC in the dose ranges and duration of use, which may offset the significance level.2 3 Additionally, a mediation analysis could have been used to address this mediation effect. Although metabolic syndrome and its severity can be identified and controlled, the likelihood of future metabolic syndrome complications cannot be assessed in most cases. However, the baseline metabolic syndrome data of the two groups were not available in this study. It is important to consider the context of metabolic syndrome when evaluating CVE for glucocorticoid-naïve patients with RA who initiate ‘low-dose’ GC over short-term intervals of use.
    Second, a family history of cardiovascular disease is a strong risk facto...

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  • Correspondence on ‘Impaired fertility in men diagnosed with inflammatory arthritis: results of a large multicentre study (iFAME-Fertility)’ by Perez-Garcia et al.

    We read with deep interest the article by Perez-Garcia LF et al1, which was aimed at investigating the impact of inflammatory arthritis (IA) on male fertility outcomes, fertility rate, family planning, childlessness and fertility problems. The authors concluded that IA could impair male fertility. We really appreciate the work done by the authors. However, there are some worthwhile issues that need to be explored.
    Firstly, although the patients were divided into three groups by age, it was not analyzed in detail whether there were differences in sample size between each disease (Spondyloarthritis (SpA) and rheumatoid arthritis (RA) etc.) in the group. Since older patients usually had longer disease course and even more serious disease, it might introduce bias to the study results. Therefore, the average onset age of each group should be consistent. Additionally, since the actual mean total number of children per man in all patients was 1.69, almost the same as the estimated number 1.7, it could hardly draw the conclusion that diagnosed with IA could impair fertility in men. Moreover, why was the mean total number of children per man in patients over 40 (1.88) higher than the estimated number and the actual number (1.79)? Was longer IA disease course associated with higher mean total number of children per man?
    Secondly, the authors mentioned that the men still having future fertility intentions were excluded in the study. As stated by the authors, the peak of r...

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  • Cyclophosphamide in parenchymal CNS involvement due to Behcet disease.

    Dear Editor,
    The authors did not clarify if there is a role of cyclophosphamide in neurobehcet disease and if there is a recommended stratification for choosing immunosuppressive agents according to the severity of neurological manifestations.

    Thank you.

  • Correspondence on ‘TGFβ promotes low IL10-producing ILC2 with profibrotic ability involved in skin fibrosis in systemic sclerosis’

    We read with great interest the recent article by Laurent et al.1 which confirmed the potential role of innate lymphoid cells-2 (ILC2) in the establishment of fibrosis in human systemic sclerosis. It provided a novel idea that transforming growth factor-β (TGFβ) downregulates KLRG1 expression on ILC2 and contributes to its low interleukin 10 (IL10) production capacity, finally resulting in skin fibrosis. However, we feel confused when reading some parts of the article.
    From the design of the overall experiment, we can clearly understand that the authors first determined the importance of ILC2 in fibrotic tissues, and then sought out the reason: the low IL10 production caused by TGF-β stimulation. Finally, they conducted relevent cell and animal experiments and draw the final conclusion. However, from the conclusion of the article, it is the reduction of IL10 that leads to the progression of fibrosis? It makes us confused because ILC2 is not the main cell producing IL10. As we all known, IL10 is a cytokine of multi-cell origin and almost all immune cells can synthesize IL102. Meanwhile, despite its relative increase in fibrotic tissues, the numberof Innate lymphoid cells is very rare3. With the diversification of IL10 sources, is the low IL10 production capacity of ILC2 the main cause of fibrosis?
    In summary, we respect the original insight and contributions of the authors, and believe an in-depth study of the role of IL10 may be a new research direction.

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  • Correspondence on ‘Impaired fertility in men diagnosed with inflammatory arthritis: results of a large multicentre study (iFAME-Fertility)’ by Perez-Garcia et al.

    With great interest, we read the paper by Perez-Garcia et al for reporting the impaired fertility of 628 male patients with inflammatory arthritis (IA) from multiple hospitals in the Netherlands.1 Based on the result, the authors suggested that treatment strategies should be appropriately re-concerned for male IA patients who want to have children. Although the author has stated the limitations of the research, some details need to be addressed clearly.
    Firstly, Disease duration may be an interfering factor of fertility.2 In this research, men diagnosed ≤40 years had a longer disease duration than men diagnosed ≥41 years, with a higher rate of low sperm quality and a lower number of children. Besides, smoking and drinking history were not included in the demographic characteristics of patients, since those factors may have great effects on male fertility.3 Then, the age of the partners of the participants were not taken into calculation which may have a great effect on the number of children of the male IA patients, and the willingness of the partners to have children as well. 4 5 The effects of disease and drugs on the results were not distinguished in the study, and both of them may have effects on the fertility.6
    Secondly, all data were collected from a questionnaire survey, including the patient’s partner time to pregnancy, female fertility evaluation, and the patient’s sperm quality, which may cause subjective bias. We noticed that out of 628 patients, onl...

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  • Response from authors

    Thank you for pointing out that the conclusion was not clear. The authors would like to modify it to 'The interim analysis revealed that up to 66% of patients receiving APR reached REM/LDA, as measured by cDAPSA at 8 months.'

  • Response to Dr. Yudong Liu

    We thank Dr. Yudong Liu for commenting on our manuscript and on many of the same issues we raised 1. There are, however, some comments that require clarification and a response. It is true that anti-phospholipid antibodies (APLA) of various specificities and immunoglobulin isotypes have been reported in COVID-19 2. However, despite a historical connection of APLA with coagulopathies and anti-phospholipid syndrome (APS), to date there is no convincing evidence that APLA have this in vivo pathogenic effect in COVID-19. In our patients, despite the presence of APLA (e.g., IgG anti-cardiolipin), there was no link to thrombotic events, a finding echoed by other referenced studies 3 and recently reviewed 2,4. The recent publication by Chang et al 5 is mentioned but it is important to appreciate that their results were compared to “normal” controls and no clinical features (coagulopathy or APS) were reported, precluding any inferences to autoimmune diseases; it is a standalone description of COVID-19 findings. Like the Chang manuscript, we also reported an extensive array of autoantibodies in COVID-19, but when we used sera from contemporaneous non-COVID patients of similar disease severity as comparator controls, we did not find significant differences in the autoantibody repertoire between the COVID positive and negative cohorts 6. Many individuals displayed “certain autoimmune features” but that cannot be taken to be equivalent to autoimmune disease. Indeed, COVID-19 patients...

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  • The autoimmune feature of severe COVID-19

    Dear Editor,

    I read with great interest the article by Trahtemberg et al.[1] on the clinical relevance of antiphospholipid antibodies (aPLs), in particular anticardiolipin antibodies (aCLs), in critically-ill COVID-19 positive and negative patients. Severe COVID-19 is associated with a hypercoagulable state. Early studies identified the presence of aPLs in critically-ill COVID-19 patients[2], which has attracted considerable attention as the presence of aPLs is one of the mechanisms leading to coagulopathy. Substantial efforts then tried to associate the thrombotic events seen in COVID-19 to aPLs status. The results seem negative, but a number of different types of autoantibodies were identified [3]. Chang et al. recently reported that autoantibodies were present in approximately half of the hospitalized COVID-19 patients, but in less than 15% of healthy controls [4]. In addition to aCLs and anti-beta 2 glycoprotein 1 antibodies (aβ2-GP1), they also identified autoantibodies targeting autoantigens associated with rare disorders such as myositis, systemic sclerosis and overlap syndromes as well as targeting interferons/interleukins and other cytokines[4]. These findings suggest that COVID-19, in particular patients with severe/critical conditions, displayed certain autoimmune features.

    In the well-designed study by Trahtemberg et al., the authors expanded the cohort by including COVID-19 negative patients who were admitted to intensive care unit (ICU) with ac...

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  • Response to 'Impact of delayed diagnoses at the time of COVID-19: increased rate of preventable bilateral blindness in giant cell arteritis' by Monti et. al.

    Monti et. al. reported a decrease in Fast Track Clinic (FTC) assessments for Giant Cell Arteritis (GCA) during the COVID-19 pandemic and an increase in irreversible visual loss; other groups have found increased incidence of GCA during the COVID-19 pandemic.1,2,3 We created an FTC in 2017 to rapidly evaluate and treat patients with possible GCA using vascular ultrasound and also noticed an increase in permanent vision loss. We conducted a medical records review study during two time periods of patients referred to the FTC with concern for GCA to evaluate how many had permanent visual loss.4 The “COVID-19 period” was defined as 3/1/2020-8/31/2020 the “pre-COVID-19 period was 3/1/2019-8/31/2019. Patients received an ultrasound for GCA performed by a specially trained vascular sonographer. A positive ultrasound for GCA had either halo sign with compression in the temporal arteries and branches or increased intima-media thickness (IMT) in the large vessels. Patients were referred for temporal artery biopsy (TAB) at the discretion of the rheumatologist.

    25 patients were referred to the FTC during both the COVID-19 period and pre-COVID-19 period and nine diagnosed with GCA in each group. 52% of patients experienced symptoms for less than two weeks prior to presenting to medical care during the COVID-19 period, 48% pre-COVID-19. The median number of days from the time first seen in the medical system until referral to the FTC was 7 days during COVID-19 compared to 8.5 day...

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  • Response to ‘Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain’ by Lee and Song

    We thank Professors Lee and Song for their interest in our genome-wide association study (GWAS) of chronic widespread musculoskeletal pain (CWP)[1]. Their correspondence has raised several methodological concerns. First, CWP is a prominent feature of fibromyalgia. Clinically, it’s impossible to diagnose fibromyalgia without having CWP[2]. Therefore, the relevance of our findings to fibromyalgia cannot be ignored although we were careful not to conflate the two traits and did not claim genetic association with fibromyalgia. Second, the authors raise the relationship of the traits with age and sex; we adjusted for these covariates in the discovery GWAS and replication study. The important issue of body mass index (BMI) was much debated in our experimental design meetings. We elected not to adjust for BMI in the study for the following reasons:- (i) adjustment for heritable covariates (such as BMI) are not recommended in GWAS as this can lead to collider bias[3, 4] (ii) we wanted to explore the shared heritability of BMI and CWP using genetic correlation, (iii) adjustment for BMI would have affected genetic correlation and partial genetic correlation estimates reported in the paper and (vi) while so few variants have been described to date using GWAS for CWP, we were keen not to reduce the variance in the phenotype even if that led us to identify variants pleiotropic for BMI and CWP. Third, we have selected our controls for GWAS carefully by excluding important diagnostic con...

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