Refractory and Recurrent Skin Manifestations in an Adult With Selective Immunoglobulin M Deficiency.

Selective immunoglobulin M (IgM) deficiency (sIgMD) is a rare immunodeficiency disorder characterized by decreased serum levels of IgM. Symptoms of sIgMD include repeated infections and allergic manifestations such as asthma and allergic rhinitis. The etiology and pathology of sIgMD remain largely unknown. Moreover, no genetic cause of sIgMD and associated symptoms has been established. Herein, we describe a 47-year-old female with sIgMD who presented with repeated fevers of unknown cause since childhood. She was referred to our department because of recently developed severe dermatitis without a history of atopic dermatitis or asthma. In addition to histological evaluation by skin biopsy, immunological parameters were investigated in her peripheral blood, and the cellular immunity profile was determined by flow cytometry. The patient with refractory skin manifestations was found to have sIgMD with normal surface levels of IgM in the B cells. Along with recurrence and exacerbation in dermatitis, she showed an increase in peripheral blood eosinophils and serum IgE levels, suggesting an underlying allergic mechanism. The present case strongly indicates the importance of measuring serum IgM levels when seeing patients with recurring fever and intractable skin manifestations.

Serum levels of AGGF1: Potential association with cutaneous and cardiopulmonary involvements in systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, aberrant immune activation, and extensive tissue fibrosis of the skin and internal organs. Because of the complicated nature of its pathogenesis, the underlying mechanisms of SSc remain incompletely understood. Angiogenic factor with a G-patch domain and a Forkhead-associated domain 1 (AGGF1) is a critical factor in angiogenesis expressed on vascular endothelial cells, associated with inflammatory and fibrotic responses. To elucidate the possible implication of AGGF1 in SSc pathogenesis, we investigated the association between serum AGGF1 levels and clinical manifestations in SSc patients. We conducted a cross-sectional analysis of AGGF1 levels in sera from 60 SSc patients and 19 healthy controls with enzyme-linked immunosorbent assay. Serum AGGF1 levels in SSc patients were significantly higher than those in healthy individuals. In particular, diffuse cutaneous SSc patients with shorter disease duration had higher levels compared to those with longer disease duration and limited cutaneous SSc patients. Patients with higher serum AGGF1 levels had a higher incidence of digital ulcers, higher modified Rodnan Skin Scores (mRSS), elevated serum Krebs von den Lungen-6 (KL-6) levels, C-reactive protein levels, and right ventricular systolic pressures (RVSP) on the echocardiogram, whereas they had reduced percentage of vital capacity (%VC) and percentage of diffusing capacity of the lungs for carbon monoxide (%DLCO) in pulmonary functional tests. In line, serum AGGF1 levels were significantly correlated with mRSS, serum KL-6 and surfactant protein D levels, RVSP, and %DLCO. These results uncovered notable correlations between serum AGGF1 levels and key cutaneous and vascular involvements in SSc, suggesting potential roles of AGGF1 in SSc pathogenesis.

Association of serum Ly6/PLAUR domain-containing protein 1 levels with skin sclerosis in systemic sclerosis.

Systemic sclerosis (SSc) is a connective tissue disease characterized by aberrant immune activation, vascular injury, and fibrosis of the skin and internal organs. Ly6/PLAUR domain-containing protein 1 (LYPD1) was reported to be secreted and to have various physiological functions such as anti-angiogenic effects. Here we investigated serum LYPD1 levels in SSc patients and the association of serum LYPD1 levels with clinical features of SSc. Serum samples were obtained from 75 SSc patients and 22 healthy individuals as controls. We measured serum LYPD1 levels using enzyme-linked immunosorbent assay kits. Then, the relationship between serum LYPD1 levels and clinical features of SSc was analyzed. Serum LYPD1 levels in diffuse cutaneous SSc (dcSSc) patients were significantly higher than those in the limited cutaneous SSc (lcSSc) patients (median [25-75th percentiles], 1693.43 [1086.61-1917.57] vs. 904.55 [714.356-1285.56] pg/mL), while there were no significant differences in the serum LYPD1 levels between lcSSc and healthy controls (904.55 [714.356-1285.56] vs. 750.71 pg/mL [544.00-912.14]). Further analysis revealed that serum LYPD1 levels in patients correlated with skin thickness scores and serum interleukin (IL)-6 levels, which were known to reflect the extent of skin thickening in SSc. Moreover, serum LYPD1 levels showed a decrease with improvement in skin thickness after treatment, along with a decrease in serum IL-6 levels. These results indicate that LYPD1 might be a potential marker for monitoring skin sclerosis and evaluating the efficacy of skin fibrosis treatment in SSc patients.

Keratinocyte proline-rich protein modulates immune and epidermal response in imiquimod-induced psoriatic skin inflammation.

Psoriasis is a persistent inflammatory skin disease thought to arise as a result of the infiltration of inflammatory cells and activation of keratinocytes. Recent advances in basic research and clinical experience revealed that the interleukin (IL)-23/IL-17 axis has been identified as a major immune pathway in psoriasis. However, it remains unclear how keratinocyte factors contribute to the pathology of psoriasis. Keratinocyte proline-rich protein (KPRP) is a proline-rich insoluble protein, which is present in the epidermis and is likely to be involved in the skin barrier function. Here, to investigate the potential roles of KPRP in psoriatic skin inflammation, Kprp-modified mice were applied in the imiquimod (IMQ)-induced skin inflammation model, which develops psoriasis-like epidermal hyperplasia and cutaneous inflammation features. Then, heterozygous knockout (Kprp+/- ) but not homozygous knockout (Kprp-/- ) mice displayed attenuated skin erythema compared to control wild-type mice. In addition, RNA sequencing, quantitative PCR and/or histological analysis detected changes in the expression of several molecules related to psoriatic inflammation or keratinocyte differentiation in Kprp+/- mice, but not Kprp-/- mice. Further analysis exhibited reduced IL-17-producing γδlow T cells and amplified epidermal hyperplasia in Kprp+/- mice, which were implied to be related to decreased expression of ß-defensins and increased expression of LPAR1 (Lysophosphatidic acid receptor 1), respectively. Thus, our results imply that KPRP has the potential as a therapeutic target in psoriatic skin inflammation.

Clinical Risk Factors for Dysphagia and Esophageal Dysmotility in Systemic Sclerosis.

Systemic sclerosis (SSc) is often associated with dysphagia and esophageal dysmotility; however, only a few clinical studies on this topic have been conducted. Patients with SSc who underwent swallowing examinations and esophagography at our institution between 2010 and 2022 were included. A retrospective evaluation of the patients' backgrounds, autoantibody positivity, swallowing function, and esophageal motility was performed using medical charts. The association between dysphagia and esophageal dysmotility in patients with SSc and respective risk factors was investigated. Data were collected from 50 patients. Anti-topoisomerase I antibodies (ATA) and anti-centromere antibodies (ACA) were detected in 21 (42%) and 11 (22%) patients, respectively. Dysphagia was present in 13 patients (26%), and esophageal dysmotility in 34 patients (68%). ATA-positive patients had a higher risk for dysphagia (p = 0.027); ACA-positive patients had a significantly lower risk (p = 0.046). Older age and laryngeal sensory deficits were identified as risk factors for dysphagia; however, no risk factors for esophageal dysmotility were identified. No correlation was found between dysphagia and esophageal dysmotility. Esophageal dysmotility is more common in patients with SSc than in those with dysphagia. Autoantibodies can be predictors of dysphagia, and dysphagia must be carefully considered in ATA-positive and elderly patients with SSc.

Native T1 mapping in early diffuse and limited systemic sclerosis, and its association with diastolic function.

BACKGROUND: Systemic sclerosis (SSc) is divided into diffuse and limited cutaneous SSc (dcSSc and lcSSc). The dcSSc subtype has more severe internal organ damage. This study aimed to assess whether cardiovascular magnetic resonance (CMR) parametric mapping could detect early cardiac involvement and evaluate differences between these two subtypes. METHODS: Eighty SSc patients (37 dcSSc and 43 lcSSc) underwent CMR at 3.0 T (Philips Healthcare, Best, The Netherlands) in our hospital between July 2018 and July 2021. We analyzed myocardial damage by CMR parametric mapping and compared it with clinical data. RESULTS: The median duration of the disease was 10.2 months. The left ventricular ejection fraction was preserved in both groups. DcSSc had significantly higher native T1 (1333.4 ±â€¯71.2 ms vs. 1295.0 ±â€¯42.7 ms, p = 0.006) and extracellular volume fraction (32.6 ±â€¯4.1 % vs. 30.3 ±â€¯4.0 %, p = 0.018) in the mid-ventricular septum as compared to lcSSc, although there were no differences in T2 values. Native T1 values were positively correlated with the E/e' ratio and left atrial volume indices evaluated by transthoracic echocardiography in overall SSc and dcSSc, but not in lcSSc. Logistic regression analysis revealed that native T1 was an independent predictor of left ventricular diastolic dysfunction in SSc patients (odds ratio, 1.194; 95 % confidence interval, 1.021-1.396; p = 0.026). Native T1 was higher in SSc patients with progressive skin lesions. Additionally, there were positive correlations between brain natriuretic peptide, New York Heart Association functional classification, and native T1. CONCLUSIONS: CMR parametric mapping is a useful tool for detecting myocardial changes. Native T1 was the most sensitive parameter for identifying diffuse myocardial changes in the early stages of SSc and was associated with left ventricular diastolic function. DcSSc had more severe myocardial involvement than lcSSc; therefore, the use of CMR parametric mapping may aid in its prediction.

Serum cold-inducible RNA-binding protein levels as a potential biomarker for systemic sclerosis-associated interstitial lung disease.

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by fibrotic, inflammatory, and vascular dysfunction. Danger-associated molecular patterns (DAMPs)-mediated inflammasome activation has been reported to be involved in the pathogenesis of SSc. Cold-inducible RNA-binding protein (CIRP) is newly identified as a DAMP. Here we examined the clinical significance of serum levels of CIRP in 60 patients with SSc and 20 healthy control patients (HCs) using an enzyme-linked immunosorbent assay. Serum CIRP levels in diffuse cutaneous SSc (dcSSc) patients were significantly increased compared with limited cutaneous SSc (lcSSc) patients or HCs. When examining the relationship with SSc-specific parameters, serum CIRP levels with the presence of interstitial lung disease (ILD) were higher than those without ILD. In detail, serum CIRP levels correlated negatively with the percent predicted diffusing capacity for carbon monoxide and positively with levels of Krebs von den Lungen-6. In addition, elevated serum CIRP levels declined along with decreased SSc-ILD activity in patients who received immunosuppressive therapy. These results suggest that CIRP may play a role in the development of ILD in SSc. Moreover, CIRP could serve as a useful serological marker of SSc-ILD in terms of disease activity and therapeutic effects.

Edema localized to the lips as a novel manifestation of myositis.

Polymyositis (PM) and dermatomyositis (DM) are idiopathic inflammatory myopathies with presumed autoimmune pathogenesis, characterized by the features of proximal skeletal muscle weakness and evidence of muscle inflammation. Skin manifestations usually prompt earlier recognition and diagnosis of DM than PM, which has no rash. Associated delayed diagnosis and treatment in PM lead to worse outcomes. Therefore, an accumulation of case reports regarding initial symptoms suggestive of PM has been required to obtain an earlier diagnosis and better clinical outcomes in PM patients. We herein report a PM patient with an unusual presentation of edema restricted to the lips, which was clinically suggestive of granulomatous cheilitis but histologically verified as a manifestation of myositis. In this patient, no myositis-specific antibodies including anti-nuclear matrix protein 2 antibodies, were detected, and histological analysis on the muscle biopsy specimen revealed CD4-dominant lymphocyte infiltration but no C5b-9 deposition nor myxovirus resistance protein A expression. Further analysis with MRI (magnetic resonance imaging) scan of the lips showed increased signal intensity in the muscle layer on short TI inversion recovery images, and these suggest the potential of MRI as a useful tool for exploring the inflammatory site and the possibility of myositis in swollen lips. Thus, our report indicates the importance of suspecting myositis in the case of unusual edema restricted to the lips.

Bitter taste receptor T2R38 is expressed on skin-infiltrating lymphocytes and regulates lymphocyte migration.

Bitter taste receptors (T2Rs) are G protein-coupled receptors involved in the perception of bitter taste on the tongue. In humans, T2Rs have been found in several sites outside the oral cavity. Although T2R38 has been reported to be expressed on peripheral lymphocytes, it is poorly understood whether T2R38 plays immunological roles in inflammatory skin diseases such as atopic dermatitis (AD). Then, we first confirmed that T2R38 gene expression was higher in lesional skin of AD subjects than healthy controls. Furthermore, skin T2R38 expression levels were correlated with serum thymus and activation-regulated chemokine and IgE levels in AD patients. In lesional skin of AD, section staining revealed that CD3+ T cells in the dermis were T2R38 positive. In addition, flow cytometry analysis showed T2R38 expression in skin T cells. Migration assays using T2R38-transduced Jurkat T cell leukemia cells revealed that T2R38 agonists exerted a dose-dependent migration inhibitory effect. Moreover, skin tissue extracts, as well as supernatants of cultured HaCaT keratinocytes, caused T2R38-dependent migration inhibition, indicating that there should be an endogenous ligand for T2R38 in the skin epidermis. These findings implicate T2R38 as a migratory inhibitory receptor on the skin-infiltrating lymphocytes and as a therapeutic target for allergic/inflammatory skin diseases.

Serum Cytokeratin 18 as a Metastatic and Therapeutic Marker for Extramammary Paget's Disease.

Extramammary Paget's disease (EMPD) is a rare cutaneous adenocarcinoma with unfavourable prognosis once it becomes invasive. A tumour marker that reflects disease progression is required for adequate management of EMPD. Cytokeratin 18 is highly expressed in many types of cancer and its soluble forms are detected by M30 (for caspase-cleaved form) and M65 (for both caspase-cleaved and intact forms) assays. We report here that tumour cells of EMPD in both lesional skin and lymph node metastasis are immunohistochemically positive for CK18, and the baseline serum M30 and M65 levels in patients with metastatic EMPD are significantly higher than those in non-metastatic patients. In addition, serial serum M30 and M65 levels might reflect recurrence of EMPD and response to chemotherapy. These results suggest that serum CK18 levels may be a useful tumour marker for advanced EMPD.

Dermatomyositis-like eruptions and fasciitis with novel compound heterozygous MEFV mutations: Newly recognized features of a variant of familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent febrile attacks and serositis. The diagnosis of FMF has been based on clinical criteria, including frequent symptoms and good response to the treatment with colchicine. Some patients with FMF show skin or muscle manifestations, which may be confused with other cutaneous or muscle disorders. Here we report a female in her 40s with periodic fever, migratory myalgia, dermatomyositis-like dermatitis, arthralgia, pharyngalgia, and lymphadenopathy. The initial clinical differential diagnosis included dermatomyositis, malignant lymphoma, and adult-onset Still's disease. However, the following examinations could not explain her pathological condition with such diseases. In particular, findings from muscle and fascial biopsy demonstrated severe inflammatory cell infiltrate in the fascia, suggesting fasciitis as a possible cause of migratory myalgia. We examined the possibility of autoinflammatory diseases by genetic testing. Accordingly, she was found to have novel compound heterozygous mutations (L110P, E148Q, and P369S) in the MEFV gene. Given her genetic mutations and favorable response to colchicine, she was finally diagnosed as a variant of FMF with myalgia and previously unprecedented skin eruptions.

Recent advances in roles of G-protein coupled receptors in intestinal intraepithelial lymphocytes.

Intestinal intraepithelial lymphocytes (IELs) potentially provide the first line of immune defense against enteric pathogens. In addition, there is growing evidence supporting the involvement of IELs in the pathogenesis of gut disorders such as inflammatory bowel diseases. Various kinds of molecules are involved in the dynamics of IELs, such as homing to the intestinal epithelium and retention in the intestinal mucosa. G protein-coupled receptors (GPCRs) comprise the largest family of cell surface receptors and regulate many biological responses. Although some GPCRs, like CCR9, have been implicated to have roles in IEL homing, little is still known regarding the functional roles of GPCRs in IEL biology. In this review, we provide a concise overview of recent advances in the roles of novel GPCRs like GPR55 and GPR18 in the dynamics of IELs.

Clinical significance of endothelial vasodilatory function evaluated by EndoPAT in patients with systemic sclerosis.

Endothelial dysfunction is a hallmark of vasculopathy associated with systemic sclerosis (SSc). Reactive hyperemia peripheral arterial tonometry is a rapid and non-invasive technique to assess peripheral microvascular endothelial function by measuring changes in digital pulse volume during reactive hyperemia. Low scores of the reactive hyperemia index (RHI) imply an impaired vasodilatory response and, accordingly, impaired endothelial and vascular health. To investigate the clinical significance of the RHI in SSc patients, RHI values were measured in 43 SSc patients and 10 healthy controls. In diffuse cutaneous SSc (dcSSc) patients, RHI values were significantly decreased compared with healthy controls, and inversely correlated with disease duration. In total SSc patients, there was a significant inverse correlation between RHI values and skin score, and interstitial lung disease was associated with the decrease in RHI values. Among vascular symptoms, the current and past history of digital ulcers was seen more frequently in patients with decreased RHI values than in those with normal RHI values. Although no SSc patients had pulmonary arterial hypertension, an inverse correlation was evident between RHI values and mean pulmonary arterial pressure measured by right heart catheterization. These results indicate that the decrease in RHI values is associated with skin fibrosis, interstitial lung disease, digital ulcers and pulmonary vascular involvement leading to pulmonary arterial hypertension, supporting the canonical idea that endothelial dysfunction is a critical event underlying the development of tissue fibrosis and vascular complications in SSc.

Rituximab therapy is more effective than cyclophosphamide therapy for Japanese patients with anti-topoisomerase I-positive systemic sclerosis-associated interstitial lung disease.

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is the most frequent cause of death for SSc but there is still no sufficient treatment available. Although cyclophosphamide (CYC) therapy is a common treatment which has shown statistical efficacy against SSc-ILD to date, its effects are temporary and not enough. Rituximab (RTX), the anti-CD20 monoclonal antibody, has recently shown efficacy in many autoimmune diseases. In SSc-ILD, RTX is also considered to be one of the novel treatment candidates. However, studies of SSc-ILD in Japanese treated with RTX have only a few case reports. Therefore, in this study, we retrospectively compared nine patients treated with RTX and 30 patients treated with CYC to investigate the efficacy of RTX treatment for Japanese anti-topoisomerase I-positive SSc-ILD patients. At the 24-month evaluation, the improvement rates of percent predicted of forced vital capacity and percent predicted of diffusing capacity of the lung carbon monoxide in the RTX-treated group were significantly higher than those in the CYC-treated group (20.6 ± 8.8% vs 1.1 ± 3.9%; P < 0.05 and 34.0 ± 6.0% vs -1.5 ± 2.8%; P < 0.01, respectively). In addition, skin thickness scores also showed a marked improvement from 13.5 points before the start of treatment to 5.8 points after 24 months by RTX therapy (P < 0.05). These results suggest that RTX treatment is more effective for Japanese SSc-ILD patients than CYC treatment. In the future, it is expected that large-scale clinical trials will show the usefulness of RTX treatment for SSc-ILD.

Dynamics and clinical significance of intestinal intraepithelial lymphocytes.

Intestinal intraepithelial lymphocytes (IELs) are one of the largest populations of lymphocytes and comprised of heterogeneous populations with varying phenotypes and physiological/pathological functions. IELs located between the basolateral surfaces of the epithelial cells and then potentially provide a first line of immune defense against enteric pathogens, although, the precise roles of each IEL populations are not well defined. A variety of molecules are involved in the IEL-homing to the intestinal epithelium. Conventional IELs originate from circulating T cells activated in lymphoid organs and imprinted for gut homing. On the other hand, unconventional IELs derive from thymocytes and migrate to the intestinal epithelium, although, some of them may arise extrathymically. Regarding the interaction between IELs and epithelial cells, IELs are known to be highly motile and actively migrate along the basement membrane, suggesting their roles in immune surveillance. In addition, there has been growing evidence to support that IELs are involved in the pathogenesis of gut disorders such as celiac disease and inflammatory bowel diseases. In this review, we provide a comprehensive overview of IEL dynamics and their clinical significance.

Skin thickness score as a surrogate marker of organ involvements in systemic sclerosis: a retrospective observational study.

BACKGROUND: Previous studies have shown the relationship between higher skin thickness score and the existence of organ involvements in systemic sclerosis (SSc). Here, we firstly investigated the correlation between skin thickness score and quantitative measurements of each organ involvement in Japanese patients with SSc. METHODS: All Japanese SSc patients hospitalized to our clinic for initial evaluation of SSc were selected. Skin thickness was evaluated by modified Rodnan total skin thickness score (mRSS). Relationship between mRSS and prevalence or incidence of organ involvements was examined by logistic analyses. Correlation between mRSS and quantitative measurements of organ involvements was examined by correlation analyses and regression analyses. RESULTS: We recruited 198 patients into our study. The mean disease duration was 7.3 years with the mean follow-up duration of 3.2 years. Multivariate logistic regression analyses revealed that higher mRSS is related to higher prevalence of interstitial lung disease (P < 0.05), restrictive impairment (P < 0.01), and diffusion impairment (P < 0.05) of the lung. Correlation analyses revealed mRSS negatively correlates with forced vital capacity (P < 0.001) and diffusing capacity (P < 0.001) of the lung. Correlation between longitudinal change of mRSS and that of forced vital capacity (P < 0.05) or diffusing capacity (P < 0.001) of the lung was also demonstrated. CONCLUSIONS: Skin thickness score significantly correlates with quantitative measurements of lung involvement in Japanese patients with SSc.

Prediction of therapeutic response before and during i.v. cyclophosphamide pulse therapy for interstitial lung disease in systemic sclerosis: A longitudinal observational study.

There have been no established parameters to predict responsiveness to i.v. cyclophosphamide (IVCY) pulse therapy in combination with corticosteroids in patients with interstitial lung disease (ILD) related to systemic sclerosis (SSc). This retrospective study was conducted to determine predictive factors for efficacy of IVCY at the time of before and during the treatment. Thirty-two Japanese SSc patients, ever treated for ILD with IVCY in combination with prednisolone, were analyzed retrospectively. We performed detailed time-course analyses of parameters derived from blood samples and pulmonary function tests. With the exclusion of eight unclassified patients, 24 patients were classified into 14 good responders (GR) or 10 poor responders (PR) on the basis of changes in percent predicted diffusing capacity for carbon monoxide (DLco). Pretreatment percent predicted DLco was significantly reduced in PR compared with GR. In addition, serum parameters such as Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D) and C-reactive protein were significantly higher in PR than in GR. Furthermore, our time-course analyses revealed a transient increase in serum KL-6 levels with a peak at 3 months after the first infusion of cyclophosphamide, which showed no relation to therapeutic efficacy. Moreover, continuously high serum KL-6 levels (>2000 U/mL) and rapid decrease in SP-D levels (<200 ng/mL) during IVCY were remarkably characteristic of PR and GR, respectively. ILD severity/activity before treatment and variability of serum KL-6 and SP-D levels during treatment may be useful to predict therapeutic effects of IVCY on SSc-ILD.

Gastroesophageal Reflux Disease-Related Disorders of Systemic Sclerosis Based on the Analysis of 66 Patients.

BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD)-related disorders of systemic sclerosis (SSc) patients have not been adequately investigated. METHODS: Sixty-six SSc patients (5 males and 61 females; 56.6 ± 14.6 years old) who underwent esophagogastroduodenoscopy were analyzed on the basis of 16 background factors. They were additionally compared with 116 matched non-SSc subjects controlling age, sex, and use of proton pump inhibitors (PPIs). RESULTS: The mean disease duration of 66 patients was 5.1 ± 8.1 years, and their breakdown was as follows: 53 (80.3%) with GERD, 38 (57.6%) with GERD-related symptoms, and 20 (30.3%) with reflux esophagitis (RE; LA-A: 10, LA-B: 5, LA-C: 4, LA-D: 1). Use of PPI (p = 0.0455), complication of interstitial lung disease (p = 0.0242), and history of cyclophosphamide therapy (p = 0.0184) denoted significant association with GERD-related symptoms. Older age (p = 0.0211) was significantly associated with RE. None of GERD-related disorders showed any difference between 37 diffuse cutaneous SSc and 29 limited cutaneous SSc patients. The matched analysis indicated that SSc patients had higher prevalence of GERD (p < 0.0001), GERD-related symptoms (p = 0.0034), and RE (p = 0.0002). CONCLUSION: SSc patients tend to have worse GERD symptoms and severer RE. However, most SSc-associated factors did not show significant association with GERD-related disorders, indicating the difficulty in predicting GERD-related disorders among SSc patients.

Rapid alteration of serum interleukin-6 levels may predict the reactivity of i.v. cyclophosphamide pulse therapy in systemic sclerosis-associated interstitial lung disease.

Systemic sclerosis (SSc) is an autoimmune disorder characterized by excessive extracellular matrix deposition. Although SSc-associated interstitial lung disease (ILD) is one of the most important complications as a cause of death in SSc, prediction factors of treatment reactivity in SSc-ILD are still unclear. To assess relationships between interleukin (IL)-6 and reactivity to treatment, we measured serum IL-6 levels in 23 of active SSc-ILD patients under i.v. cyclophosphamide (IVCY) therapy and 20 of stabilized SSc-ILD, using the high-sensitivity enzyme-linked immunoassay system. Serum IL-6 levels in active SSc-ILD patients were significantly higher than those in stabilized SSc-ILD patients. Among active SSc-ILD patients, baseline serum IL-6 levels were not significantly different between IVCY responders and non-responders. Meanwhile, serum IL-6 levels after three IVCY doses out of a total of six were decreased in responders but not in non-responders. Regarding changes of parameters by the three doses of a total of six of IVCY, change in serum IL-6 levels correlated inversely with that in values of pulmonary function test. Thus, the rapid decrease in serum IL-6 levels during a couple of doses may predict the efficacy of IVCY therapy against SSc-ILD.