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.     

Percentage of residual B cells after 2 weeks of rituximab treatment predicts the improvement of systemic sclerosis-associated interstitial lung disease

The benefit of rituximab (RTX) for systemic sclerosis-associated interstitial lung disease (SSc-ILD) has been shown in previous clinical trials. However, predictors of RTX efficacy have not been clarified. We investigated whether B-cell responsiveness to RTX is related to therapeutic effect. Ten SSc-ILD patients treated with RTX in an independent clinical trial (Japan Registry of Clinical Trials, jRCTs031180373) were included in this analysis. Peripheral B-cell counts were examined retrospectively before RTX administration (baseline) and at 2, 4, 12, and 24 weeks after the first RTX administration, along with percent-predicted forced vital capacity (%FVC) before and 24 weeks after RTX treatment. Relative to baseline, the percentage of residual peripheral blood B cells at 2 weeks after RTX was negatively correlated with the %FVC improvement at the 24-week assessment (r = ?0.41, p = 0.04). In the subgroup with less than 5% B-cell persistence at week 2, %FVC at the 24-week assessment was significantly improved compared to baseline (p = 0.02). In another subgroup with more than 5% residual B cells, %FVC was not significantly different after 24 weeks compared to baseline (p = 0.41). In conclusion, the removal rate of B cells after 2 weeks of RTX treatment may be a useful surrogate marker of subsequent SSc-ILD improvement.     

Wound,pressure ulcer and burn guidelines – 4: Guidelines for the management of connective tissue disease/vasculitis-associated skin ulcers

The Japanese Dermatological Association prepared guidelines focused on the treatment of skin ulcers associated with connective tissue disease/vasculitis practical in clinical settings of dermatological care. Skin ulcers associated with connective tissue diseases or vasculitis occur on the background of a wide variety of diseases including, typically, systemic sclerosis but also systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis (RA), various vasculitides and antiphospholipid antibody syndrome (APS). Therefore, in preparing the present guidelines, we considered diagnostic/therapeutic approaches appropriate for each of these disorders to be necessary and developed algorithms and clinical questions for systemic sclerosis, SLE, dermatomyositis, RA, vasculitis and APS.     

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.     

Diagnosis and treatment of an infant case with temporomandibular joint osteoarthritis caused by tumor

Introduction

We reported an infant with temporomandibular joint (TMJ) osteoarthritis who required long-term tracheostomy.

Case findings

At 1 year of age, he received urgent tracheostomy because of apnea due to pneumonia. The tracheal cannula could not be removed thereafter due to trismus. Computed tomography (CT) images demonstrate irregular bone formation. However, we could not diagnose osteoarthritis of temporomandibular joint because TMJ adhesion was not clear on CT images.

Interventions

Arthroplasty was performed under general anesthesia, but there was no significant improvement. A 3-D plastic model based on intraoperative findings showed that atrophic change of the muscles also disturbed movement of the mandible. Therefore, an additional procedure called “pan-muscle-release surgery” was performed, resulting in further improvement of mandible movement. After confirming that mouth opening was stable, the tracheal cannula was removed.     

Bilateral numb chin syndrome leading to a diagnosis of Burkitt's cell acute lymphocytic leukemia: a case report and literature review

Numb chin syndrome (NCS), also known as mental nerve neuropathy, is characterized by facial and oral numbness restricted to the distribution of the mental nerve. Although not a common neuropathy, the clinical importance of this syndrome is its frequent association with malignancies, particularly breast cancer and lymphoma. In this paper, we present a rare case of Burkitt cell acute lymphocytic leukemia initially presenting with bilateral NCS. In this case, no abnormalities were detected on initial blood tests and radiologic investigations except for partial loss of lamina dura around mandibular teeth. Furthermore, we found no evidence of any other signs of central nervous system involvement apart from NCS. Nevertheless, the patient continued to experience severe bilateral mandibular pain and paresthesia, prompting us to repeat the blood studies. These showed lymphomatous cells, yielding the diagnosis of leukemia 37 days after the original presentation. When a patient presents with the extremely unusual symptoms of bilateral numbness of lower lip and chin, we should suspect the presence of a malignancy even in the absence of any relevant past history. If the initial radiologic investigations and blood tests reveal no abnormalities, malignancy should not be removed from the differential diagnosis until a definite cause has been found.