Efficacy and safety of plasma exchange in interstitial lung diseases with anti-melanoma differentiation-associated 5 gene antibody positive clinically amyopathic dermatomyositis.

OBJECTIVE: Clinically amyopathic dermatomyositis (CADM) patients frequently develop refractory interstitial lung disease (ILD), with a poor prognosis. We aimed to verify the efficacy and safety of plasma exchange (PE) treatment for ILD in CADM. METHOD: A retrospective case-control study was conducted to compare clinical outcomes with and without PE treatment in CADM-ILD patients refractory to combination therapy of high-dose glucocorticoids, calcineurin inhibitors, and cyclophosphamide. Among 19 enrolled patients, 11 were further treated with PE. We compared survival rates and other clinical characteristics. PE consisted of either fresh-frozen plasma or albumin as a replacement solution. RESULTS: Basal clinical characteristics at diagnosis, including age, gender, serum ferritin, Krebs von den Lungen-6 (KL-6), C-reactive protein, and respiratory function tests, did not differ between the two groups. The survival rate for treatment with PE was higher than for treatment without PE (91% and 50%, respectively, p < 0.05). Among PE-treated patients, anti-melanoma differentiation-associated gene-5 (anti-MDA-5) antibody titre, ferritin, and KL-6 as serological activity markers were sustainably reduced only after initiating PE. Therapeutic intervention with PE reduced the frequency of exacerbation of ILD requiring methylprednisolone pulse therapy. The occurrence of bacterial, fungal, and cytomegalovirus infection did not differ between the groups with and without PE, and adverse events associated with PE resolved with appropriate intervention. CONCLUSION: Combination therapy with PE was associated with an improved survival rate, and may be effective for the management of refractory ILD in CADM patients. A personalized therapeutic strategy including PE could be introduced for fatal rapidly progressive ILD.

Delayed lupus nephritis in the course of systemic lupus erythematosus is associated with a poorer treatment response: a multicentre, retrospective cohort study in Japan.

OBJECTIVE: The objective of this study was to investigate possible differences in treatment responses between two categories for the onset of lupus nephritis. METHODS: We performed a multicentre, retrospective cohort study of class III-V lupus nephritis patients diagnosed between 1997 and 2014. The renal responses to initial induction therapy were compared between patients who developed lupus nephritis within one year from diagnosis of systemic lupus erythematosus (early (E-) LN) and the remainder (delayed (D-) LN) using the Kaplan-Meier method. We determined the predictors of renal response as well as renal flares and long-term renal outcomes using multivariate Cox regression analyses. RESULTS: A total of 107 E-LN and 70 D-LN patients were followed up for a median of 10.2 years. Log-rank tests showed a lower cumulative incidence of complete response in D-LN compared with E-LN patients. Multivariate analysis identified D-LN (hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.33-0.70), nephrotic syndrome at baseline, and a chronicity index greater than 2 as negative predictors of complete response. D-LN patients were more likely to experience renal flares. D-LN (HR 2.54, 95% CI 1.10-5.83) and decreased renal function were significant predictors of chronic kidney disease at baseline. CONCLUSION: D-LN was a predictor of poorer treatment outcomes, in addition to renal histology and severity of nephritis at lupus nephritis onset.

Successful treatment of cerebral large vessel vasculitis in systemic lupus erythematosus with intravenous pulse cyclophosphamide.

A 39-year-old woman with a six-year history of systemic lupus erythematosus (SLE) was admitted because of a prolonged high fever, discoid rash, and multiple lymphadenopathies. She also developed pericarditis, and was treated with intravenous methylprednisolone pulse therapy followed by prednisolone 50 mg daily and cyclosporine 100 mg daily. Meanwhile, she had a progressive headache, and a brain MRI revealed right pons infarction, although she did not have any abnormal neurological findings. An MRA revealed obvious irregular narrowing in the basilar, right vertebral and right posterior cerebral artery. There was no evidence of antiphospholipid syndrome. We concluded that the cause of the asymptomatic brain infarction was cerebral large vessel vasculitis associated with neuropsychiatric SLE. Intravenous cyclophosphamide pulse therapy was started, and two months later, we confirmed that the irregular arterial narrowing had markedly ameliorated.Cerebral large vessel vasculitis in neuropsychiatric SLE is very rare, and a marked amelioration has not been reported to date. Here, we present a rare case of cerebral large vessel vasculitis treated successfully with a clear visual presentation.

Three cases of lupus nephritis patients with serum interleukin-32γ detection.

PURPOSE: Interleukin-32 (IL-32) is an inflammatory cytokine that is associated with the pathogenesis of several connective tissue diseases. We measured serum IL-32γ concentrations of systemic lupus erythematosus (SLE) patients. METHODS: Serum samples were obtained from SLE patients (n = 51), and healthy controls (n = 15). Serum IL-32 concentrations were measured using ELISA. Clinical information was obtained from medical records. RESULTS: Serum IL-32γ was detectable in three cases of SLE patients, whereas it was not detected in any healthy controls. Case 1: a 44-year-old female with lupus nephritis (LN) (Class II) and antiphospholipid antibody syndrome. Serum IL-32γ was 5.1 pg/ml. Case 2: a 30-year-old female with a history of diffuse proliferative LN (Class IV G (A/C)) and pulmonary hemorrhage. Serum IL-32γ was 8.9 pg/ml. Case 3: a 45-year-old female with chronic LN. Serum IL-32γ was 9.1 pg/ml. All three cases of IL-32γ-detectable patients had histories of LN and one had an active disease. In the context of LN, serum IL-32γ was detectable in 18.8% (three of 16) of SLE patients with histories of LN. CONCLUSION: We suppose that IL-32γ could contribute to the pathogenesis of renal diseases in some LN patients.

Tumour necrosis factor inhibitor-associated sinusitis.

AIM: To describe the features of chronic sinusitis associated with the use of tumour necrosis factor (TNF) inhibitors. METHODOLOGY: A retrospective review of the medical records between 2003 and 2011 revealed that five patients had developed chronic sinusitis after the start of TNF inhibitor administration and required rhinological evaluation and treatment. RESULTS: The incidence of refractory sinusitis associated with TNF inhibitors was approximately 2%. Of the five patients identified, four patients were medicated with etanercept and one with infliximab. The maxillary sinus was most commonly involved and cultures of the sinus discharge revealed Pseudomonas aeruginosa in three cases. Two patients showed improvement of sinusitis with antibiotic medication, despite the continuous use of TNF inhibitor, while in two other patients, sinusitis was resistant to antibiotic medication. Another patient who had developed recurrence of sinusitis after complete remission of previous chronic sinusitis by endoscopic sinus surgery showed remission only after cessation of TNF inhibitor. CONCLUSION: Chronic sinusitis associated with TNF inhibitors is considered to be a new disease entity, and it will become more common due to the increasing use of TNF inhibitors.

Subacute cerebellar ataxia and atrophy developed in a young woman with systemic lupus erythematosus whose cerebrospinal fluid was positive for antineuronal cell antibody.

Subacute cerebellar ataxia in combination with cerebellar atrophy has rarely been reported as one of the manifestations of lupus in the central nervous system (CNS). We describe a 27-year-old woman with systemic lupus erythematosus who developed subacute cerebellar ataxia. Computed tomography and magnetic resonance imaging of her brain showed cerebellar atrophy in both hemispheres, particularly on the right side. Moreover, increased antineuronal cell antibody levels were detected in her cerebrospinal fluid. The cerebellar ataxia improved markedly following high-dose corticosteroid administration. This suggests that a relationship exists between autoantibodies and subacute atrophic processes in CNS lupus.

The future of lupus therapy modulating autoantigen recognition.

The mainstay of the current treatment for systemic lupus erythematosus consists of steroids and immunosuppressants. However, these non-specific immunosuppressive therapies can cause infection and other serious adverse events. The regulation of the autoantigen-specific immune response is a promising therapeutic approach with maximal efficacy and minimal adverse effects. T cells are essential components of antigen-specificity in the immune system. At present, we do not have a sufficient strategy for manipulating the responses of antigen-specific T cells. In this review, we describe the efficacy of two therapeutic approaches involving the modulation of autoantigen recognition by T cells in lupus model mice: (1) therapy involving engineered autoantigen-specific regulatory T cells generated by the gene transfer of autoantigen-specific TCR genes and appropriate regulatory genes into self lymphocytes; (2) therapy involving selective depletion of autoantigen presenting phagocytes. These selective immunosuppressive approaches could be useful strategies for the treatment of systemic lupus erythematosus.

Evaluation of therapeutic efficacy in psychogenic impotence by means of logarithmic scoring.

In an attempt to develop as objective a method for the evaluation of impotence as possible, the authors assigned numerical values to four parameters considered essential to sexual function, namely, libido, erection, ejaculation, and orgasm, and used the sum totals of these scores, collected before and after initiation of therapy, as indicators of overall sexual function. Numerical values were assigned according to a logarithmic scale, in four stages from 0 to 10, i.e., 0, 1, 3, and 10; a score of 0 signified "normal" and a score of 10, "abnormal." By comparing sum totals of scores computed before and after initiation of therapy, the authors were able to evaluate therapeutic efficacy on the basis of changes in these sum totals. Using this method, the mean total score for a control group of 24 normal subjects was 1.67 +/- 0.26 (mean +/- standard error). For the test group, which consisted of 24 patients of psychogenic impotence, the mean total score prior to initiation of therapy was 16.46 +/- 3.55, an extremely high score in comparison with the control group. After four weeks of therapy, the mean total score dropped to 9.37 +/- 1.77, indicating a statistically significant (p less than 0.05) decrease over the pre-therapy mean total score.

Growth of severed flexor tendons in chickens.

To examine tendon growth in both the distal and proximal portions of severed tendons, we investigated the growth of severed flexor tendons within the fibro-osseous tunnel in young chickens. When the tendon was severed at the proximal site in the sole, dynamic tension applied by the muscle was lost. Growth in the distal tendon was retarded considerably, although passive tension initially was maintained through the residual vincula and later by adhesion to the chiasma of adjacent flexors. When the tendon was severed at the insertion, passive tension from the extensors was lost. Proximal tendon growth continued if active tension was maintained through the residual vincula. If not, the tendon was markedly shortened and degenerated. Maintaining normal tension may be the most important factor in longitudinal tendon growth.

Prevalence of hepatitis G virus (HGV) infection in an endemic area of hepatitis C virus (HCV) infection.

BACKGROUND/AIMS: We investigated the prevalence of hepatitis G virus infection among inhabitants of a hepatitis C virus endemic area. METHODOLOGY: Two hundred and eighty-eight inhabitants, who underwent medical examinations for health screening, were enrolled in this epidemiological study. HGV RNA and HCV RNA were detected by polymerase chain reaction. We also examined anti-HGV envelope protein (E2) antibodies in all serum samples. RESULTS: In these 288 inhabitants, we found anti-HCV antibodies (HCV-Ab) and HCV RNA in 28.5% and 17.4%, respectively. HGV RNA and anti-HGV E2 were detected in 9 (3.1%) and 16 (5.5%), respectively. One patient was positive for both HGV RNA and anti-HGV E2. The exposure rate, expressed as the percentage of people with HGV RNA and/or anti-HGV E2, was 8.3%, which was significantly lower than the incidence of positive HCV-Ab. Of the 24 patients with HGV RNA and/or anti-HGV E2, 15 (62.5%) were positive for HCV-Ab, of those HCV RNA was detected in 9 (37.5%). Further, we found a higher prevalence of HGV exposure in patients with HCV-Ab than in those without (8.3% vs. 4.4%). CONCLUSIONS: HGV infection was not identical to the epidemic hepatitis C virus infection among inhabitants of this town, suggesting that hepatitis C virus might be less infectious than hepatitis C virus.

Genetic variation of putative core gene in hepatitis C virus.

Genetic variation of hepatitis C virus was assessed. We prepared RNA fractions from 21 patients' sera which were positive for hepatitis C virus RNA, synthesized their cDNAs, and amplified fragments, 406 base pairs, encoding a putative core protein, by polymerase chain reaction. One of them, N 15, was cloned and sequenced. N 15 showed 92.4% homology at the nucleotide level and 97.0% homology at the amino acid level compared with HC-J 1 which is the first isolated clone in Japan and similar to that isolated in USA. By restriction fragment length polymorphisms analysis, 14 out of 21 patients (66.7%) showed the same pattern as N 15. No patients showed the pattern of HC-J 1. We could not find a correlation between the genetic variation and clinical features of hepatitis C virus infection. These results indicate that the region, which encodes the core protein and is believed to be relatively conserved in hepatitis C virus genome, has several variations at the nucleotide level, and the major part of hepatitis C virus in Okayama district is different from HC-J 1 and the USA clone.