Oxford University Press (OUP)

Methotrexate (MTX) is indispensable for the treatment of rheumatoid arthritis (RA). However, a small number of patients treated with MTX occasionally encounter some life-threatening events, including myelosuppression. Renal insufficiency, one of risk factors for these events, is difficult to assess because the serum creatinine concentration level and estimated glomerular filtration rate are sometimes inaccurately determined in aged RA patients. As a better indicator to evaluate this pathology, we measured the serum cystatin-C (Cys-C) level in 78 RA patients ≥50 years who were treated with MTX and observed for a year. The measurement achieved successful screening of two patients with leukocytopenia, one with interstitial lung disease (ILD), and two with liver dysfunction. An additional four referral inpatients with MTX-induced adverse events (three with pancytopenia, one with ILD) were enrolled for analysis, amounting to 82 patients. The logistic regression analysis showed that a correlation was observed between myelotoxicity and serum Cys-C level (elevation per 0.1 mg/dl; odds ratio 2.34, 95% confidence interval 1.08–5.09, p = 0.03). In conclusion, elderly RA patients potentially have subclinical renal insufficiency detected by the serum Cys-C concentration level. The elevated level of serum Cys-C is a more sensitive indicator to predict MTX-induced myelotoxicity than that of serum creatinine.

Patients with ankylosing spondylitis (AS) are prone to spinal fracture after even minor trauma. We report a case of thoracic spinal fracture in a patient with AS who developed a secondary neurological deficit due to delayed diagnosis and prolonged conservative treatment. When the neurological deficit occurred, the fractured segment showed no displacement, but a spinal epidural hematoma was present. Surgical treatment produced significant neurological improvement, although incomplete paralysis persisted.

We investigated the efficacy of a high-dose intermittent dosing treatment method (weekly mizoribine pulse therapy) conceived in the hope of achieving better efficacy by increasing the peak blood levels of mizoribine in patients with refractory lupus nephritis. Seventeen patients with lupus nephritis who had been resistant to corticosteroid and immunosuppressant therapy received weekly mizoribine pulse therapy. Mizoribine (350 mg) was administered three times at 12 h intervals over 2 consecutive days (700 mg for day 1 and 350 mg for day 2), followed by a washout period from day 3 to day 7. This therapeutic strategy enabled the peak blood levels of mizoribine to be increased to more than 3 μg/mL in most of the patients. Although SLEDAI, anti-ds-DNA antibody titer, CH-50, and serum albumin level did not significantly improve, urinary protein levels decreased, and it was possible to taper the dose of concomitant steroids. Using our definition of clinical response, 10 of the 17 patients were responders and 4 of them were nonresponders. The average peak serum mizoribine concentration of the responders was as high as 3.5 μg/mL. Elevation of serum liver enzymes was seen in 1 patient, and hyperuricemia occurred in 4 cases, but none of these adverse events were serious. Intermittent administration of mizoribine can increase blood levels and may be effective for refractory lupus nephritis.

 Werner syndrome (WS), caused by the mutation of the RecQ3 DNA helicase gene (loss of function), manifests scleroderma-like skin changes and juvenile cataracts in addition to a variety of clinical and biochemical aging phenotypes at an early stage of life, followed by death at an average age of 46 years. WS has been nominated as a top-ranking premature aging syndrome, or a human model of accelerated aging. Analyses of clinical and biological deterioration of body systems observed in WS may shed a unique light on the role of gene(s) in the pathogenesis of systemic sclerosis (SSc) and normal human aging.

Aortitis, inflammation of the aortic tissue, is most commonly caused by vasculitic rheumatic conditions, and less frequently infectious organisms. Involvement of the aorta is well defined in HLA-B27-associated spondyloarthropathies such as long-standing ankylosing spondylitis and Reiter’s syndrome. However, unlike other spondyloarthropathies, aortic involvement or true aortitis is not a feature of psoriatic arthritis and has been reported in only a few cases. Herein, we report the case of a 22 year-old woman with psoriatic arthritis who developed descending aortitis while using tumor necrosis factor inhibitors.

The relationship between clinical manifestations and prognosis was examined and evaluated among systemic lupus erythematosus (SLE) patients. A total of 542 patients with SLE were selected and divided into nine groups according to their main clinical manifestation at the time of initial diagnosis. The relationship between these clinical manifestations and long-term prognosis was evaluated in respect to the survival, remission, relapse rates, the development of a new clinical manifestation, and/or damage index. Patients with neuropsychiatric SLE (NPSLE), accompanied with acute confusional state/seizure disorder, cerebral vascular disease, or pneumonitis had poor survival rates with cause of death related to their major organ involvement. Patients with nephropathy or leukopenia had lower remission rates, and an increase in relapse rates was frequently recognized in patients with pneumonitis. Body damage (damage index) was higher in patients with lupus psychosis, pneumonitis, and/or arthritis. The translation of the main manifestations after diagnosis was confirmed in 64 patients (11.8%), and often observed in patients with autoimmune hemolytic anemia and arthritis. The majority of these manifestations were nephropathy, NPSLE, thrombocytopenia, and pneumonitis, and the prognosis of patients with nephropathy and thrombocytopenia as a new main manifestation had a poor outcome. The results of long-term prognosis in SLE greatly differed with respect to the initial clinical manifestation at the time of diagnosis.