Oxford University Press (OUP)

We report the case of a 42-year-old Japanese woman with unusual diaphyseal dysplasia of bilateral femora. Radiographs showed thickening and sclerosis of the cortex with resultant enlargement of the diaphysis, unclear demarcation of the surface of the cortex, and no periosteal reaction. These changes were found on the left femur at the first presentation, and those on the right femur developed within several years. Although this patient partly presented characteristics of Ribbing disease and Camurati–Engelmann disease, the focal involvement of bilateral femora suggested an unknown pathogenesis.

Lupus profundus is a rare lupus-specific skin lesion with skin biopsies exhibiting lobular lymphocytic infiltration and destruction of subcutaneous fat tissue. In this report, a CT scan was effective in demonstrating both the presence and the extent of inflammation of lupus profundus in two patients with systemic lupus erythematosus (SLE). Case 1 was a 30-year-old woman developing erythema with subcutaneous induration on the upper arms during the quiescent phase of SLE. A skin biopsy confirmed a diagnosis of lupus profundus. A CT scan of the right upper arm demonstrated a high density area (HDA) of the subcutis under the erythema: a finding consistent with lupus profundus. Case 2 was a 28-year-old woman recently diagnosed with SLE. She also developed a skin ulcer on the right hip. A CT scan of the hip revealed an HDA and lipoatrophy of the subcutis around the ulcer: these findings were compatible with lupus profundus. Treatment with high-dose prednisolone improved the illness in the both cases. A CT scan is a useful and convenient imaging modality for confirming the diagnosis of lupus profundus.

Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) is a secretory protein that shares a structural similarity with IGFBP. Studies have shown that IGFBP-rP1 synergistically increases fibroblast growth with insulin and stimulates angiogenesis in tumor tissues. In this report, we examined the expression and function of IGFBP-rP1 in rheumatoid arthritis (RA). IGFBP-rP1 expression in synovial tissues was examined by reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR, and immunohistochemical analysis. In vitro, IGFBP-rP1 expression was examined in synovial fibroblasts established from rheumatoid synovium (RASFs) by RT-PCR, Western blot, and immunostaining. The effect of IGFBP-rP1 small interfering RNA (siRNA) on RASF proliferation was assessed by alamarBlue assay. IGFBP-rP1 mRNA was detected by RT-PCR in all synovial tissues from RA and OA patients. In immunohistochemical analysis, IGFBP-rP1 was mainly expressed in synovial cells in the lining layers and endothelial cells in the sublining layers of RA synovium. In vitro, constitutive expression of IGFBP-rP1 in RASFs was detected by RT-PCR, Western blot, and immunostaining. Treatment with IGFBP-rP1 siRNA induced a 26% decrease in RASF growth compared to control siRNA. A similar extent of growth-suppressive effect by IGFBP-rP1 siRNA was also observed when RASF proliferation was induced by TNF-α. Collectively, these data suggest that IGFBP-rP1 may regulate synovial fibroblast proliferation in RA.

We report the case of a 38-year-old female patient with systemic lupus erythematosus (SLE) who developed acquired hemophilia caused by factor VIII (FVIII) inhibitors. She manifested spontaneous bleeding symptoms such as ecchymoses and hematuria. Laboratory findings showed an isolated prolongation of the activated partial thromboplastin time, reduced FVIII activity, and a high titer of FVIII inhibitors. She was successfully treated with oral predonisolone and cyclosporine in combination with steroid and cyclophosphamide pulse therapy.

We report the case of a 56-year-old Japanese woman with BehÇet’s disease and myelodysplastic syndrome (MDS), who had a history of episodic high-grade fever, recurrent oral and genital ulcers, and erythema nodosum, during a 13-year period from 1989 to 2002. Bone marrow aspirates obtained in January 1995 showed refractory anemia with trisomy 8, a subtype of MDS. Her serum levels of soluble interleukin-2 receptor (IL-2R), interferon-Γ, IL-1Β, IL-6, IL-8, and granulocyte–macrophage colony stimulating factor in the active state were higher than those in the inactive state, whereas those of tumor necrosis factor-Α and IL-10 did not increase even in the active state. In this case, it was speculated that a T-cell immune response might have been involved in the disease pathogenesis, and that the repeated febrile episodes might have been a manifestation of neutrophil hyperfunction induced by increased serum levels of inflammatory cytokines.

Trimethoprim–sulphamethoxazole (TMP–STX), an agent used for prophylaxis against pneumocystis pneumonia (PCP) in immunocompromised hosts, causes serious adverse effects (AEs) in some patients. The objective of this study was to identify the risk factors for AEs caused by TMP–STX in connective tissue disease (CTD) patients and to describe the clinical features of the AEs. The medical records of 539 patients (CTDs 312, pulmonary diseases 227) receiving TMP–STX for prophylaxis against PCP were reviewed retrospectively. Patients with human immunodeficiency virus were excluded. Univariate and multivariate analyses were conducted to identify the risk factors. Adverse events caused by TMP–STX occurred in 22 of 312 (7.05 %) CTD patients, while only six of 227 (2.64 %) pulmonary disease patients developed AEs. The incidence of AEs was significantly higher in systemic lupus erythematosus (SLE) (11.0 %) and mixed connective tissue disease (MCTD) (33.3 %) patients than in other CTD patients. AEs occurred in 25 % of patients with anti-RNP antibody. Univariate analysis revealed that SLE, MCTD, and anti-RNP antibody were risk factors for AEs in CTD patients. Further multivariate analyses demonstrated that only anti-RNP antibody positivity was a risk factor for AEs. Systemic inflammation, including fever, was a characteristic manifestation of the AEs in CTD patients, particularly those with anti-RNP antibody. Positivity for anti-RNP antibody is a risk factor for AEs caused by TMP–STX in CTD patients. Systemic inflammation, including fever, might be a characteristic feature of the AEs in CTD patients, particularly those with anti-RNP antibody.

The introduction of biological agents targeting tumor necrosis factor-alpha (TNF-α) has brought about a paradigm shift in the treatment of rheumatoid arthritis (RA). Although these anti-TNF agents have excellent efficacy against RA, a substantial number of patients still show inadequate responses. In Western countries, such patients are already being treated with new classes of antirheumatic drugs such as abatacept and rituximab. Tocilizumab (TCZ) is a humanized monoclonal antibody developed in Japan against the human interleukin-6 (IL-6) receptor. TCZ does not only alleviate the signs and symptoms of RA but also seems to prevent progressive bone and joint destruction. However, there is a concern that TCZ might increase the risk of adverse events such as infections since IL-6 plays a pivotal role in the immune system. Calculating the relative risks of specific adverse outcomes with TCZ use remains difficult, due to insufficient patient numbers enrolled in clinical trials to date. This review presents tentative guidelines for the use of TCZ for RA patients prepared by the Japan College of Rheumatology and based on results of clinical trials in Japan and Western countries. The guidelines are intended as a guide for postmarketing surveillance and clinical practice, and will be revised periodically based on the surveillance.