Comparison between Japanese and non-Japanese features of lupus cystitis based on case reports including novel therapy and a literature review.

OBJECTIVE: This study was carried out to determine the characteristics of lupus cystitis and to compare those of Japanese cases with those of non-Japanese cases. We also report a novel therapy for lupus cystitis refractory to corticosteroid. METHODS: For the literature search, published reports on lupus cystitis were searched by MEDLINE and ICHUSHI WEB. The inclusion criterion was interstitial cystitis, fulfilling the SLE classification criteria of American College of Rheumatology in 1997 and with either hydronephrosis detected by image studies (either computed tomography or ultrasonography) or bladder histopathology consistent with lupus cystitis. Interstitial cystitis without the fulfillment of the classification criteria was excluded. Patient demographic data and clinical data were retrieved from the literature and analyzed. RESULTS: Including the present 2 cases, a total of 78 cases were identified as definitive cases of lupus cystitis (35 non-Japanese cases and 43 Japanese cases). Female patients accounted for 90.7%. The preceding gastrointestinal symptoms and subsequent urinary symptoms were the most frequent. Anti-double strand DNA antibody most often expressed in the 76.1% of the patients. Mean age and the prevalence of vomiting were significantly higher among Japanese patients compared to non-Japanese cases and the prevalence of CNS involvement was lower among Japanese patients (p=0.03, 0.04 and 0.001). We report a novel therapy (cetirizine hydrochloride) for lupus cystitis refractory to corticosteroid in one of the present cases. CONCLUSION: Lupus enteritis, female gender, and positive anti-dsDNA antibody are risk factors for lupus cystitis. Japanese cases showed older age, a higher prevalence of vomiting and a lower prevalence of CNS involvement. We also report the efficacy of the novel use of cetirizine hydrochloride for lupus cystitis refractory to corticosteroid.

Mast cell-derived tryptase inhibits apoptosis of human rheumatoid synovial fibroblasts via rho-mediated signaling.

OBJECTIVE: An abundance of mast cells are found in the synovium of patients with rheumatoid arthritis (RA). However, the role of mast cells in the pathogenesis of RA remains unclear. This study was undertaken to elucidate a role for mast cells in RA by investigating the antiapoptotic effects of tryptase, a major product of mast cells, on RA synovial fibroblasts (RASFs). METHODS: RA synovial tissue was obtained from RA patients during joint replacement surgery, and histologic changes in the tissue were examined. The expression of cell surface molecules and apoptotic markers on RASFs were detected by flow cytometry. Rho activation was determined using a pull-down assay. RESULTS: Mast cells, bearing both c-Kit and tryptase, accumulated in the sublining area of proliferating synovial tissue from RA patients. Protease-activated receptor 2 (PAR-2), a receptor for tryptase, was expressed on RASFs in the lining area, close to tryptase-positive mast cells in the RA synovium. Fas-mediated apoptosis of RASFs was significantly inhibited, in a dose-dependent manner, by the addition of tryptase, and this effect correlated with increased activation of Rho kinase. Furthermore, Y27632, a Rho kinase inhibitor, reduced the antiapoptotic effect of tryptase on RASFs, suggesting that Rho was responsible for the antiapoptotic effects of tryptase. CONCLUSION: These results demonstrate that tryptase has a strong antiapoptotic effect on RASFs through the activation of Rho. Thus, we propose that the release of tryptase by mast cells leads to the binding of tryptase to PAR-2 on RASFs and inhibits the apoptosis of RASFs via the activation of Rho. Such mechanisms could play a pivotal role in the marked proliferation of RASFs and hyperplasia of synovial tissue seen in RA synovium.

[A case of lupus cystitis in a 74-year-old woman].

The patient was a 74-year-old woman. As the history of the present illness, Raynaud's phenomenon appeared in 1998, antinuclear antibody positivity was detected in 2002, and she visited our department for the first time. Leukopenia and positivity for anti-DNA and anti-RNP antibodies were present, but active lesions were not, and thus, course observation was selected. Pollakiuria and a sensation of residual urine appeared in February 2005, diarrhea and nausea developed in November, and she was admitted to our hospital. Abdominal CT detected bilateral hydronephrosis, marked hydroureter, and hypertrophy of the urinary bladder wall, cystoscopy detected trabeculation, and features of interstitial cystitis were noted on biopsy. Edematous colon mucosa was noted on lower endoscopy, submucosal inflammatory cell infiltration on biopsy, and IgG deposition in the small vascular wall on immunostaining. Systemic lupus erythematosus (SLE) that developed as lupus cystitis was diagnosed. The clinical findings were improved by 50 mg of prednisolone. Although she developed lupus cystitis at an elderly age of 74 years, IgG deposition in the small vascular wall was detected by immunostaining of the intestinal mucosa. It is a valuable case proved that causative disease of a digestive tract symptom was enterocolitis through an immune complex as autoimmune reaction by SLE immunohistologically. There are 46 cases of lupus cystitis in Japan by 2007 since Kato reported lupus cystitis in 1985. We summarize clinical features of 46 cases and discuss difference with this case.

Long-term remission by cyclosporine in a patient with eosinophilic fasciitis associated with primary biliary cirrhosis.

A 70-year-old man was admitted to the hospital in June 1994 because of cutaneous induration of the extremities. Eosinophilic fasciitis was diagnosed on the basis of the course and distribution of the cutaneous lesions. Cyclosporine (100 mg/day) was given. After 4 weeks of treatment, cutaneous induration and limited joint mobility improved. Liver dysfunction had been diagnosed 5 years before the onset of eosinophilic fasciitis. Primary biliary cirrhosis (PBC) was diagnosed on the basis of the elevated serum biliary-enzyme levels, strongly positive antimitochondrial antibody titer, and histologic features of the liver-biopsy specimens showed stage-3 PBC. These findings suggested that eosinophilic fasciitis developed in association with PBC. PBC is often accompanied by autoimmune diseases, such as Sjögren's syndrome and Hashimoto's disease. To our knowledge, eosinophilic fasciitis associated with PBC has not been reported previously. We believe this is the first time a case of eosinophilic fasciitis occurring in a patient with PBC is documented.

Dramatic regression of mesenteric abnormalities demonstrated on angiography following prednisolone and cyclophosphamide combination therapy in a patient with polyarteritis nodosa associated with Sjögren's syndrome.

A 63-year-old woman, who had been followed for Sjögren's syndrome, was admitted due to cryoglobulinemia, leukocytoclastic vasculitis, and mononeuritis multiplexa. In spite of the administration of 60 mg prednisolone, fecal occult blood was strongly positive. The colonoscopy showed multiple colonic ulcers, and a diagnosis of polyarteritis nodosa (PAN) was made because abdominal angiography revealed markedly serpentine and narrowed superior and inferior mesenteric arteries. After steroid pulse therapy and daily oral administration of cyclophosphamide were initiated, her symptoms improved and abdominal angiographic findings were finally normalized. Although there are only three case reports on improvements in abdominal angiographic findings of PAN in the literature, our case and previously reported cases suggest that improvements in angiographic findings may reflect a good prognosis of PAN.

Marked hypocomplementemia and tubulointerstitial nephritis in a male patient with Sjögren's syndrome.

We report a case of marked hypocomplementemia and tubulointerstitial nephritis associated with Sjögren's syndrome (SS) in a male patient. Renal biopsy revealed tubulointerstitial nephritis but did not identify specific immune deposits of the tubulo-interstitium. After steroid therapy, the renal failure and hypocomplementemia diminished. Hypocomplementemia without cryoglobulinemia is not commonly observed in SS patients, and hypocomplementemic tubulointerstitial nephritis was strongly suspected. Hypocomplementemic tubulointerstitial nephritis is rare; only one case has been described in the literature. In our case and the previous case, the patients were elderly men, and they had some similar clinical characteristics. Idiopathic hypocomplementemic tubulointerstitial nephritis resembling our case has been reported. These facts suggest that hypocomplementemic tubulointerstitial nephritis may occur in patients with SS, and such cases may not be as rare as once thought because it might be appropriate to include them in the category of idiopathic cases. Such a syndrome should be included in the differential diagnosis of hypocomplementemia.

Thrombotic thrombocytopenic purpura complicating Sjögren's syndrome with crescentic glomerulonephritis and membranous nephritis.

The association of either thrombotic thrombocytopenic purpura (TTP) or crescentic glomerulonephritis with Sjögren's syndrome is rare. We report a case of TTP appearing after the diagnosis of SjOgren's syndrome with crescentic glomerulonephritis and membranous nephropathy. Circulating immune complex was detected, and immune complex deposits were shown along the capillary walls of renal biopsy specimens. Despite steroid pulse therapy and plasma exchange therapy, the patient died. The etiology of TTP is unclear. This case is important when considering the etiology of TTP related to autoimmune disease.