Neuropsychiatric manifestations are relatively common and serious complications in systemic lupus erythematosus (CNS lupus). Overall, in patients with CNS lupus, CSF IgM, IgA, IgG indexes (indicators of intrathecal Ig synthesis) as well as CSF IL-6 activities were significantly elevated. Of note, especially in patients lupus psychosis, but not in those with focal CNS lesions, anti-ribosomal P antibody (anti-P) in the sera as well as anti-neuronal antibody (anti-N) in the CSF was significantly elevated in relation to their CNS disease activities. These data indicate that the immune system activation within the CNS, possibly resulting in the elevation of CSF anti-N, plays an important role in the pathogenesis of CNS lupus, including lupus psychosis. CNS involvement in Behcet’s disease, usually called neuro-Behcet’s syndrome (NB), includes acute type and chronic progressive type. Acute NB is characterized by acute meningoencephalitis with focal lesions, presenting high intensity areas in T2-weightened images or Flare images on MRI scans, whereas chronic progressive NB is characterized by intractable slowly progressive dementia, ataxia and dysarthria with persistent elevation of CSF IL-6 activity. Chronic progressive NB is resistant to conventional treatment with steroid, cyclophosphamide, or azathioprine, but responds to low dose methotrexate. As for ANCA-related vasculitis, pachymeningitis has been found to be associated with P-ANCA as well as C-ANCA.

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Pulmonary involvement is a common feature in patients with various collagen diseases. Some types of the pulmonary involvement are resistant to currently available treatment regimens and thus considered as intractable conditions. These include acute/subacute interstitial pneumonia in dermatomyositis, pulmonary interstitial fibrosis in scleroderma, and diffuse alveolar hemorrhage. Acute/subacute interstitial pneumonia with the histology of diffuse alveolar damage (DAD) is mainly occurred in patients with amyopathic or hypomyopathic dermatomyositis who lack autoantibodies to aminoacyl tRNA synthetases. Intensive immunosuppressive treatment in the early phase of the disease may be effective for this intractable complication. Nearly one-third of patients with scleroderma have slowly progressive pulmonary interstitial fibrosis, leading to end-stage respiratory failure. Non-specific interstitial pneumonia (NSIP) with an excessive fibrotic change is a major histology of these patients. There are accumulating evidences showing the effectiveness of cyclophosphamide in patients with this intractable condition, especially those with active alveolitis. Diffuse alveolar hemorrhage is a fatal complication mainly occurred in patients with systemic lupus erythematosus and those with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, including microscopic polyangitis (MPA) and Wegener’s granulomatosus. Immediate diagnosis and introduction of intensive treatment are necessary to save the patients with this complication.

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[in Japanese]

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Collagen vascular diseases are known to present with a diverse array of gastrointestinal manifestations. These can be classified as: 1) gastrointestinal damage due to the collagen vascular disease itself; 2) adverse events caused by pharmacotherapies; or 3) gastrointestinal infections following immunosuppression due to corticosteroid (CS) administration. The first group includes lupus enteritis and protein-losing gastroenteropathy in systemic lupus erythematosus (SLE), reflux esophagitis, chronic intestinal pseudo-obstruction, and pneumatosis cystoids intestinalis in systemic sclerosis, amyloidosis in rheumatoid arthritis, bowel ulcer and bleeding in rheumatoid vasculitis and microscopic polyangiitis, and ileocecal ulcer in Behcet disease. In particular, colonic ulcers associated with SLE represent refractory lesions resistant to CS. Analysis of reported cases showing colonic lesions with SLE (22 cases in Japan) revealed that mean duration of SLE was 9.9 years and 77% of colonic lesions were observed in the rectum and sigmoid colon. Half of the patients developed intestinal perforation or penetration, and 6 of the 11 patients with perforation died. The second group includes lesions in the small and large intestine due to nonsteroidal anti-inflammatory drugs (NSAIDs) and CSs, in addition to peptic ulcers. As perforation in CS-treated patients displays relatively high incidence with poor prognosis, careful attention to such complications is needed. The third group includes candidal esophagitis and cytomegalovirus (CMV) enteritis. Prompt diagnosis is required to prevent colonic bleeding and perforation due to CMV.

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Treatment of opportunistic infections emerging in collagen diseases is very important as well as the therapy of original diseases. Lung tuberculosis, Pneumocystis carinii and lung fungal infections are main opportunistic infections. There is effective prophylaxis against them, though the cases for their administration should be carefully chosen because of their adverse effects. We have administrated INH and ST (Sulphomethoxazole and Trimethoprim) more than 15 years as the prophylaxis against tuberculosis and P. carinii to the cases who are treated more than 60 mg of prednisolone per day as an initial dose until less than 30 mg per day and completely succeeded. Infliximab treatment has been reported that it often induces tuberculosis in abroad and lots of occurrence was anticipated in Japan where high incidence of tuberculosis is observed. So far, however, there are only few patients, maybe due to the selection of the patients and actively utilizing prophylaxis.

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A 62-year-old man was admitted to our hospital because of retrosternal burning pain and high fever in May, 2002. In 1995 chronic hepatitis C was diagnosed. Five years before admission he had been suffering from recurrent oral aphthous ulcers and genital ulcers. Distal scleroderma developed and the diagnosis of systemic sclerosis was made by skin biopsy in 1999. Prednisolone therapy, 5∼30 mg/day, had been administered since then. In May 2000, he was referred to our department, and diagnosis of incomplete-type Behçet’s disease was made because he had erythema nodosa, oral aphthous ulcers and genital ulcers. Asymptomatic mild pancytopenia was also found. In November 2000, gastrofiberscopy revealed that he had esophageal and gastric ulcers resistant to regular treatment and was diagnosed as entero-Behçet’s disease, a subtype of the disease. The activity of esophageal and gastric ulcers was resistant to the low dose glucocorticoid and more than a moderate dose (30 mg/day) of prednisolone was necessary to reduce the activity. His gastrointestinal symptoms fluctuated with low dose prednisolone. Gastrofiberscopy on admission revealed that he had four shallow active oval ulcers in the middle-lower esophagus and distinct blind-fistula in the lower esophagus. Prednisolone were increased to 30 mg/day for his active entero-Behçet’s disease, however, his burning retrosternal pain remained. He died on the 81 st hospital day due to severe pneumonia. This is a rare case of Behçet’s disease complicated with esophageal ulcers, systemic sclerosis, chronic hepatitis C, and pancytopenia. Of interest is the mechanism of coincidence of these diseases from the pathological point of view.

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A 64-year-old woman was diagnosed as having rheumatoid arthritis in 1999 at a nearby hospital. She had been treated with etodolac, actarit, mizoribine (MZ) and prednisolone. On May 25, 2001, she noticed fever and nausea and was treated with diclofenac sodium and clindamycin. On May 31, a nasal bleeding, tarry stool, hyperuricemia, renal dysfunction and thrombocytopenia developed and she was admitted to our hospital. Administration of drugs except prednisolone was stopped and hemodialysis was carried out on June 1. Fever and nausea improved during several days. Hyperuricemia and renal dysfunction disappeared on June 11. The platelet count became normal after platelet transfusion and she was discharged from our hospital on July 2. She was also diagnosed as having Sjogren’s syndrome. In our case, a delay in MZ discharge by transient renal dysfunction might have caused a hyperuricemia, following an aggravation of renal dysfunction. So, care should be taken about latent renal dysfunction during the use of MZ. Moreover, it may be necessary to consider a discontinuation of MZ and administration of hemodialysis in the case of transient renal dysfunction.

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A 69-year-old man visiting our hospital with an epigastralgia and tarry stool was diagnosed as having Behçet’s disease on the basis of repetitious aphthous stomatitis, erythema nodosum and arthralgia in 1991. The next year, he suffered from double active ulcers in the antrum of the stomach, and he had been operated on for intestinal perforation. In 1994, endoscopic examination revealed the gastric mucosal bridge between the double ulcers. The double ulcer healed after an eradication therapy of H. pylori, but the gastric mucosal bridge has remained there on the gastrointestinal endoscopy. The gastric mucosal bridge with Behçet’s disease has not been reported in Japan, being considered to be very rare.

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