A 78-year-old man visited a hospital with a complaint of painful and swelling scrotums for 7 months. Although left epididymitis was suspected, antibiotic and non-steroidal anti-inflammatory drugs (NSAIDs) had no effects. After visit to our department, we performed left orchiectomy for the diagnosis and pain control. Pathological examinations showed necrotizing vasculitis in the epididymis, so he was diagnosed as polyarteritis nodosa (PN) in the left epididymis. He had no systemic symptoms, which made the diagnosis of isolated PN. One and a half years after operation, he felt the same pain in the right scrotum. We performed right orchiectomy. Pathological findings showed necrotizing vasculitis in the epididymis. Blood examinations revealed negative for myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA) and proteinase 3-ANCA, and computed tomography revealed that other organs were not involved. One year later, he had no recurrence.
We report the case of a 71-year-old Japanese woman with adult-onset Still's disease (AOSD) in whom macrophage activation syndrome (MAS) developed despite therapy with oral high-dose prednisolone and intravenous methylprednisolone pulse therapy twice. She was successfully treated with tocilizumab (TCZ). Soon afterward, her fever ceased and high levels of both ferritin and C-reactive protein levels decreased. Her course was complicated by disseminated intravascular coagulation, cytomegalovirus infection, and Pneumocystis jirovecii pneumonia. After these were resolved, AOSD-associated MAS was well controlled. She was discharged on hospital day 87. Although biologics such as TCZ are becoming established for the treatment of AOSD, there is no recommended therapy for AOSD-associated MAS. Several biologics have been tried for this complication, but their efficacy and safety remain controversial. We reviewed reported cases of AOSD-associated MAS successfully treated with various biologics. TCZ initiation after adequate nonselective immunosuppressive therapy, such as methylprednisolone pulse therapy or a prednisolone-based combination of immunosuppressants, can be an effective treatment for AOSD-associated MAS. On the other hand, biologics given after insufficient immunosuppressive therapy may cause MAS. A strategy combining adequate immunosuppression and a biologic could be safe if special attention is given to adverse events such as opportunistic infections or biologic-associated MAS.
To address whether the gamma haplotype at exon 3 of the SAA1 gene is directly associated with type AA amyloidosis or is merely in linkage with an unknown polymorphism that is primarily associated with disease risk, we examined the SAA1 gene for new polymorphisms.We analyzed DNA samples from 44 rheumatoid arthritis (RA) patients with AA amyloidosis (amyloid group), 55 RA patients without AA amyloidosis (RA group), and 58 non-RA healthy subjects (non-RA group). We also examined DNA samples from 50 Caucasians to compare linkage disequilibrium relationships involving SAA1 region polymorphisms between Japanese and Caucasoid populations.We observed 3 novel single-nucleotide polymorphisms (SNPs) in the 5'-flanking region of SAA1: -61C/G, -13T/C, and -2G/A. Comparison of allele frequencies and ratios of individuals with particular alleles between the study groups revealed statistically significant differences between the amyloid and RA groups and between the amyloid and non-RA groups. Statistical analysis revealed that the -13T/C SNP was strongly associated with AA amyloidosis. In addition, we found tight linkage between the -13T allele and the alpha haplotype, rather than the beta haplotype, at exon 3 in the Caucasoid population, while -13T was closely linked to the gamma and beta haplotypes, rather than the alpha haplotype, in the Japanese population. Since the linkage disequilibrium relationship was reversed between the Japanese and Caucasoid populations, different exon 3 haplotypes of SAA1 are found to be associated with the risk of AA amyloidosis in different ethnic groups.Our data suggest that the SAA1 -13T allele, rather than SAA1 exon 3 haplotypes, is primarily associated with AA amyloidosis risk.
Peripheral polyneuropathy and the complication of eosinophilic fasciitis (EF) is rare; only 2 such cases have been described previously. A 40-year-old woman suffered from swelling of the extremities after strenuous exercise and complained of bilateral paresthesia on the soles of her feet. The diagnosis was EF according to clinical symptoms, peripheral eosinophilia, and histological examination of the fascia. Nerve conduction tests also revealed sensory disturbance as mononeuritis multiplex. After administration of prednisolone, the swelling and tenderness of the extremities improved immediately but the neuropathy lasted for 6 months.(Internal Medicine 37: 417-420, 1998)
The optimal methotrexate dose differs between rheumatoid arthritis (RA) patients, and dose-escalation strategies also differ among rheumatologists. By taking advantage of the heterogeneous methotrexate dosing that occurs among Japanese rheumatologists, we analyzed the efficacy and safety of different methotrexate doses. A large observational cohort of RA patients, IORRA, was established in 2000. A dataset from April 2003 that included 4578 RA patients was used for a cross-sectional analysis, while a dataset of 1649 patients who received methotrexate from October 2000 to October 2005 was used for a longitudinal analysis. The cross-sectional analysis included 12 rheumatologists who prescribed methotrexate to more than 60 patients. Mean methotrexate dose ranged widely (4.8–9.0 mg/week) among rheumatologists with a significant positive relationship between average methotrexate dose and the percentage of patients with Disease Activity in 28 Joints (DAS28) scores below 3.2. During the longitudinal analysis, both methotrexate prescription frequency and the average dose prescribed by 16 rheumatologists increased. Overall disease activity as assessed by DAS28-area under the curve (AUC) and disability progression as assessed by Japanese version of the Health Assessment Questionnaire (JHAQ)-slope inversely correlated with the extent of methotrexate use. This study demonstrated that extensive methotrexate use effectively suppressed RA disease activity and inhibits disability progression. In addition, we have found that it is critical to pay attention to patient-reported adverse reactions.
