Purpose and Methods
We investigated the relationship of the presence or absence of sleep disorder (awakeness that patients remembered)with blood sedimentation, a depression test (Zung’s self-rating depression scale, SDS), C reactive protein (CRP), and MHAQ in 207 patients with rheumatoid arthritis (RA) (32 males, 175 females), with a mean age of 58.3 years. We employed the values of blood sedimentation and CRP obtained within 1 month1from the date of this survey (mean: 11 days). Results
In patients with night awakeness, the blood sedimentation value was higher than that in those without night awakeness (57.1±35.4 vs. 47.5±30.2). The values of CRP (mg/dl) (2.71±3.05 vs. 1.69±2.02), SDS (39.5±8.3vs.34.4±8.4), MHAQ (6.8±6.8 vs. 3.6±4.5), and VAS (4.22±2.55 vs. 3.38±2.32) were significantly higher (p＜0.05). In addition, the frequency of night awakeness was classified: once, twice, and 3 times or more. In patients reporting a frequency of 1, the SDS score was significantly higher than that in patients without night awakeness. In those reporting a frequency of 2, the SDS and MHAQ scores were significantly higher, and in those reporting a frequency of 3 or more, the SDS, MHAQ, VAS, and face scale scores were significantly higher.
In patients with depression, the MHAQ, VAS, and face scale scores were significantly higher than the values in those without depression. However, there were no significant differences in blood sedimentation or CRP. Among the patients with night awakeness, in those who reported that they had awakened due to night pain, the blood sedimentation, CRP, MHAQ, VAS, and face scale values were higher than the values in those without night pain. In the group with night awakeness, excluding patients with night pain, the CRP level was higher than that in the group without night awakeness, although there was no significant difference. The SDS and MHAQ scores were significantly higher.
The results of this study suggest that sleep disorder is related to RA-related pain, depression, and RA activity. Few studies have reported the relationship between RA and sleep disorder. In the future, this issue should be further investigated.
We evaluated the effects of fasting on symptoms in 15 fibromyalgia syndrome (FMS) patients and 6 rheumatoid arthritis (RA) patients over 10 days in an open, non-randomized, controlled study. The results revealed significantly greater improvement (p＜0.05) in the visual analogue scale (VAS) of pain in the 13 out of 15 FMS patients who completed the fasting versus the 6 RA patients in the10 days duration.
Both groups reduced in body weight with a significant average loss of 5 kg (p＜0.01) respectively. The appearance of Ketone bodies in urine did not seem to affect the level of pain reduction. Obviously, the VAS score of the RA group showed a different pattern in the10days duration compared to the FMS group.
The RA group showed a relatively “straight line pattern”. That is within the10 days, relatively insignificant fluctuation in the VAS was observed within the entire group. On the other hand, almost every one in the FMS group showed a “fluctuated line pattern” of aggravation, and after that the VAS score rapidly decreased. As a marked decrease in the VAS score occurred when starvation appeared, it suggested the sensation of starvation played an important role in the disappearance of bodily pains with the FMS group.
It is therefore concluded that fasting therapy has a beneficial effect on FMS symptoms, as compared to the insignificant effect on RA symptoms, at least in a short period such as 10 days.
We studied on the health status of the patients with juvenile rheumatoid arthritis into adulthood, using long-term follow-up study by self-assessment questionnaire. We examined clinical and functional outcomes, but also socio-economical status, including educational level, marital status, and orthopedic intervention. Eighty patients answered the questionnaire, but 17 cases in this group had been died. Almost all cases have showed polyarticular manifestation at the time of follow-up, but 13 cases have continuded oligoarticular manifestation. In all cases, the average age of disease onset was 10.47 years. The average age of cases at the time of folow-up is 38.0 years old. In general, the outcome of juvenile rheumatoid arthritis is better than that of adult―onset rheumatoid arthritis, but some cases who continues persistent disease activity into adulthood show severe disability and handicap of living activities. However educational level and marital status are not worse than that of the general population. In marital cases pregnancies generally have a good outcome. However, a flare of disease often appeare after delivery. The risk for a postpartum flare may be present in the patients with drug treatment at the onset of pregnancy. There seem to be correlation between the incidence of postpartum flare of disease and the activity of disease at conception. Concernig major surgical intervation, half of cases have undergone one or more total hip replacemant, or total knee replacement for improving of functional disabilities in adulthood. Cause of death for 13 cases have ascribed to various complications. Only 2 cases with secondary amyloidosis have proved by autopsy.
Further research by a more accurate follow-up study of outcomes of juvenile rheumatoid arthritis patients is required.
A 42-year-old woman was admitted to our hospital because of skin ulcers and an arthritis. She had been suffered from rheumatoid arthritis (RA) since she was 18 years old. Disease activity of RA increased in October, 2001. Neuropsychiatric symptoms such as mood fluctuations and cognitive deficit presented and deteriorated in June, 2002. Based on clinical features and immunologic tests, she was diagnosed with overlap syndrome of RA and systemic lupus erythematosus (SLE) with various clinical conditions such as hemophagocytic syndrome, skin ulcersdue to vasculitis, and CNS lupus. The disease activity of SLE decreased and confusion diminished with the application of the steroid therapy, but schizophreniform disorder, cognitive dysfunction, memory disturbance, and cognitive deficit did not improve. The treatment was changed to a combination therapy of steroid, azathioprine, immune adsorption, and intrathecal injection with methotrexate plus dexamethasone. CNS lupus was markedly improved by these combination therapies. We also demonstrated the utility of CNS lupus markers such as IL-6, anti-neuronal cell antibody, anti-ribosomal P antibody in serum and cerebrospinal fluid. Anti-neuronal cell antibody in cerebrospinal fluid was useful in this case. There have been a few reports of intrathecal methotrexate plus dexamethasone injection therapy for CNS lupus. Based on the information obtained in this case, we discussed the efficacy of immunosuppressive therapies including intrathecal injection and the method for evaluating disease activity in CNS lupus.
A 55-year-old Japanese woman with four years history of rheumatoid arthritis (RA) developed muscle weakness, and showed skin ulcers and ischemic colitis. Her renal function was within the normal range except for relatively severe proteinuria. Her serum showed positive results for proteinase 3 (PR3)-anti-neutrophil cytoplasmic antibody (ANCA), but she did not fulfill the diagnostic criteria of ANCA-associated vasculitis syndromes, such as microscopic polyangiitis, Wegener’s granulomatosis, and allergic granulomatous angiitis. Thus, the diagnosis of malignant rheumatoid arthritis (MRA) was made also considering the low level of serum complements. Steroid pulse therapy was not effective, and she developed the perforation of rectum, and died of the subsequent sepsis. Autopsy findings revealed old vasculitis lesions with little inflammatory cell infiltration predominantly showing the destruction of vascular wall structure with following fibrosis, mainly involving small muscular arteries in heart, gastrointestinal tracts, mesenterium, liver, gallbladder, both ovaries and retroperitoneal adipose tissue. Peripheral nerve tissues in the psoas major muscle, however, showed edema, and still exhibited the vascular lesions with active inflammatory cell infiltration. Up to 3% of renal glomeruli showed crescentic glomerulonephritis with the slight deposit of IgM, Clq and C3, revealed with immunohistochemistry. In addition to RA complicated with ANCA-associated vasculitis syndromes, ANCA is sometimes detected in patients of MRA. However, myeloperoxidase-ANCA is almost exclusively detected in such cases, and, as for the cases positive for PR3-ANCA, only one case of histologically proven rheumatoid vasculitis and two cases of RA complicated with Wegener’s granulomatosis have been reported in Western countries. The current case is the first Japanese case of MRA positive for PR3-ANCA.
A 42-year old man with a 13-year history of rheumatoid arthritis (RA) was treated with oral administration of methotorexate and predonisolone, and activity of RA decreased.
From 2003, he was started on anti-TNF-alfa (Infliximab) treatment because of a decreased response to methotrexate and predonisolone. Polyarthralgia decreased after Infliximab administration but arthralgia of bilateral shoulder joints still continued. X-ray findings revealed erosive lesion at both humeral heads and narrowing of the joint space. MRI revealed erosive changes at the humeral head and the glenoid but neither rotator cuff degeneration nor synovitis at the sub acromial bursa were seen.
In 2005 and 2006, the patient underwent arthroscopic synovectomy of left and right shoulder joints, respectively under general anesthesia. Mild inflamed and hyperplastic synovium and fibrous tissue in the shoulder joint were removed as much as possible using a shaver and YAG laser and the joint was irrigated with 5 liters of saline. Arthralgia of shoulder joints was soon reduced, and the range of motion of the shoulder joint was improved to a normal level one to two weeks after the operation. He returned to work one month after the operation.
In early stages of RA shoulder, synovectomy is an effective way to relieve pain and improve the range of motion, and can save time for implant arthoplasty. Arthroscopic surgery has a minimum degree of invasiveness and enables the patient to return to work. However, preoperative existence of the degeneration of articular cartilage or rotator cuff deficiency will worsen the post operative course.
A 42-year-old female developed sore throat and high-grade fever in the beginning of May 2005. Antibiotic therapy was not effective for her symptoms, so she was transferred to our hospital. On admission day, we found erythema nodosum and marked by elevated CRP (21.0 mg/dl) and erythrocyte sedimentation rate (130 mm/hr), accompanying severe anemia (Hb 8.4 g/dl). All the immunological tests including antinuclear antibodies, rheumatoid factor, MPO-ANCA were negative while ASO was marked by elevates. The urinalysis was normal. By an abdominal angiography, we found both partial stenosis and dilation in upper mesenteric artery. A diagnosis of polyarteritis nodosa (PN) was made. After 40 mg daily prednisolone therapy, her symptoms and the abnormal laboratory data have recovered in a short period. We consider that this is a kind of rare case of adult PN, which developed in association with preceding acute streptococcal infection.
A 64-year-old man was diagnosed with MPO-ANCA-related systemic vasculitis in March, 2004, because of multiple mononeuropathies, an interstitial pneumonia, a rapidly-progressive glomerulonephritis which was demonstrated by a biopsied-specimen from kidney. High dose intraveneous methylprednisolne bolus-therapy following an oral prednisolone were transiently effective. In August, 2004, the serum level of MPO-ANCA elevated again, and a macular purpura appeared in both arms. A hundred mg/day of oral cyclophosphamide was added to the prednisolone. In February, 2005, he was re-admitted to our hospital because of muscle weakness of extremities mainly in the left arm and leg. Laboratory examination showed a pancytopenia, high serum levels of ferritin (more than 3000μg/ml) and of MPO-ANCA. Bone marrow-aspirated smear showed a number of hemophagocytosis by macrophages. His general status worsened with continuous pyrexia and a decreased level of consciousness. He died in April, 2005, in spite of the treatments including several antibiotics and anti-fungal agents. An abscess formation in the right frontal lobe demonstrated by the autopsy seemed to be responsible for his final outcome. Histologically, the narrowing of lumen and thickening of small vessels in several organs such as kidneys and lungs were observed.
In this case, the serum levels of cytokines such as INF-γ, TNF-α, which play an important role for the pathogenesis of hemophagocytic syndrome were undetectable. On the other hand, the serum levels of IL-6, IL-10 and soluble IL-2 receptor were high. These cytokine profiles were compatible with those in compensatory anti-inflammatory response syndrome (CARS) which reflects a cachexic condition but not systemic vasculitis nor hemophagocytic syndrome.