[A case of primary Sjögren syndrome with repeated purpura].

In Sjögren syndrome, purpura is one of its various well known eruptions. Although this disease state is assumed to be based on hypergammaglobulinemia, the details of its mechanism are unknown. We experienced a case involving a female patient with primary Sjögren syndrome showing repeated purpura on the legs, and examined her blood viscosity and histopathology. This girl developed Sjögren syndrome and was admitted to our hospital at 12-years-old. She underwent steroid treatment because of aggravation of the xerosis state and prominent purpura on the legs. Hypergammaglobulinemia was improved during the course; however, purpura appeared repeatedly. Although her blood viscosity was slightly higher than normal, this had no relation to purpura and serum gamma globulin values. Skin biopsy revealed necrotizing angiitis. These results suggest that the purpura of this case was caused not only by hyperviscosity from the hypergammaglobulinemia but also involvement of vasculitis by the primary disease.

[A case report of systemic lupus erythematosus patient with severe lupus retinopathy and antiphospholipid antibody].

An eleven-year-old boy with systemic lupus erythematosus (SLE) developed severe bilateral lupus retinopathy when he was in active stage of SLE. The patient, who had suffered from SLE for 3 years, was admitted to our hospital because of high grade fever, systemic lymphadenopathy, leukopenia, elevation of erythrocyte sedimentation rate and hypocomplementemia. The dose of prednisolone was increased considering he was exacerbated of SLE, however, the convulsion as CNS lupus occurred to him. After the event he noted loss of vision in his bilateral eyes. The ophthalmologic examination revealed the lesions of cotton-wool spots, retinal vessel dilatations and diffuse occlusions of the retinal arterioles and venules which were compatible with lupus retinopathy. Although the coagulation time was normal, antiphospholipid antibodies were positive at the time of ocular involvement. Careful attention should be paid to the occurrence of lupus retinopathy when the patients with SLE developed in the active stage or CNS lupus, especially they have antiphospholipid antibodies.

[Two cases with SLE and MCTD developed after a long period of chronic arthritis that was initially diagnosed as JRA].

In order to discuss the diversity of clinical features and the difficulty in diagnosis of children with juvenile rheumatoid arthritis (JRA), we present two cases who have documented the development of systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) after a long period of disease characterized only by arthritis that was initially diagnosed as JRA. The first case was a girl diagnosed for her arthritic joints as polyarticular JRA at 15 years of age. At onset, she had Raynaud phenomenon but autoantibodies such as anti-nuclear antibody (ANA), anti-DNA antibody, and rheumatoid factor were negative. Five years after onset, she became ANA positive and 3 years later she became pregnant. During her pregnancy, she became positive for anti-DNA antibody without any signs of nephritis. One month after the delivery, however, she developed butterfly rash, carditis, nephritis, and was diagnosed as SLE. No destructive changes were observed in her joints though arthritis continued for 8 years form onset to pregnancy. The second case was a 3 years old girl who was diagnosed as polyarticular JRA. Treatment by aspirin induced complate remission after one year from the onset. However, 10 years after that remission, she developed Raynaud phenomenon and arthralgia in her knees and hip joints. Her laboratory findings showed hypergammaglobulinemia, positive ANA, positive anti-DNA antibody, positive anti-RNP antibody. She was eventually diagnosed as MCTD when she was found to have polymyositis by EMG and serum CK. In the present paper, two cases imply the difficulty in diagnosing JRA and diversity of rheumatic diseases such as JRA, SLE and MCTD. Closer and longer period of observation is essential for the JRA patients with nondestructive arthritis.

Clinical features of Japanese children and adolescents with systemic lupus erythematosus: results of 1980-1994 survey.

Marked advances have been made in the past decade in the management of adults with systemic lupus erythematosus (SLE). Therefore, a nationwide retrospective survey was conducted between 1980 and 1994 to investigate the clinical manifestations of SLE in Japanese children and adolescents. Questionnaires were sent to 340 hospitals. Of 405 patients reported by 176 hospitals, 373 patients, diagnosed by the criteria established by the Pediatric Study Group of the Japanese Ministry of Health and Welfare in 1985, were enrolled in the study. Forty-nine of the 354 patients (13.8%) had relatives with a connective tissue disease within the third degree of consanguinity. The frequent manifestations in 373 patients were the presence of antinuclear antibody (98.9%), immunologic disorders (93.0%), hypocomplementemia (87.1%), malar rash (79.6%) and fever (74.0%). Lupus nephritis was present in 148 of the 309 patients (47.9%) at their first visit to a clinic, and 261 of the 373 patients (70.0%) developed renal involvement during the observation period. Of 370 patients, 92 patients (24.9%) exhibited central nervous system lupus. Of 368 patients, 192 patients (52.2%) were treated by methylprednisolone pulse therapy and 148 patients (40.2%) received immunosuppressants in combination with steroid therapy at some stage during the observation period, Survival rate at 5 years from onset was 95.9%. Management of infection, coagulopathies, and central nervous system involvement is essential to improve the prognosis of SLE in Japanese children and adolescents.

Serum levels of hyaluronic acid indicate the severity of joint symptoms in patients with systemic and polyarticular juvenile rheumatoid arthritis.

OBJECTIVE: Elevated serum levels of hyaluronic acid (HA) correlate with joint inflammation in adult rheumatoid arthritis (RA). There are no laboratory indices for specifically assessing joint inflammation. Therefore, serial measurements of HA were assessed as a possible tool for measuring the severity of arthritic symptoms in children with juvenile rheumatoid arthritis (JRA). METHODS: Serum levels of HA, measured by a sandwich assay method using HA binding protein, were correlated with the severity of joint symptoms and with laboratory test values in 71 patients with JRA, 30 children with other rheumatic diseases, and 138 children without rheumatic disease. RESULTS: Serum levels of HA showed significant correlation with the severity of joint symptoms, but not with systemic symptoms, in patients with systemic and polyarticular JRA. No other laboratory tests, including C-reactive protein and erythrocyte sedimentation rate, reflected the severity of joint symptoms. This correlation of serum levels of HA with joint symptoms was observed in patients with systemic and polyarticular JRA, but not in pauciarticular JRA, other rheumatic diseases, or nonrheumatic diseases, even when signs of arthritis were present in the latter 3 groups. CONCLUSION: Serum levels of HA are useful in objectively evaluating arthritic symptoms in patients with systemic and polyarticular JRA, and may have diagnostic value in this disease.

Acute rheumatic fever and poststreptococcal acute glomerulonephritis caused by T serotype 12 Streptococcus.

We present a rare case of a 10 year old Japanese boy with acute rheumatic fever accompanied with poststreptococcal acute glomerulonephritis. We isolated group A Streptococcus serotype T 12, a strain that was thought to be nephritogenic but not rheumatogenic, from throat culture. Although rare, physicians should be aware that acute renal disease may accompany rheumatic fever.

[Clinical features of infantile patient with juvenile rheumatoid arthritis].

Little is known about clinical features of infantile juvenile rheumatoid arthritis (JRA) because it is very rare for the patients to develop JRA within one year of age. In the past 20 years, we experienced three JRA patients whose onset was under 1 year of age. The incidence of infantile JRA was 3.2% of all JRA patients in our facility. They are 9 month-old male with systemic onset, 6-month-old female with polyarticular onset and 8 month-old female with systemic onset. It was difficult to evaluate subjective symptoms such as arthralgia or morning stiffness since the patients could not complain precisely. Therefore, careful observation on their behaviors, such as the delayed development of their motor function and bad humor and/or loss of activity in the morning, was important for evaluating joint symptoms. In case 1, measuring the serum level of hyaluronic acid was specifically useful to evaluate the arthritis. Drug therapy was not successful especially in infantile JRA. One of the reason for this ineffectiveness of drug therapy might be explained by poor adsorption of drugs in infants; the serum acetyl salicylic acid level was lower in infantile patients than the other patients with JRA even though they received enough dose of aspirin. Infantile JRA was revealed to have specific difficulties in early diagnosis and adequate treatment. Therefore, accumulated case studies about clinical features of infantile JRA is essential for their better prognosis.

Quality of life and daily management of children with rheumatic disease.

Appropriate management of the daily life of patients with rheumatic diseases is an important part of therapy for favorable results and a high quality of life. At home, gymnastic exercise, night splints and appropriate fun activities will help to preserve the function of affected joints of patients with juvenile rheumatoid arthritis (JRA). Improvement of home fixtures according to patient disability will provide a higher quality of life for the patients. The patient should be helped to perform as many school activities as would normally be possible. Instructional charts for management of school life for patients with JRA and systemic lupus erythematosus is shown in this article. Cooperation with school personnel is also crucial to support the patient emotionally and physiologically. For the best long-term treatment and a good relationship between patient and physician, comprehensive management is essential. Not only physicians, but also psychiatrists, occupational therapists, physical therapists and social workers should be involved in the treatment of children with rheumatic diseases.

Experimental studies on the initial focus of invasion of group A streptococci.

Rabbits were infected with group A streptococci type 12 by an aerosol method, that seems to resemble closely the human natural infection, in order to investigate the mechanism of invasion, especially the initial focus of invasion of streptococci. Living streptococci and FITC-labelled streptococci were exposed to several groups of rabbits, which were sacrificed and divided according to the duration after exposure. The specimens of organs were examined by light microscopy, fluorescent microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Histologically, the adherence of streptocossi was found on the pharyngeal mucosa and tonsils and the mucocilial clearance in the larynx and the trachea. Phagocytosis was also found in the bronchus and lung. By SEM, invading streptococci and cell debris-like masses were observed in the micropore of the tonsillar crypt of the rabbit. From these results it was supposed that there should be differences of tissue tropisms and defence mechanisms against streptococci among the mucosa and that micropores of the tonsillar crypts should play an important role in the initial focus of invasion of group A streptococci.

Study of antibody response to 4 streptococcal antigens in rheumatic fever and Kawasaki disease with or without cardiovascular lesions.

Patients with rheumatic fever (RF) and Kawasaki disease (MCLS) were divided into two groups, one with and the other without cardiovascular lesions, and their sera were examined for antibodies to 4 streptococcal antigens: anti-streptococcal polysaccharide (ASP), anti-deoxyribonuclease B (ADN-B), anti-streptolysin O (ASO) and anti-streptokinase (ASK) in order to clarify the relationship between group A streptococci and these two diseases. In RF the frequency of positive levels of ASP at its early stage was lower than those of the other 3 antibodies, but the ASP titer tended to persist at elevated levels. The frequency of ADN-B in patients with rheumatic heart disease (RHD) was higher than that in those without RHD, but with regard to the other antibodies no difference was found between the two. Of the 4 antibodies the frequency of at least one positive level was 100% in all the sera of RF patients within 3 months from onset. The differences in the frequencies of positive levels of all 4 antibodies in both MCLS and the controls did not prove to be significant. The frequencies of ASP, ADN-B and ASO in the sera of patients without cardiovascular lesions tended to be slightly higher than those in patients with cardiovascular lesions.

Impaired granulocyte chemotaxis and increased circulating immune complexes in Kawasaki disease.

Our study was carried out to clarify the changes in granulocyte functions and circulating immune complexes in 32 children with Kawasaki disease. Patients were divided into two groups, those with or without coronary aneurysm. In the group with coronary aneurysm, impairment of both granulocyte chemotaxis and phagocytosis was found, together with higher circulating immune complexes and normal intracellular killing activity. In the group without coronary aneurysm, impaired phagocytosis was observed, with normal granulocyte chemotaxis, circulating immune complexes, and intracellular killing activity. No correlation was observed between granulocyte chemotaxis and circulating immune complexes. Impairment of granulocyte chemotaxis and circulating immune complexes may yield pertinent information as to the degree of severity of vasculitis in Kawasaki disease.

Circulating immune complexes and granulocytes chemotaxis in Kawasaki disease.

Serum immunoglobulin levels, complement titers, circulating immune complex levels, and chemotaxis of granulocytes were evaluated in 32 patients with Kawasaki disease with or without coronary aneurysm. The group of patients with coronary aneurysm showed relatively higher levels of IgG. Regardless of the presence of coronary aneurysm, the level of IgE in the acute phase was higher than that in the convalescent phase. The level of immune complexes was higher in the group of patients with coronary aneurysm (p less than 0.05). There was a low negative correlation between immune complexes and CH50. The chemotaxis of the patients with coronary aneurysm was significantly impaired (p less than 0.01).