Myalgia in Patients with Dermatomyositis and Polymyositis Is Attributable to Fasciitis Rather Than Myositis: A Retrospective Study of 32 Patients who Underwent Histopathological Examinations.

OBJECTIVE: To determine the association between fasciitis and the clinical variables in patients with dermatomyositis (DM) and polymyositis (PM). METHODS: We retrospectively reviewed the medical records of 32 patients (24 DM, 8 PM) with newly diagnosed DM and PM and in whom fascia and muscle specimens were histopathologically examined. The relationship between fasciitis and the clinical variables was statistically analyzed. These included age, sex, myalgia, muscle weakness, creatine kinase (CK) and aldolase activities, anti-Jo1 antibody, interstitial lung disease, and malignancy. RESULTS: Twenty (62.5%) of the 32 patients who underwent the histopathological examination of a fascia specimen had fasciitis, including 18 (75%) of 24 patients with DM and 2 (25%) of 8 patients with PM. The frequency of fasciitis was significantly higher among the patients with DM than among the patients with PM (p < 0.05). Histopathologically, fasciitis in PM was very mild in comparison to that in DM. The frequency of myalgia in patients with fasciitis was significantly higher than that in patients without fasciitis (p < 0.05). However, myalgia was not associated with myositis. There were no significant differences in the patients with and without fasciitis in age, sex, manual muscle test 8 scores, CK or aldolase activities, or the presence of anti-Jo1 antibodies and malignancy. CONCLUSION: The frequency of fasciitis was significantly higher among patients with DM than among those with PM. Fasciitis, rather than myositis, was associated with myalgia.

Brief Report: Power Doppler Ultrasonography for Detection of Increased Vascularity in the Fascia: A Potential Early Diagnostic Tool in Fasciitis of Dermatomyositis.

OBJECTIVE: We previously demonstrated that fasciitis is a common lesion of dermatomyositis (DM) that is detectable early after disease onset by en bloc muscle biopsy combined with magnetic resonance imaging (MRI). Power Doppler ultrasonography (PDUS) is a useful method for detection of inflammation and vascularity in rheumatic diseases. We undertook this study to determine whether fasciitis was detectable by PDUS in patients with DM. METHODS: We prospectively evaluated 7 patients with DM and 7 patients with polymyositis (PM) for the detection of fasciitis with PDUS. MRI and PDUS were both performed in all patients. Fasciitis was histologically confirmed by en bloc biopsy. RESULTS: Among all patients with DM, 4 showed signs of fasciitis on MRI, while increased blood flow signals were observed along the fascia by PDUS in 6 DM patients, including 4 patients with early disease (<2 months after the onset of muscle symptoms). Histologically, significant fasciitis was confirmed in 4 patients with DM. In the remaining 3 patients with DM, significant fasciitis was not evident histologically, but mild proliferation of capillaries and mild inflammation were notable in the area of the fascia. Immunohistochemical staining for CD31 indicated abnormal neovascular proliferation in the fascia in patients with DM. None of the PM patients showed signs of fasciitis or increased vascularity by MRI, PDUS, or en bloc biopsy. CONCLUSION: In our limited population, PDUS was useful for the detection of fasciitis associated with DM, especially in the early stage of disease. The increased blood flow signal as detected by PDUS is involved in angiogenesis accompanying fasciitis in patients with DM.

[A case of abortive type of Heerfordt syndrome associated with paralysis of trigeminal nerve].

We report a 39-year-old female admitted for fever. She showed physical findings of bilateral granulomatous uveitis, swelling of the bilateral parotid glands, and paralysis of the left second branch of the trigeminal nerve. Her chest X-ray showed evidence of bilateral hilar lymphadenopathy. We performed biopsy of her parotid gland, and leading to a diagnosis of noncaseating epithelioid granuloma characterized by lymphocyte and multinucleated giant cell invasion. Therefore, she was diagnosed with the abortive type of Heerfordt syndrome which is a subtype of sarcoidosis. This is the only case associated with paralysis of the trigeminal nerve without paralysis of facial nerves to be reported in Japan.

Fasciitis as a common lesion of dermatomyositis, demonstrated early after disease onset by en bloc biopsy combined with magnetic resonance imaging.

OBJECTIVE: To investigate whether fasciitis is histopathologically demonstrable in patients with dermatomyositis (DM), and to analyze the process of inflammatory progression in myopathy accompanying DM. METHODS: STIR or fat-suppressed T2-weighted magnetic resonance imaging (MRI) and en bloc biopsy were performed in 14 patients with newly diagnosed adult-onset DM. The severity of inflammatory cell infiltration around the fascial and intramuscular small blood vessels was evaluated using the total vascular inflammation score (TVIS). RESULTS: In all patients, MRI revealed abnormal hyperintensity in the fascia and in marginal sites of the muscle, predominantly over central sites. En bloc biopsy revealed the presence of fasciitis in most of the patients, as shown by inflammatory infiltrates around the fascial small blood vessels. In those patients who underwent en bloc biopsy earlier than 2 months after the appearance of muscle symptoms, the TVIS of the fascia was significantly higher than the TVIS of the muscle. In contrast, in those patients who underwent en bloc biopsy >2 months after muscle symptom onset, the TVIS of the fascia did not differ significantly from the TVIS of the muscle. CONCLUSION: Fasciitis was histopathologically demonstrated in patients with newly diagnosed adult-onset DM as early as 2 months after the onset of muscle symptoms. These results indicate that fasciitis is a common lesion of DM and suggest that the fascial microvasculature is the primary site of inflammatory cell infiltration in DM. Fasciitis may contribute to muscle symptoms in patients with DM without myositis.

Clinical significance of serum levels of vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 in patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the clinical significance of serum levels of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), and angiopoietin-2 (Ang-2) in patients with rheumatoid arthritis (RA). METHODS: The subjects were 70 patients with RA. Serum VEGF, Ang-1, and Ang-2 levels were determined by ELISA. As indices of disease activity, serum levels of C-reactive protein (CRP) and matrix metalloprotease (MMP)-3 were examined, and the 28-joint count Disease Activity Score (DAS28)-CRP was calculated. Power Doppler ultrasonography was performed in the bilateral wrists, elbows, shoulders, knees and ankles. The synovial blood flow signals were scored using a 3-grade scale (0-2), and the total of the scores in the 10 joints was regarded as the total signal score (TSS). RESULTS: Serum VEGF level showed significant correlations with serum CRP and MMP-3 levels, DAS28-CRP, and TSS. Serum Ang-1 level showed significant correlations with serum MMP-3 level and DAS28-CRP. Serum Ang-2 level showed significant correlations with serum CRP level and TSS. CONCLUSION: The serum VEGF level is important as an index of the activity of RA based on angiogenesis and a prognostic factor regarding joint destruction. Serum Ang-1 level may be useful as an index of sustained arthritis based on the maintenance of newly formed vessels. Serum Ang-2 level may reflect a state of marked angiogenesis.

[Onset of modified measles after etanercept treatment in rheumatoid arthritis].

Treatment with corticosteroid and etanercept was started for a 69-year-old woman with rheumatoid arthritis. Eight weeks later, she developed fever and anorexia, and was admitted to our hospital with a poor general condition. With the suspicion of bacterial infection, antibiotic treatment was started on the first hospital day, but was ineffective. From the fourth hospital day, multiple generalized, partially confluent, erythematous papules appeared. To exclude viral infection, we measured antibody titers against various viruses, and found that the levels of anti-measles IgG and IgM antibodies were elevated, which led to a diagnosis of modified measles. During the course of measles, she developed severe leukopenia, and bone marrow aspiration revealed bone marrow suppression. This was considered to be due to measles infection, leading to a diagnosis of severe modified measles. This is the first case report of modified measles which developed during the use of an anti-TNF-alpha preparation, and suggests that immunosuppression induced by the preparation may play a role in measles reinfection and its aggravation.

Elevation of Bombina variegata peptide 8 in mice with collagen-induced arthritis.

BACKGROUND: Bombina variegate peptide 8 (Bv8) is a small protein secreted by frog skin. Recently it has been shown to contribute to tumor angiogenesis in mouse model. The purpose of this study was to investigate Bv8 in mice with type II collagen-induced arthritis (CIA). METHODS: We induced CIA in male DBA/1J mice. The severity of arthritis was evaluated based on an arthritis score. RNA was extracted from the joint, and examined for Bv8 mRNA expression by RT-PCR and real-time RT-PCR. Synovial tissue and bone marrow were immunohistochemically examined using anti-Bv8 antibody. RESULTS: The level of Bv8 mRNA expression in the joint was below the detection limit in the control group, but was elevated in the CIA group, and was correlated with the arthritis score. In addition, an increase in Bv8-positive cells was observed in the synovium and bone marrow in the CIA group. CONCLUSION: Bv8 was elevated in the synovium and bone marrow of CIA mice, suggesting that Bv8 plays an important role in the pathogenesis of arthritis.

Pneumomediastinum in dermatomyositis itself is not a poor prognostic factor: report of a case and review of the literature.

We describe a 38-year-old man who presented with proximal muscle weakness, myalgia, polyarthralgia, and skin rash and was diagnosed as having dermatomyositis (DM). The patient's symptoms improved with prednisolone therapy. However, myopathy relapsed and pneumomediastinum with subcutaneous emphysema developed. Pneumomediastinum with subcutaneous emphysema rapidly disappeared by the administration of ciclosporin. We reviewed the present case and previously reported cases regarding the clinical characteristics. All of the reported death cases were accompanied by interstitial lung disease (ILD). Although it has been reported that pneumomediastinum in DM can be fatal, the direct cause of patient's death was due to respiratory failure resulting from progressive ILD. Pneumomediastinum without ILD shows a good prognosis.

Pancytopenia, including macrocytic anemia, associated with leflunomide in a rheumatoid arthritis patient.

A female rheumatoid arthritis patient was admitted for productive cough and general fatigue that had gradually developed after leflunomide therapy. Side effects including severe hypoxia, thrombocytopenia, lymphocytopenia, and macrocytic anemia with schistocytes (probably drug-induced megaloblastic anemia) were noted. Leflunomide-eliminating cholestyramine therapy successfully treated all conditions excluding severe hypoxia, which occurred owing to deteriorating interstitial pneumonia and complicated bacterial pneumonia following antibiotic treatment. This is a rare case of leflunomide-associated multiple hematopoietic impairments.

Decreased numbers of signal-joint T cell receptor excision circle-containing CD4+ and CD8+ cells in systemic lupus erythematosus patients.

Systemic lupus erythematosus (SLE) patients have a decreased number of peripheral blood T cells containing signal-joint T cell receptor excision circles (Sj TRECs), which are considered an indicator of thymic output. The objective of this study was to investigate the mechanism of the decrease in such T cells. Peripheral blood T cells from SLE patients were classified into CD4+ and CD8+ cells. Sj TREC levels were measured by real-time PCR. Telomerase activity was determined by the telomeric repeat amplification protocol assay. The numbers of Sj TREC containing CD4+ and CD8+ cells were lower in the peripheral blood of SLE patients than in the controls. A correlation was found between the numbers of Sj TREC-positive CD4+ and CD8+ cells. The level of TRECs is influenced by an increase in cell division. To examine this increase, telomerase activity as an indicator of cell division was measured simultaneously; however, there was no correlation between the Sj TREC level and telomerase activity. These results suggest that decreased thymic output occurs in SLE patients.

A case of pure red cell aplasia complicated by Evans syndrome.

A 33-year-old woman complaining of severe anemia was admitted to our hospital for polyclonal hyperglobulinemia. She was diagnosed with pure red cell aplasia (PRCA) associated with Evans syndrome. Initially, the presence of human parvovirus B19 (HPV B19) IgM appeared to indicate that the cause of PRCA was HPV B19 infection. Evans syndrome improved with steroid therapy, but PRCA was refractory. Cyclosporine was administered; consequently, the patient markedly recovered from PRCA and was discharged. PRCA complicated by Evans syndrome occurred during the course of polyclonal hyperglobulinemia. The most direct etiology for the onset of PRCA was unclear; however, immunological disorders such as polyclonal hyperglobulinemia, in addition to HPV B19 infection, may have been partly responsible for the etiology of PRCA.

Cryofibrinogenemia associated with Sjögren's syndrome: a case of successful treatment with high-dose corticosteroid.

Cryofibrinogenemia (CF) has not been often reported as a complication of various rheumatic diseases. We describe a 44-year-old woman with CF associated with Sjögren's syndrome (SS), who developed digital necrotic ulcerations and purpura of the lower legs. Cryoprecipitate was detected in her plasma, and immunoelectrophoresis showed that the cryoprecipitate was cryofibrinogen. Alprostadil was intravenously administered, but the ulceration was aggravated. Subsequently, administration of high-dose prednisolone (PSL) at 60 mg/day was started, and the ulceration remarkably improved. Cryofibrinogen, detected before the administration of high-dose PSL, was negative after PSL. This is the first case presentation of CF associated with SS successfully treated with high-dose corticosteroid.

Abnormal telomerase activity and telomere length in T and B cells from patients with systemic lupus erythematosus.

OBJECTIVE: To evaluate the clinical significance of telomerase activity and telomere length in T and B lymphocytes from patients with systemic lupus erythematosus (SLE). METHODS: CD3+ (T cell) and CD19+ (B cell) lymphocytes were isolated from the peripheral blood of SLE patients and healthy controls by means of magnetic bead-coupled antibodies. SLE patients were classified as active or inactive cases according to the SLE Disease Activity Index (SLEDAI). Telomere activity of lymphocytes was measured by telomeric-repeat amplification protocol. Telomere length was measured by flow cytometry-fluorescence in situ hybridization. RESULTS: T cell telomerase activity was significantly higher in patients with both active and inactive SLE than in controls, but was lower than B cell telomerase activity in patients with active SLE, and was not correlated with SLEDAI results. B cell telomerase activity was only significantly higher than in controls in patients with active SLE, and was strongly correlated with SLEDAI. Four laboratory results, anti-dsDNA antibody titer, IgG level, C3 level, and CH50 level, were correlated with B cell telomerase activity. Telomere length in T cells was significantly shorter than in controls. In contrast, the telomere length in B cells did not differ significantly from controls. CONCLUSION: In patients with SLE, many T cells divide continuously. Their telomerase activity was higher than that in control T cells, but not so high as to prevent telomere shortening. In contrast, B cells do not divide abnormally in the inactive phase of SLE, but divide rapidly in the active phase.

Kinetics of circulating endothelial progenitor cells in mice with type II collagen arthritis.

OBJECTIVE: To examine the significance in arthritis of circulating endothelial progenitor cells (cEPCs) reportedly increasing in neovascularization. METHODS: Arthritis was induced by immunizing DBA/1J mice with bovine type II collagen on day 0. Age-matched normal DBA/1J mice were used as controls. Blood was collected from these mice on days 7, 14, 21, 28, and 35. Peripheral blood CD45-, CD34+, Flk-1+, CD117+ cells were regarded as cEPCs (Flk-1=vascular endothelial growth factor receptor 2). The number of cEPCs per 100 CD45+ cells was calculated by four-color flow cytometry, and compared with the arthritis score. RESULTS: Arthritis developed about 3 days after booster immunization (day 21). On days 7, 14, and 21, no difference in cEPCs/100 CD45+ cells was noted between the arthritis and control groups. On days 28 and 35, cEPCs/100 CD45+ cells in the arthritis group were significantly greater in number than those in the control group. cEPCs/100 CD45+ cells on day 28 were greater in number than those on day 35. On day 28, a correlation was found between cEPCs/100 CD45+ cells and arthritis score. CONCLUSION: In mice with type II collagen-induced arthritis, an increase in cEPCs was associated with the onset of arthritis. The number of cEPCs was greater during the development and progression of arthritis than that at the time of its establishment, suggesting that cEPCs are involved in the pathogenesis of arthritis.

Two cases of adult Still's disease with abnormally high level of telomerase activity in peripheral blood mononuclear cells.

We report two patients with adult Still's disease with an abnormally high level of telomerase activity. The first patient was a 61-year-old woman. The mean telomerase activity value for peripheral blood mononuclear cells of healthy adults measured by our method was 0.13 +/- 0.03, whereas that in this patient during the active phase was abnormally high, at more than 27.56. The patient was treated by steroid therapy and successfully brought into remission, during which the telomerase activity value for peripheral blood mononuclear cells was reduced to 2.22. The second patient was a 19-year-old man. Although he stayed in remission after steroid therapy, a reduction in the steroid dose resulted in recrudescence, at which time the telomerase activity value peripheral blood mononuclear cells was high, at 11.76. Elevated levels of telomerase activity have been reported in patients with various pathological conditions other than malignant tumors. However, our literature search failed to reveal a report on such a high level of telomerase activity in association with a benign disease.

Telomerase activity and telomere length of peripheral blood mononuclear cells in SLE patients.

We evaluated the clinical significance of the telomerase activity and telomere length of peripheral blood mononuclear cells (PBMC) in systemic lupus erythematosus (SLE). PBMC were isolated from 55 patients with SLE and the telomerase activity was measured by TRAP assay. The telomere length of PBMC was also measured in 30 of these subjects. As a control group, 45 healthy adults with no particular clinical history were studied. The results were compared with clinical data. In patients with active SLE, the telomerase activity of PBMC was significantly increased compared with the control group. In patients with inactive SLE, the PBMC telomerase activity was not different compared with the controls in their 20s, 30s and 40s, but it was significantly increased compared with the controls in their 50s. In SLE patients, the telomerase activity of PBMC was significantly correlated with modified SLEDAI. The telomere length of PBMC in younger SLE patients tended to be shorter than that in the controls, but no difference was observed in older patients. The correlation coefficient between the telomerase activity and telomere length of PBMC in SLE patients was not significant. Abnormalities in the telomerase activity and telomere length observed in SLE patients are considered to be important findings for evaluation of the pathology of SLE.