Early diagnosis and treatment in lupus nephritis: how we can influence the risk for terminal renal failure.
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Early Diagnosis↗
Biomedical subjects
Christoph Fiehn
Publications and source records attributed to Christoph Fiehn.
Pathologic skeletal muscle perfusion in patients with myositis: detection with quantitative contrast-enhanced US--initial results.
PURPOSE: To prospectively determine whether contrast material-enhanced ultrasonography (US) can depict inflammation-induced changes in muscle perfusion for patients suspected of having dermatomyositis or polymyositis and to compare these findings with those of magnetic resonance (MR) imaging and muscle biopsy. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Perfusion in skeletal muscles was quantified with contrast-enhanced intermittent power Doppler US by applying a modified model that analyzed the replenishment kinetics of microbubbles. In 22 patients (16 women, six men; mean age, 52 years +/- 17) who were suspected of having myositis and in 10 healthy volunteers (two women, eight men; mean age, 28 years +/- 4), contrast-enhanced US of the clinically affected right biceps muscle was performed to measure blood flow, blood volume, and blood flow velocity. Additionally, the right upper arm was examined with a 1.5-T unit by using three different MR imaging techniques. Findings were compared with the results of clinical examinations and muscle biopsy. Data for perfusion-related parameters obtained at contrast-enhanced US were analyzed by using a nonparametric Mann-Whitney U test. RESULTS: Eight patients had histologically confirmed myositis and showed significantly higher blood flow velocity (P = .01), blood flow (P = .001), and blood volume (P = .002) at contrast-enhanced US than did patients who did not have myositis. Blood flow velocity (P = .001) and blood flow (P = .002) were significantly higher in patients with myositis than in volunteers. An increase in signal intensity on T2-weighted MR images was found in all patients with myositis, while contrast material enhancement on fat-suppressed T1-weighted MR images was found in only four of seven patients with myositis. CONCLUSION: Initial results show that contrast-enhanced US is a feasible method for noninvasively demonstrating increased perfusion in the involved muscle groups in patients with myositis.
Biopsy↗
Successful treatment of chronic tophaceous gout with infliximab (Remicade).
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Adult↗
Celecoxib, a selective inhibitor of cyclooxygenase 2 for therapy of diffuse anterior scleritis.
PURPOSE: Scleritis is a painful inflammation of the sclera that is often difficult to treat. Oral nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective. Results of treating 24 cases of diffuse anterior scleritis with the novel selective COX-2 inhibitor celecoxib are reported. DESIGN: Nonrandomized prospective study. METHODS: Twenty-four patients suffering from diffuse anterior scleritis were seen in the Interdisciplinary Uveitis Center in Heidelberg between April 2001 and April 2003. All patients were treated with a 200- to-800 mg dose of celecoxib per day, in divided doses, depending on the degree of discomfort and clinical severity. RESULTS: Twenty-two patients experienced significant clinical improvement within an average of 5 days of starting celecoxib. These patients reported a complete loss of pain and scleral redness. As they experienced complete symptomatic remission, the dose of celecoxib was tapered. Three of these patients suffered from a second attack of scleritis, with one patient requiring long-term low-dose therapy, one patient showing a nodular form, and the third showing no improvement. Treatment with celecoxib was associated with no side effects apart from allergic exanthema in two patients. CONCLUSION: Due to its anti-inflammatory potency and low rate of side effects, celecoxib is an effective drug for the treatment of diffuse anterior scleritis. Compared with other NSAIDs it shows minimal gastrointestinal side effects, so its high cost is justified. It represents an alternative drug therapy before systemic immunosuppressive treatment.
Adult↗
Management of sight-threatening uveitis: new therapeutic options.
Over the past 2 decades therapy for the treatment of intraocular inflammation (uveitis) has developed into a highly differentiated approach with an increasing number of drug options. This paper primarily summarises literature from the past 5 years (2000 to May 2004), gives an update on systemic immunosuppressive therapy for non-infectious uveitis and speculates about new developments that could become relevant in the near future for the treatment of uveitis patients. The spectrum of immunosuppressive drugs has been notably expanded by tumor necrosis factor inhibitors, but with some limitations to uveitis. Behcet's disease is an example of uveitis where a multisystem disorder can affect the eye very severely. This clinical example has been used to investigate the utility of many different types of immunosuppressive therapies and the clinical approach is extensively discussed in this review. An accompanying table summarises the proposed mode of action, standard dosage, common adverse effects, as well as estimated cost of current treatment options.
Adrenal Cortex Hormones↗
Autologous stem cell transplantation for systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is responsive to treatment with immunosuppressives and steroids, but often pursues a relapsing or refractory course resulting in increasing incapacity and reduced survival. Autologous stem cell transplantation (ASCT) following immunoablative chemotherapy is a newer therapy for autoimmune disease of potential use in severe SLE. A retrospective registry survey was carried out by the European Blood and Marrow Transplant and European League Against Rheumatism (EBMT/EULAR) registry. Data was collected from 53 patients with SLE treated by ASCT in 23 centres. Disease duration before ASCT was 59 (2-155) months (median, range), 44 (83%) were female, and median age was 29 (9-52) years. At the time of ASCT a median of seven American College of Rheumatology (ACR) diagnostic criteria for SLE were present (range 2-10) and 33 (62%) had nephritis. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte colony stimulating factor in 93% of cases. Ex vivo CD34 stem cell selection was performed in 42% of patients. Conditioning regimens employed cyclophosphamide in 84%, anti-thymocyte globulin in 76% and lymphoid irradiation in 22%. The mean duration of follow-up after ASCT was 26 (0-78) months. Remission of disease activity (SLEDAI < 3) was seen in 33/50 (66%; 95%CI 52-80) evaluable patients by six months, of which 10/31 (32%; 95%CI 15-50) subsequently relapsed after six (3-40) months. Relapse was associated with negative anti-double stranded DNA (anti-dsDNA) antibodies before ASCT (P = 0.007). There were 12 deaths after 1.5 (0-48) months, of which seven (12%; 95%CI 3-21) were related to the procedure. Mortality was associated with a longer disease course before ASCT (P = 0.036). In conclusion, this registry study demonstrates the efficacy of ASCT for remission induction of refractory SLE, although mortality appeared high. The safety of this procedure is likely to be improved by patient selection and choice of conditioning regimen. The return of disease activity in one-third of patients might be reduced by long-term immunosuppressive therapy post-ASCT.
Adolescent↗
Lack of evidence for inhibition of angiogenesis as a central mechanism of the antiarthritic effect of methotrexate.
OBJECTIVES: The aim of this study was to investigate whether methotrexate (MTX) has an antiangiogenic effect and whether this property plays a role in the control of rheumatoid arthritis (RA). METHODS: A human placenta angiogenesis assay was used to examine the antiangiogenic effects of MTX in vitro. In addition, DBA/1 mice were used to compare the antiarthritic effect of MTX in collagen-induced arthritis (CIA) and its antiangiogenic effect in a murine in vivo matrigel model for angiogenesis. RESULTS: The spreading of microvessels from placental vessel fragments was not significantly inhibited by MTX. Treatment with MTX reduced significantly the incidence of CIA in DBA/1 mice in a dose-dependent manner. However, treatment with the same doses of MTX did not significantly reduce vessel growth in subcutaneous depots of bFGF-enriched matrigel. CONCLUSION: These data support the hypothesis that inhibition of angiogenesis does not significantly contribute to the antiarthritic effect of MTX seen in patients and animal models for RA. Therefore, the combination of MTX with antiangiogenic drugs appears to be a rational strategy in the treatment of RA.
Angiogenesis Inhibitors↗
Albumin-based drug delivery as novel therapeutic approach for rheumatoid arthritis.
We reported recently that albumin is a suitable drug carrier for targeted delivery of methotrexate (MTX) to tumors. Due to pathophysiological conditions in neoplastic tissue, high amounts of albumin accumulate in tumors and are metabolized by malignant cells. MTX, covalently coupled to human serum albumin (MTX-HSA) for cancer treatment, is currently being evaluated in phase II clinical trials. Because synovium of patients with rheumatoid arthritis (RA) shares various features observed also in tumors, albumin-based drug targeting of inflamed joints might be an attractive therapeutic approach. Therefore, the pharmacokinetics of albumin and MTX in a mouse model of arthritis was examined. Additionally, uptake of albumin by synovial fibroblasts of RA patients and the efficacy of MTX and MTX-HSA in arthritic mice were studied. The results show that when compared with MTX, significantly higher amounts of albumin accumulate in inflamed paws, and significantly lower amounts of albumin are found in the liver and the kidneys. The protein is metabolized by human synovial fibroblasts in vitro and in vivo. MTX-HSA was significantly more effective in suppression of the onset of arthritis in mice than was MTX. In conclusion, albumin appears to be a suitable drug carrier in RA, most likely due to effects on synovial fibroblasts, which might increase therapeutic efficacy and reduce side effects of MTX.
Albumins↗
[Stem cell transplantation in primary systemic vasculitis].
BACKGROUND: Many patients with various autoimmune diseases fail to respond to conventional immunosuppressive therapy and develop irreversible organ damage. In some cases the complications might be fatal. Furthermore, prolonged immunosuppression with cyclophosphamide or corticosteroids often leads to long-term side effects, cumulative organ damage, and development of secondary malignancies. THERAPY: Thus, short-term, high-dose immunosuppressive therapy with autologous stem cell transplantation might be an alternative for otherwise refractory patients. This concept has been used mainly in patients with scleroderma, systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. PATIENTS: Patients with primary systemic vasculitis (PSV) seem to be suitable candidates for high-dose chemotherapy (HDCT). Although complete, long-term remissions are possible with standard immunosuppressive therapy, there is a subgroup of patients who cannot be cured by standard therapy. They need long-term immunosuppression and eventually die due to progression of the disease or cumulative therapy-related toxicity. In large series, the 5-year mortality rate was > 20%. The severity of vasculitis rather than the distinction between subgroups should determine whether HDCT might be a life-saving treatment. RESULTS AND CONCLUSION: Careful patient selection with the help of scoring systems and determination of the optimal time in the course of disease are now the major goals in the approach to HDCT. First reports as well as our own single-center experience in HDCT with a limited number of patients with severe PSV have shown that long-term remissions are possible even in patients refractory to conventional immunosuppression.
Adrenal Cortex Hormones↗
A family with a variant form of primary hypertrophic osteoarthropathy restricted to the lower extremities.
We report a case of a family with a variant form of primary hypertrophic osteoarthropathy (HOA) restricted to the lower extremities without digital clubbing or cutaneous changes. Three family members suffered from pain, swelling and hyperhidrosis of both feet. X-rays showed destruction and osteoproliferative changes of the metatarsal bones with periostal hyperostosis close to the talus. There was an increased 99m-Tc-MDP uptake in the early phase of bone scintigraphy. Fibrosis of the marrow with stimulated osteoclastic resorption and the presence of detritus synovialitis were visible in a bone and joint biopsy. All known infectious, neurologic, metabolic and malignant diseases, which affect the bone and joints, were excluded.
Adult↗
Predictors of psychiatric comorbidity in medical outpatients.
OBJECTIVE: Psychiatric comorbidity in medical outpatients is associated with personal suffering and reduced psychosocial functioning. Simple clinical indicators are needed to improve recognition and treatment of psychiatric comorbidity. This study aimed to identify predictors of psychiatric comorbidity for diagnostic use in busy medical settings and to describe their criterion validity. METHODS: The SCID was adopted as the independent criterion standard for the presence of a psychiatric comorbidity in 357 patients (68% female; mean age, 43 years) of six internal medicine outpatient clinics and 12 general practices. Potential indicators of psychiatric comorbidity were investigated by means of patient and physician questionnaires. Logistic regression analyses were used to identify independent predictors of psychiatric comorbidity, and their operating characteristics were determined. RESULTS: Of 18 indicators, the four most important predictors of psychiatric comorbidity were identified: a screening question for nervousness, anxiety, or worries (odds ratio, 11.9; p <.001), a screening question for depressed mood (odds ratio, 8.8; p <.001), the self-report of three or more bothersome physical symptoms (odds ratio, 3.2; p =.001), and feeling distressed by partner difficulties (odds ratio, 2.7; p =.006). The combined assessment of the four predictors resulted in positive predictive values as high as 100%, negative predictive values as high as 91%, sensitivities as high as 86%, and specificities as high as 100%. CONCLUSIONS: The identification of mental disorders in medical outpatients could be substantially improved by the knowledge and use of four easily accessible predictors. When the presence of one or more of these predictors can be confirmed, it is suggested that the patient undergo further evaluation to determine more precisely the presence and specific type of psychiatric disorder being identified.
Adult↗
Psychiatric comorbidity and work disability in patients with inflammatory rheumatic diseases.
OBJECTIVE: To determine the relative contribution of psychiatric comorbidity to work disability in patients with inflammatory rheumatic diseases (IRD). Parallel analyses were also performed in a matched control group with no diagnosis of IRD to investigate if predictors of work disability in medical patients are independent from the presence of IRD. METHOD: The patient group with IRD (73.9% female; mean age, 42.7 years) and the control group (73.9% female; mean age, 42.2 years) consisted of 356 outpatients each. Psychiatric comorbidity was diagnosed using the Patient Health Questionnaire (PHQ), functional disability was measured with the 12-item Short-Form Health Survey (SF-12), and severity of illness was assessed by the treating physicians. Stepwise logistic regression analyses were performed to identify independent predictors of work disability controlling for psychiatric comorbidity, functional disability, severity of illness, additional clinical variables, and demographics. RESULTS: Psychiatric comorbidity increased work disability in patients with severe IRD from 25% to 50%, and from 5% to 17% in mild disease. Physical functioning (OR = 0.6; p <.0001), depression severity (OR = 1.6; p =.005), and illness severity (OR = 1.8; p =.006) were identified as independent predictors of work disability in patients with IRD. Similar predictors of work disability were identified in the control group, but depression severity did not meet statistical significance at the 5% level. CONCLUSIONS: This study provides evidence that depression is an independent risk factor of work disability in patients with IRD, but this result cannot be generalized to other medical conditions. Improved diagnosis and treatment of depressive disorders in patients with IRD may help avoid work disability.
Adult↗