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Biomedical subjects

T J Lehman

Publications and source records attributed to T J Lehman.

At least 19 recordsLinked to original sources

Clinical trials for post-streptococcal reactive arthritis.

Post-streptococcal reactive arthritis is a frequently observed entity that has an uncertain relationship with acute rheumatic fever. Although different criteria have been suggested for delineating these two conditions, none have been validated. In the absence of a clear definition, it has been impossible for investigators to carry out meaningful studies. Some children who were initially labeled as having post-streptococcal reactive arthritis later suffered from carditis and definite rheumatic fever with subsequent streptococcal infections. Some physicians now recommend that all children with post-streptococcal reactive arthritis receive penicillin prophylaxis. However, the proper duration of treatment and appropriate guidelines for patient selection have not been determined. It will be impossible to answer these questions until collaborative efforts are made to accurately define this illness and then begin a careful analysis of its etiopathogenesis and natural history. In the interim, each physician must evaluate the potential risks and benefits of penicillin prophylaxis in view of the risk of rheumatic fever in the community.

Adolescent↗

Use of biologics in the treatment of childhood rheumatic diseases.

Over the last two decades, progression in the knowledge of molecular biologic techniques has led to a better understanding of immunopathogenesis and identification of several cytokines, which propagate chronic arthritis in both adult and pediatric patients. A number of biologic agents have been developed in targeting different immune markers or mediators with the hope that they may help in controlling the inflammation in the group of patients who are resistant to disease-modifying antirheumatic drugs (DMARDs) and may alter the natural history of the diseases. Tumor necrosis factor (TNF)-alpha is the first to be targeted and its antagonists have been approved. Other biologic agents targeting different markers/mediators have followed and have been tested in clinical trials especially in adult rheumatoid arthritis (RA). Experiences in pediatric use are limited and agents proved to be effective in adult RA are not always transferred the same efficacy in different subtypes of juvenile idiopathic arthritis (JIA). It is reasonable to see the efficacy, and more importantly the safety profiles of each agent before the decision is made to use them in children. This article reviews the published and anecdotal reports of biologic agents that have been used in children with JIA and also focuses on the potential use of other biologic agents in JIA that have been used in trials to combat adult RA.

Adult↗

Intermittent intravenous cyclophosphamide arrests progression of the renal chronicity index in childhood systemic lupus erythematosus.

OBJECTIVE: To assess prospectively the safety and efficacy of a 36-month course of systematic bolus intravenous cyclophosphamide therapy (IVCY) for children with lupus nephritis. STUDY DESIGN: Sixteen children with lupus nephritis were treated with IVCY for 36 months. Renal biopsies performed before and after treatment were scored for activity and chronicity. SLEDAI scores, laboratory measures, and prednisone dosage were recorded at the time of each treatment. RESULTS: After 36 months of IVCY therapy, the renal biopsy activity index decreased from 9 +/- 4 to 1 +/- 1 (P <.001) without a change in chronicity. The mean creatinine clearance increased from 90 +/- 23 to 107 +/- 23 mL/min/1.73 mol/L(2) (P <.01), and the mean 24-hour urine protein excretion decreased from 2.0 +/- 2.4 g/24 h to 0.5 +/- 0.7 g/24 h (P <.05). The mean SLEDAI score decreased from 19 +/- 5.2 to 2.9 +/- 3.1 (P <.001). The mean prednisone dosage decreased from 35.5 +/- 20 mg/d to 14.0 +/- 3 mg/d (P <.001). No significant complications occurred. CONCLUSIONS: Thirty-six months of systematic IVCY therapy led to decreased renal biopsy activity without progression of chronicity, with excellent disease control and a greater than 50% reduction in mean corticosteroid dose.

Adolescent↗

Suppression of coronary vasculitis in a murine model of Kawasaki disease using an angiogenesis inhibitor.

Coronary arteritis can be induced in C57BL/6 mice with a single intraperitoneal (ip) injection of Lactobacillus casei cell fragments. Histologic sections resemble the vasculitis and aneurysms observed in the medium-sized coronary arteries of children with Kawasaki disease. Since endothelial cells could play an important role in the development of vasculitis, a recently described angiogenesis inhibitor that is not an immunosuppressive agent, AGM-1470 (derived from Aspergillus fumigatus), was used to evaluate its therapeutic potential in this model. A total of 32 mice were administered 0.5 mg of sterile L. casei preparation ip on day 0 and randomized to either a treatment (AGM-1470, 27mg/kg sc alternate days) or a control (vehicle only) protocol. Hearts were harvested on day 14 (early disease) or at the end of the study on day 28 (established disease). Histologic sections were scored blindly for vasculitis. Day 14 sections from both protocols manifested only minimal disease, indicating that the vasculitis had not yet matured. By day 28, the AGM-1470 group had significantly less coronary vasculitis than the control group (0.7 vs 2.6, p < 0.005, respectively). These studies suggest that endothelial cells may play an active role in this pathologic process and that angiogenesis inhibitors, such as AGM-1470, could be useful tools for the treatment and understanding of vasculitis.

Animals↗

Systemic lupus erythematosus and related disorders of childhood.

Systemic lupus erythematosus (SLE) remains a challenging autoimmune disease in term of its etiology, pathogenesis, and management. Much progress has been made in the past year in searching for the SLE susceptibility genes, particularly by several genome-wide screening groups. Cumulative evidence about the association of infections and hormones with SLE has been gathered. Researchers believe that childhood SLE involves more severe organ involvement than adult SLE. Central nervous system complicated lupus continues to be problematic because functional imaging can be abnormal in otherwise asymptomatic lupus individuals. Whether these abnormalities result from subclinical central nervous system involvement or from false positives remains to be determined. With the wide use of corticosteroids as a cornerstone therapy for major organ involvement in childhood SLE, potential complications, especially those involving the growing bone or osteoporosis, are a cause of concern. Evidence suggests that regular exercise, as well as calcium and vitamin D supplementation, may help alleviate bone complications. Researchers have also updated information about pediatric antiphospholipid antibody syndrome. Follow-up studies on neonatal lupus and its pathogenesis have progressed, leading to a better understanding of its natural history and, in turn, to proper counseling of mothers of infants with neonatal lupus and of women with positive anti-Ro or anti-La antibodies. Drug-induced lupus in children is not uncommon. Minocycline and zafirlukast have been increasingly used, and were reported to induce lupus in children.

Central Nervous System Diseases↗

Thalidomide responsiveness in an infant with Behçet's syndrome.

BACKGROUND: Behçet's syndrome is a chronic relapsing vasculitis characterized by aphthous stomatitis, genital ulcerations, and uveitis. The disease is a multisystem illness, which may involve the skin, joints, gastrointestinal tract, blood vessels, central nervous system, and other organs. CASE STUDY: We report a case of an infant with features of Behçet's syndrome who did not respond to conventional immunosuppression with high-dose corticosteroids and cytotoxic agents. Thalidomide, a potent immune response-modifying drug, was used with marked improvement and resolution of symptoms. CONCLUSION: This finding supports a trial of thalidomide treatment in patients with Behçet's syndrome who are unresponsive to other forms of immunosuppressive therapy or develop undesirable side effects.

Behcet Syndrome↗

Enthesitis, arthritis, and heel pain.

Often, individuals who present with "isolated" heel pain but with normal laboratory findings are dismissed without diagnosis. However, if these patients are carefully questioned and examined, a significant proportion are found to have a spondyloarthropathy. The keys to making this diagnosis are obtaining a thorough medical history and performing a complete physical examination. The classic complaints of back pain and enthesitis in other areas are frequently not reported by patients unless specifically sought, because they are thought to be unrelated to the heel pain.

Arthritis↗

An increased prevalence of Epstein-Barr virus infection in young patients suggests a possible etiology for systemic lupus erythematosus.

An unknown environmental agent has been suspected to induce systemic lupus erythematosus (lupus) in man. Prompted by our recent immunochemical findings, we sought evidence for an association between Epstein-Barr virus infection and lupus. Because the vast majority of adults have been infected with Epstein-Barr virus, we chose to study children and young adults. Virtually all (116 of 117, or 99%) of these young patients had seroconverted against Epstein-Barr virus, as compared with only 70% (107 of 153) of their controls (odds ratio 49.9, 95% confidence interval 9.3-1025, P < 0. 00000000001). The difference in the rate of Epstein-Barr virus seroconversion could not be explained by serum IgG level or by cross-reacting anti-Sm/nRNP autoantibodies. No similar difference was found in the seroconversion rates against four other herpes viruses. An assay for Epstein-Barr viral DNA in peripheral blood lymphocytes established Epstein-Barr virus infection in the peripheral blood of all 32 of the lupus patients tested, while only 23 of the 32 matched controls were infected (odds ratio > 10, 95% confidence interval 2.53-infinity, P < 0.002). When considered with other evidence supporting a relationship between Epstein-Barr virus and lupus, these data are consistent with, but do not in themselves establish, Epstein-Barr virus infection as an etiologic factor in lupus.

Adolescent↗

Nineteen-year-old female with unilateral ankle pain. What is your diagnosis?

The case history of a 19-year-old female with left ankle pain of 18 months' duration is presented. The reader is encouraged to make his or her own diagnosis after reviewing the history, laboratory values, and imaging. The final diagnosis with a full explanation and differential diagnosis will follow.

Adult↗

Systemic and localized scleroderma in children.

All forms of scleroderma are rare in childhood. The most common form in childhood is localized scleroderma, which may take the form of morphea or linear scleroderma. Localized scleroderma is often benign but may cause significant deformity if it occurs on the face or extends across joint surfaces. Progressive systemic sclerosis is much less frequent in childhood but may have a rapidly progressive and ultimately fatal course. CREST (calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangieactasia) syndrome also may occur in childhood with manifestations similar to those seen in adults. In addition, some children in whom mixed connective tissue disease is initially diagnosed ultimately develop progressive systemic sclerosis. Research into both the causes and the optimal therapy for childhood scleroderma is hampered by the small number of patients treated at individual centers. This limitation has made it difficult to perform well-controlled studies.

Child↗

Levels of soluble Fas/APO-1/CD95 in systemic lupus erythematosus and juvenile rheumatoid arthritis.

OBJECTIVE: To quantify soluble Fas/APO-1 (sFas/APO-1) protein in the serum of patients with systemic lupus erythematosus (SLE) and juvenile rheumatoid arthritis (JRA). METHODS: Soluble Fas/APO-1 was quantified using a sandwich enzyme-linked immunosorbent assay. Disease activity in SLE patients was assessed by the SLE Disease Activity Index. RESULTS: Increased serum sFas/APO-1 levels were observed in only 1 of the 27 SLE patients (4%) and 3 of the 10 JRA patients (30%). CONCLUSION: Increased levels of sFas/APO-1 occurred infrequently in SLE, and the levels were lower than 10 ng/ml. Increased levels of sFas/APO-1 are not specific for SLE. Soluble Fas/APO-1 is unlikely to be of major pathogenetic significance in SLE.

Arthritis, Juvenile↗

A practical guide to systemic lupus erythematosus.

Systemic lupus erythematosus is a challenging disease with varied manifestations resulting from widespread immune complex deposition. It may present in the general pediatric office as an acute illness with fever, rash, and hematuria, or as chronic fatigue and malaise that might be mistaken for "school phobia". Although SLE remains an infrequent disease in general pediatric practice, mild cases are more frequent than was previously recognized. These children benefit from therapy if the physician is alert to their occurrence and makes the appropriate diagnosis. The understanding of the role of genetics and environmental agents in the pathogenesis of SLE has improved over the past 10 years. In addition, the past 10 years have seen refinements in the use of immunosuppressive regimens, such as cyclophosphamide, that have led to both improved quality of life and improved survival for children with active SLE unresponsive to corticosteroids. Although long-term concerns regarding the safety and efficacy of immunosuppressive drug regimens persist, the future is increasingly bright for children with SLE who receive appropriate care in a timely fashion.

Adolescent↗

Intravenous immunoglobulin in the treatment of systemic juvenile rheumatoid arthritis: a randomized placebo controlled trial. Pediatric Rheumatology Collaborative Study Group.

OBJECTIVE: To assess the efficacy and safety of intravenous immunoglobulin (IVIG) in juvenile rheumatoid arthritis (JRA). METHODS: Thirty-one children with active, refractory, systemic JRA were randomized into a multicentered, double blinded, placebo controlled trial. Patients received infusions of 1.5 g/kg of IVIG or placebo (0.1% albumin) every 2 weeks for 2 months, then monthly for 4 months (total: up to 9 infusions over 6 months). Twenty-nine of the 31 patients were included in the efficacy subset. RESULTS: Fourteen patients discontinued prematurely from study, 7 in each treatment group. A higher proportion of patients in the IVIG group improved (50 vs 27%) as assessed by the physician's global assessment. However, the sample size was small and this difference was not statistically significant. IVIG was not more effective than placebo in reducing the number of days with fever or other systemic manifestations. Changes from baseline in the joint count, hemoglobin, albumin, platelet count, and erythrocyte sedimentation rate did not differ between treatment groups. CONCLUSION: Our results suggest that high dose IVIG has limited clinical utility in systemic JRA. However, this trial failed to enroll adequate numbers of patients to permit valid statistical intergroup comparisons, and the results must be considered nondefinitive.

Adolescent↗

Current concepts in immunosuppressive drug therapy of systemic lupus erythematosus.

The routine use of intravenous cyclophosphamide has led to advances in the preservation of renal function and quality of life for patients with systemic lupus erythematosus complicated by diffuse proliferative glomerulonephritis. Most patients receiving 3 years of intravenous cyclophosphamide according to a rigorous protocol experience longterm remission of their disease. However, in some the disease continues to progress or flares recurrently. Early intervention and combined immunosuppressive regimens modeled on protocols developed for the treatment of neoplastic disease appear to offer the greatest likelihood of attaining permanent remission for large numbers of patients. Pilot studies of these regimens are in progress.

Child, Preschool↗