Identification of clonal T cells in the blood of patients with systemic sclerosis: positive correlation with response to photopheresis.

OBJECTIVES: To search for circulating clonal T-cell populations in patients with systemic sclerosis (SSc), and to determine whether T-cell clonality in the blood predicts therapeutic response to photopheresis. DESIGN: Analysis of clonal T-cell receptor gamma gene rearrangements before photopheresis treatment and blinded clinical evaluation of cutaneous response to photopheresis in a case series. SETTING: University hospital setting. PATIENTS: Thirteen consecutive patients with SSc. INTERVENTIONS: Photopheresis in 11 patients. MAIN OUTCOME MEASURES: Clonality of T cells in the blood before photopheresis and clinical response to photopheresis. RESULTS: Screening of blood samples from 13 SSc patients for clonal T-cell receptor gamma gene rearrangements revealed a monoclonal T cell population in 6 (46%) of 13 SSc patients. Clinical response to photopheresis in 11 patients was evaluated in a blinded manner using skin severity scores. Clonality of T cells appeared to be associated with a higher chance of response to photopheresis therapy, as 4 (67%) of 6 patients in the clone-positive group vs 1 (20%) of 5 in the clone-negative group experienced a clinically significant response to treatment. CONCLUSIONS: A high proportion of patients with SSc have detectable expanded clonal T-cell populations in the peripheral blood, and such patients appear more likely to respond to photopheresis.

Photopheresis: clinical applications and mechanism of action.

Photopheresis is a leukapheresis-based therapy that utilizes 8-methoxypsoralen and ultraviolet A irradiation. Photopheresis is currently available at approximately 150 medical centers worldwide. Recent evidence suggests that this therapy used as a single agent may significantly prolong life, as well as induce a 50%-75% response rate among individuals with advanced cutaneous T cell lymphoma (CTCL). Furthermore, a 20%-25% complete response rate with photopheresis alone, or in combination with other biologic response modifiers, has been obtained at our institution among patients with Sezary syndrome. These complete responses have been characterized by the complete disappearance of morphologically atypical cells from the skin and blood. The use of sensitive molecular techniques has also confirmed the sustained disappearance of the malignant T cell clone from the blood of patients with complete responses. In addition to the treatment of CTCL, numerous reports indicate that photopheresis is a potent agent in the therapy of acute allograft rejection among cardiac, lung, and renal transplant recipients. Chronic graft versus host disease also appears to be quite responsive to photopheresis therapy. Likewise, there may also be a potential role for photopheresis in the therapy of certain autoimmune diseases that are poorly responsive to conventional therapy. The immunologic basis for the responses of patients with these conditions is likely due to the induction of anticlonotypic immunity directed against pathogenic clones of T lymphocytes. Treatment-induced apoptotic death of pathogenic T cells and activation of antigen presenting cells are postulated to have important effects in this therapeutic process.

Treatment of cutaneous T-cell lymphoma with extracorporeal photopheresis monotherapy and in combination with recombinant interferon alfa: a 10-year experience at a single institution.

BACKGROUND: Extracorporeal photopheresis is a pheresis-based therapy that permits the direct targeting of psoralen-mediated photochemotherapy to circulating pathogenic T cells. Although photopheresis is currently used to treat cutaneous T-cell lymphoma (CTCL), limited data are available regarding overall response rates and durability of responses among patients with advanced disease. Furthermore, little is known about the effectiveness and tolerability of combined regimens employing other biologic response modifiers including interferon alfa. OBJECTIVE: Our purpose was to determine the efficacy of photopheresis among 41 patients with the clinical and laboratory diagnosis of CTCL; the majority of patients had stage III or IV disease with the presence of circulating malignant T cells. METHODS: A retrospective chart review during a 10-year period at a single university hospital was performed for all patients receiving either photopheresis monotherapy on two consecutive days every 4 weeks (one cycle) and for an additional 12 patients who also received interferon alfa 1.5 to 5 million U subcutaneously three to five times weekly. RESULTS: Thirty-one of 41 patients (76%) were treated for six or more cycles. The remaining 10 were treated with less than six cycles because of rapidly progressing disease (n = 6), death unrelated to CTCL (n = 2), or withdrawal from treatment (n = 1); one of the 10 patients had only received five cycles of treatment but is still receiving therapy. Twenty-eight of the 31 patients treated for six or more cycles received photopheresis alone. Among the 28, seven patients (25%) had a complete remission, 13 (46%) had a partial remission defined as more than 50% clearing of skin disease, and eight (29%) did not respond to treatment. The presence of Sézary cells in the peripheral blood was associated with a favorable response. Median time to treatment failure was 18 months, whereas median survival from initiation of therapy was 77 months and from the time of diagnosis exceeded 100 months. Nine of these 28 patients went on to receive combination therapy with interferon alfa and, in some cases, other agents. Among these nine patients, five had an enhanced clinical response to the combination therapy compared with treatment with photopheresis monotherapy. The combined regimen was well tolerated. CONCLUSION: These results indicate that patients with advanced CTCL can achieve a high response rate for an extended period with photopheresis and that interferon alfa combined with photopheresis is a well-tolerated regimen that appears to produce higher response rates than photopheresis alone.

Parents of children with rheumatic disease as peer counselors.

OBJECTIVE: A parent consultant program was established to promote active family involvement in the health care process and to provide parent-to-parent support, education, and training. METHODS: Parents of children with rheumatic disease were hired by 7 pediatric rheumatology centers to serve as role models and advocates for other parents whose children attended the clinics. In the clinic, the parent consultants provided support, advocacy, and education regarding specific nonmedical issues. At the local level, they assisted parents in obtaining community-based services, such as individual educational plans at school, local physical therapy, or access to recreational resources. RESULTS: Program impact was evaluated by an anonymous, mail-response questionnaire sent to parents who met with a parent consultant during a clinic visit for their child. Surveys were sent within 6 months of the initial parent consultant meeting; 257 questionnaires were mailed, 33% were returned. The majority of respondents (87%) felt their interaction with the parent consultant was helpful. The general support received and the specific information and/or assistance received were found to be equally useful by respondents. The majority of respondents (98%) stated they would recommend that other parents meet with the parent consultant. CONCLUSION: Parents of children with rheumatic disease are effective peer counselors, providing general support and specific assistance to enhance family involvement in care.

Use of extracorporeal photochemotherapy in heart transplant recipients during acute rejection: a case study.

Despite the growing availability of improved immunosuppressive agents, acute and chronic rejection episodes remain a major complication in heart transplant recipients. The rejection of allografts is a normal part of the body's response to foreign antigens. The key to controlling this response is to administer a regimen of multiple immunosuppressive drugs. Evidence indicates that by adding extracorporeal photochemotherapy to a standard immunomodulatory regimen, the rejection process can be reversed without significantly increasing patient risk. In this case study we examine extracorporeal photochemotherapy and the care of patients receiving this therapy.

Demography of a regional pediatric rheumatology patient population. Affiliated Children's Arthritis Centers of New England.

OBJECTIVE: To examine the descriptive epidemiology of a regional cohort of children with rheumatic disease, and to document the variety and frequency of diseases encountered among pediatric rheumatology centers. METHODS: Pediatric rheumatology centers in southern New England participated in a prospective multicenter patient registry. All outpatients attending clinics at 8 pediatric rheumatology centers were enrolled as subjects during the 8-year period of study (n = 4585). Diagnostic criteria defined the rheumatic disease cases which were determined by clinical examination by a pediatric rheumatologist, and record linkage was achieved to avoid duplication of subjects. RESULTS: Rheumatic conditions were diagnosed in 1742 subjects. Juvenile rheumatoid arthritis (JRA) was the most frequently encountered rheumatic condition (53%), followed by spondyloarthropathy syndromes (13%), vasculitis (10%), systemic lupus erythematosus (SLE) (6%), isolated Raynaud's phenomenon (5%), dermatomyositis/polymyositis (DM/PM) (5%), and scleroderma (2%). The mean annual incidence of JRA, spondyloarthropathy syndromes, SLE and DM/PM among children referred to pediatric rheumatology centers in Massachusetts was 4.0, 2.0, 0.4 and 0.4 per 100,000 children at risk, respectively. Nonrheumatic conditions were diagnosed in 2843 subjects, among which musculoskeletal conditions were most frequent (56%) followed by infectious disorders (18%), psychogenic disorders (3%), fever of unknown origin (2%), and abnormal immune serology without a specific diagnosis (2%). CONCLUSION: The use of a multicenter patient registry was successful in allowing the collection of descriptive epidemiologic data on a large and well defined sample of children with rare disorders.

Methotrexate treatment of recalcitrant childhood dermatomyositis.

OBJECTIVE: To review the clinical course of 16 children with recalcitrant dermatomyositis (DM), who were treated with oral methotrexate (MTX) in addition to prednisone. METHODS: Sixteen patients with recalcitrant DM who were treated with MTX in addition to prednisone were followed between 1984 and 1990. The patients' clinical responses to treatment, including alterations in muscle strength and muscle enzyme levels, changes in prednisone dosage, and development of toxicity or complications were reviewed retrospectively. RESULTS: All 12 patients who received MTX for at least 8 months regained normal muscle strength. In 11 of the 12, the prednisone dosage could eventually be tapered to < or = 5 mg/day. Complications during MTX treatment required discontinuation of MTX in 5 patients, and were unrelated to the cumulative dose of the drug. Active disease recurred in 5 patients in whom MTX had been discontinued after apparent clinical remission had been achieved. CONCLUSION: MTX, in combination with prednisone, is a useful adjunct in the treatment of recalcitrant childhood DM. However, recurrence of disease after withdrawal of MTX suggests that the drug may have a suppressive, rather than a remittive, effect.

The economic impacts of juvenile rheumatoid arthritis.

Our study documents the direct costs, family costs and community (extra school) costs. One hundred and twenty families with children who had juvenile rheumatoid arthritis (JRA) diagnosed by established criteria and who lived in New England were asked to participate. All data except inpatient charged were collected via questionnaire. The questionnaire return rate was 59% (N = 70). The mean annualized direct cost/child was 7,905 (inpatient, $1,717; outpatient, $5,700; and nonmedical, $488). Family costs averaged $1,524/year (out of pocket medical and nonmedical, $1,196; lost salary, $328), which represented 5% of mean family income. The mean extra school cost was $1,449/9 months. The economic impacts of JRA appear to be substantial.

Ultrasonography in the study of prevalence and clinical evolution of popliteal cysts in children with knee effusions.

The prevalence and clinical evolution of popliteal cysts in children with knee arthritis is not well known. Using ultrasonography, we studied 44 children with clinically detectable knee effusions secondary to juvenile rheumatoid arthritis (n = 35), spondyloarthritis (n = 3) and psoriatic (n = 2), septic (n = 2) and lupus (n = 2) associated arthritis. Popliteal cysts, defined as anechoic or hypoechoic masses measuring at least 1 cm in 2 of 3 dimensions, were identified in 27 children (61%). Of the 30 children with bilateral arthritis, 11 (37%) had bilateral cysts. The size of the cysts ranged from 1 to 40 cm3 (median 3.0 cm3). There was a significant correlation between the presence of a cyst and popliteal pain and the size of the suprapatellar effusion (p less than 0.001) but not the child's age or underlying diagnosis (p greater than 0.05). A cohort of 25/27 children with cysts were followed prospectively with serial sonograms for 18-24 months. The resolution of the cyst followed that of the suprapatellar effusion in those children whose arthritis improved or resolved. Two children (8%) had rupture of the popliteal cysts. Popliteal cysts are readily documented in children with knee effusions using ultrasonography, and their presence and evolution correlates with the size of the suprapatellar effusion.