PURPOSE: Hodgkin's disease (HD) is a potentially curable malignant lymphoma with distinct histology, biologic behavior and clinical characteristics. Renal involvement in HD is rare, but it may be underestimated because renal lesions are not the major manifestation of the disease. The pathogenesis of proteinuria in HD remains unknown. CASE REPORT: The case of a 17-year-old girl suffering from Hodgkin's disease and nephrotic syndrome has been described. CONCLUSION: The authors would like to underline the very rare coincidence of Hodgkin's disease and nephrotic syndrome, the lack of remission after routine prednisone administration and disappearance of nephrotic proteinuria after anticancer therapy.

OBJECTIVE: To prospectively study the clinical features, pathophysiology, treatment and prognosis of Wegener granulomatosis. DESIGN: Of the 180 patients with Wegener granulomatosis referred to the National Institute of Allergy and Infectious Diseases during the past 24 years, 158 have been followed for 6 months to 24 years (a total of 1229 patient-years). MEASUREMENTS: Characteristics of clinical presentation, surgical pathology, course of illness, laboratory and radiographic findings, and the results of medical and surgical treatment have been recorded in a computer-based information retrieval system. SETTING: The Warren Magnuson Clinical Center of the National Institutes of Health. MAIN RESULTS: Men and women were equally represented; 97% of patients were white, and 85% were more than 19 years of age. The mean period of follow-up was 8 years. One hundred and thirty-three patients (84%) received "standard" therapy with daily low-dose cyclophosphamide and glucocorticoids. Eight (5.0%) received only low-dose cyclophosphamide. Six (4.0%) never received cyclophosphamide and were treated with other cytotoxic agents and glucocorticoids. Ten patients (6.0%) were treated with only glucocorticoids. Ninety-one percent of patients experienced marked improvement, and 75% achieved complete remission. Fifty percent of remissions were associated with one or more relapses. Of 99 patients followed for greater than 5 years, 44% had remissions of greater than 5 years duration. Thirteen percent of patients died of Wegener granulomatosis, treatment-related causes, or both. Almost all patients had serious morbidity from irreversible features of their disease (86%) or side effects of treatment (42%). CONCLUSIONS: The course of Wegener granulomatosis has been dramatically improved by daily treatment with cyclophosphamide and glucocorticoids. Nonetheless, disease- and treatment-related morbidity is often profound. Alternative forms of therapy have not yet achieved the high rates of remission induction and successful maintenance that have been reported with daily cyclophosphamide treatment. Despite continued therapeutic success with cyclophosphamide, our long-term follow-up of patients with Wegener granulomatosis has led to increasing concerns about toxicity resulting from prolonged cyclophosphamide therapy and has encouraged investigation of other therapeutic regimens.

BACKGROUND AND METHODS. Most hemangiomas are small, harmless birthmarks that appear soon after birth, proliferate for 8 to 18 months, and then slowly regress over the next 5 to 8 years, leaving normal or slightly blemished skin. In rare cases, hemangiomas can endanger vital structures, with a mortality of up to 60 percent. About a third of these life-threatening hemangiomas respond to treatment with corticosteroids, but for the others there is no safe and effective treatment. We evaluated the effects of daily subcutaneous injections of interferon alfa-2a (up to 3 million units per square meter of body-surface area) in 20 neonates and infants with life-threatening or vision-threatening hemangiomas that failed to respond to corticosteroid therapy. RESULTS. In 18 of the 20 patients the hemangiomas regressed by 50 percent or more after an average of 7.8 months of treatment (range, 2 to 13). One infant died of refractory proliferation of a lesion and consumptive coagulopathy. The condition of three other patients who had large hemangiomas associated with consumptive coagulopathies that were unresponsive to conventional therapies stabilized after seven days of treatment with interferon alfa-2a alone. Transient side effects of treatment with interferon alfa-2a included fever, neutropenia (one patient), and skin necrosis (one patient). No long-term toxicity has been observed after a mean follow-up of 16 months. CONCLUSIONS. Interferon alfa-2a appears to induce the early regression of life-threatening corticosteroid-resistant hemangiomas of infancy.

Eighty-five patients with Wegener's granulomatosis were studied for 21 years at the National Institutes of Health. Patients were treated with a protocol consisting of cyclophosphamide, 2 mg/kg body weight d, together with prednisone, 1 mg/kg body weight d, followed by conversion of the prednisone to an alternate-day regimen. Complete remissions were achieved in 79 of 85 patients (93%). The mean duration of remission for living patients was 48.2 (+/- 3.6) months. Twenty-three patients are off all therapy for a mean duration of 35.3 (+/- 6.3) months without therapy. This study provides a prospective experience with Wegener's granulomatosis and shows that long-term remissions can be induced and maintained in an extremely high number of patients by the combination of daily cyclophosphamide and alternate-day prednisone therapy.

BACKGROUND: Acute rejection episodes after renal transplantation are an important clinical challenge, despite use of multidrug immunosuppressive regimens. We did a prospective, multicentre, randomised, double-blind trial to investigate the impact of the addition of sirolimus, compared with azathioprine, to a cyclosporin and prednisone regimen. METHODS: 719 recipients of primary HLA-mismatched cadaveric or living-donor renal allografts who displayed initial graft function were randomly assigned, after transplantation, sirolimus 2 mg daily (n=284) or 5 mg daily (n=274), or azathioprine (n=161). We assessed the primary composite endpoint of efficacy failure, occurrence of biopsy-confirmed acute rejection episodes, graft loss, or death, and various secondary endpoints that characterise these episodes at 6 months and 12 months. Analyses were done by intention to treat. FINDINGS: The rate of efficacy failure at 6 months was lower in the two sirolimus groups (2 mg 18.7%, p=0.002; 5 mg 16.8%, p<0.001) than in the azathioprine group (32.3%). The frequency of biopsy-confirmed acute rejection episodes was also lower (2 mg 16.9%, p=0.002; 5 mg 12.0%, p<0.001; azathioprine 29.8%). At 12 months, survival was similar in all groups for grafts (97.2%, 96.0%, and 98.1%) and patients (94.7%, 92.7%, and 93.8%). Patients on sirolimus showed a delay in the time to first acute rejection episode and decreased frequency of moderate and severe histological grades of rejection episodes and related antibody treatment, compared with the azathioprine group. Rates of infection and malignant disorders were similar in all groups. INTERPRETATION: Use of sirolimus reduced occurrence and severity of biopsy-confirmed acute rejection episodes with no increase in complications. Further studies are needed to establish the optimum doses for the combined regimen.

Paraneoplastic pemphigus has been established as a newly recognized but distinctive syndrome. The syndrome has distinctive clinical, histologic, and immunopathologic features that are consistent between affected individuals. It is intriguing that the autoimmune disease is associated with a very small number of unusual lymphoreticular malignancies. Its very restricted association is encouraging in that it implies there may be a common and identifiable mechanism by which these tumors induce the autoimmunity. Future important goals include the following. First, the genes that encode the as yet uncharacterized protein antigens must be identified and their exact nature determined. It is possible that one of these antigens may represent a biologically important epithelial adhesion molecule. Second, the mechanism or mechanisms by which the tumor cells drive the autoimmune disease must be determined. This may have broader implications for other paraneoplastic diseases such as tumor-associated autoimmune cytopenias or myasthenia. Finally, defining the basic mechanisms of disease induction may lead to improved treatment for the disease. At present it remains a devestating disease with a frighteningly high mortality. Fortunately, recent early diagnosis and intervention with combined prednisone-cyclosporine therapy have provided at least some hope of controlling the disease.

Cyclosporine, a cyclic endecapeptide of fungal origin, has recently been released for use in clinical transplantation. Trials in kidney, heart, liver and bone marrow recipients were encouraging: 1-year graft survival rates were 70% to 80% for kidney and heart recipients, and 60% to 65% for liver allograft recipients. Cyclosporine is also effective in treating bone marrow recipients with acute graft-versus-host disease. The drug selectively inhibits T-helper cell production of growth factors essential for B cell and cytotoxic T-cell differentiation and proliferation, while allowing expansion of suppressor T-cell populations. Drug absorption varies greatly, necessitating monitoring of drug level and individualization of therapy. Nephrotoxicity is the most frequent side effect of cyclosporine. An increased incidence of B-cell lymphomas seen when cyclosporine was used in conjunction with cytotoxic agents or anti-lymphocyte globulin has very rarely been observed when concomitant immunosuppression has been limited to low-dose corticosteroids. Lower initial doses of cyclosporine, followed by more rapid tapering may reduce the incidence of nephrotoxicity without compromising improved graft outcome.

The changing pattern of mortality in systemic lupus erythematosus (SLE) led to an examination of the deaths in a long-term systematic analysis of 81 patients followed for five years at the University of Toronto Rheumatic Disease Unit. During the follow-up 11 patients died; six patients died within the first year after diagnosis (group I) and five patients died an average of 8.6 years (from 2.5 to 19.5 years) after diagnosis (group II). In those who died early, the SLE was active clinically and serologically, and nephritis was present in four. Their mean prednisone dose was 53.3 mg/day. In four patients a major septic episode contributed to their death. In those who died late in the course of the disease, only one patient had active lupus and none had active lupus nephritis. Their mean prednisone dose was 10.1 mg/day taken for a mean of 7.2 years. In none was sepsis a contributing factor to their death. All five of these patients had had a recent myocardial infarction at the time of death; in four, ti was the primary cause of death. Mortality in SLE follows a bimodal pattern. Patients who die early in the course of their disease, die with active lupus, receive large doses of steroids and have a remarkable incidence of infection. In those who die late in the course of the disease, death is associated with inactive lupus, long duration of steroid therapy and a striking incidence of myocardial infarction due to atherosclerotic heart disease.