Lymphoma and hypercalcemia in a pediatric orthotopic liver transplant patient.

We present a case report of a pediatric orthotopic liver transplant recipient who developed lymphoma with hypercalcemia on cyclosporine and prednisone immunosuppression. This is the first reported posttransplant lymphoproliferative disorder complicated by hypercalcemia, with a finding of an elevated 1,25 dihydroxyl vitamin D state, suggesting that it has a role in the pathophysiology of this B cell lymphoma hypercalcemia. The clinical course and management of this disorder with a 31-month follow-up are described.

Pyoderma gangrenosum as a manifestation of leukemia in childhood.

Pyoderma gangrenosum is an uncommon skin lesion often associated with autoimmune diseases. A clear association between leukemia and pyoderma gangrenosum in adults has been established. Two cases of pyoderma gangrenosum in children with leukemia in whom it may be an initial finding are presented.

Varicella in pediatric orthotopic liver transplant recipients.

From May 1981 to May 1984, 90 pediatric patients underwent liver transplantation and 65 patients survived as of May 1986. Two of the nonsurvivors died with complications related to clinical varicella. Of these 67 patients (65 survivors and two nonsurvivors who died of varicella-related causes), 51 patients were determined to be varicella susceptible. Clinical disease developed in no patients with serologic evidence or clinical history of varicella prior to transplantation. Eighteen susceptible patients were exposed and received zoster immune globulin and varicella did not develop. Clinical disease developed in eight patients despite zoster immune globulin, although one patient received it 96 hours after exposure. Six patients received no zoster immune globulin and clinical varicella developed. In all, varicella developed in 14 patients. Thirteen were admitted to the hospital and treated with intravenous acyclovir. Of those treated, two died of causes related to complications of varicella. The remaining patients treated with acyclovir had mild disease. The one patient not treated with acyclovir also had mild disease. We conclude that patients contracting varicella after liver transplantation while receiving maintenance immunosuppressive agents should be treated with intravenous acyclovir. Generally, when treated with acyclovir while receiving maintenance immunosuppressive drugs, these patients have mild clinical disease. Patients recently treated with high-dose prednisone and cyclosporine may have severe clinical disease resulting in death.

Evaluation of the pediatric patient for liver transplantation.

In a 36-month period from 1981 to 1984, 209 pediatric patients were evaluated for liver transplantation. The purpose of the evaluation was to assess the severity and progression of the disease, anatomical suitability for transplantation, and psychosocial stability and to initiate family education. Of the 209 patients evaluated, 85 (41%) underwent transplantations and 64 (75%) survived at least 12 months. Thirty-four (16%) patients were not considered candidates for transplantation. The mean waiting period increased from 80.3 days to 232 days. Of 174 patients considered for transplantation, 41 (24%) died prior to surgery. A formal evaluation for liver transplantation permitted appropriate selection of candidates and provided education for informed consent. We also stress the need for greater participation in pediatric organ donation.

Changes in life-style after liver transplantation.

Sixty-five pediatric patients who received liver transplants between May 1981 and May 1984 were observed for as many as 5 years and examined for changes in life-style. Children were less frequently hospitalized, spent less time hospitalized, required fewer medications, and generally had excellent liver and renal function after hepatic transplantation as compared with their pretransplantation status. Most children were in age-appropriate and standard school classes or were only 1 year behind. Cognitive abilities remained unchanged. Children improved in gross motor function and patients' behavior significantly improved according to parents' perceptions. Enuresis was more prevalent, however, than in the population of children who had not received liver transplants. Parental divorce rates were no greater than those reported for other families with chronically ill children. Overall, objective changes in life-style as well as parents' perceptions of behavior of children appear to be improved after liver transplantation.

Pediatric liver transplantation: patient evaluation and selection, infectious complications, and life-style after transplantation.

Liver transplantation is an increasingly accepted treatment for children with end-stage liver disease. Evaluation of the patient and appropriate patient selection for transplantation will become increasingly important issues as more and more children come to transplantation and compete for available organs. Numerous complications occur after transplantation, including infections. We have summarized our experience with bacterial, fungal, and viral infections in these patients and emphasize the need for continued improvement in immune suppressive drugs and regimens to minimize such complications. And finally, information presented on 65 pediatric patients followed 2 to 5 years suggests that, despite numerous complications and often prolonged hospitalization for transplantation, life-style after transplantation appears to be significantly improved.

Hepatic infarction and acute liver failure in children with extrahepatic biliary atresia and cirrhosis.

Acute hepatic failure developed in four patients (aged 7 to 13 months) who had extrahepatic biliary atresia treated initially by portoenterostomy. Two were stable outpatients with minimal jaundice, while the other two were hospitalized for metabolic or nutritional complications. Postmortem examination in each patient revealed massive acute hepatic infarction with few surviving hepatocytes. In all cases, the hepatic failure had been preceded by an episode of hypotension and/or hypovolemia. The exact pathogenesis of the infarction remains unclear but it may be related to decreased hepatic blood flow secondary to biliary obstruction. The only effective treatment for these patients is intensive supportive care and urgent liver transplantation.

Orthotopic liver transplantation, Epstein-Barr virus, cyclosporine, and lymphoproliferative disease: a growing concern.

Lymphoproliferative disease (LPD) is a well-recognized complication of both solid organ and bone marrow transplantations. The occurrence of LPD in these settings is related in part to the use of the immunosuppressive agent cyclosporine. We report 12 cases of LPD after orthotopic liver transplantations in 132 pediatric patients. Lymphoproliferative disease occurred as one of three clinical syndromes: (1) lymphadenopathic, (2) systemic, and (3) lymphomatous. Effective management of LPD with excisional therapy or reduction of immunosuppressive medications or both resulted in the survival of 7 of 12 patients. In an alarming and increasing percentage of patients after orthotopic liver transplantation, progressive LPD develops with lethal outcome (5/12 patients). Early recognition of LPD and aggressive intervention may improve outcome in this group.

Proteus syndrome: emphasis on the pulmonary manifestations.

Published articles on the radiologic aspects of Proteus syndrome are sparse. This report highlights the features of this disease with specific attention to the serious pulmonary manifestations that may occur at an early age. Two cases of Proteus syndrome and severe lung disease are presented, with complete autopsy in one case and correlative surgical pathologic data in the other. Multiple superficial and visceral vascular abnormalities were present in both cases. Both patients developed rapidly progressive diffuse cystic emphysematous pulmonary disease leading to the death of one patient at age 18 years and a heart-lung transplant in the other at age 8 1/2 years. Extensive gross pulmonary cysts were evident pathologically with diffuse panlobar emphysema microscopically. Studies of collagen and cultured fibroblasts in one patient revealed no abnormality. The early presentation, rapid progression and potentially lethal nature of lung involvement has not previously been emphasized.

Animal-induced injuries and disease, neonatal jaundice, viral infections, and immunizations.

This section features recent information in four areas of interest to the practicing pediatrician: animal-induced injuries and disease, neonatal jaundice, viral infections, and immunizations. The focus is on areas of major current discussion: the clinical spectrum and etiology of cat-scratch disease, the debate on new neonatal bilirubin recommendations, viral etiology of previously recognized clinical diagnoses, new immunization recommendations, and new vaccines. In addition, isolated but thought-provoking papers in the four areas over the past year are briefly discussed. By paying careful attention to highlighted articles, the busy practitioner should be able to keep abreast of rapid new developments.

Kawasaki disease and perineal rash.

During the past several years, we treated seven children with Kawasaki disease who developed a distinctive but rarely described perineal rash. This rash began three to four days from onset of the illness and desquamated in all instances by days 5 to 7. The presence of this rash may facilitate early diagnosis of Kawasaki disease and, hence, may influence the initiation of early treatment.

Systemic lupus erythematosus in a boy with chronic granulomatous disease: case report and review of the literature.

We describe a patient with X-linked chronic granulomatous disease (CGD) who developed systemic lupus erythematosus, which was characterized by photosensitivity, malar rash, glomerulonephritis, leukopenia, hypocomplementemia, antinuclear antibodies, and anti-double-stranded DNA antibodies, at age 3. The patient's mother is an asymptomatic carrier of CGD, and her other son (the patient's half-brother) also has CGD. Neither the mother nor the brother has clinical or serologic evidence of systemic lupus erythematosus. Previous cases of discoid lupus-like skin lesions have been reported both in carriers and in patients with CGD. Our patient represents the first reported case of an individual with convincing clinical, serologic, and pathologic evidence of systemic lupus erythematosus. The association between defective host defense mechanisms and autoimmune phenomena has been described previously in patients with Job's syndrome and in patients with B cell and T cell deficiency disorders, including the acquired immunodeficiency syndrome. The relationship between the known leukocyte defects in CGD and the pathogenesis of a lupus-like illness is unclear.

Linear growth following pediatric liver transplantation.

The linear growth of 29 patients was evaluated from two to 41/2 years after liver transplantation. All patients received cyclosporine and low-dose prednisone. Eight patients (28%) displayed acceleration of linear growth velocity and were above the fifth percentile at the end of the evaluation period. Four patients (14%) grew normally prior to transplantation and continued to grow normally after the surgical procedure. Only four patients (14%) dropped from higher levels to below the fifth percentile. Thirteen patients (45%) were less than the fifth percentile before and after surgery; ten of these 13 patients have attained normal or accelerated growth velocity. Good linear growth has been achieved in more than three fourths of patients who underwent liver transplantation.

Choosing a pediatric recipient for orthotopic liver transplantation.

Between March 3, 1981, and June 1, 1984, 216 children were evaluated for orthotopic liver transplantation. Of the 216 patients, 117 (55%) had received at least one liver transplant by June 1, 1985. Fifty-five (25%) died before transplantation. The 117 patients who received transplants were grouped according to severity of disease and degree of general decompensation at the time of transplantation. The severity of a patient's medical condition with the possible exception of deep hepatic coma, did not predict outcome following orthotopic liver transplantation. Seventy variables were assessed at the time of the evaluation. Twenty-three of the 70 variables were found to have prognostic significance with regard to death from progressive liver disease before transplantation. These 23 variables were incorporated into a multivariate model to provide a means of determining the relative risk of death among pediatric patients with end-stage liver disease. This information may allow more informed selection of candidates awaiting liver transplantation.

Acquired immunodeficiency syndrome in the child of a haemophiliac.

Oral thrush developed during the second month of life in the 5-month-old son of a patient with haemophilia A. He did not feed well, and interstitial pneumonitis, lymphadenopathy, hepatosplenomegaly, and a cellular immune defect consistent with the acquired immunodeficiency syndrome (AIDS) followed. Both parents had signs of pre-AIDS during the year before their son's illness. Transmission presumably occurred in 3 steps: parenterally, via factor VIII concentrate in the haemophiliac; heterosexually, from the haemophiliac to his wife; and vertically, from mother to infant, or via close paternal-infant or maternal-infant contact. This first report of AIDS in the child of a haemophiliac supports the theory that AIDS is caused by an infectious agent. Concentrate-treated haemophiliacs may transmit this agent to their spouses or children, resulting in pre-AIDS or AIDS.

Angiography of liver transplantation patients.

Over 45 months, 119 angiographic examinations were performed in 95 patients prior to liver transplantation, and 53 examinations in 44 patients after transplantation. Transplantation feasibility was influenced by patency of the portal vein and inferior vena cava. Selective arterial portography, wedged hepatic venography, and transhepatic portography were used to assess the portal vein if sonography or computed tomography was inconclusive. Major indications for angiography after transplantation included early liver failure, sepsis, unexplained elevation of liver enzyme levels, and delayed bile leakage, all of which may be due to hepatic artery thrombosis. Other indications included gastrointestinal tract bleeding, hemobilia, and evaluation of portal vein patency in patients with chronic rejection who were being considered for retransplantation. Normal radiographic features of hepatic artery and portal vein reconstruction are demonstrated. Complications diagnosed using results of angiography included hepatic artery or portal vein stenoses and thromboses and pancreaticoduodenal aneurysms. Intrahepatic arterial narrowing, attenuation, slow flow, and poor filling were seen in five patients with rejection.