Hypophyseal-pituitary-adrenal axis in autoimmune and rheumatic diseases.

This article discusses the effects of sex steroids and anterior pituitary hormones on the immune system. Data from clinical and experimental studies on the effects of CRH, FSH, LH, and prolactin are reviewed. This is followed by a summary of results from our studies on the effects of FSH, LH, and prolactin on PBMC, CD4+ cells, and CD8+ cells in vitro.

Neurologic manifestations in children with Lyme disease.

OBJECTIVE: Lyme disease (LD) is a tick-borne spirochetal infection with a wide range of neurologic and non-neurologic manifestations. The clinical diversity of LD and limitations in serologic diagnosis often make it difficult to document the diagnosis of neuroborreliosis with certainty. METHODS: We reviewed clinical manifestations in 97 seropositive children with particular attention to neurologic manifestations. Diagnostic criteria used in other case surveys were applied to determine how often a definitive diagnosis of neuroborreliosis could be made in children. RESULTS: Of 69 children who met criteria for LD, 32% (22) had new neurologic signs, 73% (16) of which were accounted for by facial palsy and aseptic meningitis. Five of those with neurologic findings also had erythema migrans (EM), and one had both EM and arthritis. Among those with neurologic involvement, boys outnumbered girls two to one. Neurologic abnormalities resolved spontaneously in five children before their serologic results were known. CONCLUSION: In our series, only 27% of children with neurologic abnormalities due to LD had a history of EM or arthritis. Seropositivity commonly constituted the primary basis for diagnosis of LD. Despite its nonspecificity, seropositivity for LD in children with neurologic symptoms usually signifies active neuroborreliosis.

Utility of rheumatoid factor in the diagnosis of juvenile rheumatoid arthritis.

Rheumatoid factor is commonly used by clinicians to assess children with possible juvenile rheumatoid arthritis. To assess its usefulness, we reviewed the case histories of patients in whom latex agglutinating rheumatoid factor was determined during 1981 to 1982 at our institution. A total of 437 charts were available for review. There were 11 patients with positive tests for rheumatoid factor, of whom five had juvenile rheumatoid arthritis, all polyarticular. A total of 426 children had negative results, of whom 100 had juvenile rheumatoid arthritis. This yields a sensitivity of 4.8% and a specificity of 98%. We then estimated the prevalence of juvenile rheumatoid arthritis in three clinical settings: a primary practitioner's office, a tertiary children's hospital walk-in clinic, and a pediatric rheumatology center. The predictive values and marginal benefits for rheumatoid factor were then calculated in those settings using Bayes' theorem. In the two general outpatient settings, the primary practitioner's office and tertiary walk-in clinic, the positive predictive values were 0.7% and 0.5%, respectively; marginal benefits were 0.4% and 0.3%, respectively. Rheumatoid factor testing appeared to be of some benefit in the pediatric rheumatology center with a positive predictive value of 72.5% and marginal benefit of 22.5%. In no case was rheumatoid factor testing helpful in establishing a diagnosis of juvenile rheumatoid arthritis or in ruling it out. Testing for rheumatoid factor is a poor screening procedure for juvenile rheumatoid arthritis in the general situations in which it is more likely to be requested and of supportive diagnostic value only in the highly restricted population of older children with polyarticular arthritis.

Pulmonary functions in children with progressive systemic sclerosis.

The patterns of pulmonary involvement in 13 children with progressive systemic sclerosis were investigated. Eight patients (61%) had respiratory symptoms or signs and 7 patients (55%) had abnormalities on chest roentgenogram. Twelve patients (92%) had abnormal pulmonary function tests: 7 had restrictive disease, 2 had obstructive disease, 2 had small airway disease, and 1 had an isolated reduction in the diffusing capacity of carbon monoxide. Nine patients had the test performed during the first year of illness, 3 during the second year, and 1 at 5 years. All patients had abnormal pulmonary function tests when first studied. Subsequent pulmonary function tests over a period of 3 to 10 years (mean 6.2 years) showed substantial changes in only 2 patients (1 patient had initial worsening of diffusing capacity of carbon monoxide followed by normalization and another patient showed improvement of obstructive disease). Two patients died during follow-up, 1 of pulmonary hypertension, the other of severe restrictive lung disease and myocardial fibrosis. The major findings of this study were (1) high frequency of pulmonary disease in children with progressive systemic sclerosis, (2) early involvement of the lungs, (3) relatively indolent progression of lung disease, and (4) the prognostic importance of the severity of pulmonary disease. Pulmonary manifestations of progressive systemic sclerosis in children appear to be similar to those of affected adults.

Sjögren's syndrome in children.

Sjögren's syndrome is a relatively uncommon condition in the pediatric age group. The clinical and immunological features of this disease in childhood have not been adequately described in the literature. Herein, we present details of the clinical features and results of laboratory investigations including minor salivary gland biopsy, parotid scintigraphy, and renal biopsy on two children with Sjögren's syndrome associated with systemic lupus erythematosus.

Pericarditis and cardiac tamponade in juvenile rheumatoid arthritis.

Cardiac tamponade is a rare complication of juvenile rheumatoid arthritis. Three cases seen in the last two years at the Children's Hospital of Philadelphia are reported and compared to four previously reported cases. All three children had systemic-type juvenile rheumatoid arthritis with tachypnea, shortness of breath, and chest pain. Cardiac signs in these children included decreased heart sounds, pericardial friction rub, jugular venous distention, and pulsus paradoxus greater than 12 mm Hg. Roentgenograms of the chest showed cardiomegaly with bilateral pleural effusions. Electrocardiograms showed sinus tachycardia and nonspecific ST-T wave changes. Echocardiograms demonstrated pericardial effusions in all subjects and poor ventricular movements in one child. All three children were treated with short-acting anti-inflammatory drugs and/or prednisone. Pericardiocentesis was performed in two cases. There was no significant morbidity after a mean follow-up of two years.

Esophageal motor abnormalities in children and adolescents with scleroderma and mixed connective tissue disease.

To determine the frequency and nature of esophageal motor abnormalities in children and adolescents with scleroderma syndromes and mixed connective tissue disease, esophageal manometry was performed on seven patients with progressive systemic sclerosis, four patients with mixed connective tissue disease, and two patients with linear scleroderma. A total of 73% of patients with progressive systemic sclerosis and mixed connective tissue disease had symptoms of esophageal dysfunction. A significant association between the presence of Raynaud phenomenon and esophageal symptoms was noted. Esophageal motor abnormalities were detected in 73% of patients with progressive systemic sclerosis and mixed connective tissue disease; these abnormalities were characterized by decreased lower esophageal sphincter pressure and abnormal peristalsis in the distal two thirds of the esophageal body. They resemble those described among adults with progressive systemic sclerosis and mixed connective tissue disease but were not related to disease duration or to the presence of Raynaud phenomenon. Patients with linear scleroderma did not have esophageal symptoms and demonstrated only nonspecific motor abnormalities that did not worsen during several years of follow-up.

Successful treatment of severe cytophagic histiocytic panniculitis with cyclosporine A.

Cytophagic histiocytic panniculitis (CHP) can be a severe variant of Weber-Christian disease characterized by the histopathologic appearance of lobular panniculitis infiltrated by histiocytes containing blood cell fragments and by a clinical course with marked systemic features including multiorgan failure, hypertriglyceridemia, and coagulopathy, which may lead to death. Therapy of CHP includes standard treatment for panniculitis, such as antimalarials, plus immunosuppressives for more severe cases. The response to treatment, however, is unpredictable. In several recent reports, cyclosporine A has been successfully used to treat panniculitis. We report a patient and review the literature on CHP and the use of cyclosporine A as therapy. Published reports reveal that in instances of severe CHP when cyclosporine A was not given, 19 of 27 patients died (70% mortality). When severe CHP was treated with cyclosporine A, rapid remission was achieved in our patient and all five previously published cases (0% mortality). We believe cyclosporine A is the drug of choice in severe CHP and should be considered in all such patients.

Preliminary observations on maternal rating of health of children: data from three subspecialty clinics.

Although routinely used in health surveys, the factors affecting maternal perceptions of health in children, especially those with health problems, have received little examination. This question has been addressed using a telephone interview of families of 483 children followed in one of three clinics at Children's Hospital of Philadelphia: the Neonatal Follow-up Program, the Pediatric Rheumatology Center and the Spina Bifida Program. Limitations in activities of daily living due to the health of the child, medical care use and variables indicative of socio-economic disadvantage were associated with a maternal rating of child health as fair/poor in all groups. The relationship was strongest in the rheumatologic group and less strong in the other two, suggesting that mothers may distinguish between a chronic active disease in a previously healthy child and the disability following a neonatal event in conceptualizing health. The results add to our information about maternal perceptions in assessing child health and suggest ways in which such ratings may prove useful in assessing health and health services for children with health problems.

Current status of the medical treatment of children with juvenile rheumatoid arthritis.

Based on clinical experience and the aforementioned studies, a number of opinions can be entertained concerning the historically traditional conservative management of children with JRA. 1. Because the inflammatory changes of JRA on the bones and joints once established are irreversible in most children, there are ample theoretical reasons to start more effective therapy (if available) early. 2. Most of the currently available drugs control inflammation only partially or temporarily. 3. Most children stop taking the various SAARDS after approximately 2 years of disease because of lack of efficacy or the development of toxicity. 4. Whereas corticosteroids are the most potent and effective anti-inflammatory agents, long-term use in children, even in low dosage, is severely limited, especially by their effect on growth. 5. Methotrexate appears to be the most effective of the alternative agents and much safer than expected when used in the currently recommended protocol. 6. More effective therapy must await a better understanding of the pathogenesis of JRA, although currently available medications might be used more rationally by taking into consideration available pharmacologic studies.

Impact of chronic illness on families.

Standard scales were used to measure the reaction of the parent and family to long-term disability in a child in terms of family stress, both emotional and financial. The most significant factors that bear upon family impact were the level of education of the respondent, parenteral perception of the health of the child, and the number of limitations of activities of daily living that were experienced by that child.

Syndromes and arthritis.

There are many questions and no clear answers raised by these children. These syndromes, however, seem to be biologic experiments of nature and present unique opportunities to study the various elements involved in the pathogenesis of arthritis. Pediatric rheumatologists are in a unique position to study these syndromes.

Adolescents with chronic disease. Transition to adult health care.

Older adolescents are in the midst of many life changes related to physical and emotional development, education and career choices, family and peer relationships. The presence of a chronic disease adds an additional burden. At this stage of development, transfer of care to an adult facility becomes a major challenge for the adolescent, parents, and pediatric and adult care providers. This article describes an interdisciplinary transition program from pediatric to adult health care for older adolescents with rheumatic diseases. Care is transferred to an internist-rheumatologist who collaborates closely with the pediatric team. Scope of the program includes pretransitional assessments and interventions, including education, counseling, and referral around career, postsecondary education, sexuality, and other transitional issues. Benefits of and barriers to a structured transition program are discussed.

Pulmonary manifestations of juvenile rheumatoid arthritis. A report of eight cases and review.

Pleuropulmonary disease was seen in 4 per cent of patients with juvenile rheumatoid arthritis. Roentgenographic abnormalities seen in association with juvenile rheumatoid arthritis include: transient pneumonitis, interstitial reticular and nodular infiltrates, pleural and pericardial effusions, and patchy pleural infiltrates. Pathologic abnormalities seen in association with juvenile rheumatoid arthritis include pulmonary hemosiderosis, lymphoid follicular bronchiolitis, and lymphocytic interstitial pneumonitis. Patients with juvenile rheumatoid arthritis and pleural disease recover fully. In children with parenchymal disease, residual abnormalities include roentgenographic evidence of interstitial fibrosis and minimal abnormalities of pulmonary function.

Juvenile arthritis in Turner's syndrome: a multicenter study.

OBJECTIVE: Turner's syndrome (TS) is a disorder associated with characteristic defects in the X chromosome. Autoimmune conditions such as thyroiditis, inflammatory bowel diseases and diabetes have been described in association with TS. METHODS: We have studied the association between TS and juvenile arthritis (JA) by using a survey in which 28 pediatric rheumatology centers (15 in the USA, 10 in Europe, and 3 in Canada) participated. RESULTS: Eighteen cases of TS in a population of approximately 15,000 JRA patients have been found. Two different patterns of arthritis were present: polyarticular (7) and oligoarticular (11). Children with polyarticular disease had early onset, seronegative, progressively deforming arthritis and growth retardation. Those with oligoarticular arthritis had a benign course and were ANA+ (8/11). The oligoarticular children had varying karyotypes whereas almost all of the polyarthritic patients shared the same 45X0 karyotype (6/7). The light and electron microscopic studies of synovium performed in two patients showed chronic inflammation and hyperplasia of the synovial lining cells, vascular proliferation and infiltration with lymphocytes, plasma cells and mononuclear phagocytes. CONCLUSION: Juvenile arthritis is a new autoimmune condition association with Turner's syndrome. The prevalence seems to be at least six times greater than would be expected if the two conditions were only randomly associated. This is the first description of the synovium in Turner's syndrome; no differences from other forms of juvenile rheumatoid arthritis were found.

Estrogen receptor levels in a murine model of systemic lupus erythematosus.

Offspring of a cross between the NZB and NZW mice (F1) develop a disease similar to SLE in humans. Female mice of the F1 strain develop the disease at a younger age and die earlier than the males. In order to test the hypothesis that estrogen receptor concentrations in the lymphoid organs of these mice may correlate with increased female susceptibility, estrogen receptor assays were performed on cytosol from the uterus, thymus, spleen, and liver of affected animals and the parental stock using the dextran-charcoal method. Specific binding of the receptor was analysed by Scatchard analysis. There were no differences among receptor concentrations in the uterus, thymus, and spleen of NZB, NZW, and F1 mice. However, the estrogen receptor concentrations in the liver from NZW and F1 mice were twice that of NZB mice. This observation may be of importance since the liver is involved in steroid metabolism and abnormalities of estrogen metabolism have been reported in human SLE.

Vasospastic disorders in children.

A number of conditions can cause color and temperature changes in the extremities. These include physical and chemical insults (eg, frost-bite; ergot), vasculitis (eg, systemic lupus erythematosus), or conditions associated with vascular tone. This article reviews two conditions that are commonly seen in children (Raynaud syndrome and reflex sympathetic dystrophy) and a recently recognized condition associated with antiphospholipid antibody. The emphasis is on differences between the adult and childhood forms of these disorders.

Vasculitis in children.

Common vasculitic disorders in children include those associated with infections (e.g., Rickettsiae, subacute bacterial endocarditis), Schonlein-Henoch purpura, and Kawasaki disease. Recent advances have occurred in understanding the pathogenesis of vasculitides. In this review, the reader will be exposed to some of the developments in adhesion molecules, antineutrophil cytoplasmic antibodies, antiendothelial antibodies, and antiphospholipid antibodies. Classification criteria and diagnostic strategies are also summarized.

Lyme disease. Difficulties in diagnosis and management.

LB is a multisystem illness caused by the spirochete B. burgdorferi. As with other spirochetal diseases, LB evolves in stages. Some manifestations are the result of persistent infection, whereas other symptoms are a consequence of immunologic changes secondary to the infection. Most disease manifestations are not specific to this illness. In addition, in endemic areas, almost 100% of the tick vector, the Ixodes species, are infected and the incidence rate of LB is as high as 1%. Because of these factors, the illness is overdiagnosed and overtreated. We have reviewed the current state of diagnosis and treatment of LB as well as questions that arise during the management of this illness.

Physical and occupational therapy for children with rheumatic diseases.

Total management of rheumatic disorders of children includes antiinflammatory drugs, active therapy, maintenance of ADLs, and attention to the psychosocial development of the child. This article focuses on the role that physical and occupational therapists play in the management of children with arthritis. The complexity of the problems of these children necessitates a multidisciplinary team approach, with professionals who are committed to helping the child lead as normal a life as possible. This objective can be accomplished only by teaching families and school personnel how to manage the child's daily therapeutic needs.