Pediatric reference ranges for serum aldolase.

Most investigators have found that serum aldolase levels normally are higher in children than in adults. Although several earlier studies have included sufficient subjects to establish statistically reliable reference ranges, pediatric reference ranges have not been made available for the now widely used assay method of Pinto and associates (Clin Chem 1969;15:349-360.). The authors present age-related ranges determined by this method.

Musculoskeletal pain syndromes that affect adolescents.

Musculoskeletal pain is one of the most common pains of adolescence, along with headache and abdominal pain, and arthralgia is the single most common reason for referral to the pediatric rheumatologist. Not surprisingly, the pediatric rheumatologist is frequently called to distinguish organic from functional symptoms. During the past decade, the pediatric rheumatology community has been evaluating increasing numbers of adolescents and preadolescents who experience musculoskeletal symptoms presumably as a defense against emotional stress from achievement either in academic work or in sports. To complicate the challenge further, coexistent organic and psychologic disturbance is not rare. Clearly, organic illness does not protect a patient from emotional plan, and it may be most difficult to differentiate nonorganic pain in a patient with a known organic illness. Conversely, adolescents with organic illness may use their disease for secondary gain. Fear of misdiagnosis of physical illness as psychiatric and the notion that all of the patient's complaints should be explained by a unifying diagnosis cause diagnostic error in both psychogenic illness with physical manifestations and physical illness with psychogenic symptoms.

High dose methotrexate in the treatment of refractory juvenile rheumatoid arthritis.

OBJECTIVE: To assess the response to and safety of long term, high dose (> or = 1 mg/kg/week or > or = 15 mg/m2/week) methotrexate (MTX) administration, in a cohort of 21 children with longstanding, severe juvenile rheumatoid arthritis (JRA). METHODS: Children received MTX at an average weekly dose of 27 mg for a mean of 15.2 months. Outcome was assessed using a disease activity score based on changes in concomitant therapy, laboratory parameters, physician's global assessment, and radiologic evaluation. RESULTS: Seven patients (33%) improved, including one child who achieved complete remission, while 14/21 children (67%) did not benefit from high dose MTX. Subsequently, 6/14 (43%) of the non-responders discontinued high dose MTX and began cyclosporine. Radiologic progression, regardless of clinical outcome, was documented in 10/15 (67%) of the patients. The drug was well tolerated despite mild gastrointestinal symptoms and transient liver enzyme elevation. CONCLUSION: The results of this open retrospective pilot trial suggest that high dose MTX is well tolerated, but that its role in the treatment of children with refractory JRA may be limited. Radiologic progression, despite improvement in the clinical status or in the laboratory parameters, supports the hypothesis that MTX acts as a potent antiinflammatory agent.

Gastrointestinal and renal involvement in vasculitis: management strategies in Henoch-Schönlein purpura.

The joint pain, inflammation, and painful cutaneous edema of Henoch-Schölein purpura (HSP) are effectively treated with analgesics, nonsteroidal anti-inflammatory agents, and corticosteroids, but the optimal management of HSP-associated gastrointestinal and renal involvement has not yet been determined. The results of mostly anecdotal and uncontrolled studies favor a short course of oral corticosteroids for severe abdominal pain and aggressive immunosuppressive therapy for patients with progressive HSP nephritis.

Henoch-Schönlein purpura.

Henoch-Schönlein purpura (HSP) is the most common vasculitis syndrome of childhood. It is also known as anaphylactoid purpura, leukocytoclastic vasculitis, allergic vasculitis, and rarely, as rheumatoid purpura. It is generally a benign, self-limited disorder that follows an intercurrent illness, usually of the upper-respiratory tract. The classic triad of clinical symptoms and signs includes purpuric rash, abdominal cramping, and hematuria, but the spectrum of the clinical expression of HSP may vary from only minimal petechial rash to severe gastrointestinal, renal, neurologic, pulmonary, and joint disease. Most children have self-limited disease, and on long-term follow-up, systemic involvement or serious sequelae are not frequent. The current lack of knowledge about the factors underlying both the etiology and pathogenesis and the extent of clinical expression of HSP is illustrated in the recent literature. In addition, there is no agreement regarding the role of corticosteroids in the clinical management of HSP, and this subject has not received adequate attention during the past year. The recent clinical literature emphasizes the distinction between HSP and other hypersensitivity vasculitides and provides several in-depth reviews and multiple case reports illustrating the expanding clinical spectrum of the disorder. Exciting developments regarding immunologic aspects of HSP have been published and are summarized. The utility of antineutrophil cytoplasmic antibody as it applies to HSP remains to be elucidated.

Henoch-Schönlein purpura: when and how to treat.

The many facets of Henoch-Schönlein purpura are described with emphasis on the gastrointestinal and renal manifestations. The controversy surrounding management of children with abdominal pain and nephritis is discussed with a review of the current literature to support recommendations for treatment options.

Clinical development in the management of lupus in the neonate, child, and adolescent.

The recent literature in pediatric aspects of systemic lupus erythematosus has focused primarily on the spectrum and management of antiphospholipid syndrome in children; this review summarizes developments in this area. In addition, the neonatal lupus syndrome is discussed in detail, and newer approaches to the management of children and adolescents with systemic lupus erythematosus will be summarized.

Disseminated Nocardia brasiliensis infection: an unusual complication of immunosuppressive treatment for childhood dermatomyositis.

The use of steroids combined with cytotoxic drugs has increased in the last decade. The concomitant increase of opportunistic infections has contributed significantly to morbidity and mortality of patients treated with immunosuppressive agents. We describe a child with dermatomyositis who developed disseminated Nocardia brasiliensis infection while receiving steroids and methotrexate. Infectious etiology was established by gram stain. The patient was treated successfully. Disseminated Nocardia brasiliensis infection is rare with a high reported mortality. Diagnosis may be delayed secondary to insidious onset, similarity of clinical manifestations to other pathogens and slow growth in routine culture media. Nocardia should be considered early in the evaluation of infection in patients treated with immunosuppressive agents.

The long-term course of Lyme arthritis in children.

BACKGROUND AND METHODS: The natural history of Lyme disease is not completely known. We studied the long-term course of Lyme arthritis in 46 children in whom the onset of the disease occurred between 1976 and 1979 and who received no antibiotic therapy for at least the first four years of the illness. RESULTS: Of the 46 children (age range, 2 to 15 years), 33 (72 percent) initially had erythema migrans, 7 (15 percent) had influenza-like symptoms, and 6 (13 percent) had migratory joint pain. These manifestations were followed by brief attacks of arthritis, particularly affecting the knee. The percentage of children with recurrent episodes of arthritis declined each year. By year 4, only 10 children still had a mean of two episodes of arthritis per year; the duration of arthritis was generally longer in older children (P less than 0.05). During the sixth year of illness, two children (4 percent) had keratitis, and more than 10 years after the onset of disease, a subtle encephalopathy developed in two other children. Of the 39 children whom we were able to contact in 1988-1989, 12 (31 percent) still had occasional brief episodes of joint pain and 1 (3 percent) had marked fatigue. All 46 children had positive IgG antibody responses to Borrelia burgdorferi throughout the illness and on long-term follow-up. As compared with those who became asymptomatic, the children with recurrent symptoms more often had IgM responses to the spirochete and had significantly higher IgG titers (P less than 0.05). CONCLUSIONS: The course of initially untreated Lyme disease in children may include acute infection followed by attacks of arthritis and then by keratitis, subtle joint pain, or chronic encephalopathy.

Antinuclear antibody profile in juvenile rheumatoid arthritis.

Immunoblot positive sera from children with juvenile rheumatoid arthritis detected from 1 to greater than or equal to 10 proteins in HeLa nuclear sonicates. Thirty percent of the sera reacted with histone H1. Antibodies to at least 1 of 6 most frequently detected nonhistone proteins were present in 85% of the sera. Using immunopurified antibodies to each of the 6 common antigens, we found that 4 of them were associated with mitotic chromosomes. Most sera detected at least 1 of these 4 nonhistone chromosomal proteins. Fifteen percent of the sera immunoprecipitated ribonucleoproteins; some exhibited a novel specificity, precipitating mature transcripts of RNA polymerase III. When present, antibodies to a 45 kDa protein occur only in sera from children without iritis and not in those with active iritis. Overall, the antibody profiles were highly individual and did not appear to correlate with disease subtype or activity.

Autoantibodies to DNA topoisomerase II in juvenile rheumatoid arthritis.

Sera from 58 children with juvenile rheumatoid arthritis were examined for the presence of antibodies to DNA topoisomerase II. Eight sera were reactive in immunoblotting with purified human topoisomerase II and a protein encoded by a cloned cDNA expressed in Escherichia coli which represents the carboxy-terminal domain of the human enzyme. In addition, the sera detect topoisomerase II in mitotic chromosomes and chromosome scaffolds. Five of the sera bind to the native enzyme in solution and deplete such solutions of the active enzyme. All eight sera also contain antibodies to nuclear antigens other than topoisomerase II.

A novel autoantibody to the putative oncoprotein DEK in pauciarticular onset juvenile rheumatoid arthritis.

OBJECTIVE: To define the frequency of a novel autoantibody reactive with a 45 kDa protein in children with juvenile rheumatoid arthritis (JRA). This protein is expressed by the putative oncogene DEK associated with a subtype of acute myeloid leukemia. METHODS: The sera of 158 children with JRA were analyzed for the presence of anti-DEK by immunoblotting using purified DEK protein and compared with sera of 109 children with other rheumatic diseases and 25 healthy controls with no connective tissue disease. RESULTS: Antibodies to DEK were found significantly more frequently among children with JRA than among children with other rheumatic diseases or controls (p < 0.001). Among children with JRA, anti-DEK was significantly more often associated with pauciarticular onset than with poly-articular and systemic onset subtypes (77 vs 29 and 8%, respectively, p < 0.001). Anti-DEK was no more frequent among children with pauciarticular JRA complicated by iritis than among those without iritis (88 vs 71%, respectively). The frequency of anti-DEK in other rheumatic diseases varied from 0 in children with spondyloarthritis to 31% in scleroderma. CONCLUSION: Antibodies to DEK are highly associated with pauciarticular onset JRA.

The putative oncoprotein DEK, part of a chimera protein associated with acute myeloid leukaemia, is an autoantigen in juvenile rheumatoid arthritis.

The 45-kD autoantigen associated with juvenile rheumatoid arthritis (JRA) has been isolated from HeLa cell nuclei and purified about 2500-fold to near homogeneity in a five-step chromatographic procedure. Purification of the antigen was monitored by immunoblot assays using a nearly monospecific anti-45-kD serum from a child with JRA. Tryptic peptide mapping and partial amino acid sequencing of the purified 45-kD antigen demonstrated its identity with the DEK protein. DEK is a 43-kD protein of unknown function expressed by the putative oncogene dek located on chromosome 6. As a result of a (6;9) translocation offociated with a rare subtype of acute myeloid leukaemia a chimeric protein containing most of DEK amino acids at the N-terminus is found in leukaemic cells (von Linden et al., Mol Cell Biol. 1992; 12: 1687-97). The 43-kD DEK was detected by immunoblotting with serum from a patient with JRA in a variety of rat tissues, and was most abundant in the spleen and in bone marrow.

Arthritis as a manifestation of self-mutilation in childhood.

Traumatic arthritis resulting from self-aggression is rarely encountered in children. Differentiation from child abuse and common causes of childhood arthritis is difficult and rests upon a high level of suspicion. We describe a 10-year-old girl with hand deformities associated with joint pain and swelling managed as juvenile rheumatoid arthritis for 3 years. Reevaluation revealed both physical and radiographic evidence of recurrent trauma. Psychiatric assessment confirmed the diagnosis of autoaggression leading to self-mutilation and psychosocial rehabilitation was essential in successful management.

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.

Cerebral perfusion abnormalities in children with central nervous system manifestations of lupus detected by single photon emission computed tomography.

OBJECTIVE: Central nervous system (CNS) abnormalities have been reported in 30-60% of children with systemic lupus erythematosus (SLE) during the course of the disease. Unlike most other manifestations of childhood lupus, few laboratory studies and imaging modalities aid in the documentation of CNS lupus. Single photon emission computed tomography (SPECT) provides a means of assessing cerebral blood flow and may reveal subtle areas of decreased perfusion or loss of functioning brain parenchyma. METHODS: We evaluated 5 children with clinical signs of CNS lupus using SPECT, lumbar puncture, electroencephalogram (EEG), computerized tomogram (CT) and magnetic resonance imaging (MRI), as well as autoantibody and complement serologic testing. All patients fulfilled classification criteria for SLE and within one year of onset presented with the following CNS manifestations: grand mal seizures with encephalopathy or psychosis (2) and transverse myelitis (1), focal seizure and depression (1), and severe headache and ophthalmitis (1). RESULTS: Four patients had anticardiolipin (aCL) antibodies. One girl with positive aCL had a concurrent ischemic event involving both parietal lobes and another had a CNS bleed. Both of these children had abnormal EEG, CT and MRI scans. All children had normal cerebral spinal fluid analyses. No correlation was found between serologic variables and CNS disease. All 5 children had abnormal SPECT perfusion studies. CT and MRI failed to demonstrate abnormalities in 3 children. Although CT and MRI documented parietal lobe infarcts in one child and focal hemorrhage in another, poor perfusion found with SPECT extended beyond these abnormalities and into areas which appeared intact using the conventional imaging techniques. All children improved clinically and 4/5 had additional SPECT studies. In all 4, the perfusion abnormalities improved but did not resolve. One of these patients had a recurrence of hallucinations and worsening of SPECT findings which improved again after the patient stabilized. CONCLUSIONS: We conclude that the cerebral perfusion SPECT scan is a sensitive tool and may prove useful in the documentation of CNS lupus in children.

Prolonged course of illness in a child with malignant lymphoma mimicking sarcoidosis.

We describe a case of malignant lymphoma mimicking the rheumatic presentation of sarcoidosis in an adolescent with a 3-year history of febrile illness. Final diagnosis was established by tissue biopsy after multiple studies failed to provide histological evidence of granulomas consistent with sarcoidosis. We discuss the limited diagnostic specificity of serum angiotensin converting enzyme in sarcoidosis and emphasize the need for aggressive diagnostic evaluation of a patient whose clinical presentation is not fully explained by a known rheumatologic illness.