Erythrocyte-methotrexate and disease activity in children treated with oral methotrexate for juvenile chronic arthritis.

The concentration of methotrexate (MTX) in erythrocytes (E-MTX) was measured twice with three months interval in 21 children suffering from juvenile chronic arthritis (JCA). At the same time joint score, visual analogue scale (VAS), and laboratory parameters (CRP, WBC, PMNs, and ALAT) were obtained. There was only a weak insignificant correlation between the dose of MTX/m2 and E-MTX (r=0.24, p=0.11). No significant relations between the clinical or laboratory parameters and E-MTX was found. However, ALAT above normal range was associated with a lower dose of MTX (p=0.02) and lower VAS (p=0.02), indicating that toxicity may be associated with less articular discomfort. At present we consider routine determination of E-MTX in children with JCA of limited value.

Role of parvovirus B19 infection in childhood idiopathic thrombocytopenic purpura.

Although parvovirus B19 exhibits a strong tissue-tropism for erythroid progenitor cells leading to anaemia, several case reports indicate that parvovirus B19 infection may also cause the development of thrombocytopenia. Despite recent studies, the frequency and clinical relevance of this association have remained questionable. Consequently, and in view of the paucity of evidence regarding a viral aetiology for idiopathic thrombocytopenic purpura (ITP), we examined the role of parvovirus B19 in 47 children with newly diagnosed ITP. Specific viral DNA indicating a current or recent parvovirus B19 infection was demonstrated in 6 of 47 patients (13%) employing the polymerase chain reaction technique. Our study suggests that children with ITP and associated parvovirus B19 infection are characterized by acute onset of profound thrombocytopenia. Among the parvovirus B19 positive children, duration of disease was brief in three children treated with immunoglobulin but chronic in the remaining three patients given high-dose steroids. Prospective studies are needed to confirm these initial observations. This virus should be considered as a possible aetiologic agent in some children with ITP.

Final height, armspan, subischial leg length and body proportions in juvenile chronic arthritis. A long-term follow-up study.

OBJECTIVE: Assessment of growth disturbances in adults with a history of juvenile chronic arthritis (JCA). MATERIAL AND METHODS: Sixty-five subjects, 52 premenopausal females and 13 males with a mean age (range) of 32.2 years (22.3-49.4) participated. Mean age at disease onset was 5.7 years (0.8-15.8) and mean disease duration was 12.4 years (0.4-32). The follow-up time ranged from 18.7 to 46.9 years with a mean of 26.4 years. For each participant standard deviation scores (z-scores) for final height, delta-height (the difference between observed and expected height), armspan, subischial leg length and sitting height ratio, were calculated. RESULTS: The study group as a whole did not exhibit linear growth impairment. The categorical distribution of heights differed significantly from a expected distribution in a healthy population (p < 0.001). A height z-score < -2 SD was present in 10.7% of the study group, of whom all had polyarticular course of JCA. Polyarticular and systemic course of JCA (versus pauciarticular) (p = 0.022), systemic steroid treatment (p = 0.006) and Steinbrocker functional class II-IV (vs. I) in 1979 (p = 0.043) were variables associated with reduced delta-height. In linear regression analyses, disease severity defining variables were statistically significant predictors of reduced final height and armspan. 27% of the study subjects had significantly reduced arm span (p < 0.001). Subischial leg length and body proportions (sitting height ratio) were normal. CONCLUSION: Our findings suggest that functionally impaired polyarticular and systemic JCA patients treated with systemic steroids may be at an increased risk of developing reduced final height and armspan. Disease control achieved by an aggressive therapeutic approach, if possible with a minimal use of systemic steroids, may reduce growth impairment in JCA.

Sodium cromoglycate as a replacement for inhaled corticosteroids in mild-to-moderate childhood asthma.

We investigated whether sodium cromoglycate 10 mg three times daily, delivered as an aerosol via Nebuhaler (in addition to terbutaline 0.5 mg three times daily), could replace inhaled steroid in children with mild-to-moderate asthma. Children (mean age 10.3 years) were randomly allocated to 12-week treatment with sodium cromoglycate 10 mg plus terbutaline 0.5 mg (group A; n = 30) or placebo plus terbutaline 0.5 mg (group B; n = 32), both taken three times a day. The daily steroid dose was reduced by 50 microg/week for 4 weeks from a starting dose of 200 microg. Fewer patients withdrew owing to worsening asthma from group A (n = 1) than group B (n = 11). Symptom scores, morning and evening peak flows, and additional beta2-agonist usage, recorded on diary cards, were better in group A than group B. Lung function measured at clinic visits was unchanged in either group. Overall opinions of efficacy favoured Group A. Adverse events were similar in the groups. Sodium cromoglycate plus terbutaline substituted effectively for inhaled steroid therapy.

Restriction fragment length polymorphism of two HLA-B-associated transcripts genes in five autoimmune diseases.

The restriction fragment length polymorphism of the two human HLA-B-associated transcripts (BATs) genes, BAT1 and BAT2, identifying polymorphic bands of 12, 8, 2.5, and 1.1 kb, and at 3.3, 2.7, 2.3, and 0.9 kb, respectively, was investigated in patients with primary biliary cirrhosis (PBC), systemic lupus erythematosus (SLE), pauciarticular juvenile rheumatoid arthritis (P-JRA), rheumatoid arthritis (RA), and primary Sjögren's syndrome (pSS), and in healthy Danes. The BAT2/RsaI 2.7-kb band fragment was more frequent in PBC, pSS, and SLE than in controls, but the p values did not reach significance when corrected for multiple comparisons. For pSS and SLE, the associations may be secondary to primary associations with HLA-B8 because the BAT2/RsaI 2.3-kb band, which is allelic to the BAT2/RsaI 2.7-kb band, is strongly negatively associated with HLA-B8 and HLA-DR3. The only significance obtained shows that the HLA-B8 frequency is increased in BAT2/RsaI 2.7-kb positive pSS patients as compared to the corresponding controls indicating that the HLA-B8 association may be strongest. No missing or extra DNA fragments were observed in the disease groups when compared with controls indicating that gross deletions or duplications of the BAT1 and BAT2 genes in the patients are unlikely. In conclusions, it cannot be excluded that the BAT2/RsaI 2.7-kb band may contribute to the susceptibility to PBC, pSS, and SLE.

IL-6 gene polymorphism in rheumatoid arthritis, pauciarticular juvenile rheumatoid arthritis, systemic lupus erythematosus, and in healthy Danes.

The restriction enzymes MspI and BglII identify two different two-allele restriction fragment length polymorphisms (RFLP) in the human IL-6 genes of healthy Danes. Co-dominant segregation was demonstrated for both marker-systems and the test for Hardy-Weinberg equilibrium showed no significant deviation from expectations. There is a strong correlation between the two marker systems. The two IL-6 RFLP's were studied in Danish patients with rheumatoid arthritis, pauciarticular juvenile rheumatoid arthritis, and systemic lupus erythematosus. The frequencies of the MspI and BglII marker phenotypes did not differ between healthy controls and the three disease groups. No extra or missing DNA fragments were observed in the disease groups when compared with controls.

NcoI restriction fragment length polymorphism (RFLP) of the tumor necrosis factor (TNF alpha) region in four autoimmune diseases.

The two-allele NcoI Restriction Fragment Length Polymorphism (RFLP) of the TNF alpha region yielding bands of 5.5 and 10.5 kb was investigated in patients with systemic lupus erythematosus (SLE), pauciarticular juvenile rheumatoid arthritis (P-JRA), rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS). In all four disease, we found a decreased frequency of the 10.5 kb allele which, however, was significant only in the SLE group. In all conditions except RA, the frequency of the 5.5 kb fragment was increased. In pSS and SLE, the frequency of HLA-B8 was increased in 5.5 kb fragment positive patients compared with corresponding controls and thus, the increase of this band and the decrease of the 10.5 kb band may be secondary to HLA-B8 associations owing to strong positive linkage disequilibrium between HLA-B8 and the 5.5 kb band.

HLA antigen frequencies in juvenile chronic arthritis.

HLA-A, B, C, D, and DR typing was performed in 104 patients with Juvenile Chronic Arthritis (JCA). The majority of these (88 patients) participated in a follow-up study of a series of consecutive patients including patients in remission. The study confirmed that JCA is positively associated with B27, Dw8, and possibly Dw5, and negatively associated with Dw2 and Dw7. In JCA patients in remission, the frequency of Dw4 was significantly decreased to 5.0%, compared with 25.0% in healthy Danes and 23.7% in JCA patients with active disease. In pauciarticular onset JCA, the frequency of Dw4 was significantly decreased to 8.1% compared with 25.0% both in controls and in polyarticular onset JCA. These data indicate that Dw4 may be a risk factor of chronicity and multiple joint involvement in JCA. Chronic iritis was present in 18.2% of Dw8-positive patients, compared with 7.0% in Dw8-negative patients, and the frequency of Dw8 was 50.0% in JCA patients with chronic iritis. Thus, Dw8 may be a risk factor of chronic iritis in JCA. Genetically, three distinct subgroups seem to exist: (i) a B27-associated group; (ii) a D/DR5- and D/DRw8-associated group, and (iii) a D/DR4-associated group.

Recurrent pneumococcal infections in a patient with lack of specific IgG and IgM pneumococcal antibodies and deficiency of serum IgA, IgG2 and IgG4.

Disseminated pneumococcal infections in a young woman are described. Serum from the patient showed reduced opsonic capacity for pneumococci and absence of pneumococcal anticapsular IgG and IgM antibodies even after pneumococcal immunization. Total serum IgG level was normal, but IgG2, IgG4, and IgA were deficient. The possible location of pneumococcal IgG antibodies in the IgG2 subclass is discussed as well as the existence of serious antibody deficiencies in patients with normal total IgG levels.

Immunological studies in two children with recurrent parotitis.

In two children with recurrent parotitis, labial salivary gland biopsies showed chronic sialoadenitis. Immunofluorescence studies disclosed deposits of immunoglobulins and complement in juxta-acinar small vessels. Case 1 had gluten enteropathy, IgA deficiency and high titres of antinuclear antibodies (ANA), and in vivo fixation of ANA to nuclei of different cells in lip, skin and jejunum was present. Case 2 showed deposition of IgM in the dermo-epidermal junction of the skin. These findings suggest that autoimmune reactivity and immune complexes may play a role in the pathogenesis of this disorder.

Failure of pneumococcal vaccination in a splenectomized child.

Recurrent Streptococcus pneumoniae septicaemia occurred in a splenectomized child with idiopathic thrombocytopenic purpura. Fatal infection took place 1 year after pneumococcal vaccination and was caused by sero-type 18C which was included in the vaccine. The efficacy of pneumococcal vaccination is discussed in relation to specific pneumococcal polysaccharide antibody titers, and it is concluded that vaccination alone is insufficient in preventing overwhelming infections in splenectomized individuals.