Search

OBJECTIVES: To determine the health of mothers of offspring with complete congenital heart block (CHB) both at the time of delivery of the affected child and in the long-term, and the percentage of mothers of children with CHB who had anti SSA/RO and/or SSB/LA antibodies. PATIENTS AND METHODS: Sixty-four mothers of 64 children with CHB (seen between 1964 and 1993) were identified through the Cardiology database of The Hospital for Sick Children, Toronto, Canada. Medical information from these of children with CHB was evaluated. Data were obtained from the mothers by mailed questionnaire, telephone interview, and/or from the attending physicians. The presence of anti-Ro antibodies and anti-La antibodies were evaluated by ELISA assay. RESULTS: The mean age at the time of delivery of the first child with CHB was 28 [+ or -]6 years. At the time of delivery 42 (66%) mothers were healthy, 2 (3%) had systemic lupus erythematosus (SLE), 2 (3%) had linear scleroderma, 2(3%) had rheumatoid arthritis; 3(5%) had a history of rheumatic fever (but were otherwise well), 1(2%) had Sjogren's syndrome (SS), and 12(19%) had an undifferentiated autoimmune syndrome (UAS) (arthralgia, myalgia, photosensitivity, skin vasculitis, Raynaud's phenomenon). The mean time to follow-up from delivery to study was 121 [+ or -]88 months. The mean maternal age at study was 38 [+ or -]9 years. Three of 12 mothers who initially had a UAS progressed to SLE (average follow-up time of 80 months, median 96), and 2 developed SS (with average follow-up time 140 months, median 132) and 1 went into remission. The mean follow-up time for the other mothers who did not develop an autoimmune disease was 150 [+ or -]102 months. Thirty-six of the 42 initially healthy mothers remained well. One mother developed SLE; 1 developed hyperthyroidism; 1 developed ankylosing spondylitis; and 3 developed an UAS. The mean follow-up time of the 36 mothers who remained healthy was similar (123 [+ or -]97 months) to the 6 initially healthy mothers who developed an autoimmune disease (121 [+ or -]36 months). Anti-Ro and/or anti-La antibodies were positive in 32 of 53 (60%) mothers tested. Fourteen of the 53 mothers were symptomatic at the time of delivery and 39 were asymptomatic. Anti-Ro and/or anti-La antibodies were positive in 12 of 13 mothers tested at the time of delivery. CONCLUSIONS: The long-term maternal outcome in our cohort was very good as most of the initially healthy mothers remained well at follow-up. Twenty-five percent of the mothers with a UAS and only 2% of the initially healthy mothers developed SLE. The development of an autoimmune disease in an asymptomatic mother identified by the birth of a child with CHB was less common in our study than in previous studies. However, close follow-up of mothers with UAS is warranted.

The aim of this study was to examine the impact of timing of a childhood‐onset systemic lupus erythematosus (SLE) diagnosis relative to menarchal status, on final height, accounting for disease‐associated factors. We conducted a cohort study of female patients age <18 years at childhood‐onset SLE diagnosis, followed at a tertiary care pediatric center from July 1982 to March 2016 and restricted to patients with documented age of menarche and final height. We compared final height between patients diagnosed pre‐ and postmenarche. We tested the association of the timing of childhood‐onset SLE diagnosis with final height, adjusted for ethnicity, in linear regression models. We performed subgroup analyses of patients with growth during follow‐up, additionally adjusting for average daily corticosteroid dose and disease activity. Of 401 female childhood‐onset SLE patients in the study, 115 patients (29%) were diagnosed premenarche and 286 (71%) postmenarche. Patients diagnosed premenarche were older at menarche compared with patients diagnosed postmenarche (mean ± SD age 13.5 ± 1.4 versus 12.5 ± 1.3 years; P< 0.001). The mean ± SD final height for girls diagnosed postmenarche (161.4 ± 6.9 cm) was greater than for those diagnosed premenarche (158.8 ± 7.3 cm; P= 0.001). In regression analysis, those diagnosed postmenarche were significantly taller than those diagnosed premenarche, as adjusted for ethnicity and disease severity (mean ± SD β = 2.6 ± 0.7 cm; P= 0.0006). In this large cohort study of girls with childhood‐onset SLE, patients diagnosed postmenarche achieved a taller final height than those diagnosed premenarche, even after accounting for ethnicity and disease severity.

Dermatomyositis is a connective tissue disease characterized by muscle inflammation and deterioration, skin inflammation, and accumulation of tissue fluid. This condition is most often treated with prednisone (a steroid), although some patients have little or no response to steroid treatment. Other patients become dependent on steroids or develop drug-related side effects. Patients who do not respond to, or cannot tolerate, steroid treatment are given immunosuppressive agents, which reduce immune function. However, immunosuppressive drugs, such as methotrexate, azathioprine, cyclophosphamide, chlorambucil, and cyclosporin A have not been consistently effective in treating dermatomyositis and may cause toxic effects, particularly in children. High doses of intravenous gammaglobulin (IVGG), an immune protein preparation, have been effective in treating various immune disorders, including one reported case of infantile polymyositis, a condition occurring in children that is similar to dermatomyositis. The effectiveness of IVGG was assessed in five patients with juvenile dermatomyositis. Prior treatment with steroids did not improve muscle weakness in these patients and caused toxic effects in three patients. In addition, previous therapy with immunosuppressive agents caused toxic effects in two patients. Treatment with IVGG increased muscle strength and improved skin inflammation. Muscle strength was increased from 56 to 606 percent in the legs, and from 30 to 186 percent in the arms. The use of IVGG eliminated or reduced the need for steroid therapy. These findings show that IVGG is effective in treating juvenile dermatomyositis, reduces the need for steroid treatment, and may be considered as an alternative to traditional therapy for juvenile polymyositis. (Consumer Summary produced by Reliance Medical Information, Inc.)

Kawasaki disease (KD) causes high fever, rash, and frequent cardiac complications in young children; the cause of disease disorder is unknown. KD is currently treated with aspirin, or other salicylates, and gamma-globulin. The reason that salicylate therapy is effective and the best dosage have been debated, and have not been well-studied. Previous research has suggested that the handling of salicylates in children with KD is altered; absorption is decreased, while excretion is increased during the acute phase of the illness. This has led to treatment with higher doses to keep blood levels of salicylates in the therapeutic range. Aspirin and other drugs are chiefly transported in blood by albumin (a protein). A small portion remains free, or unbound, and this free portion is the therapeutically effective fraction. One study has found decreased salicylate-protein binding in KD patients, which should lead to higher free levels of salicylate, so that more would be available for the therapeutic effect. If this is not accounted for, and salicylate dosage is increased, toxic effects may occur. Salicylate-protein binding was evaluated in 36 patients with KD. Protein binding of salicylate during the acute phase of KD averaged 73 percent, and increased significantly during the subacute phase to 90 percent. Albumin levels were 29.2 grams per liter of blood (gm/L) during the acute phase and 36.7 gm/L during the subacute phase. Normally, total salicylate levels correlate closely with protein-salicylate binding, but patients with KD had lower than normal protein-salicylate binding per level of total salicylates. Protein-salicylate binding in KD patients correlated significantly with albumin levels. Calculations showed that children with low albumin levels had twice as much free salicylates. Tinnitus (ringing in ear), a sign of salicylate toxicity, was not reported in these patients. These findings should be considered when adjusting salicylate dosage in children with KD. (Consumer Summary produced by Reliance Medical Information, Inc.)

This report discusses the case of a two-month-old boy who entered a hospital with fever, pallor, irritability, and cyanosis (blue skin color, indicating reduced hemoglobin in the blood). Three weeks before admission, the infant had a fever and raspy breathing, but a chest X-ray revealed no signs of pneumonia. He was treated with an antibiotic and subsequently developed a widespread red rash and lip bleeding, which disappeared three days after discontinuing the antibiotic. The infant seemed better, but did not sleep well and was constipated; he then developed blood in the stool, cyanotic toes, and a pink stain on his diaper indicated a urinary problem. The infant's course in the hospital and in the critical care unit to which he was transferred is described. An initial diagnosis of meningitis was considered, for which antibiotics were given, but no bacteria could be isolated. The possibility of pneumonia was then considered. The infant had raised levels of white blood cells, continued peripheral cyanosis, but normal heart rate and respiration 10 hours after admission to critical care. He suddenly developed cardiac fibrillation (very fast, ineffective heart beat) and could not be resuscitated. The signs and symptoms are reviewed with reference to possible causes. Sudden death in an infant with no resuscitation of a previously beating heart is very rare. The final diagnosis was infantile polyarteritis nodosa, with involvement of coronary and systemic arteries. The pathologist's report corroborated this diagnosis, which is more appropriately called Kawasaki disease, as the disorder does not resemble the adult form of polyarteritis nodosa. Typical signs of Kawasaki disease normally include five of the six following signs: high fever lasting more than five days; eye inflammation; redness and swelling of the oral cavity; swelling of palms of hands and feet with redness and peeling; trunk rash; or swelling of neck lymph nodes. However, this case history indicates that these signs may not consistently appear in young infants, who have a higher death rate from the disease. Kawasaki disease should be considered as a possible diagnosis in young infants with persisting, unexplained fever. Examination of the heart (by echocardiography) and of the eyes (with a slit lamp) may be helpful in early diagnosis so that treatment can be instituted as soon as possible. (Consumer Summary produced by Reliance Medical Information, Inc.)

Kawasaki syndrome (KS) is an acute febrile (fever-causing) disease that is associated with skin rash, peeling, and swollen lymph nodes. Relatively serious long-term effects are coronary artery disease and aneurysm of the heart wall or arteries. The cause of KS is unknown, but altered immune system function has been implicated. High-dose aspirin therapy has been the accepted treatment, and is effective in reducing fever and inflammation in the acute stage. Intravenously administered gamma globulin (GG), which contains a particular group of antibodies made by the immune system, is effective in decreasing the cardiovascular complications that follow KS when treated with aspirin, but the best dosage and treatment schedule in unknown. Children with KS, aged 9 to 111 months, were put on aspirin therapy, and the effectiveness of two doses and schedules of GG was studied. The first group of 25 children was given a single dose of 1 gram (gm) GG per kilogram (kg) body weight, while the second group of 22 children were given 400 milligrams GG per kg once daily for four days. Alterations in blood levels of several types of immune globulins were observed, the significance of which is unclear. Two patients from the first group developed small coronary artery aneurysms by 21 days after the start of KS, which persisted at least until day 49, but which were not visible by echocardiography at one year. One patient from the second group developed multiple small aneurysms with a similar time course, but after one year, several aneurysms were still visible. Fevers declined more rapidly in the group given 1 gm GG per kg and this led to a decrease in hospitalization by one day, on average. Four children in the first group and three in the second group had mild adverse reactions to treatment with GG. These included flushing, chills, nausea and vomiting, or hypotension. The study indicates that GG given in a single dose of 1 gm per kg is associated with more rapid improvement, but further research on the effects of GG and immune system function in Kawasaki syndrome is needed. (Consumer Summary produced by Reliance Medical Information, Inc.)

Juvenile rheumatoid arthritis (JRA) is a chronic inflammatory systemic disease that effects, but is not limited to the joints; the disease can be very debilitating. Like other rheumatoid diseases, JRA is thought to have an autoimmune component, in which the body makes antibodies against its own tissues. Other dysfunctions of the immune system may be present, including deficiency of some types of antibodies. Drug treatment includes aspirin-like drugs, but steroids, which can retard growth in children, are frequently necessary. Treatment with gamma globulin (GG), a type of antibody, has been successfully used in other autoimmune diseases, and its effects on eight patients with JRA were evaluated in this report. The children had been unresponsive to previous drug therapies. Following six monthly GG injections, arthritis was significantly improved in five children, and seven non-joint symptoms were also improved. One child did not improve in either of these areas. Of the six patients receiving steroids at the start of the study, half were able to discontinue these drugs, and the other half decreased dosage by more than 50 percent. GG treatment caused improvement in anemia and blood protein levels and in blood cell responses, while the children's production of native GG decreased. These results suggest that intravenous GG may benefit patients with JRA. (Consumer Summary produced by Reliance Medical Information, Inc.)

Kawasaki disease is an acute illness, which causes inflammation of blood vessels, especially coronary arteries, and may lead to cardiovascular complications, such as aneurysm. It has been proposed that activation of the immune system contributes to the development of Kawasaki disease. In rheumatic arthritis and other immune diseases, elevated levels of immune factors, such as interleukin-2 (IL-2) and the receptor to which it attaches, have been found. In particular, white blood cells appear to release forms of the IL-2 receptor which are soluble in the blood stream, and in some cases levels of the IL-2 receptor correlate with the disease severity. Early identification of Kawasaki patients in whom coronary arteries may be affected is important, because timely treatment appears to prevent aneurysm formation. Blood samples from 57 patients with Kawasaki disease were studied, and levels of soluble IL-2 receptor were elevated during the acute phase, and remained elevated during the succeeding early subacute stage. IL-2 receptor levels dropped during the subsequent convalescent phase, but were still greater than in control patients. No correlations were found between levels of soluble IL-2 receptor and coronary artery abnormalities or treatment with intravenous gamma globulin. Levels of the receptor decreased with increasing age of patients. Although a marker for coronary complications was not found, soluble IL-2 receptor is a sensitive marker of immune activation in cases of Kawasaki disease. (Consumer Summary produced by Reliance Medical Information, Inc.)

Behcet's syndrome is a chronic, recurring disease characterized by: ulcer formation in the mouth and genitals; iritis, or inflammation of the iris (the colored contracting membrane of the eye that controls the entry of light into the eye); and joint pain. Additional symptoms include inflammation of the skin blood vessels; inflammation of the membrane lining the joints; ulcer formation in the gastrointestinal system; inflammation of the brain and its membranes; inflammation of veins with blood clot formation; and other blood vessel disorders associated with vessel blockage. Behcet's syndrome is rarely complicated by myositis, the inflammation of muscle tissue. A case is described of a 15-year-old girl who developed unusual symptoms of Behcet's syndrome, including myositis affecting the calf muscle, and neutropenia, an abnormally low amount of neutrophils (a type of white blood cell). Behcet's syndrome is rare in children, and is associated with symptoms that are different from those in adults. Complications of the eye tend to occur less frequently in children with Behcet's syndrome than in adult patients. In addition, unusual symptoms occur more often in children with this disorder than in adults with Behcet's syndrome. (Consumer Summary produced by Reliance Medical Information, Inc.)

Objective.Specific risk alleles for childhood-onset systemic lupus erythematosus SLE (cSLE) vs adult-onset SLE (aSLE) patients have not been identified. The aims of this study were to determine if there is an association (1) between non-HLA–related genetic risk score (GRS) and age of SLE diagnosis, and (2) between HLA-related GRS and age of SLE diagnosis.Methods.Genomic DNA was obtained from 2001 multiethnic patients and genotyped using the Immunochip. Following quality control, genetic risk counting (GRCS), weighted (GRWS), standardized counting (GRSCS), and standardized weighted (GRSWS) scores were calculated based on independent single-nucleotide polymorphisms from validated SLE loci. Scores were analyzed in a regression model and adjusted by sex and ancestral population.Results.The analyzed cohort consisted of 1540 patients: 1351 females and 189 males (675 cSLE and 865 aSLE). There were significant negative associations between all non-HLA GRS and age of SLE diagnosis: P= 0.011 and r2= 0.175 for GRWS; P= 0.008 and r2= 0.178 for GRSCS; P= 0.002 and r2= 0.176 for GRSWS (higher GRS correlated with lower age of diagnosis.) All HLA GRS showed significant positive associations with age of diagnosis: P= 0.049 and r2= 0.176 for GRCS; P= 0.022 and r2= 0.176 for GRWS; P= 0.022 and r2= 0.176 for GRSCS; P= 0.011 and r2= 0.177 for GRSWS (higher GRS correlated with higher age of diagnosis).Conclusion.Our data suggest that there is a linear relationship between genetic risk and age of SLE diagnosis and that HLA and non-HLA GRS are associated with age of diagnosis in opposite directions.

Undervaluing the effectiveness of conventional treatments may lead to overtreatment with biologic medications in children with juvenile idiopathic arthritis (JIA). Using data from a nationwide inception cohort and strict methods to control bias, the aim of our study was to estimate the real‐world effectiveness of simple JIAtreatment strategies recommended in current guidelines. Children with JIAwho were recruited at 16 Canadian centers from 2005 to 2010 were followed for up to 5 years. For each child, all observed treatment changes over time were assessed by independent physicians using prospectively collected data and published response criteria. Success was defined as attainment of inactive disease or maintenance of this state when stepping down treatment; minimally active disease was deemed acceptable for children with polyarticular JIA. Success rates were calculated for treatments tried ≥25 times, and logistic regression analysis identified features associated with success. A total of 4,429 treatment episodes were observed in 1,352 children. Nonsteroidal antiinflammatory drug (NSAID) monotherapy was attempted 697 times, mostly as initial treatment when <5 joints were involved, with a 54.4% success rate (95% confidence interval [95% CI] 50.3–58.6). NSAIDs plus joint injections had a 64.7% success rate (95% CI59.8–69.7). Adding methotrexate to NSAIDs and/or joint injections (attempted 566 times) had a 60.5% success rate (95% CI55.7–65.3). In adjusted analyses, each additional active joint reduced chances of success for treatment with NSAIDs (odds ratio [OR] 0.90 [95% CI0.85–0.94]) and for methotrexate combinations (OR0.96 [95% CI0.94–0.99]). Each additional year after disease onset reduced chances of success for treatment with methotrexate combinations (OR0.83 [95% CI0.72–0.95]). These real‐world effectiveness estimates show that conventional nonbiologic treatment strategies that are recommended in current guidelines are effective in achieving treatment targets in many children with JIA.

Various connective tissue disorders, such as systemic lupus erythematosus (SLE), may be complicated by thyroid disease. Thyroid disorders develop in 7.5 to 8.9 percent of patients with SLE, and include hypothyroidism, or decreased activity of the thyroid gland; the production of antithyroid antibodies, or immune proteins, directed against the thyroid gland; or hyperthyroidism, abnormally increased activity of the thyroid glands. Hashimoto thyroiditis, characterized by an enlarged thyroid and hypothyroidism, and Grave's disease, characterized by an enlarged thyroid gland and protrusion of the eyeballs, are autoimmune diseases, conditions in which the immune system attacks the body's own tissues. These autoimmune thyroid disorders are rare in children. The incidence of autoimmune thyroid disorders in children with SLE was assessed. Thyroid abnormalities were detected in six of 35 children with SLE, including four with hypothyroidism and two with elevated levels of the thyroid hormone thyroxine. Antithyroid antibodies were detected in 43 percent of patients. Antibodies directed against microsomes, cell structures found in the nucleus, were detected in 31 percent of patients, whereas 29 percent of patients had antibodies against thyroglobulin, an iodine-containing protein released by the thyroid. There was no relation between the presence of antithyroid antibodies and drug therapy or antibodies associated with SLE. These findings show that thyroid abnormalities and thyroid antibodies are increased in patients with SLE. Thyroid antibodies may serve as an indicator of immune abnormalities or may reflect inflammation of the thyroid gland, which may be suppressed by anti-inflammatory agents used to treat SLE. Patients with SLE should be monitored for the presence of thyroid abnormalities. (Consumer Summary produced by Reliance Medical Information, Inc.)