A Japanese pediatric patient with coexisting systemic lupus erythematosus and familial Mediterranean fever.

This case report describes a Japanese girl with systemic lupus erythematosus who had recurrent fevers and erythema nodosum. She was later found to carry the complex allele E148Q/R202Q/P369S/R408Q of MEFV, the gene responsible for familial Mediterranean fever.

Spontaneous pneumomediastinum complicating pneumonia in children infected with the 2009 pandemic influenza A (H1N1) virus.

We report two occurrences of spontaneous pneumomediastinum (SPM) complicating pneumonia in Japanese children infected with the novel influenza A (H1N1) virus (IV). General practitioners especially should suspect possible SPM when examining and treating children with the novel influenza accompanied by status asthmaticus or wheezing. The presented patients illustrate the specific clinical and radiological signs associated with SPM complicating pneumonia in children infected with A(H1N1)v.

Limited availability of nutritional vitamin D causing inappropriate treatment of vitamin D deficiency rickets with a response resembling pseudohypoparathyroidism type II in a Japanese patient.

Vitamin D deficiency rickets occasionally resembles pseudohypoparathyroidism type II (PHP type II) with respect to the response to exogenous PTH in the presence of hypocalcemia. We encountered a Japanese patient with stage 2 vitamin D deficiency rickets, who had increased urinary cAMP excretion and no response of urinary phosphate or N-acetyl-beta-D-glucosaminidase excretion to exogenous PTH under normocalcemic and normophosphatemic conditions, after treatment with 1,25(OH)2 vitamin D3. This case shows that it is possible for a response mimicking that of PHP type II to occur when the serum calcidiol level is low due to causes other than hypocalcemia and secondary hyperparathyroidism. When the serum calcidiol level is low, the appropriate treatment should be cholecalciferol or ergocalciferol. However, because neither is commercially available as a useful formulation in Japan, physicians are forced to inappropriately use calcitriol or analogs.

A case report: a pediatric patient with acute lupus hemophagocytic syndrome; differences from reactive hemophagocytosis caused by hypercytokinemia.

Abstract We report the youngest known girl with acute lupus hemophagocytic syndrome (ALHS) at the onset of her illness. We investigated the pathogenesis of ALHS by assessment of factors thought to influence the onset, such as cytokines, Th1/Th2 balance, immune complexes, and autoantibodies. A girl 8 years and 10 months old with systemic lupus erythematosus (SLE) had high fever, pancytopenia, and hemophagocytosis in the bone marrow. We diagnosed SLE complicated by ALHS. Treatment with predonisolone (2 mg/kg/day) was started, and her clinical features improved. Th2 dominance of the Th1/Th2 balance, hypocomplementemia, and high levels of anti-ds-DNA antibody, PAIgG, and immune complexes were seen, but no hypercytokinenemia, hyperferritinemia, or hypertriglyceridemia. ALHS at the onset of SLE, excluding that caused by infections, could be a form of reactive hemophagocytosis caused by excessive production of autoantibodies and immune complexes. High-dose steroid therapy is effective without need for immunosuppressive drugs. Our patient showed hypocomplementemia along with high levels of anti-dsDNA antibody, anticardiolipin antibody, platelet-associated IgG (PAIgG), and immune complexes. The autoimmune-associated hemophagocytic syndrome (AAHS) is thought to involve an autoantibody-mediated mechanism or an immune complex-mediated mechanism. On the basis of our data, ALHS could simultaneously involve both these mechanisms. We demonstrated that there was no hypercytokinemia and no hyperferritinemia in ALHS associated with Th2 dominance. Autoantibodies and immune complexes may cause histiocytic hemophagocytosis in ALHS. High-dose steroids and high-dose immunoglobulin are effective but immunosuppressive drugs are not needed.

A case of growth failure caused by 13-CIS-retinoic acid administration after bone marrow transplantation for neuroblasoma.

We report an 11-year-old girl with growth failure caused by long-term administration of 13-cis-retinoic acid after bone marrow transplantation for neuroblastoma. Her growth velocity was 1-2 cm/year after 13-cis-retinoic acid administration. Her endocrinological findings were normal except for peak growth hormone levels of 6.4 ng/ml (clonidine) and 9.7 ng/ml (arginine). IGF-1 and IGFBP-3 were normal. It is not possible to conclude that her severe growth failure was caused by partial growth hormone deficiency, but premature epiphyseal closure was seen on radiographic examination. We concluded that the growth failure was caused by pediatric cancer therapy for the musculoskeletal system but not by endocrinological disturbance.

Systemic sclerosis in children: a national retrospective survey in Japan.

A retrospective questionnaire survey of pediatric departments, for childhood collagen disease from 1985 to 1994 was used to clarify the clinical features of scleroderma in Japan. In the primary survey, 0.9% of the children with a rheumatic condition and scleroderma. Answers to this questionnaire were received on 18 (localized 9; systemic 9) patients from 15 institutions. In order to examine systemic sclerosis (SSc), seven cases of SSc in Japanese articles during the same period as the questionnaire were added to these answers and compared to the Japanese epidemic study investigated by Fukuyama in 1974. There were 16 children, seven boys and nine girls, with SSc during the 10-year period in Japan. The mean age of onset of symptoms was 8.0 +/- 2.8 years and the age at diagnosis 10.1 +/- 3.0 years. Eighty percent of children had Raynaud's phenomenon at the onset of SSc, and skin and musculoskeletal involvement was highly recognized during the course of the disease. Atrophy of the frenulum linguae and lung fibrosis were commonly seen in SSc. In serological studies, 80% of children have antinuclear antibodies and approximately 50% of patients have anti-Scl-70 (topoisomelase I) antibodies at the onset and during the course of childhood SSc. The prognosis is poor, as remission occurred in only one child. The clinical symptoms and examination of serological autoimmune antibodies were supportive of an early diagnosis of SSc. When compared to the previous national survey of children with SSc, the present results showed that the male-to-female ratio was reduced, the age at onset was low, the positive incidence of serological autoimmune antibodies elevated, and the usage of vasodilators and nonsteroid anti-inflammatory drugs (NSAID) increased, with corticosteroids decreased. But, the positive percentage of clinical symptoms were not changed in both studies. For a complete retrospective nationwide epidemic survey carried out on children with scleroderma, especially SSc, it is important to include dermatology departments.

Antinuclear antibody positivity in pediatric patients with autoimmune thyroid disease.

OBJECTIVE: The incidence of antinuclear antibody (ANA) positivity was investigated in pediatric patients with autoimmune thyroid diseases. METHODS: Subjects were 21 untreated patients with Graves' disease, 12 untreated patients with Hashimoto's disease, and 16 untreated patients with non-autoimmune thyroid disease, including one patient with Plummer's disease, 11 patients with simple goiter (probable), and 4 patients with cretinism. Patients with Graves' disease were treated with either propylthiouracil or methimazole. ANA was measured using HEp-2 cells. Anti-dsDNA antibody was measured using double stranded DNA derived from an Escherichia coli plasmid. RESULTS: The incidence of ANA positivity was significantly higher in patients with untreated Graves' disease (n = 21; age range 9-15 yrs) than in Hashimoto's thyroiditis (n = 12; age range 7-15 yrs) (p < 0.03, Fisher's exact probability test). However, the 2 diseases were not significantly different with respect to anti-dsDNA antibody positivity. Most of the ANA positive patients with Graves' disease required treatment for more than 2 years, unlike the 6 ANA negative patients (p < 0.002, Fisher's exact probability test). CONCLUSION: We conclude that ANA positivity may predict a poor response to antithyroid drugs in Graves' disease.

Increase of activated factor VIIA and haemostatic molecular markers in juvenile chronic arthritis.

Activated factor VIIa (FVIIa), von Willebrand factor antigen (vWF:Ag), D-dimer and thrombin-antithrombin III complex (TAT) were measured to monitor coagulation status in patients with juvenile chronic arthritis (JCA). Subjects included 14 patients with systemic JCA, 16 with pauciarticular JCA and 16 with polyarticular JCA without disseminated intravascular coagulopathy, thrombosis or liver dysfunction. All types of JCA showed an increase of FVIIa, D-dimer and TAT, indicating enhanced activation of coagulation. In systemic JCA only there was also characteristically an elevation of vWF:Ag. We conclude that all types of JCA constitute a state of subclinical hypercoagulopathy caused by tissue damage and that additionally systemic JCA involves a prothrombotic state associated with or precipitated by vasculitis.

Chronic, infantile, neurological, cutaneous and articular syndrome in Japan; two case reports.

We report two Japanese children with chronic, infantile, neurological, cutaneous and articular syndrome. Although the shoulder joint lesion has been rare in the literature of Europe and America, our first case showed overgrowth of the epiphysis in the bilateral shoulder joints. The second case exhibited severe growth retardation caused by early closure of the physis. The influence of GH is irrelevant in this syndrome. The existence of this syndrome in the Orient should be recognized.

Findings on magnetic resonance imaging of the spine and femur in a case of McCune-Albright syndrome.

Polyostotic fibrous dysplasia, a major osseous change in McCune-Albright syndrome, is seen in the cranium, facial bones, bones of the extremities, and ribs, but rarely in the spine. Spinal X-rays revealed no abnormalities in an 8-year-old girl with this syndrome, but 99mTc-methylene diphosphonate bone scintigraphy disclosed high-density areas in the thoracic and lumbar vertebrae. Multiple well-circumscribed areas of low signal intensity were seen on T1-weighted magnetic resonance imaging (MRI) of the spine. Although MRI spine scans in this disease have never been reported, our findings in this case proved interesting for evaluating osseous lesions. MRI made it possible to differentiate between fibrous lesions (low signal intensity on T1- and T2-weighted MRI) and cartilaginous lesions (low signal intensity on T1-weighted MRI and high signal intensity on T2-weighted MRI).

Precocious puberty caused by an hCG-producing tumor of the septum pellucidum.

A 6 year 9 month old boy with rapidly progressing precocious puberty was immunohistochemically and histologically diagnosed as having an hCG-producing mixed tumor consisting of choriocarcinoma and teratoma in the septum pellucidum. His serum hCG was elevated, but the serum LH was low as determined by LH immunoradiometric assay (IRMA). He did not exhibit a characteristic endocrinological pattern, e.g., high basal levels of LH and failure to respond with high LH levels to the LH-RH stimulation test using the conventional LH RIA method.

Host responses and neuroendocrinological changes in pyrexia in childhood.

Host responses and neuroendocrinological changes during pyrexia in childhood were studied. Serum IL-1 beta could not be detected in most subjects either during pyrexia or in afebrile periods. IL-1 beta was detected in two cases, increasing during pyrexia and decreasing during the afebrile period. Plasma ACTH increased during pyrexia, but this was not statistically significant. Serum cortisol during pyrexia increased to around twice the normal value, and many subjects showed a high level of arginine vasopressin. The subjects, who did not develop dehydration, showed a decrease in serum osmolality and serum sodium during the pyrexia period. Serum Fe and Zn decreased, but serum Cu increased during both periods. It could not be confirmed that IL-1 activates the hypothalamic-pituitary-adrenal axis during pyrexia. It is concluded that AVP is important in the control of fever and the maintenance of homeostasis of body fluid during pyrexia.

Serum content of zinc and vitamin C in severely handicapped children.

As fracture is known to occur more easily in severely handicapped children (SHC), bone mineral content, serum zinc level and serum vitamin C level were determined in 65 SHC. These parameters were found to be greatly reduced in all patients. The decreases in zinc and vitamin C in the serum appeared to be associated with that in bone mineral content. Supplements of zinc and vitamin C may be important to decrease the chance of fracture due to diminished bone mineral content in SHC.