Hereditary vitamin D-resistant rickets in Greek children: genotype, phenotype, and long-term response to treatment.

We describe four patients (two pairs of children from two unrelated kindreds) from a Greek island, suffering from hereditary vitamin D-resistant rickets (HVDRR) with alopecia. There were two different homozygous mutations in the vitamin D receptor (VDR) gene of the affected members of the two kindreds that resulted in a truncated or missing receptor. The disorder began in early infancy with similar clinical, biochemical and radiological findings in all four patients, namely, alopecia (which provided the initial diagnostic evidence for HVDRR), rachitic deformities, hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, and elevated serum levels of 1,25-dihydroxyvitamin D; however, the patients of kindred B had a more severe clinical expression. Treatment options include oral or intravenous calcium and active vitamin D metabolites. The response varies widely in different cases. Our patients were initially treated with high doses of 1alpha(OH)D3 and oral calcium supplementation. Kindred A patients had a satisfactory response to this regimen, while kindred B patients presented clinical and biochemical improvement when 1alpha(OH)D3 was changed to 1,25(OH)2D3. In the older patients of each kindred, treatment requirements gradually decreased during puberty, and therapy was finally discontinued before adulthood.

Low serum insulin values in children with multiple lesions of granuloma annulare: a prospective study.

BACKGROUND: The relationship between granuloma annularae (GA) and diabetes mellitus (DM) is controversial. OBJECTIVE: To investigate the relationship between multiple lesions of GA and carbohydrate metabolism in children. SUBJECTS AND METHODS: Fifteen children (seven boys, eight girls, mean age 4.8 years) with five or more lesions of GA were evaluated. A personal and family history of DM or other autoimmune diseases was obtained and the glycaemic and insulin response during an oral glucose tolerance test (OGTT) was determined. Thirteen children with a negative personal and family history of DM served as controls for the OGTT and 100 other children as 'clinical controls'. RESULTS: At the 30-min sampling of the OGTT the mean insulin values were comparable in GA children and controls (P=0.1), while the mean glucose values were significantly higher in GA children than in controls (P=0.005). All other insulin values during the OGTT were significantly lower in GA children than in controls, while all other glucose values were comparable in GA children and controls with all indices applied. Eleven out of 15 GA children had a positive family history of DM (73.3% vs. 16% of the clinical controls; P<0.0001). CONCLUSION: Multiple lesions of GA in children are associated with significantly lower serum insulin values than in controls and mildly impaired glucose tolerance.

Hodgkin's disease in a child with sickle cell disease treated with hydroxyurea.

Hydroxyurea (HU) is an oral drug that ameliorates the clinical course of sickle cell anemia by increasing the levels of fetal hemoglobin and decreasing the adhesion of red cells to endothelium. Although HU has minimal short-term toxicity, few data are available about the long-term safety and the potential risk for carcinogenesis or leukemogenesis. An 8-year-old child with sickle cell/beta 0-thalassemia who received HU treatment for painful crises is described. Six months after the initiation of the HU treatment he developed Hodgkin's disease, lymphocyte predominance subtype. Chemotherapy induced a complete remission. After discontinuation of chemotherapy the painful crises recurred and bone marrow transplantation was decided at the age of 12 years. Two years after the bone marrow transplantation, the child is in complete remission without painful crises. Although the authors suggest that the development of Hodgkin's disease is a coexisting event, questions arise about the safety of HU treatment in childhood.

Erythema nodosum in children: a prospective study.

BACKGROUND: The studies of series of children with erythema nodosum (EN) are limited and mostly retrospective. OBJECTIVE: We evaluated the epidemiology, etiology, clinical manifestations, course, and prognosis of EN in children. METHODS: Thirty-five children with EN (17 boys, 18 girls; mean age, 8.79 years) have been studied. Four excluded children proved, on biopsy, to have leukocytoclastic vasculitis (n = 3) or eosinophilic cellulitis (n = 1). RESULTS: In 27 of the 35 children (77%), the etiology of EN was established by laboratory investigations. In 25 children the causative factor of EN was an infectious agent (including beta-hemolytic streptococcus [n = 17], and Mycobacterium tuberculosis [n = 2]), whereas in 2 patients, EN was associated with Crohn's disease in one and Hodgkin's disease in the other. In 8 of the 35 children (23%) the etiology of EN remained undetermined. The mean duration of the rash was 11.5 days. Recurrences were noted in only 2 children (1 episode in 1 child and 3 episodes in the other). CONCLUSION: Currently the most common provoking agent of EN in children in Greece is beta-hemolytic streptococcus. However, Mycobacterium tuberculosis should still be considered as a cause of the disorder. Also, the course of EN is benign and recurrences are exceptional.

Idiopathic intracranial hypertension in children.

We studied prospectively the etiology, clinical presentation, and outcome of idiopathic intracranial hypertension in 36 patients (20 boys and 16 girls) aged 3.5 months to 14 years. The etiology was identified in 28 (77.7%) patients. The most common predisposing factor was middle-ear infection, followed by obesity. Of the 36 cases seen, 26 presented with the classic picture of headaches, papilledema, and elevated cerebrospinal fluid pressure; 8 children had intracranial hypertension in the absence of papilledema and 2 had fundoscopic evidence of papilledema with normal cerebrospinal fluid pressure initially. In four children resolution of intracranial hypertension occurred with removal of the causative agent or appropriate treatment of the underlying condition. In 8 of 17 patients intracranial hypertension resolved with acetazolamide therapy and in 22 of 24 patients it resolved with corticosteroids in combination with acetazolamide. Subnormal visual acuity, narrowing of visual fields, or both were present on the initial examination in 10 patients; 2 of them, who presented with loss of vision, have permanent visual impairment. Four additional patients presented a transient, mild impairment of visual acuity during treatment. Our study confirms the wide clinical spectrum and the difficulties encountered in diagnosis of idiopathic intracranial hypertension. A wide variety of etiologic associations should be investigated to provide definitive therapy. Loss of visual function is the only serious complication.

Persistent hyperinsulinemic hypoglycemia of infancy: long-term results.

Data from 15 infants with persistent hyperinsulinemic hypoglycemia of infancy (PHHI), presented to our hospital from 1976 to 1995, were retrospectively analyzed. Nine patients were successfully managed with prolonged (1.25-13 yr) diazoxide therapy and frequent, low protein feeds. Three of them are still being treated with diazoxide, 7.75, 9.25 and 13 yr post diagnosis. Four patients were managed only with frequent, low protein feeds. One patient had 2/3 pancreatectomy, and another had excision of a focal lesion which proved to be focal nesidioblastosis. Two patients were lost to follow up. No patient has shown neurological damage. One girl developed seizures at age 11.5 yr without hypoglycemia. The patient with 2/3 pancreatectomy developed diabetes mellitus at the age of 20 years. Although conservative management of PHHI is very laborious for the family and the physician, it should be applied as long as euglycemia is accomplished. Definition of the anatomical lesion (focal or diffuse) prior to pancreatectomy is recommended.

Arthritis and vasculitis during the incubation period of varicella.

Arthritis and vasculitis are very rare complications of varicella occurring almost exclusively after the eruption of the characteristic rash. We report two children, aged three and seven years, who developed vasculitis and polyarthritis (patient No. 1) and arthritis (patient No. 2) 13 and 9 days, respectively, before the onset of their typical varicella. Arthritis and vasculitis so early in the incubation period of varicella have not been described previously. In all previously reported cases the arthritis occurred after or together with the onset of varicella and only in one instance preceded the exanthem by 2 days. Although this may have been an unfortunate coincidence, an association between varicella zoster virus and these manifestations should be seriously considered. Clinicians confronted with such cases must be cautious and search for varicella infection, especially in times of epidemics.