Juvenile Paget's Disease: Report of a successful treatment throughout the complete growth of a patient with a missense TNFRSF11B mutation.

INTRODUCTION: Juvenile Paget's Disease (JPD) is an ultra-rare inherited osteopathy featuring markedly accelerated bone turnover. Several clinical characteristics have been reported, including bone deformities developing in childhood and hearing loss. CASE REPORT: We report the case of a 2 ¾-year-old girl that presented with progressive bowing of both legs since the age of 2, lower limb pain and frequent falls with one consequent femur fracture. Plain radiographs revealed osteoectasia of the long bone's diaphysis, and laboratory tests showed extremely high serum total alkaline phosphatase levels. A missense mutation on the gene TNFRSF11B was identified in homozygosity, and the diagnosis of JPD was made. Treatment with bisphosphonates was initiated early and markedly improved lower limb bowing and pain. The patient reached adulthood with normal height, minor bone deformities, and no functional impairment. Despite the good skeletal symptom's response, bisphosphonates failed to prevent or improve sensorineural hearing loss. CONCLUSIONS: In this clinical case, early treatment with bisphosphonates was effective for the treatment of JPD skeletal deformities. New therapeutic strategies need to be developed to better control the extraskeletal manifestations of JPD.

Association of body mass index with Juvenile Idiopathic Arthritis disease activity: a Portuguese and Brazilian collaborative analysis.

OBJECTIVE: To investigate the relationship between body mass index (BMI) and disease activity in patients with Juvenile Idiopathic Arthritis (JIA). METHODS: Patients with JIA, aged ≤18 years, registered at the Rheumatic Diseases Portuguese Register (Reuma.pt) in Portugal and Brazil were included. Age- and sex-specific BMI percentiles were calculated based on WHO growth standard charts and categorized into underweight (P <3), normal weight (3≤P≤85), overweight (85

97). Disease activity was assessed by Juvenile Arthritis Disease Activity Score (JADAS-27). Uni- and multivariate analyses were performed. RESULTS: A total of 275 patients were included. The prevalence of underweight, normal weight, overweight and obesity was 6.9%, 67.3%, 15.3% and 10.5%, respectively. Underweight patients had significantly higher number of active joints (p <0.001), patient's/parent's global assessment of disease activity (PGA) (p=0.020), physician's global assessment of disease activity (PhGA) (p <0.001), erythrocyte sedimentation rate (ESR) (p=0.032) and overall higher JADAS-27 (p <0.001), compared to patients with normal weight, overweight and obesity. In the multivariate regression, underweight persisted significantly associated with higher disease activity, compared to normal weight (B=-9.430, p <0.001), overweight (B=-9.295, p=0.001) and obesity (B=-9.120, p=0.001), when adjusted for age, gender, country, ethnicity, JIA category and therapies used. The diagnosis of RF- (B=3.653, p=0.006) or RF+ polyarticular JIA (B=5.287, p=0.024), the absence of DMARD therapy (B=5.542, p <0.001) and the use of oral GC (B=4.984, p=0.002) were also associated with higher JADAS-27. CONCLUSION: We found an independent association between underweight and higher disease activity in patients with JIA. Further studies are needed to understand the underlying mechanisms of this association.

Genetic Screening of Mutations Associated with Fabry Disease in a Nationwide Cohort of Juvenile Idiopathic Arthritis Patients.

Fabry's disease (FD) is a lysosomal storage disorder associated with an alpha-galactosidase A deficiency. The prevalence of FD among juvenile idiopathic arthritis (JIA) patients with established diagnosis is unknown, but as musculoskeletal pain may be an important complaint at presentation, misdiagnosed cases are anticipated. With this study, we aim to calculate the frequency of FD-associated mutations in a cohort of JIA patients. Children with JIA from a national cohort were selected. Clinical and laboratorial information was recorded in the Portuguese rheumatic diseases register (http://Reuma.pt). Molecular genetic testing to detect GLA gene mutations was performed. After the multiplex polymerase chain reactions technique for DNA amplification, direct sequencing of the complete sequence of GLA gene was completed. From a cohort of 292 patients with JIA (188 females, 104 males), mutations were identified in 5 patients (all female). Four patients had the mutation D313Y, a rare GLA variant, which is associated with low enzymatic levels in plasma, but normal lysosomal levels. One patient presented the missense mutation R118C, which was previously described in Mediterranean patients with FD. This is the first screening of FD mutations in a cohort of JIA patients. No "classic" pathogenic FD mutations were reported. The late-onset FD-associated mutation, R118C, was found in a frequency of 0.34% (1/292).

Recurrent Fever, Anemia, Arthralgia, and Genu Varum as Late Manifestations of Congenital Syphilis.

We report an unusual case of recurrent fever, inflammatory knee pain, genu varum, persistent anemia, and high erythrocyte sedimentation rate in a 28-month-old boy as late manifestations of congenital syphilis (CS). Despite standard penicillin treatment at the end of the first month of life, it recurred later in life, more than once. In the first relapse, manifested by a likely gumma lesion, the prior penicillin treatment plus a negative venereal disease research laboratory result unduly led to exclusion of CS. A second treatment with penicillin led to complete clinical resolution. Although rare, bow legs, recurrent fever, anemia, and inflammatory arthralgias may be manifestations of late CS. Congenital syphilis should be considered throughout early childhood, especially if history of syphilis infection is present. A negative venereal disease research laboratory result does not exclude late syphilis, present in nearly 30% of these patients. The possibility of atypical symptoms of this "great masquerader" should always be borne in mind.

Genetic Predictors of Poor Prognosis in Portuguese Patients with Juvenile Idiopathic Arthritis: Data from Reuma.pt.

INTRODUCTION: This study aimed to assess the genetic determinants of poor outcome in Portuguese patients with juvenile idiopathic arthritis (JIA). METHODS: Our study was conducted in Reuma.pt, the Rheumatic Diseases Portuguese Register, which includes patients with JIA. We collected prospectively patient and disease characteristics and a blood sample for DNA analysis. Poor prognosis was defined as CHAQ/HAQ >0.75 at the last visit and/or the treatment with biological therapy. A selected panel of single nucleotide polymorphisms (SNPs) associated with susceptibility was studied to verify if there was association with poor prognosis. RESULTS: Of the 812 patients with JIA registered in Reuma.pt, 267 had a blood sample and registered information used to define "poor prognosis." In univariate analysis, we found significant associations with poor prognosis for allele A of TNFA1P3/20 rs6920220, allele G of TRAF1/C5 rs3761847, and allele G of PTPN2 rs7234029. In multivariate models, the associations with TRAF1/C5 (1.96 [1.17-3.3]) remained significant at the 5% level, while TNFA1P3/20 and PTPN2 were no longer significant. Nevertheless, none of associations found was significant after the Bonferroni correction was applied. CONCLUSION: Our study does not confirm the association between a panel of selected SNP and poor prognosis in Portuguese patients with JIA.

Overdose with antiepileptic drugs: the efficacy of extracorporeal removal techniques.

Drug overdose is a growing problem among adolescents. Clinical severity depends on the drug and ingested amount, which in some cases may be life-threatening. We present a clinical case of a previously healthy teenage girl who ingested 16.4 g of carbamazepine and 14.5 g of valproic acid. She presented with profound disturbance of consciousness and toxic levels of both drugs, raised in the first hours after the ingestion. She was successfully treated with charcoal haemoperfusion followed by continuous venovenous hemodiafiltration. Overdose with the two drugs separately is common, but there are no reports of intoxication by simultaneous ingestion. High levels of carbamazepine and valproic acid can lead to severe systemic effects and management is made difficult by the absence of specific antidotes. Extracorporeal removal techniques are a good therapeutic option in these cases as they enhance the clearance by reducing the half-life of both drugs thereby preventing serious complications.

Bowel-associated dermatosis-arthritis syndrome in an adolescent with short bowel syndrome.

Bowel-associated dermatosis-arthritis syndrome (BADAS) is a neutrophilic dermatosis, characterized by the occurrence of arthritis and skin lesions related to bowel disease with or without bowel bypass. We report an unusual case of BADAS in a 15-year-old white male with congenital aganglionosis of the colon and hypoganglionosis of the small intestine and multiple bowel surgeries in childhood complicated by short bowel syndrome. He presented with recurrent peripheral polyarthritis, tenosynovitis, and painful erythematous subcutaneous nodules located on the dorsolateral regions of the legs and on the dorsa of the feet. Histological examination disclosed a neutrophilic dermatosis confirming the diagnosis of BADAS.Although an uncommon disease, especially at pediatric age, it is important to evoke the diagnosis of BADAS in children and adolescents with bowel disease, because treatment options and prognosis are distinct from other rheumatologic conditions.

Goldbloom's syndrome - a case report.

The Goldbloom's syndrome (GS) is a rare clinical condition of unknown aetiology, occurring exclusively in the pediatric population. It consists in an idiopathic periosteal hyperostosis with dysproteinemia, whose symptoms can mimic a neoplastic disease. We present a case report illustrating the diagnostic challenge of this condition. The exclusion of the common causes of bone pain, associated with generalized periostitis and increased gammaglobulins suggested the diagnosis of GS. The self-limited symptoms, the resolution of radiological findings in four months and the normalization of laboratory abnormalities within ten months, allowed to establish definitely the diagnosis of GS. GS must be considered when diffuse bone pain, prolonged fever and weight loss are present after exclusion of malignant disease with bone involvement.

Portuguese recommendations for the use of biological therapies in children and adolescents with juvenile idiopathic arthritis--December 2011 update.

OBJECTIVE: To update the Portuguese recommendations in order to assist the rational and safe prescribing of biological therapies in children and adolescents with Juvenile Idiopathic Arthritis (JIA) as more evidence and experience with these drugs are available. METHODS: The recommendations were formulated by Rheumatologists and Pediatricians, with experience in Pediatric Rheumatology, based on literature evidence and consensus opinion. The evidence was sought through a MEDLINE search. The retrieved results were discussed and a set of recommendations proposed. All propositions were extensively debated and the final recommendations formulated. RESULTS: A consensus was achieved regarding the eligibility, response criteria, maintenance of biologic thera py, and procedures in case of non-response. Also, specific recommendations concerning safety procedures before and while on biologic therapies were formulated. CONCLUSIONS: Thirteen recommendations for guidance biological therapy in children and adolescents with JIA were developed using both evidence-based and expert consensus. These recommendations will be updated as more evidence becomes available and more biological therapies are licensed.