Case report: Sulfasalazine-induced hypersensitivity

Drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is a systemic inflammatory condition that is characterized by multisystemic involvement (liver, blood, and skin), heterogeneous manifestations (fever, rash, lymphadenopathy, and eosinophilia), and an unpredictable course; cases of DiHS/DRESS caused by sulfasalazine are rare in children compared to adults. We report a case of a 12-year-old girl with juvenile idiopathic arthritis (JIA) and sulfasalazine-related hypersensitivity who developed fever, rash, blood abnormalities, and hepatitis complicated with hypocoagulation. The treatment with intravenous and then oral glucocorticosteroids was effective. We also reviewed 15 cases (67% male patients) of childhood-onset sulfasalazine-related DiHS/DRESS from the MEDLINE/PubMed and Scopus online databases. All reviewed cases had a fever, lymphadenopathy, and liver involvement. Eosinophilia was reported in 60% of patients. All patients were treated with systemic corticosteroids, and one patient required emergency liver transplantation. Two patients (13%) died. A total of 40.0% of patients satisfied RegiSCAR definite criteria, 53.3% were probable, and 80.0% satisfied Bocquet's criteria. Only 13.3% satisfied typical and 20.0% atypical DIHS criteria from the Japanese group. Pediatric rheumatologists should be aware of DiHS/DRESS due to its similarities to other systemic inflammatory syndromes (especially systemic JIA, macrophage activation syndrome, and secondary hemophagocytic lymphohistiocytosis). Further studies of DiHS/DRESS syndrome in children are needed to improve its recognition and differential diagnostic and therapeutic options

Glucocorticoid receptor gene polymorphism and juvenile idiopathic arthritis

<p>Abstract</p> <p>Background</p> <p>The glucocorticoid receptor gene (NR3C1) has been suggested as a candidate gene affecting juvenile idiopathic arthritis (JIA) course and prognosis. The purpose of this study is to investigate the glucocorticoid receptor gene <it>Bcl</it>I polymorphism (rs41423247) in JIA patients, the gene's role in susceptibility to juvenile idiopathic arthritis, and its associations with JIA activity, course and bone mineralization.</p> <p>Methods</p> <p>One hundred twenty-two Caucasian children with JIA and 143 healthy ethnically matched controls were studied. We checked markers of clinical and laboratory activity: morning stiffness, Ritchie Articular Index (RAI), swollen joint count (SJC), tender joint count (TJC), physician's visual analog scale (VAS), hemoglobin level (Hb), leukocyte count (L), platelet count (Pl), Westergren erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), albumin, DAS and DAS28. Bone mineralization was measured by dual-energy X-ray absorptiometry (DXA) of lumbar spine L1-L4. Assessments of bone metabolism included osteocalcin, C-terminal telopeptide (CTT), parathyroid hormone (PTH), total and ionized calcium, inorganic phosphate and total alkaline phosphatase (TAP). <it>Bcl</it>I polymorphism was genotyped by polymerase chain reaction restriction fragment length polymorphism.</p> <p>Results</p> <p>No association was observed between glucocorticoid receptor gene polymorphism and the presence or absence of JIA. In girls with JIA, the presence of the G allele was associated with an unfavorable arthritis course, a younger age of onset of arthritis (p = 0.0017), and higher inflammatory activity. The higher inflammatory activity was demonstrated by the following: increased time of morning stiffness (p = 0.02), VAS (p = 0.014), RAI (p = 0.048), DAS (p = 0.035), DAS28 (p = 0.05), Pl (p = 0.003), L (p = 0.046), CRP (p = 0.01). In addition, these patients had bone metabolism disturbances as follows: decreased BA (p = 0.0001), BMC (p = 0.00007), BMD (0.005) and Z score (p = 0.002); and higher levels of osteocalcin (p = 0.03), CTT (p = 0.036), TAP activity (p = 0.01) and ionized calcium (p = 0.017). In boys with JIA, no significant differences were observed related to the polymorphic alleles or genotypes.</p> <p>Conclusions</p> <p>We suggest that G allele and the GG genotype of the glucocorticoid receptor gene <it>Bcl</it>I polymorphism contribute to an unfavorable course and low bone mineral density in girls with JIA.</p

Генетические аспекты патогенеза системной красной волчанки у детей

The paper presents data on the pathogenesis of systemic lupus erythematosus (SLE), and depicts various molecular mechanisms for the development of SLE and lupus-like syndromes. It describes groups of diseases, such as apoptotic defects; NETosis; interferonopathies; complement deficiency; autotolerance disorders associated with mutations in the RAG1/RAG2 genes; hereditary metabolic diseases (prolidase deficiency, deficiency of adenosine deaminase 2; lysinuric protein intolerance; and α-mannosidase deficiency). The table summarizes clinical data on most of the known lupus-like syndromes and their molecular mechanisms.The pathogenesis of many forms of monogenic lupus-like diseases is being studied. The main sign suggesting in favor of the possible monogenic disease in a patient with SLE is its onset in infancy, especially in males. Attention should be also paid to a compromised family history, including to the marriage between close relatives, the resistance of disease to standard therapy, as well as atypical symptoms. В статье приведены данные о патогенезе системной красной волчанки (СКВ), описаны различные молекулярные механизмы развития СКВ и волчаночноподобных синдромов. Описаны такие группы заболеваний, как дефекты апоптоза, нетоз, интерферонопатии, дефицит системы комплемента, нарушения системы аутотолерантности, связанные с мутациями в генах RAG1/RAG2, наследственные болезни обмена (дефицит пролидазы, дефицит аденозиндезаминазы 2-го типа, лизинурическая непереносимость белка, дефицит α-маннозидазы). В виде таблицы представлены обобщенные клинические данные о большинстве известных волчаночноподобных синдромов и их молекулярных механизмах.Патогенез многих форм моногенных волчаночноподобных заболеваний находится в процессе изучения. Основным признаком, свидетельствующим в пользу возможного моногенного заболевания у больного СКВ, является его начало в раннем детском возрасте, особенно в сочетании с мужским полом. Также следует обращать внимание на отягощенный семейный анамнез, в том числе на факт близкородственного брака, устойчивость заболевания к стандартной терапии и нетипичную симптоматику.

Spatial variations in the field of velocities and real solar granulation

In this paper, the physical conditions within the inhomogeneous solar atmosphere have been reconstructed by means of solving the inverse problem of Non Local Thermodynamic Equilibrium (NLTE) radiative transfer. The profiles of $\lambda=523.42$ nm FeI spectral line of high spatial and time resolution were used as observational data. The velocity field has been studied for the real solar granulation in superadiabatic layer and overshooting convection region. Also, we investigate the vertical structure of inhomogeneous solar photosphere and consider penetration of granules from convective region into upper layers of stable atmosphere. The microturbulent velocity appears to be minimal at the bottom of overshooting convection region and increases sharply through superadiabatic layer and upper photosphere. High-turbulent layers emerge either in the central part of a flow or at the boundary of an incipient flow with following drift toward the centre of the flow. Wide descending flows tend to disintegrate into structures having turbulence augmented, these structures correspond to the flows of matter. High microturbulence of the intensive flows provokes steep temperature depression in upper photosphere leading to the second inversion of temperature for the intergranules. The inversion of vertical velocities is observed to be frequent in the solar granulation. Some of the convective flows reach the minimum temperature region. Vertical convective velocities of the matter flows were found to be smaller in the middle and upper photosphere. Also, the effect of finite resolution on the spacial variations of the velocities in solar photosphere has been estimated.Comment: 8 pages, 7 figure

Surface temperature and synthetic spectral energy distributions for rotationally deformed stars

The spectral energy distribution (SED) of a non-spherical star could differ significantly from the SED of a spherical star with the same average temperature and luminosity. Calculation of the SED of a deformed star is often approximated as a composite of several spectra, each produced by a plane parallel model of given effective temperature and gravity. The weighting of these spectra over the stellar surface, and hence the inferred effective temperature and luminosity, will be dependent on the inclination of the rotation axis of the star with respect to the observer, as well as the temperature and gravity distribution on the stellar surface. Here we calculate the surface conditions of rapidly rotating stars with a 2D stellar structure and evolution code and compare the effective temperature distribution to that predicted by von Zeipel's law. We calculate the composite spectrum for a deformed star by interpolating within a grid of intensity spectra of plane parallel model atmospheres and integrating over the surface of the star. Using this method, we find that the deduced variation of effective temperature with inclination can be as much as 3000 K for an early B star, depending on the details of the underlying model.Comment: 38 pages, 9 figures (AAStex preprint format). Accepted for publication in the Ap

A NLTE line blanketed model of a solar type star

We present LTE and NLTE atmospheric models of a star with solar parameters, and study the effect of treating many thousands of Iron group lines out of LTE on the computed atmospheric structure, overall absolute flux distribution, and the moderately high resolution spectrum in the visible and near UV bands. Our NLTE modeling includes the first two or three ionization stages of 20 chemical elements, up to and including much of the Fe-group, and includes about 20000 Fe I and II lines. We investigate separately the effects of treating the light metals and the Fe-group elements in NLTE. Our main conclusions are that 1) NLTE line blanketed models with direct multi-level NLTE for many actual transitions gives qualitatively similar results as the more approximate treatment of Anderson (1989) for both the Fe statistical equilibrium and the atmospheric temperature structure, 2) models with many Fe lines in NLTE have a temperature structure that agrees more closely with LTE semi-empirical models based on center-to-limb variation and a wide variety of spectra lines, whereas LTE models agree more with semi-empirical models based only on an LTE calculation of the Fe I excitation equilibrium, 3) the NLTE effects of Fe-group elements on the model structure and flux distribution are much more important than the NLTE effects of all the light metals combined, and serve to substantially increases the violet and near UV flux level as a result of NLTE Fe over-ionization. These results suggest that there may still be important UV opacity missing from the models.Comment: Accepted for publication in The Astrophysical Journa

Роль генетического полиморфизма гена рецептора витамина D (VDR ) в п атогенезе ювенильного идиопатического артрита : теоретические и практические аспекты

Juvenile idiopathic arthritis (JIA) is a chronic inflammatory joint disease associated with impaired immune system performance. The specific features of JIA may be genetically determined.Objective: to assess JIA activity in children with vitamin D receptor (VDR) gene ApaI and BsmI polymorphism genotypes.Subjects and methods. The investigation enrolled 71 patients with JIA. When included in the investigation, all the patients were in an active state of disease. JIA activity was assessed using the most commonly used clinical and laboratory indicators, including the Ritchie articular index (RAI), JADAS10, JADAS27, JADAS71, CDAI, DAS, and DAS28. Molecular genetic studies determined VDR gene ApaI and BsmI polymorphisms by polymerase chain reaction, followed by restriction analysis.Results. The boys who were carriers of a bb BsmI polymorphic marker in the VDR gene had a significantly higher activity of JIA measured by RAI (p=0.03), DAS (p&lt;0.05), JADAS10 (p=0.04), JADAS27 (p=0.04), and JADAS71 (p=0.04) than those who were carriers of B allele (BB + Bb genotypes).Conclusion. The carriage of the VDR gene bb BsmI genotype of the polymorphic marker is associated with high JIA activity, which may be regarded as a marker of poor prognosis in boys with JIA.Ювенильный идиопатический артрит (ЮИА) – хроническое воспалительное заболевание суставов, связанное с нарушением работы иммунной системы. Особенности течения ЮИА могут быть генетически детерминированы.Цель исследования – дать оценку активности ЮИА у детей с ApaI и BsmI полиморфными генотипами гена рецептора витамина D (VDR).Материал и методы. В исследование включен 71 ребенок, страдающий ЮИА. На момент включения в исследование все пациенты находились в активном состоянии болезни. Оценка активности ЮИА осуществлялось при помощи наиболее часто используемых клинических и лабораторных показателей, в том числе суставного индекса Ричи (CИР), индексов JADAS10, JADAS27, JADAS71, CDAI, DAS и DAS28. Молекулярно-генетические исследования – определение ApaI и BsmI полиморфизмов гена VDR при помощи полимеразной цепной реакции с последующим рестрикционным анализом.Результаты исследования. Мальчики – носители генотипа bb BsmI полиморфного маркера гена VDR – имели достоверно более высокие показатели активности ЮИА, измеренного при помощи СИР (p=0,03), индексов DAS (p&lt;0,05), JADAS10 (p=0,04), JADAS27 (p=0,04) и JADAS71 (p=0,04) по сравнению с носителями аллеля B (BB+Bb генотипы).Заключение. Носительство генотипа bb BsmI полиморфного маркера гена VDR связано с высокой активностью ЮИА, что может рассматриваться как маркер неблагоприятного прогноза у мальчиков, больных ЮИА

On the Absorption of X-rays in the Interstellar Medium

We present an improved model for the absorption of X-rays in the ISM intended for use with data from future X-ray missions with larger effective areas and increased energy resolution such as Chandra and XMM, in the energy range above 100eV. Compared to previous work, our formalism includes recent updates to the photoionization cross section and revised abundances of the interstellar medium, as well as a treatment of interstellar grains and the H2molecule. We review the theoretical and observational motivations behind these updates and provide a subroutine for the X-ray spectral analysis program XSPEC that incorporates our model.Comment: ApJ, in press, for associated software see http://astro.uni-tuebingen.de/nh

Numerical Simulations of Magnetoacoustic-Gravity Waves in the Solar Atmosphere

We investigate the excitation of magnetoacoustic-gravity waves generated from localized pulses in the gas pressure as well as in vertical component of velocity. These pulses are initially launched at the top of the solar photosphere that is permeated by a weak magnetic field. We investigate three different configurations of the background magnetic field lines: horizontal, vertical and oblique to the gravitational force. We numerically model magnetoacoustic-gravity waves by implementing a realistic (VAL-C) model of solar temperature. We solve two-dimensional ideal magnetohydrodynamic equations numerically with the use of the FLASH code to simulate the dynamics of the lower solar atmosphere. The initial pulses result in shocks at higher altitudes. Our numerical simulations reveal that a small-amplitude initial pulse can produce magnetoacoustic-gravity waves, which are later reflected from the transition region due to the large temperature gradient. The atmospheric cavities in the lower solar atmosphere are found to be the ideal places that may act as a resonator for various oscillations, including their trapping and leakage into the higher atmosphere. Our numerical simulations successfully model the excitation of such wave modes, their reflection and trapping, as well as the associated plasma dynamics

Evaluation of etanercept (a tumor necrosis factor alpha inhibitor) as an effective treatment for joint disease in mucopolysaccharidosis type I. A case report with whole-body magnetic resonance imaging

SummaryA 12-year-old girl with mucopolysaccharidosis (MPS) type I (Gurler-Scheie syndrome, Q70X/del C683 of the IDUA gene in the compound heterozygous state) regularly received enzyme replacement therapy (laronidase) since the preclinical stage (6 months old) due to positive family history, and started etanercept treatment due to progression of joint pain and decreasing capability to walk. The patient had a significant reduction of pain in the joints and an expansion of daily physical activity without adverse events. A decrease in bone marrow edema without foci progression compared to baseline assessment was observed in the whole-body MRI.During the treatment (baseline/6 months/12 months) the following was observed: childhood health assessment questionnaire (CHAQ) index of 1.88/2.13/1.63 points; patient’s pediatric quality of life inventory (PedsQL) of 37/30/31 points; parental PedsQL of 26/27/34 points; and patient’s pain visual-analog scale (VAS) of 75/45/40, with no VAS recorded for the mother. Juvenile arthritis functional assessment report (JAFAR) scores of 35/34/8 points were observed. A significant reduction in the taking of NSAIDs was observed. In the second half of the year, the nasal breathing became normal, and remission in chronic rhinitis and adenoiditis was achieved (no infection episodes) without otitis episodes.ConclusionEtanercept in mucopolysaccharidosis type 1 is safe and well tolerated. The reduction of joint pain and increased walking capacity were observed. A decreased number of respiratory infection episodes and nasal breathing improvement were noted during the treatment. The observation shows the role of inflammation in the different aspects of MPS. Further investigations on immune system dysregulation in patients with MPS I are needed. Additional studies on the efficacy and safety of anti-rheumatic biological drugs in patients with MPSI are required