Objective

Glucocorticoid (GC) therapy for giant cell arteritis (GCA) is effective but requires prolonged administration, resulting in adverse side effects. The goal of the current study was to test the hypothesis that induction treatment with high-dose pulse intravenous (IV) methylprednisolone permits a shorter course of therapy.



Methods

Twenty-seven patients with biopsy-proven GCA were enrolled in a randomized, double-blind, placebo-controlled study to receive IV methylprednisolone (15 mg/kg of ideal body weight/day) or IV saline for 3 consecutive days. All patients were started on 40 mg/day prednisone and followed the same tapering schedule as long as disease activity was controlled. The numbers of patients with disease in remission after 36, 52, and 78 weeks of treatment and taking ≤5 mg/day prednisone were compared. Cumulative prednisone dose, number of relapses, and development of adverse GC effects were assessed.



Results

Ten of the 14 IV GC–treated patients, but only 2 of 13 control patients, were taking ≤5 mg/day prednisone at 36 weeks (P = 0.003). This difference was maintained; there was a higher number of sustained remissions after discontinuation of treatment in the IV GC–treated group and a lower median daily dose of prednisone at 78 weeks (P = 0.0004). The median cumulative dose of oral prednisone, excluding the IV GC dose, was 5,636 mg in the IV GC–treated group compared with 7,860 mg in the IV saline–treated group (P = 0.001).



Conclusion

Initial treatment of GCA with IV GC pulses allowed for more rapid tapering of oral GCs and had long-term benefits, with a higher frequency of patients experiencing sustained remission of their disease after discontinuation of treatment.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.22163

Treatment of giant cell arteritis using induction therapy with high‐dose glucocorticoids: A double‐blind, placebo‐controlled, randomized prospective clinical trial

Background Determining drug-disease associations is an integral part in the process of drug development. However, the identification of drug-disease associations through wet experiments is costly and inefficient. Hence, the development of efficient and high-accuracy computational methods for predicting drug-disease associations is of great significance. Results In this paper, we propose a novel computational method named as layer attention graph convolutional network (LAGCN) for the drug-disease association prediction. Specifically, LAGCN first integrates the known drug-disease associations, drug-drug similarities and disease-disease similarities into a heterogeneous network, and applies the graph convolution operation to the network to learn the embeddings of drugs and diseases. Second, LAGCN combines the embeddings from multiple graph convolution layers using an attention mechanism. Third, the unobserved drug-disease associations are scored based on the integrated embeddings. Evaluated by 5-fold cross-validations, LAGCN achieves an area under the precision-recall curve of 0.3168 and an area under the receiver-operating characteristic curve of 0.8750, which are better than the results of existing state-of-the-art prediction methods and baseline methods. The case study shows that LAGCN can discover novel associations that are not curated in our dataset. Conclusion LAGCN is a useful tool for predicting drug-disease associations. This study reveals that embeddings from different convolution layers can reflect the proximities of different orders, and combining the embeddings by the attention mechanism can improve the prediction performances.

Predicting drug-disease associations through layer attention graph convolutional network.

Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are inflammatory diseases that typically affect white individuals >50 years. Women are affected ∼2-3 times more often than men. PMR and GCA occur together more frequently than expected by chance. The main symptoms of PMR are pain and stiffness in the shoulders, and often in the neck and pelvic girdle. Imaging studies reveal inflammation of joints and bursae of the affected areas. GCA is a large-vessel and medium-vessel arteritis predominantly involving the branches of the aortic arch. The typical clinical manifestations of GCA are new headache, jaw claudication and visual loss. PMR and GCA usually remit within 6 months to 2 years from disease onset. Some patients, however, have a relapsing course and might require long-standing treatment. Diagnosis of PMR and GCA is based on clinical features and elevated levels of inflammatory markers. Temporal artery biopsy remains the gold standard to support the diagnosis of GCA; imaging studies are useful to delineate large-vessel involvement in GCA. Glucocorticoids remain the cornerstone of treatment of both PMR and GCA, but patients with GCA require higher doses. Synthetic immunosuppressive drugs also have a role in disease management, whereas the role of biologic agents is currently unclear.

Clinical features of polymyalgia rheumatica and giant cell arteritis.

Licorice extract has always been recognized as a sweetener and a thirst quencher. Its nutritive value is overrated by many who consume significant amounts and are prone to complications. Glycyrrhetic acid, the active metabolite in licorice, inhibits the enzyme 11-s-hydroxysteroid dehydrogenase enzyme type 2 with a resultant cortisol-induced mineralocorticoid effect and the tendency towards the elevation of sodium and reduction of potassium levels. This aldosterone-like action is the fundamental basis for understanding its health benefits and the wide spectrum of adverse effects. Herein, we present a comprehensive review of licorice along with the reported complications related to excess intake. Despite its apparent use in a few clinical scenarios, the daily consumption of licorice is never justified because its benefits are minor compared to the adverse outcomes of chronic consumption. The review highlights the importance of investigating the dietary habits and herbal remedies which are being used worldwide on cultural and habitual bases rather than reliable scientific evidence. Licorice is a US Food and Drug Administration (FDA) approved food supplement used in many products without precise regulations to prevent toxicity. Increased awareness among the public is required through TV commercials, newspapers, internet sites, magazines and product labels regarding the upper limit of ingestion and health hazards associated with excess intake. We hope that this review will serve as a warning message that should be transmitted from physicians to patients to avoid excessive licorice intake as well as a message to the FDA to start regulating the use of this substance.

/pdf/licorice-abuse-time-to-send-a-warning-message-1f6830flqk.pdf

Licorice abuse: time to send a warning message

The classification of onychomycosis, infection of the nail apparatus caused by fungi, has changed over time with the recognition of new pathways of nail infection, new organisms, and new variations in the appearance of diseased infected nail. Taking into account published descriptions of nail morphology in fungal infection, the following forms of onychomycosis are recognized: distal and lateral subungual, superficial, endonyx, proximal subungual, mixed, totally dystrophic, and secondary onychomycosis. These can be subdivided, where appropriate, by color and pattern of nail plate change. The purpose of the revised classification is to provide a framework to assist selection of treatment, estimate prognosis, and evaluate new diagnostic methods.

Onychomycosis: A proposed revision of the clinical classification

Resume Propos. – Evaluer lˈefficacite et la tolerance du traitement de la maladie de Horton non compliquee par trois bolus de 500 mg/j de methylprednisolone suivis d’une dose quotidienne de 20 mg/j d’equivalent-prednisone. Methode. – Etude retrospective de 15 observations. Resultats. – Six hommes et neuf femmes d’âge moyen de 70,9 ans ont ete traites et suivis en moyenne 41,5 mois. La vitesse de sedimentation moyenne initiale etait de 83 mm, la proteine C reactive de 94,6 mg/L. La biopsie d’artere temporale etait positive chez 11 patients. Les bolus ont ete bien toleres, a l’exception d’un cas (bouffee delirante aigue). Apres relais oral, deux patients ont presente des signes d’evolutivite clinique au cours du premier mois, necessitant une majoration de la corticotherapie. A un mois, 12 patients etaient asymptomatiques, dont neuf avec normalisation de la vitesse de sedimentation et de la proteine C reactive. La vitesse de sedimentation moyenne etait de 23 mm, la proteine C reactive de 13 mg/L. A trois mois, la dose moyenne de prednisone etait de 18,2 mg/j. La vitesse de sedimentation moyenne etait a 12 mm. La dose cumulee moyenne de prednisone au cours de la premiere annee etait de 5 349 mg (± 2 312 mg). Parmi les patients n’ayant pas recu plus de 20 mg/j de prednisone, aucun n’a developpe de sequelles de sa maladie de Horton, ni d’intolerance au traitement necessitant une intervention medicamenteuse au cours des deux premieres annees de suivi. En particulier, aucune fracture osseuse n’a ete observee. Huit patients ont ete sevres dans un delai moyen de 48,6 mois. Conclusion. – La prescription de trois bolus de 500 mg/j de methylprednisolone suivie de 20 mg/j de prednisone, sous couvert d’une surveillance clinique et biologique rigoureuse, pourrait etre une strategie d’epargne cortisonique interessante chez de nombreux patients presentant une maladie de Horton non compliquee.

Maladie de Horton non compliquée : traitement initial par trois bolus de 500 mg de méthylprednisolone suivis de 20 mg/j d’équivalent-prednisone. Évaluation chez 15 patients

Cat scratch responsible for primary cutaneous Nocardia asteroides in an immunocompetent patient.

Resume Introduction . – L'histoplasmose americaine est une infection mycotique tropicale partageant avec la tuberculose quelques similitudes : la transmission par voie aerienne, la primo-infection souvent asymptomatique, la resurgence polyviserale en cas d'immunodepression, le caractere granulomateux des lesions histologiques. En metropole, l'histoplasmose est mal connue et peut etre prise a tort pour une tuberculose. Observation . – Un patient de 78 ans presente une lesion framboisee du plancher buccal genant l'alimentation. Il a perdu 14 kg. Le diagnostic de tuberculose est evoque devant la presence d'un granulome gigantocellulaire. La serologie d'histoplasmose, demandee en raison d'un sejour en Afrique, est positive. La relecture des lames histologiques retrouve des spores intrahistiocytaires evocatrices d'histoplasmose. Le traitement par itraconazole est efficace. Conclusion . – Le diagnostic d'histoplasmose doit etre evoque comme diagnostic differentiel d'une tuberculose chez des patients ayant vecu en zone d'endemie. Si la serologie d'histoplasmose peut etre utile, les examens de reference restent l'observation microscopique des spores et la mise en culture.

Une histoplasmose du plancher buccal 34 ans après un retour d'Afrique

Resume Nous avons conduit une etude retrospective sur les facteurs pronostiques des hypercalcemies neoplasiques dans le cadre de l'activite d'un service de Medecine Interne. Les dossiers de 51 patients qui associaient une hypercalcemie et un cancer histologiquement demontre ont ete analyses; 42 avaient une tumeur solide et 9 un myelome; 61 % des patients ont vu leur cancer revele par l'hypercalcemie. Les principaux signes cliniques d'appel etaient une alteration de l'etat general (68,6 %), des douleurs osseuses (54,9 %) et une polyurie avec deshydratation (58,8 %). Une lyse osseuse etait observee dans 75 % des cas. La mediane de survie globale est de 86 jours, significativement plus elevee dans les myelomes par rapport aux autres tumeurs (312 jours versus 60 jours, p

Hypercalcémies néoplasiques: facteurs pronostiques pour la survie des patients; à partir de 51 cas observés en Médecine Interne

To the editor: Acquired C1 esterase inhibitor (C1 INH) deficiency is usually found in association with a B-cell lymphoproliferative disorder (1). Treatment with antiepileptic drugs, i.e., phenytoin (2) and carbamazepine (3-6), may induce lymphadenopathy and, in some cases, malignant lymphoma. We describe here the unique observation of a patient treated with both phenytoin and carbamazepine who developed a Bcell lymphocytic leukaemia associated with acquired C1 INH deficiency and angioedema. A 61-year-old woman was referred to the Centre Hospitalo-Universitaire Toulouse Rangueil for evaluation of a 2-yr history of angioedema. She had a long history of petit ma1 epilepsy for which she had been treated daily with 400 mg of carbamazepine and 100 mg of phenytoin. She had no childhood or family history of angioedema. At the time of referral, she had suffered from intermittent episodes of limb or facial swelling for 2 yr, the symptoms becoming increasingly severe. Physical examination revealed only mild hepatosplenomegaly. The complete blood count demonstrated a haemoglobin of 13.3 g/ dl, a white cell count of 12000/pl (neutrophils 30%, eosinophils 4%, lymphocytes 60%, monocytes 6%), and a platelet count of 1880OO/pl. The erythrocyte sedimentation rate was 15 mm/h. Peripheral blood lymphocytes were 70 % CD 19-positive and 26 % CD3-positive. Blood and urine contained a monoclonal IgM kappa component. Quantitative immunoglobulins showed an IgG of 7.9 g/1 (normal 6-13), an IgA of 0.9g/1 (normal 0.7-3.1), and an IgM of 1.4 g/1 (normal 0.5-3.5). Antinuclear antibodies were negative. Serological tests for cytomegalovirus, Epstein-Barr virus, and human immunodeficiency virus were negative. C1 INH deficiency was confirmed by immunonephelemetric method (0.054 g/l, with normal levels exceeding 0.075 g/l). While the C4 level was undetectable, the C3 level was normal (1.16 g/l; normal 0.83-1.77 g/l). A computerized tomographic scan of the thorax and abdomen was a r ssociated deficienc W

Antiepileptic drug-induced lymphoproliferative disorder associated with acquired C1 esterase inhibitor deficiency and angioedema.

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