Oral Janus kinase inhibitors and venous thromboembolic events in atopic dermatitis: protocols for a case-time control study and a nested case-control study based on the French national health insurance (SNDS) cohort.

INTRODUCTION: Atopic dermatitis (AD) is a highly prevalent, chronic, inflammatory skin disease. Several orally administered Janus kinase inhibitors (JAKis, including baricitinib, upadacitinib and abrocitinib) have received a marketing authorisation for AD.Clinical trials in rheumatoid arthritis (RA) have flagged up a potential risk of JAKi-induced venous thromboembolic events (VTEs). Accordingly, the summary of product characteristics for a JAKi must mention VTEs as potential adverse drug reactions. In contrast to RA, AD per se is not associated with an elevated risk of VTEs. Assessing this potential risk among patients with AD would shed further light on the putative underlying relationship between JAKis and VTEs.Our research question is to investigate whether JAKi administration increases the risk of VTEs in adults with AD. Our primary objective is to assess the risk of VTEs in adults with AD exposed to JAKis compared to AD adults not exposed to JAKis, and our secondary objective is to evaluate whether JAKi initiation acts as a trigger of VTEs in adults with AD within 3 months. METHODS AND ANALYSIS: Hence, we have designed (1) a nested case-control study and (2) a case-time control study in a cohort of adults with AD with data from the French national health insurance system (2017-2025).Here, we describe the study protocol, our methodological choices and certain novel aspects, including the combined value of the two assumptions and the use of an exhaustive national health insurance database with potentially greater statistical power for studying rare events in the population of patients with AD at a low risk of VTEs (thus limiting the influence of confounding factors). ETHICS AND DISSEMINATION: The protocol has been approved by an independent ethics committee and registered with the French National Data Protection Commission. The study's findings will be published in peer-reviewed scientific journals and presented at international conferences.

[Weight gain during treatment with thalidomide: a case report]. / Prise de poids lors d'un traitement par thalidomide: à propos d'un cas.

We report a case of weight gain induced by thalidomide in a 39-year-old female patient with Behçet's disease treated for an indication of severe, bipolar, aphthous stomatitis.

Pulse methylprednisolone therapy for threatening periocular haemangiomas of infancy.

Periocular haemangiomas of infancy can cause severe and rapid ocular damage. Oral corticosteroids remain the front-line treatment to minimize the consequences of these haemangiomas. The aim of this report is to summarize our experience with pulse intravenous methylprednisolone as an alternative therapy for periocular haemangioma when visual prognosis is engaged. Fifteen infants, who presented periocular haemangioma with functional impact on vision, received 2 mg/kg methylprednisolone intravenously twice a day for 2 days. Following pulse therapy, 2 mg/kg/day prednisolone was given orally with gradual tapering. No further visual impact was noticed following pulse therapy. Two patients relapsed, needing new pulses or, in one case, vincristine. No serious side-effects were recorded. Pulse methylprednisolone therapy permitted a particularly rapid shrinkage of haemangiomas and a complete disappearance of their visual impact within 2 days. Apparently more rapid than the usual oral corticosteroids, pulse intravenous methylprednisolone decreases the risk of ocular complications, which correlates with the duration of the influence of haemangiomas.

Activation of the prostaglandin D2 receptor DP2/CRTH2 increases allergic inflammation in mouse.

Allergic pathologies are often associated with IgE production, mast cell activation, and eosinophilia. PGD2 is the major eicosanoid, among several inflammatory mediators, released by mast cells. PGD2 binds to two membrane receptors, D prostanoid receptor (DP)1 and DP2, endowed with antagonistic properties. In humans, DP2 is preferentially expressed on type 2 lymphocytes, eosinophils, and basophils and mediates chemotaxis in vitro. Although not yet supported by in vivo studies, DP2 is thought to be important in the promotion of Th2-related inflammation. Herein, we demonstrate that mouse eosinophils express both DP1 and DP2 and that PGD2 exerts in vitro chemotactic effects on eosinophils through DP2 activation. Furthermore, 13,14-dihydro-15-keto-PGD2, a specific DP2 agonist not only increases eosinophil recruitment at inflammatory sites but also the pathology in two in vivo models of allergic inflammation: atopic dermatitis and allergic asthma. By contrast, DP1 activation tends to ameliorate the pathology in asthma. Taken together, these results support the hypothesis that DP2 might play a critical role in allergic diseases and underline the interest of DP2 antagonists in human therapy.

Activation of the D prostanoid receptor 1 regulates immune and skin allergic responses.

The mobilization of Langerhans cells (LCs) from epithelia to the draining lymph nodes is an essential process to initiate primary immune responses. We have recently shown that in mice, PGD2 is a potent inhibitor of epidermal LC emigration. In this study, we demonstrate that activation of the D prostanoid receptor 1 (DP1) impedes the TNF-alpha-induced migration of human LCs from skin explants and strongly inhibits the chemotactic responses of human LC precursors and of maturing LCs to CC chemokine ligands 20 and 19, respectively. Using a murine model of atopic dermatitis, a chronic Th2-type allergic inflammatory disease, we demonstrate that the potent DP1 agonist BW245C dramatically decreases the Ag-specific T cell activation in the skin draining lymph nodes and markedly prevents the skin lesions following repeated epicutaneous sensitization with OVA. Interestingly, analysis of the local response indicates that BW245C treatment strongly reduces the recruitment of inflammatory cells into the dermis and disrupts the Th1/Th2 balance, probably through the increased production of the immunoregulatory cytokine IL-10, in the skin of sensitized mice. Taken together, our results suggest a new function for DP1 in the regulation of the immune and inflammatory responses. We propose that DP1 activation by specific agonists may represent a strategy to control cutaneous inflammatory Th2-associated diseases.

Congenital elephantiasis-like lymphangiomatosis of a lower limb.

The case of a newborn girl with a rare, giant, congenital, tissue lymphangioma giving rise to elephantiasis of the right lower limb is presented. The different imaging methods, especially magnetic resonance imaging, showed no extension of the lesions into the deep structures. At the age of 2 years, the child underwent a roentgenographic skeletal survey, which revealed osteolytic lesions in the femurs and the right tibia. There was no clinical evidence of systemic involvement. The place of this affection among the different lymphatic malformations was discussed and the diagnosis of elephantiasis-like lymphangiomatosis of the limb, an extremely rare disorder, has been retained. Early surgical reduction was performed, followed by application of a pressure dressing. Five years later the result remains satisfactory, but the excision of a persistent fluid-filled pouch around the knee will probably be necessary in the future.