Rare association between rheumatoid arthritis and Vogt-Koyanagi-Harada syndrome: A case-based review

IntroductionVogt-Koyanagi-Harada (VKH) syndrome is a systemic autoimmune disorder that targets tissues containing melanocytes such as the eye, inner ear, meninges and skin. Despite a common genetic susceptibility, the association between VKH syndrome and rheumatoid arthritis (RA) has been rarely reported.Aim of the workTo report a rare case with RA who developed incomplete VKH syndrome. The case is described and a review of the literature on similar cases is presented.Case reportA 26 year-old Tunisian woman, with a medical history of Hashimoto’s thyroiditis, was diagnosed on 2011 with seropositive and erosive RA treated with Leflunomide. She presented to the emergency department on June 2018 with bilateral blurred vision associated with photophobia, vomiting and severe headache that had gradually progressed over the preceding five days. Ophthalmological examinations showed typical findings of VKH syndrome. The patient received intravenous infusions of methylprednisolone at a daily dose of 1000 mg for 3 days that was followed orally with 2 mg/kg of prednisone equivalent. Given the lack of improvement in visual acuity after 3 weeks of treatment, azathioprine was added and VKH remission was achieved on September 2018 as confirmed on optical coherence tomography. However, the patient passed away on October 2018 due to infectious complications of the immunosuppressant agents.ConclusionTreatments and outcomes of VKH are variable. Pharmacological management of such an association between RA and VKH may be challenging, so care must be taken to balance treatment escalation with adverse events in patients at risk.     

Epidemiological serosurvey and molecular characterization of sexually transmitted infections among 1890 sheltered homeless people in Marseille: Cross-sectional one day-surveys (2000–2015)

ObjectivesWe observed the prevalence and distribution of potential risk factors for sexually transmitted infections (STIs) among Marseille homeless population.MethodsOver the 2000-2015 period, we enrolled 1890 sheltered homeless adults and collected serum samples. Markers of hepatitis B and C viruses (HBV, HCV) and Treponema pallidum were searched using the CMIA testing. Positive HBsAg or anti-HCV samples underwent sequencing; positive anti-T. pallidum sera were subjected to the RPR test.ResultsThe overall prevalence of HBsAg, anti-HBs, anti-HBc, anti-HCV and anti-T. pallidum (by CMIA and RPR) was 4.1%, 22.9%, 35.5%, 5.3% and (6.8%, 1.0%), respectively. We found a significantly higher prevalence of HBsAg and anti-T. pallidum among individuals born in sub-Saharan Africa (or Asia) compared to those born in Europe. Being older (>42 years), toxicomania status, cannabis use and underweight status (compared to normal status) were independent factors associated with HCV seropositivity. Using sequencing, we obtained a substantial diversity of HBV and HCV genotypes. One HCV sequence harbouring a L31M substitution in the NS5a protein may be associated with reduced drug sensitivity.ConclusionsThe positive relationship between toxicomania and HCV suggests the need for effective prevention programmes including health education activities and addiction treatment.     

Combined Induction Therapy with Rabbit Antithymocyte Globulin and Rituximab in Highly Sensitized Renal Recipients

Compared to non-sensitized renal transplant recipients, patients with preformed alloantibodies are at greater risk of cellular and humoral rejection and premature graft failure. We explored the effects of adding B-cell depleting agent (rituximab) to standard rabbit anti-thymocyte globulin (rATG) induction regimen for patients with panel reactive antibody levels >50%. Following induction therapy, 14 recipients were given two doses of rituximab (375?mg/m²) within the first month post-transplantation. Their long-term outcomes were compared to a historical control group of 23 recipients who received rATG alone. Graft survival at 5 years was superior with combination therapy compared to induction therapy alone (92.9 versus 48.3%, respectively, p?=?0.02). While 30% of the rATG alone group experienced cellular rejection and 26% humoral rejection, none of rituximab plus rATG renal transplant recipients group had rejection. Thus, addition of rituximab to rATG provided superior outcomes to rATG alone. This combination induction therapy should be considered for a high-risk population.     

A case of a giant left ventricular pseudoaneurysm

A Left ventricular pseudoaneurysm is an outpouching resulting from myocardial free wall rupture which is contained by an adherent pericardium or scar tissue. It most often occurs after transmural myocardial infarction, but may also follow cardiac operations, trauma, inflammation, or infection. In contrast to patients with true ventricular aneurysms, those with false aneurysms most commonly die of hemorrhage.Transthoracic echocardiogram, computed tomography scan and cardiac MRI are currently the noninvasive modalities, whereas coronary arteriography and left ventriculography are invasive modalities used for diagnosis. As this condition is lethal, prompt diagnosis and timely management are vital.We present a case report of a patient with no prior risk factors who presented for 1 year with palpitations during exercise and rest, as well as intermittent chest pain. A transthoracic echocardiogram was performed. Echocardiogram revealed an unexpected outpouching of the left ventricle. A computed tomography scan confirmed the diagnosis by revealing a massive left ventricule pseudomanoeuvre. The patient was offered surgery, but he refused the procedure due to the surgical risk.     

Blocking S-adenosylmethionine synthesis in yeast allows selenomethionine incorporation and multiwavelength anomalous dispersion phasing

Saccharomyces cerevisiae is an ideal host from which to obtain high levels of posttranslationally modified eukaryotic proteins for x-ray crystallography. However, extensive replacement of methionine by selenomethionine for anomalous dispersion phasing has proven intractable in yeast. We report a general method to incorporate selenomethionine into proteins expressed in yeast based on manipulation of the appropriate metabolic pathways. sam1(-) sam2(-) mutants, in which the conversion of methionine to S-adenosylmethionine is blocked, exhibit reduced selenomethionine toxicity compared with wild-type yeast, increased production of protein during growth in selenomethionine, and efficient replacement of methionine by selenomethionine, based on quantitative mass spectrometry and x-ray crystallography. The structure of yeast tryptophanyl-tRNA synthetase was solved to 1.8 A by using multiwavelength anomalous dispersion phasing with protein that was expressed and purified from the sam1(-) sam2(-) strain grown in selenomethionine. Six of eight selenium residues were located in the structure.     

Langerhans cell histiocytosis revealed by painful hip: A case report

Langerhans cell histiocytosis is a rare disease in childhood. It has a very polymorphous clinical expression, ranging from a single bony disease to a multisystemic disease involving vital organs. Prognosis has been improved by use of chemotherapy. We report a 2-year-old girl with multifocal Langerhans cell histiocytosis of bone and skin, revealed by a pain of the left hip and a limp trailing from 2 months. The diagnosis has been established by histological exam. The patient received chemotherapy and steroids. Outcome was favourable over 6-month follow-up. Trailing limp should evoke diagnosis of Langerhans cell histiocytosis. Skin biopsy should be preferred to a bone biopsy because of its safety.     

The fatty acid receptor GPR40 plays a role in insulin secretion in vivo after high-fat feeding

OBJECTIVE—The G-protein–coupled receptor GPR40 is expressed in pancreatic β-cells and is activated by long-chain fatty acids. Gene deletion studies have shown that GPR40 mediates, at least in part, fatty acid–amplification of glucose-induced insulin secretion (GSIS) but is not implicated in GSIS itself. However, the role of GPR40 in the long-term effects of fatty acids on insulin secretion remains controversial. This study aimed to test the hypothesis that GPR40 plays a role in insulin secretion after high-fat feeding.RESEARCH DESIGN AND METHODS—GPR40 knockout (KO) mice on a C57BL/6 background and their wild-type (WT) littermates were fed a high-fat diet (HFD) for 11 weeks. Glucose tolerance, insulin tolerance, and insulin secretion in response to glucose and Intralipid were assessed during the course of the diet period.RESULTS—GPR40 KO mice had fasting hyperglycemia. They became as obese, glucose intolerant, and insulin resistant as their WT littermates given HFD and developed a similar degree of liver steatosis. Their fasting blood glucose levels increased earlier than those of control mice during the course of the HFD. The remarkable increase in insulin secretory responses to intravenous glucose and Intralipid seen in WT mice after HFD was of much lower magnitude in GPR40 KO mice.CONCLUSIONS—GPR40 plays a role not only in fatty acid modulation of insulin secretion, but also in GSIS after high-fat feeding. These observations raise doubts on the validity of a therapeutic approach based on GPR40 antagonism for the treatment of type 2 diabetes.Fatty acids do not initiate insulin release in the absence of glucose, but they potentiate glucose-induced insulin secretion (GSIS) upon acute exposure. Their mechanisms of action are, however, incompletely understood. The discovery of GPR40 as a G-protein–coupled receptor highly expressed in pancreatic β-cells and activated by long-chain fatty acids (1–4) has enabled the identification of a novel mechanism of action of fatty acids on insulin secretion. Loss of function of GPR40 via small interfering RNA (2,5–7), antisense oligonucleotides (8), pharmacological inhibitors (9), or gene deletion in the mouse (10,11) partially suppresses fatty acid potentiation of GSIS in vitro. We (10) and others (11) have shown that whole-body GPR40 knockout (KO) mice have normal glucose tolerance and unaltered insulin secretion in response to glucose in vivo and in vitro, but that isolated islets from these mice secrete less insulin in response to fatty acids. Furthermore, insulin secretion induced by Intralipid in vivo is reduced in GPR40 KO mice, demonstrating a physiological role for GPR40 in fatty acid–potentiation of GSIS (10).GPR40 has received considerable attention as a potential therapeutic target in type 2 diabetes (12–15). Surprisingly, whether an agonist or antagonist should be developed as a therapeutic agent remains debated (13,15). This uncertainty stems, in part, from conflicting reports regarding the role of GPR40 in β-cell function (10,11). Steneberg et al. (11) found that islets isolated from GPR40 KO mice were protected from the inhibitory effects of prolonged fatty acid exposure on GSIS, in contrast to our findings in a different line of GPR40 KO mice (10) and a recent study using GPR40 agonists (16). Steneberg et al. (11) further showed that GPR40 KO mice were protected from high-fat diet (HFD)-induced insulin resistance, glucose intolerance, and hepatic steatosis. Given these discrepancies and the importance of determining whether an agonist or antagonist approach should be pursued for drug development, the present study was designed to test the hypothesis that GPR40 contributes to the enhancement of insulin secretion after HFD. Specifically, we sought to examine whether GPR40 KO mice are more susceptible to HFD-induced hyperglycemia and, if so, whether this is due to changes in insulin secretion in vivo or associated with changes in the expression of genes controlling fatty acid metabolism in islets.