La Revue de medecine interne最新文献

Janus kinase (JAK) molecules are involved in important cellular activation pathways. Over the past decade, many targeted therapies have emerged, including the increasingly promising role of JAK inhibitors (JAKi) in the treatment of inflammatory and autoimmune diseases. The spectrum of use of these small molecules is increasingly broader. JAKi have been approved in several autoimmune diseases. Currently, four molecules (tofacitinib, baricitinib, upadacitinib and filgotinib) have been labeled for moderate to severe rheumatoid arthritis (RA) with failure or poor tolerance of one or more conventional disease-modifying antirheumatic drug (csDMARDS), or biologics (bDMARDS). JAKi are now also commonly used in other diseases such as psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis. They have also shown promising results in clinical trials for the treatment of other autoimmune conditions. We present here their mechanisms of action, and the main data about JAKi use on systemic and autoimmune diseases.

Background: Human papillomavirus (HPV) infections cause cancer of the cervix, vagina, vulva, anus, penis and upper respiratory tract. The prevention of HPV-induced cancers is a public health issue. Patients with systemic lupus are at increased risk of persistent HPV infection and cervical cancer due to treatment-induced immunosuppression. HPV vaccination and screening for precancerous lesions are two effective means of preventing cervical cancer. Despite the demonstrated safety and efficacy of the HPV vaccine, coverage of HPV vaccination in SLE adults remains low. Screening for cervical cancer is only carried out as recommended in one lupus patient in two. Catch-up HPV vaccination, therapeutic vaccination and vaginal self-sampling are innovative prevention strategies adapted to patients at risk of HPV-induced cancer.

Conclusions: Measures to prevent HPV-induced cancers are insufficiently implemented in patients managed for systemic lupus. Healthcare professionals and patients need to be made aware of the importance of HPV preventing vaccination.

Hepatic encephalopathy is a severe complication with high mortality in patients with hepatopathy and/or portosystemic shunts, partly due to the presence of hyperammonemia because of defective hepatic detoxification. Diagnosis is essentially clinical, characterized by various neuropsychiatric symptoms, possibly associated with hyperammonemia. Complementary tests, such as electroencephalogram to identify metabolic encephalopathy, or specific abnormalities on cerebral magnetic resonance imagery, may also support the diagnosis. Management is essentially based on treatment of triggering factors such as ionic disorders or sepsis, and symptomatic therapy with non-absorbable disaccharides (notably lactulose) or polyethylene glycol, possibly combined with rifaximin. Progression varies according to the initial severity and management of hepatic encephalopathy, but this condition is potentially reversible with treatment.

Purpose: An updated revision of the 2016 recommendations from the French Study Group for Large Vessel Vasculitis (GEFA) was needed to better delineate the place and management of immunosuppressants or biologics in giant cell arteritis (GCA).

Methods: A panel of 18 physicians, including internists and rheumatologists, constituted the task force of this project and drafted the recommendations. Twelve additional readers were asked to analyse and comment on the recommendations. Two face-to-face virtual meetings were held to discuss and validate the recommendations. Each member voted individually, and a>85% consensus was required to validate each recommendation.

Results: From the initial 6 questions, 26 recommendations were validated. The following main recommendations were validated. (1) Subcutaneous 162mg tocilizumab (TCZ) for at least 12months should be used first when glucocorticoid (GC)-sparing treatment is needed with the objective of discontinuing GCs within the subsequent 6months. (2) GCA patients who have experienced any of the following conditions must receive TCZ at GCA diagnosis with 6months of GC therapy: major cardiovascular event, osteoporosis with fracture, psychiatric event with GC use, complicated diabetes mellitus, or any previous>6months of GC treatment. (3) In patients in whom GC discontinuation is not possible after 12months of treatment because of persistent disease activity or in patients in whom GC-related adverse events are unacceptable, TCZ (or alternatively methotrexate) may be proposed.

Conclusions: These recommendations were constructed based on the results of the published literature and the experts' experiences to standardise therapeutic practices in France. Further updates will likely be necessary following new publications.

Fibrillary glomerulonephritis (FGN) is a glomerular disease described since 1977, with a prevalence in renal biopsies of less than 1%. It presents as renal failure, proteinuria, haematuria and hypertension in middle-aged adults. It is defined histologically, using light microscopy, which reveals organised deposits of fibrils measuring around 20nm, which are negative for Congo red staining. Electron microscopy, the first gold standard for diagnosis, has now been superseded by immunohistochemistry using the anti-DNAJB9 antibody. The discovery of this molecule has revolutionised the diagnosis of GNF, thanks to its excellent sensitivity and specificity (98% and 99% respectively). The association of GNF with hepatitis C virus, autoimmune diseases, neoplasia or haemopathy is debated. Renal prognosis is guarded, with 50% of patients progressing to end-stage renal failure within 2 to 4years of diagnosis. In the absence of randomised controlled trials, the recommended treatment is based on nephroprotective measures, corticosteroid therapy and possibly a second-line immunosuppressant such as rituximab. After renal transplantation, recovery or recurrence is possible. The pathophysiology of the disease is still poorly understood, and further studies are needed.

Giant cell arteritis (GCA) is a large-vessel vasculitis that mainly affects women over fifty. GCA usually involves branches from the external carotid arteries, causing symptoms such as headaches, scalp tenderness, and jaw claudication. The most severe complication is ophthalmologic involvement, including acute anterior ischemic optic neuropathy and, less frequently, central retinal artery occlusion with a risk of permanent blindness. Approximately 40% of patients may have involvement of the aorta or its branches, which has a poor prognosis, although this is often asymptomatic at diagnosis. Diagnosis is largely based on imaging techniques such as FDG-PET combined with CT, CT angiography, or MRI angiography of the aorta and its branches. Polymyalgia rheumatica is associated with GCA in 30-50% of cases but may also occur independently. Treatment must be initiated urgently in the presence of ophthalmologic signs or when GCA is strongly suspected to prevent vision loss. The gold standard to confirm the diagnosis is temporal artery biopsy. However, Doppler ultrasound and vascular imaging are also reliable diagnostic techniques. Initially, high doses of corticosteroids like prednisone (40-80mg per day) are the mainstay of treatment. Tocilizumab can be discussed in combination with prednisone for corticosteroid sparing. Long-term management is essential, including monitoring for disease recurrence and corticosteroid-related side effects. General practitioners play a crucial role in early diagnosis, directing patients to specialized centres, and in managing ongoing treatment in collaboration with specialists. This collaboration is essential to address potential long-term complications such as cardiovascular events. They can occur five to ten years after the diagnosis of GCA even when the disease is no longer active, meaning that vigilant follow-up is required due to the patients' age and status.