Changes in amyloidosis phenotype over 11 years in a cardiac amyloidosis referral centre cohort in France.

BACKGROUND: Early cardiac amyloidosis (CA) diagnosis enables patients to access effective treatments for better long-term outcomes, yet it remains under-recognised, misdiagnosed and inadequately managed. AIM: To reduce diagnostic delays, we aimed to describe the epidemiological and clinical characteristics and changes over an 11-year period. METHODS: This was a retrospective, observational cohort study of all patients referred to the Henri-Mondor Hospital for suspected CA. RESULTS: Overall, 3194 patients were identified and 3022 were included and analysed. Our patients came from varied ethnic backgrounds, and more than half (55.2%) had confirmed CA. Over 11 years, referrals increased 4.4-fold, mostly from cardiologists. Notably, wild-type transthyretin amyloidosis (ATTRwt) became the predominant diagnosis, with referrals increasing 15-fold from 20 in 2010-2012 to 308 in 2019-2020. The number of amyloid light chain (AL) diagnoses increased, whilst variant transthyretin amyloidosis (ATTRv) numbers remained relatively stable. Concerning disease severity, AL patients presented more frequently with severe cardiac involvement whereas an increasing number of ATTRwt patients presented with National Amyloid Centre stage I (22.0% in 2013-2014 to 45.9% in 2019-2020). Lastly, among patients diagnosed with ATTRv in 2019-2020, 83.9% had ATTR Val122Ile cardiac phenotype. CONCLUSIONS: This study shows that increasing cardiologist awareness and referrals have increased CA diagnoses. With improved awareness and non-invasive diagnostic techniques, more patients with ATTRwt with milder disease and more ATTRv Val122Ile mutations are being referred and diagnosed. Although more AL cases are being recognised, patients are diagnosed with severe cardiac involvement.

Bone Status According to Neurofibromatosis Type 1 Phenotype: A Descriptive Study of 60 Women in France.

There is an increased risk of osteoporosis and an abnormal bone turn over in neurofibromatosis 1 (NF1). Our objective is to evaluate bone status in NF1 and to look for associations with cutaneous phenotype. We conducted a descriptive, monocentric study. We included 60 NF1 women, 18-51 years old, non-menopausal, divided in 2 groups: «at risk phenotype¼ (ARP) composed by 30 patients with at least 2 subcutaneous neurofibromas (SC-NF) and «classical phenotype¼ (CP) composed by 30 patients with none or 1 SC-NF. We evaluated low bone mineral density (BMD) risk factors and measured BMD, calcium and phosphorus homeostasis and bone turnover markers. Before 50 years old, Z-score has to be used to assess BMD. Z-score < - 2 is below expected range and represents 2.5% of the population. There was no difference between the two groups. Overall, Z-scores were low and 5 patients had a Z-score < - 2 (8.3%), which is 3 times general population low BMD frequency. 10 fragility fractures occurred in 8 patients, among which 2 were vertebral fractures. 85% had low calcium intake. 12 patients had hypophosphoremia, 25 elevated PTH. Vitamin D levels were low for 86.4%. 41 patients (69.5%) had at least one abnormal bone turnover markers. Low BMD is 3.3 times more frequent in NF1 than in general population, with high fracture risk, regardless of the skin phenotype, classical or at risk, because of high bone turn over and secondary hyperparathyroidism due to vitamin D deficiency and poor calcium intake.

Acute Symptomatic Calcific Discitis Mimicking a Septic Spondylodiscitis.

Acute symptomatic calcific discitis is a poorly understood condition that has been mostly reported in children. Cases in adults have been scarcely reported and may mimic an infectious process. Imaging, including computed tomography, can show the disc calcification but might fail to show it because its resorption can occur early after the onset of symptoms. We report the case of an adult patient presenting with severe cervical-dorsal junction pain, fever, high C-reactive protein (CRP) levels, and imaging findings mimicking an infectious spondylodiscitis, including an erosion of the anterior part of the vertebral endplate. However, the patient improved spontaneously and rapidly, with pain and fever disappearing and C-reactive protein (CRP) returning to normal within a week.

Dermatitis herpetiformis and bone mineral density: analysis of a French cohort of 53 patients.

The characteristics of patients with dermatitis herpetiformis (DH) in France is poorly documented. Furthermore, the risk of fractures and bone mineral density (BMD) in DH remain under-described, and recommendations for systematic screening for osteoporosis in DH are lacking. To describe the characteristics of DH in a large French cohort and evaluate the association between BMD and features of osteoporosis. Patients were recruited from the French Association of Gluten Intolerants (AFDIAG) and a single university dermatology department. A telephone questionnaire was used to record features of DH, history of fractures, calcium intake, treatment, and the gluten-free diet (GFD). Serum calcium and 25(OH) vitamin D3+D2 levels, as well as BMD, were measured. We included 53 patients (27 men) with a median age of 49 years (range: 23-86). Median disease duration before inclusion was 14 years (range: 2-55); 51 patients (96%) were adherent to a GFD and had no digestive symptoms. Overall, 18 (34%) had a history of fractures; 16 high-velocity (traumatic) and two low-velocity (non-traumatic). Mean BMD, measured in 48 patients, was normal (femoral neck: 0.956 ± 0.210 g/cm2; lumbar spine: 1.091 ± 1.199 g/cm2). In all, 18 patients (38%) had osteopenia and one (2%) osteoporosis. T-score for bone density did not differ with and without fractures. Calcium intake and serum calcium level were normal in all patients. Screening for osteoporosis does not appear to be mandatory for DH patients with good adherence to a GFD and without digestive symptoms or additional risk factors of osteoporosis.

Efficacity and feasibility of vertebroplasty for severe vertebral fracture: a retrospective study of 12 vertebroplasties.

Vertebroplasty is commonly contraindicated for severe vertebral fractures, or vertebra plana. However, we decided after multidisciplinary staff decision to perform vertebroplasty for few severe vertebral fractures which were still painful after optimal medical treatment. We retrospectively studied the charts of patients who benefited from vertebroplasty for severe vertebral body compression fracture between May 2006 and January 2012 in a rheumatology department. Clinical and biological data were collected and patients were consulted to assess effectiveness of that technique. We performed vertebroplasty of 12 severe vertebral fractures in 10 patients (nine women and one man). Mean age was 74.9±10.7 years. Mean VAS score was 9/10±1.15 before vertebroplasty and 2.4±2 after. Global improvement was 80% and patient satisfaction was 7/10. After vertebroplasty, use of drugs was significantly reduced or even stopped. The complications observed were: three infraclinical cement leakages, one haematoma at the site of the puncture, one atrial fibrillation and one classic pulmonary embolism. Mean follow-up was 28.6±22.3 months. Vertebroplasty is indeed a delicate procedure for severe vertebral fracture but quickly and sustainably effective.

Antisynthetases syndrome associated with right heart failure.

Cardiac involvement is a complication of end stage polymyositis with left heart insufficiency reported to be the most frequent manifestation. We here describe an unusual clinical presentation of antisynthetases syndrome, beginning with right-sided cardiomyopathy associated with right heart failure. A 26 year-old Caucasian male experienced a 6-month clinical course of polyarthritis, fever, sweats, and myalgia. Laboratory studies showed elevated C reactive protein, elevated sedimentation rate, and myolysis associated with anti SSA and anti JO1 antibodies. Electromyography showed a myopathic pattern. Muscle biopsy confirmed the diagnosis of polymyositis. Chest X ray, chest scan, and cardiac echography were normal. One week after hospital admission, the patient developed acute right heart insufficiency, and magnetic resonance imaging showed a right ventricular myocarditis with myocardial inflammatory thickening. Treatment with corticosteroids rapidly improved both symptoms and biological abnormalities.

C-reactive protein predicts tumor necrosis factor-alpha blocker retention rate in axial ankylosing spondylitis.

OBJECTIVE: In ankylosing spondylitis (AS), tumor necrosis factor (TNF) blockers are recommended for patients with high symptomatic disease activity. Few data are available about objective signs of inflammation such as increased C-reactive protein (CRP). We assessed the retention rate of TNF blockers in patients with axial AS, according to baseline CRP and other potentially predictive measures. METHODS: A retrospective study of all patients treated with TNF blockers for axial AS. Retention rate was evaluated using a survival-data analysis technique with discontinuation of the drug because of inefficacy (Kaplan-Meier method). Potential factors explaining the retention rates (demographic and clinical indicators and CRP) were evaluated using log-rank tests and a Cox proportional-hazards regression model. RESULTS: For axial AS, 175 patients received TNF blockers (men 78%, mean disease duration 12.4 +/- 9.1 yrs); 100 patients (of 143 with available data) had an increased CRP (> 10 mg/l). An increased CRP at baseline was the only variable explaining the retention rate in the Cox model (p = 0.003, hazard ratio = 3.3, 95% CI 1.5-7.3). CONCLUSION: Interruption for expert opinion of inefficacy was more frequent for patients with low baseline CRP; however, even in these patients retention was high. Increased CRP should not be considered mandatory for proposing TNF blocker treatment in axial AS.

Retention rates of tumor necrosis factor blockers in daily practice in 770 rheumatic patients.

OBJECTIVE: Tumor necrosis factor (TNF) blockers are efficacious in clinical trials in rheumatic diseases. However, their efficacy in daily practice, depending on the specific diagnosis or the use of concomitant therapy, remains to be confirmed. Our objective was to evaluate TNF blocker retention rates and their predisposing factors in daily practice. METHODS: Retrospective evaluation of all TNF blocker therapies in one center. Retention rate was evaluated using a Kaplan-Meier survival data analysis technique in which the event was discontinuation of the drug due to inefficacy or toxicity with log-rank tests and a Cox proportional-hazards regression model. RESULTS: From 1997 to 2004, 770 patients with inflammatory rheumatism received at least one TNF blocker; 142 received more than one agent (975 treatment courses: 493 etanercept, 335 infliximab, 147 adalimumab). The underlying disease was mainly rheumatoid arthritis (RA), found in 57.1% of patients, and spondyloarthropathies (SpA) in 37.7%. The percentage of patients receiving the same treatment at Month 12, 24, and 36 was 64.0%, 50.3%, and 39.4%, respectively. No difference between the 3 TNF blockers was found (p = 0.48). The retention rate was longer for the first treatment course [hazard ratio (HR) 2.17, 95% confidence interval (95% CI) 1.82-2.58, p < 0.0001]; longer for patients with SpA (HR 1.60, 95% CI 1.20-2.13, p = 0.001); and longer without concomitant DMARD (HR 0.70, 95% CI 0.51-0.97, p = 0.03). CONCLUSION: Our results indicate a lower retention rate of TNF blockers in daily practice compared with clinical trials, with no difference between the 3 currently available agents. Moreover, results suggest greater benefit in SpA. The role of concomitant DMARD remains to be confirmed.