The objective was to evaluate concordance between 2002 American-European Consensus Group (AECG) and 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) ...classification criteria for primary Sjögren's syndrome (pSS) and to assess how salivary gland ultrasonography (SGUS) might improve the classification of patients.
Patients with suspected pSS underwent a standardised evaluation, including SGUS, at inclusion into the single-centre Brittany DIApSS cohort. Agreement between the two criteria sets was assessed using Cohen's κ coefficient. Characteristics of discordantly categorised patients were detailed.
We prospectively included 290 patients between 2006 and 2016, among whom 125 (43%) met ACR/EULAR criteria and 114 (39%) also met AECG criteria; thus, 11 (4%) patients fulfilled only ACR/EULAR, no patients AECG only, and 165 (57%) patients neither criteria set. Concordance was excellent (κ = 0.92). Compared to patients fulfilling both criteria sets, the 11 patients fulfilling only ACR/EULAR criteria had similar age and symptom duration but lower frequencies of xerophthalmia and xerostomia (p < 0.01 for each) and salivary gland dysfunction (p < 0.01); most had systemic involvement (91%), including three (27%) with no sicca symptoms; 91% had abnormal salivary gland biopsy and 46% anti-Sjögren's-syndrome-related antigen A (anti-SSA); 64% were diagnosed with pSS by the physician. SGUS was abnormal in 12% of the 165 patients fulfilling no criteria set. Including SGUS among the ACR/EULAR criteria increased sensitivity from 87.4% to 91.1% when physician diagnosis was the reference standard.
Agreement between AECG and ACR/EULAR criteria sets is excellent. ACR/EULAR criteria are slightly more sensitive and classified some patients without sicca symptoms as having pSS. Including SGUS in the ACR/EULAR criteria may further improve their sensitivity.
Background Small-fiber neuropathies (SFN) are diseases of small nerve fibers that are characterized by autonomic and sensory symptoms. Objective We sought to evaluate sensory symptoms, especially ...pruritus, in patients with SFN. Methods A questionnaire was given to patients with SFN. Results In all, 41 patients responded to the questionnaire (71.9% response rate). The most frequent sensory symptoms were burning (77.5%), pain (72.5%), heat sensations (70.2%), and numbness (67.5%). Pruritus was present in 68.3% of patients. It appeared most often in the evening, and was localized to the limbs in a distal-to-proximal gradient, although the back was the most frequent location (64%). Exacerbating factors were fatigue, xerosis, sweating, hot temperature, and stress. Cold water was an alleviating factor. Limitations Recall bias associated with filling out the questionnaire, relatively small sample size, and the uncontrolled, retrospective nature of the study were limitations. Conclusion Pruritus occurs frequently in patients with SFN and could be recognized as a possible presenting symptom, especially if there are other sensory or autonomic symptoms.
Small fiber neuropathies (SFNs) are disorders of skin nerve endings inducing pruritus, burning pain, numbness, and paresthesia. The aims of this study were to search for putative etiologies of SFN ...and their occurrence in a cohort of patients and to compare patients with SFN to a group of patients without SFN to highlight potential factors associated with SFN.
This study was observational, retrospective, and monocentric. All patients with symptoms of SFN who underwent skin biopsies with intraepidermal nerve density counts were included. Patients with a count lower than 5 percentiles were considered to be in the SFN group. Other patients were considered to be the control group.
A total of 162 patients with SFN and 161 controls were included. No cause was identified for 108 patients (61.7%). The established causes were autoimmune diseases (9.1%), diabetes or glucose intolerance (8%), medication (4%), liver disease (3.4%), and monoclonal gammopathy of undetermined significance (2.9%). Current or former smokers were more numerous in the SFN group (26.5%) than in the control group (16.1%), while vitamin D amounts were significantly lower in the SFN group than in the control group.
Hence, tobacco smoking and vitamin D deficiency might be new putative causes of SFN.
myriam.chebbah@ph-expertise.com (M. Chebbah).
Le diagnostic et le suivi de la sclérose latérale amyotrophique (SLA) reposent sur différents systèmes de gradation et classification, dont certains sont ...utilisés majoritairement dans les essais cliniques.
Un consensus d’experts a déterminé la pertinence des échelles et des critères utilisés en pratique clinique, ainsi que la place d’un futur traitement dans la stratégie thérapeutique.
Le consensus d’experts a été réalisé en France selon la méthodologie Delphi. Un Comité de pilotage (CoPil) regroupant 5 experts de la pathologie a été constitué afin de construire le questionnaire soumis à distance en deux tours de vote aux praticiens spécialistes des centres référents. Les résultats ont été validés lors d’une réunion finale avec le CoPil. Le consensus a été considéré atteint pour une réponse lorsque 66 % des votants étaient en accord sur celle-ci.
Vingt-quatre experts ont participé aux deux tours de Delphi. Un consensus a été atteint sur l’utilisation des critères Gold Coast pour établir le diagnostic SLA en pratique, alors qu’El Escorial-R est seulement utilisé dans les essais cliniques pour caractériser les patients à inclure et non pour guider la prise en charge. L’ALSFRS-R utilisée en routine mesure l’atteinte fonctionnelle (en points ou pente évolutive, non en pourcentage). Un score ≤ 38/48 témoigne d’un déficit fonctionnel significatif.
Le diagnostic et le suivi de la SLA reposent sur des critères et échelles variés, sans recommandation précise sur leur utilisation en dehors des essais cliniques. Les critères Gold Coast sont utilisés pour établir un diagnostic et non les critères d’El Escorial-R en pratique, démontrant que les critères utilisés dans les essais ne sont pas complètement transposables en pratique quotidienne.
Ces résultats permettent de définir et différencier les échelles utilisées au diagnostic et lors du suivi des patients SLA, en essais cliniques et en pratique quotidienne.
Pruritus, also known as itch, is a very common, unpleasant sensation that elicits an urge to scratch. Its origin is not always in the skin, and neuropathic itch that is caused by neuronal or glial ...damage is common, but poorly understood by both dermatologists and neurologists. Although pruritus has not been considered as serious a symptom as pain, it is difficult to treat and--if chronic--can severely impair quality of life. Neuropathic itch is often associated with other clinical symptoms, most commonly neuropathic pain, and hypersensitization to stimuli is present in both pruritus and pain of neuropathic origin. The shared aetiology can aid in finding suitable treatment for itch in some cases, but more detailed knowledge of the mechanisms of itch, along with standardized, well-controlled trials, is needed. Pruritus research is an emerging but currently very active field, and our understanding of this sensation is rapidly increasing. Here, we review new discoveries regarding the role of the nervous system and the contribution of different pathways in pruritus, discuss the different aetiologies of neuropathic itch, and outline currently available and potential strategies for managing neuropathic pruritus.
Focal iron accumulation associated with brain iron dyshomeostasis is a pathological hallmark of various neurodegenerative diseases (NDD). The application of iron-sensitive sequences in magnetic ...resonance imaging has provided a useful tool to identify the underlying NDD pathology. In the three major NDD, degeneration occurs in central nervous system (CNS) regions associated with memory (Alzheimer’s disease, AD), automaticity (Parkinson’s disease, PD) and motor function (amyotrophic lateral sclerosis, ALS), all of which require a high oxygen demand for harnessing neuronal energy. In PD, a progressive degeneration of the substantia nigra pars compacta (SNc) is associated with the appearance of siderotic foci, largely caused by increased labile iron levels resulting from an imbalance between cell iron import, storage and export. At a molecular level, α-synuclein regulates dopamine and iron transport with PD-associated mutations in this protein causing functional disruption to these processes. Equally, in ALS, an early iron accumulation is present in neurons of the cortico-spinal motor pathway before neuropathology and secondary iron accumulation in microglia. High serum ferritin is an indicator of poor prognosis in ALS and the application of iron-sensitive sequences in magnetic resonance imaging has become a useful tool in identifying pathology. The molecular pathways that cascade down from such dyshomeostasis still remain to be fully elucidated but strong inroads have been made in recent years. Far from being a simple cause or consequence, it has recently been discovered that these alterations can trigger susceptibility to an iron-dependent cell-death pathway with unique lipoperoxidation signatures called ferroptosis. In turn, this has now provided insight into some key modulators of this cell-death pathway that could be therapeutic targets for the NDD. Interestingly, iron accumulation and ferroptosis are highly sensitive to iron chelation. However, whilst chelators that strongly scavenge intracellular iron protect against oxidative neuronal damage in mammalian models and are proven to be effective in treating systemic siderosis, these compounds are not clinically suitable due to the high risk of developing iatrogenic iron depletion and ensuing anaemia. Instead, a moderate iron chelation modality that conserves systemic iron offers a novel therapeutic strategy for neuroprotection. As demonstrated with the prototype chelator deferiprone, iron can be scavenged from labile iron complexes in the brain and transferred (conservatively) either to higher affinity acceptors in cells or extracellular transferrin. Promising preclinical and clinical proof of concept trials has led to several current large randomized clinical trials that aim to demonstrate the efficacy and safety of conservative iron chelation for NDD, notably in a long-term treatment regimen.
Sensory neuropathies (SNs) are often classified as idiopathic even if immunological mechanisms can be suspected. Antibodies against the intracellular domain of the fibroblast growth factor receptor 3 ...(FGFR3) possibly identify a subgroup of SN affecting mostly the dorsal root ganglion (DRG). The aim of this study was to identify the frequency of anti-FGFR3 antibodies and the associated clinical pattern in a large cohort of patients with SN.
A prospective, multicentric, European and Brazilian study included adults with pure SN. Serum anti-FGRF3 antibodies were analysed by ELISA. Detailed clinical and paraclinical data were collected for each anti-FGFR3-positive patient and as control for anti-FGFR3-negative patients from the same centres ('center-matched').
Sixty-five patients out of 426 (15%) had anti-FGFR3 antibodies, which were the only identified autoimmune markers in 43 patients (66%). The neuropathy was non-length dependent in 89% and classified as sensory neuronopathy in 64%, non-length-dependent small fibre neuropathy in 17% and other neuropathy in 19%. Specific clinical features occurred after 5-6 years of evolution including frequent paresthesia, predominant clinical and electrophysiological involvement of the lower limbs, and a less frequent mixed large and small fibre involvement. Brazilians had a higher frequency of anti-FGFR3 antibodies than Europeans (36% vs 13%, p<0.001), and a more frequent asymmetrical distribution of symptoms (OR 169, 95% CI 3.4 to 8424).
Anti-FGFR3 antibodies occur in a subgroup of SN probably predominantly affecting the DRG. Differences between Europeans and Brazilians could suggest involvement of genetic or environmental factors.
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