Association of antibodies against myelin and neuronal antigens with neuroinflammation in systemic lupus erythematosus.

OBJECTIVES: To determine frequency and syndrome specificity of novel and known nervous system (NS)-directed antibodies in a large, unbiased cohort of SLE patients in the Swiss SLE Cohort Study. METHODS: This retrospective pilot study included 174 patients in a cross-sectional and 102 in a longitudinal study. Antibodies against 12 NS antigens [myelin oligodendrocyte glycoprotein (MOG), neurofascin 186 (NF186), aquaporin-4 (AQP4), N-methyl-D-aspartate receptor (subunit NR1) (NMDAR-NR1), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (subunits 1 and 2) (AMPAR1/2), gamma-aminobutyric acid B receptor (subunits B1 and B2) (GABABR1/2), glutamate decarboxylase 65 (GAD65), glycine receptor (GlyR), contactin-associated protein-like 2 (CASPR2), leucine-rich glioma-inactivated 1 (LGI1), metabotropic glutamate receptor 5 (mGluR5) and dipeptidyl-peptidase-like protein 6 (DPPX)] were screened with validated cell-based assays and correlated with clinical and diagnostic findings. RESULTS: Twenty-three of one hundred and seventy-four (13.2%) patients harboured antibodies against MOG (n = 14), NF186 (n = 6), GAD65 (n = 2), AQP4 and GlyR (n = 1). Anti-MOG antibodies were most frequently found in the cohort (8%). Thirteen of the anti-NS antibody-positive patients showed clinical symptoms of NS involvement, a subgroup of which (n = 8) resembled the syndrome associated with the antibody. Nine patients harboured antibodies without neurological symptoms and one patient was lost to follow-up. The frequency of NPSLE was significantly higher in the anti-NS antibody-positive patients (13/23, 56.5%: MOG 6/14, 42.9%; NF186 5/6, 83.3%; GAD65 2/2, 100%; AQP4/GlyR 0/1, 0%) compared with the antibody-negative cohort (21/151, 13.9%) (chi-square test, P < 0.0001). CONCLUSION: Anti-NS antibodies, most prevalently anti-MOG antibodies, are significantly associated with NPSLE and manifest with the distinct neurological syndrome associated with the antibody in a subgroup. Follow-up studies in large, independent cohorts will reveal whether these anti-NS antibodies could serve as a diagnostic and prognostic biomarker for NPSLE and enable tailored treatment decisions in this challenging and diverse patient cohort.

[VIPoma : a rare etiology of diarrhea with hypokalemia]. / VIPome : étiologie rare d'une diarrhée hypokaliémiante.

VIPoma or Verner Morrison syndrome is a very rare disease with an incidence rate of 1 case per 10 000 000 person-years. It is a neuroendocrine tumor issue from ß-pancreatic islets leading to profuse diarrhea, hypokalemia and gastric achlorydria due to secretion of vasoactive intestinal polypeptide (VIP) hormone. Diagnosis is based on histology of tumor and the dosage of VIP in a blood sample. Somatostatin analog is a simple and efficient treatment for diarrhea. Curative treatment with surgery could be proposed for a localized disease. For disseminated disease, there are different treatments and a multimodal assessment that should be discussed in a multidisciplinary team might be curative.

Le VIPome ou syndrome de Verner Morrison est une maladie très rare, avec une incidence annuelle estimée à 1/10 000 000 habitants. Il s'agit d'une tumeur neuroendocrine issue des îlots ß pancréatiques qui sécrète une hormone appelée vasoactive intestinal polypeptide (VIP), à l'origine d'une achlorhydrie gastrique et de diarrhées profuses entraînant une hypokaliémie. Le diagnostic est posé à partir d'une analyse anatomopathologique de la tumeur et du dosage du VIP sanguin. Le traitement symptomatique par les analogues de la somatostatine est efficace sur la diarrhée. Un traitement curatif par la chirurgie peut être proposé pour une maladie tumorale localisée. Pour les maladies disséminées, différentes modalités thérapeutiques existent et dans certains cas une approche multimodale discutée dans un colloque spécialisé peut être curative.

[Erdheim-Chester disease : a differential diagnosis of retroperitoneal fibrosis]. / La maladie d'Erdheim Chester : un diagnostic différentiel de fibrose rétropéritonéale.

Erdheim-Chester disease is a rare multisystemic non-Langerhans histiocytosis with about 500 reported cases. Typical features include retroperitoneal and perirenal fibrosis (hairy kidney), periaortitis with a coated aorta, osteosclerosis of the lower limbs, and sometimes exophthalmia or diabetes insipidus. Histology is the cornerstone for diagnosis showing an infiltrate with foamy histiocytes and occasional multinucleated giant cells (Touton cells). There is no standard treatment regimen, current options include corticosteroids, interferon alpha, systemic chemotherapy, and radiation therapy ; however, a better understanding of the pathophysiological mechanisms has allowed the emergence of novel targeted treatments such as vemurafenib, imatinib, and anakinra.

La maladie d'Erdheim-Chester, une histiocytose non langerhansienne, caractérisée par une atteinte multisystémique, est rare avec environ 500 cas décrits. Les manifestations typiques sont une fibrose rétropéritonéale et périrénale (reins chevelus), une périaortite avec engainement circulaire (manchon aortique), une ostéosclérose des membres inférieurs et parfois une exophtalmie ou un diabète insipide. L'histologie montre un infiltrat d'histiocytes spumeux et parfois de cellules géantes polynucléées (cellules de Touton). Il n'y a pas de traitement standard et les options actuelles comprennent les corticoïdes, l'interféron alpha, la chimiothérapie et la radiothérapie ; cependant, une meilleure compréhension des phénomènes physiopathologiques a permis l'émergence de traitements ciblés comme l'anakinra, l'imatinib et le vémurafénib.

[Whipple disease: a differential diagnosis of polyarthritis to keep in mind]. / Maladie de Whipple: un diagnostic différentiel de polyarthrite à ne pas oublier.

Whipple disease is a rare and potentially fatal bacterial infection induced by a Gram-positive bacillus, Tropheryma whipplei. It is responsible for articular, digestive, neurological, ophthalmological and cardiological symptoms that occur either concomitant or isolated. Thus, the diagnosis is difficult to make and therefore often delayed. A paradoxal exacerbation of the symptoms under immunosuppressive drugs such as glucocorticoids and anti-TNF mAb, or inexpected improvements under antibiotic treatment applied for other reasons should raise a clinicial suspicion of Whipple's disease. Detection of the germ on stool and saliva samples by molecular biology methods has become straightforward with very good positive and negative predictive values. Long-term antibiotic treatment close follow-up are required for the induction of remission and to recognize relapse.

Mycosis fungoides palmaris and plantaris.

Mycosis fungoides (MF) palmaris and plantaris is a rare form of MF. Only few cases are reported in the literature. Different forms are described: eczematous lesions, dyshidrosis lesions, verrucous lesions, dry pulpitis, ulcerated lesions, pustulosis, and hyperkeratotic lesions. Histology is typical for MF with a positive T-cell receptor gene rearrangement in majority of cases. Prognosis is good. Resistance to topical steroids is common, and classical treatment consist of chlormethine gel and radiotherapy.

Novel Multidisciplinary Salivary Gland Society (MSGS) Questionnaire: An International Consensus.

OBJECTIVES: First, establishment and validation of a novel questionnaire documenting the burden of xerostomia and sialadenitis symptoms, including quality of life. Second, to compare two versions regarding the answering scale (proposed developed answers Q3 vs. 0-10 visual analogue scale Q10) of our newly developed questionnaire, in order to evaluate their comprehension by patients and their reproducibility in time. STUDY DESIGN: The study is a systematic review regarding the evaluation of the existing questionnaire and a cohort study regarding the validation of our new MSGS questionnaire. MATERIALS AND METHODS: A Multidisciplinary Salivary Gland Society (MSGS) questionnaire consisting of 20 questions and two scoring systems was developed to quantify symptoms of dry mouth and sialadenitis. Validation of the questionnaire was carried out on 199 patients with salivary pathologies (digestive, nasal, or age-related xerostomia, post radiation therapy, post radioiodine therapy, Sjögren's syndrome, IgG4 disease, recurrent juvenile parotitis, stones, and strictures) and a control group of 66 healthy volunteers. The coherence of the questionnaire's items, its reliability to distinguish patients from healthy volunteers, its comparison with unstimulated sialometry, and the time to fill both versions were assessed. RESULTS: The novel MSGS questionnaire showed good internal coherence of the items, indicating its pertinence: the scale reliability coefficients amounted to a Cronbach's alpha of 0.92 for Q10 and 0.90 for Q3. The time to complete Q3 and Q10 amounted, respectively, to 5.23 min (±2.3 min) and 5.65 min (±2.64 min) for patients and to 3.94 min (±3.94 min) and 3.75 min (±2.11 min) for healthy volunteers. The difference between Q3 and Q10 was not significant. CONCLUSION: We present a novel self-administered questionnaire quantifying xerostomia and non-tumoral salivary gland pathologies. We recommend the use of the Q10 version, as its scale type is well known in the literature and it translation for international use will be more accurate. Laryngoscope, 132:322-331, 2022.

Three cases of BRAF mutation negative Erdheim-Chester disease with a challenging distinction from IgG4-related disease.

BACKGROUND: Erdheim-Chester disease (ECD) is a rare non-Langerhans histiocytosis with slow progression over the years that is particularly difficult to diagnose. CASES: Here we report three cases of ECD without BRAF mutation presenting with a renal mass, hairy kidney appearance, and a rather benign course, for which the diagnosis of ECD was delayed, characterized by multiple investigations and unsuccessful treatments attempts. In two cases the distinction from IgG4-related disease required multiple investigations and reevaluation of the clinical, radiological, histological, and immunological characteristics. CONCLUSION: A correct diagnosis of ECD may take several years and often requires revisiting previous hypotheses. Reassessment of histological slides and more modern complementary exams such as PET-CT or BRAF and MAPK-ERK mutation analysis can help to confirm the diagnosis of ECD and to select effective therapy.

Comparison of Clinical Characteristics and Magnetic Resonance Imaging of Salivary Glands With Magnetic Resonance Sialography in Sjögren's Syndrome.

OBJECTIVES/HYPOTHESIS: To compare the results of magnetic resonance imaging with magnetic resonance sialography (MRSIAL) and the clinical and laboratory characteristics in a well-characterized cohort of patients with primary or secondary Sjögren's syndrome (SS) meeting the American-European Consensus Group criteria. STUDY DESIGN: Retrospective, observational, monocentric study. METHODS: Thirty-six patients (81% female, mean age = 48 ± 35 years) with primary or secondary SS who underwent MRSIAL were included in the study. RESULTS: MRSIAL revealed characteristic radiological signs in the parotid, sublingual, and submandibular salivary glands in 35/36 patients (97%). Patients presenting with anti-Sjögren's syndrome-related antigen A (SSA) autoantibodies showed more often fatty infiltration, a "pepper-and-salt" appearance, ductal stenosis, and/or ductal dilation of the parotid gland (88%, 88%, and 72% respectively) than patients negative for anti-SSA (12%, 4%, and 28% respectively). MRSIAL demonstrated signs characteristic of SS in all 11 patients with negative minor salivary gland biopsy. For 15 patients undergoing ultrasound examination only, 11 (73%) had SS findings, but all 15 had SS findings on MRSIAL. Two cases of parotid lymphoma were detected by MRSIAL (6%). CONCLUSIONS: MRSIAL is a reliable technique to detect glandular anomalies in patients with SS, and seems to provide a valuable aid in the diagnosis of SS. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E83-E89, 2021.

Pseudolymphomatous Granuloma Annulare: A Case Report.

Granuloma annulare is an idiopathic granulomatous condition. Clinical variants of granuloma annulare include classical and localized, large erythematous patch, generalized, perforating, and subcutaneous/deep forms. Rarely, granuloma annulare shows a prominent lymphoid infiltration. This form is called pseudolymphomatous granuloma annulare. Here, we describe a new case of pseudolymphomatous granuloma annulare.

Sign of Leser-Trélat and Cutaneous T-Cell Lymphoma: A Rare Association.

Sign of Leser-Trélat is a rare paraneoplastic cutaneous manifestation, characterized by the sudden appearance and rapid increase in size and number of seborrheic keratoses, accompanied by pruritus. Edmund Leser and Ulysse Trélat described this sign in 1890. Since their first description, their conclusions have been considered controversial and some authors assert the absence of a causal link. It seems to be frequently associated with solid tumors and in particular gastrointestinal cancer. Here, we describe a new case associated with a cutaneous T-cell lymphoma and a partial response to extracorporeal photopheresis.

Central nervous system involvement in eosinophilic granulomatosis with polyangiitis (Churg-Strauss): Report of 26 patients and review of the literature.

BACKGROUND: Although peripheral nervous system involvement is common in eosinophilic granulomatosis with polyangiitis (EGPA), central nervous system (CNS) manifestations are poorly described. This study aimed to describe CNS involvement in EGPA. PATIENTS AND METHODS: This retrospective, observational, multicenter study included patients with EGPA and CNS involvement affecting cranial nerves, brain and/or spinal cord. We also undertook a systematic literature review. RESULTS: We analyzed 26 personal cases and 62 previously reported cases. At EGPA diagnosis, asthma was noted in 97%, eosinophilia in 98%, peripheral neuropathy in 55% and cardiac involvement in 41%. 38/71 (54%) were ANCA-positive, with a perinuclear-labeling pattern and/or anti-MPO specificity. CNS was involved in 86% at EGPA diagnosis, preceded EGPA in 2%, and occurred during follow-up in 12% after a median of 24months. Main neurological manifestations were ischemic cerebrovascular lesions in 46 (52%), intracerebral hemorrhage and/or subarachnoid hemorrhage in 21 (24%), loss of visual acuity in 28 (33%) (15 with optic neuritis, 9 with central retinal artery occlusion, 4 with cortical blindness), and cranial nerves palsies in 18 (21%), with 25 patients having ≥1 of these clinical CNS manifestations. Among the 81 patients with assessable neurological responses, 43% had complete responses without sequelae, 43% had partial responses with long-term sequelae and 14% refractory disease. After a mean follow-up of 36months, 11 patients died including 5 from intracerebral hemorrhages. CONCLUSION: EGPA-related CNS manifestations form 4 distinct neurological pictures: ischemic lesions, intracerebral hemorrhages, cranial nerve palsies and loss of visual acuity. Such manifestation should prompt practitioners to consider EGPA in such conditions. Long-term neurological sequelae were common, and intracerebral hemorrhages had the worst prognostic impact.