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Introduction We designed a retrospective study of 59 patients with congenital sporadic nonprogressive bilateral facial and abducens palsies. Methods Examinations included needle electromyography (EMG) of facial and oral muscles, facial nerve motor latency and conduction velocity (FNCV), and blink responses (BR). Results Neurogenic EMG changes were found in 1 or more muscles in 55 of 59 patients, with no abnormal spontaneous activity. EMG changes were homogeneously neurogenic in 17 patients, homogeneously myopathic in 1 patient, and heterogeneous in 41 of 59 patients. Motor latency was increased according to recordings from 52 of 137 facial muscles. An increase of motor latency was not associated with neurogenic EMG (Fischer's test: right, P = 1; left, P = 0.76). FNCV was slowed in 19 of 36 patients. BR was absent bilaterally in 35 of 58 patients; when present, R1 and R2 latencies were normal. Discussion Our results support the hypothesis of an early developmental defect localized in motor cranial nerves with spared V-VII internuclear pathways. Muscle Nerve, 2018.

INTRODUCTION Patients with renal failure who are being treated with dialysis frequently develop neuromuscular manifestations. Renal failure-associated calciphylaxis, also termed calcific uremic arteriolopathy (CUA), is a life-threatening condition usually observed in patients with end-stage renal disease on chronic dialysis or after renal transplantation. METHODS We describe a hemodialyzed patient who presented with rapidly progressive unexplained systemic vasculopathy, muscle atrophy, and proximal weakness, that unexpectedly proved to be caused by calciphylaxis. RESULTS Quadriceps muscle biopsy disclosed diffuse vascular calcific deposits on medium- and small-sized vessels, characteristic of CUA. Other changes included ischemic myopathy, focal intracellular calcium accumulation within myofibers, and calcium deposits in endomysial capillaries associated with marked complement activation and C5b9 formation. CONCLUSION There are only a few descriptions of muscle involvement in the context of CUA, a condition with a prognosis that depends on early diagnosis and treatment. This report underscores the usefulness of muscle biopsy in the diagnosis of systemic calciphylaxis. Muscle Nerve 56: 529-533, 2017.

Inflammatory bowel diseases (IBD) is a systemic disorder with possible renal involvement, yet data regarding the outcome of kidney transplantation (KT) in those patients, and IBD course post KT, are scarce. In this retrospective analysis, we studied the outcome of 12 IBD kidney recipients (seven Crohn's disease, five ulcerative colitis; primary kidney disease was IgA nephropathy in five, polycystic disease in four), compared to two control groups: matched controls and a cohort of recipients with similar kidney disease. During a follow-up period of 60.1 (11.0-76.6) months (median, interquartile range), estimated 5-year survival was 80.8 vs. 96.8%, with and without IBD, respectively (P = 0.001). Risk of death with a functioning graft was higher with IBD (HR = 1.441, P = 0.048), and with increased age (HR = 1.109, P = 0.05). Late rehospitalization rate was higher in IBD [incidence rate ratio = 1.168, P = 0.030], as well as rate of hospitalization related to infection [1.42, P = 0.037]. All patients that were in remission before KT, remission was maintained. Patients that were transplanted with mild or moderate disease remained stable or improved with Infliximab or Adalimumab treatment. In conclusion, IBD is associated with an increased risk of mortality, hospitalization because of infection and late rehospitalization after KT. Clinical course of IBD is stable after KT.

The anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody is specifically associated with dermatomyositis (DM). Nevertheless, anti–MDA5 + -patients experience characteristic symptoms distinct from classic DM, including severe signs of extramuscular involvement; however, the clinical signs of myopathy are mild or even absent. The morphological and immunological features are not yet described in adulthood. Data concerning the pathophysiology of anti-MDA5 DM are sparse; however, the importance of the interferon (IFN) type I pathway involved in DM has been shown. Our aim was to define morphological alterations of the skeletal muscle and the intrinsic immune response of anti–MDA5-positive DM patients. Immunohistological and RT-PCR analysis of muscle biopsy specimens from anti-MDA5 and classic DM were compared. Those with anti-MDA5 DM did not present the classic features of perifascicular fiber atrophy and major histocompatibility complex class I expression. They did not show significant signs of capillary loss; tubuloreticular formations were observed less frequently. Inflammation was focal, clustering around single vessels but significantly less intense. Expression of IFN-stimulated genes was up-regulated in anti-MDA5 DM; however, the IFN score was significantly lower. Characteristic features were observed in anti-MDA5 DM and not in classic DM patients. Only anti-MDA5 DM showed numerous nitric oxide synthase 2–positive muscle fibers with sarcoplasmic colocalization of markers of regeneration and cell stress. Anti–MDA5-positive patients demonstrate a morphological pattern distinct from classic DM.

Background The course of dermatomyositis (DM) can be chronic with relapses, which are associated with major morbidity. Objective The aim of this study was to identify presentation features that predict DM relapses. Methods We retrospectively reviewed data of patients with DM recorded from 1990 to 2011, including muscle biopsy results. Characteristics of patients with and without relapses were compared. Hazard ratios (HRs) were estimated using a Cox model. Results We identified 34 patients, with a mean age of 46 ± 17 years (range, 18–77) and 24 (71%) women. The muscle and skin abnormalities relapsed in 21 (61%) patients. By univariate analysis, two presentation features were significantly associated with a subsequently relapsing course, namely, dysphonia [HR = 3.2 (1.2–8.5)] and greater skin lesion severity defined as a Cutaneous Disease Area Severity Index [CDASI] > 20 [HR = 3.5 (1.2–7.9)]. Conclusion Dysphonia and skin lesion severity at disease onset must be recorded, as they significantly predict a relapsing disease course.

Objectives Myositis-specific autoantibodies (MSAs) are increasingly used to delineate distinct subgroups of JDM. The aim of our study was to explore without a priori hypotheses whether MSAs are associated with distinct clinical-pathological changes and severity in a monocentric JDM cohort. Methods Clinical, biological and histological findings from 23 JDM patients were assessed. Twenty-six histopathological parameters were subjected to multivariate analysis. Results Autoantibodies included anti-NXP2 (9/23), anti-TIF1γ (4/23), anti-MDA5 (2/23), no MSAs (8/23). Multivariate analysis yielded two histopathological clusters. Cluster 1 (n = 11) showed a more severe and ischaemic pattern than cluster 2 (n = 12) assessed by: total score severity ⩾ 20 (100.0% vs 25.0%); visual analogic score ⩾6 (100.0% vs 25.0%); the vascular domain score >1 (100.0% vs 41.7%); microinfarcts (100% vs 58.3%); ischaemic myofibrillary loss (focal punched-out vacuoles) (90.9 vs 25%); and obvious capillary loss (81.8% vs 16.7). Compared with cluster 2, patients in cluster 1 had strikingly more often anti-NXP2 antibodies (7/11 vs 2/12), more pronounced muscle weakness, more gastrointestinal involvement and required more aggressive treatment. Furthermore, patients with anti-NXP2 antibodies, mostly assigned in the first cluster, also displayed more severe muscular disease, requiring more aggressive treatment and having a lower remission rate during the follow-up period. Conclusion Marked muscle ischaemic involvement and the presence of anti-NXP2 autoantibodies are associated with more severe forms of JDM.

The aim of this study was to characterize brain metabolic abnormalities in patients with macrophagic myofascitis (MMF) and the relationship with cognitive dysfunction through the use of PET with 18F-FDG. Methods:18F-FDG PET brain imaging and a comprehensive battery of neuropsychological tests were performed in 100 consecutive MMF patients (age [mean ± SD], 45.9 ± 12 y; 74% women). Images were analyzed with statistical parametric mapping (SPM12). Through the use of analysis of covariance, all 18F-FDG PET brain images of MMF patients were compared with those of a reference population of 44 healthy subjects similar in age (45.4 ± 16 y; P = 0.87) and sex (73% women; P = 0.88). The neuropsychological assessment identified 4 categories of patients: those with no significant cognitive impairment (n = 42), those with frontal subcortical (FSC) dysfunction (n = 29), those with Papez circuit dysfunction (n = 22), and those with callosal disconnection (n = 7). Results: In comparison with healthy subjects, the whole population of patients with MMF exhibited a spatial pattern of cerebral glucose hypometabolism (P < 0.001) involving the occipital lobes, temporal lobes, limbic system, cerebellum, and frontoparietal cortices, as shown by analysis of covariance. The subgroup of patients with FSC dysfunction exhibited a larger extent of involved areas (35,223 voxels vs. 13,680 voxels in the subgroup with Papez circuit dysfunction and 5,453 voxels in patients without cognitive impairment). Nonsignificant results were obtained for the last subgroup because of its small population size. Conclusion: Our study identified a peculiar spatial pattern of cerebral glucose hypometabolism that was most marked in MMF patients with FSC dysfunction. Further studies are needed to determine whether this pattern could represent a diagnostic biomarker of MMF in patients with chronic fatigue syndrome and cognitive dysfunction.

Introduction Les myopathies auto-immunes comprennent : – les polymyosites (PM) et myosites a inclusions (inclusion body myositis [IBM]) ; – les dermatomyosites (DM) ; – les myopathies necrosantes auto-immunes (MNAI) ; – les myosites de connectivites et de chevauchement (overlap myositis [OM]). Au plan immunopathologique, les IBM et les OM se differencient des autres myopathies auto-immunes par la presence d’une expression myocytaire anormale des antigenes du complexe majeur d’histocompatibilite de classe II (CMH2). L’interferon (IFN)γ etant le principal inducteur du MHC2, nous faisons l’hypothese que les IBM et OM se caracterisent par une activation du systeme de l’interferon (IFN)γ. Materiel et methodes Pour tester cette hypothese, nous avons evalue par qPCR l’expression de l’IFNγ, de six genes induits par l’IFNγ (HLA-DM, -DO, -DP, -DR, CIITA, GBP2), et d’un gene induit par l’IFNα (ISG15) dans les biopsies musculaires de patients avec IBM (n = 10), DM (n = 10), MNAI (n = 10), syndrome antisynthetase (SdAS, n = 10), et muscle histologiquement normal (temoins, n = 10). Resultats L’expression musculaire d’IFNγ etait augmentee dans les SdAS (×50) et les IBM (×80), celle de CIITA ×4 et ×3 (respectivement) de meme que celle de HLA-DR (×5 et ×8), HLA-DM (×16 et ×15). Aucun des ces genes n’etait surexprime dans la DM et les MNAI. ISG15 etait fortement surexprime (×300) dans la DM, mais pas dans les autres pathologies. Conclusion Nos resultats confirment que les IBM et SdAS sont caracterises par la presence d’une signature interferon-type II a la difference de la DM caracterisee par une signature interferon-type I.

The aim of this study was to characterize brain metabolic abnormalities in patients with macrophagic myofascitis (MMF) and the relationship with cognitive dysfunction through the use of PET with

Brain Positron Emission Tomography/Computed Tomography with (18)F-fluorodeoxyglucose (FDG PET/CT) was performed in a 44-year-old woman with marked cognitive impairment, diffuse myalgias, sensory, memory and visual disorders, and chronic fatigue, presenting with histopathological features of macrophagic myofasciitis (MMF) at deltoid muscle biopsy. Cerebromedullary Magnetic Resonance Imaging (MRI), electromyography, ophthalmic examination, and cerebrospinal fluid analysis were normal. Visual analysis of FDG PET/CT images showed an atypical pattern of hypometabolism, involving symmetrically the occipital cortex, temporal lobes, and limbic system (including in particular amygdalo-hippocampal complexes), and the cerebellum. Posterior cingulate cortex and parietal areas were preserved. This pattern was confirmed by a voxel-based procedure using Statistical Parametric Mapping (SPM12) that compared a patient's images to normal reference samples from six healthy subjects with adjustment to age obtained using the same PET/CT camera. These results provide a glucose metabolism substrate for cognitive complaints in patients with long-lasting aluminium hydroxide-induced MMF.

International audience; Introduction: Sudden sensorineural hearing loss is an unusual presenting clinical feature of systemic lupus erythematosus.Case report: We report the case of a young woman who was admitted to hospital for sudden sensorineural hearing loss and hemophagocytic syndrome which was attributed to systemic lupus erythematosus on the basis of specific renal involvement, thrombocytopenia, and consistent autoantibodies. Favorable outcome was obtained on high-dose corticosteroids, and the hearing fully recovered.Discussion: Sudden sensorineural hearing loss in systemic lupus erythematosus is seemingly more frequently associated with severe systemic involvement and antiphospholipid antibodies may be present. Although management remains empirical, the high risk of permanent hearing impairment seems to justify emergency treatment with high-dose corticosteroids. When the clinical and laboratory criteria of antiphospholipid syndrome are met, antiplatelets agents or anticoagulation therapy shall be considered.

Preventive treatment of focal and segmental glomerulosclerosis (FSGS) allograft recurrence in high risk recipients having a prior history of graft loss caused by FSGS recurrence is still a challenging question. We retrospectively identified four patients who underwent a second renal transplantation because of recurrent FSGS and who received Rituximab therapy as a prophylactic treatment. Loss of their first allograft was directly related to an early (

Aluminum oxyhydroxide (Alhydrogel(®)) is a nano-crystalline compound forming aggregates that has been introduced in vaccine for its immunologic adjuvant effect in 1926. It is the most commonly used adjuvant in human and veterinary vaccines but mechanisms by which it stimulates immune responses remain ill-defined. Although generally well tolerated on the short term, it has been suspected to occasionally cause delayed neurologic problems in susceptible individuals. In particular, the long-term persistence of aluminic granuloma also termed macrophagic myofasciitis is associated with chronic arthromyalgias and fatigue and cognitive dysfunction. Safety concerns largely depend on the long biopersistence time inherent to this adjuvant, which may be related to its quick withdrawal from the interstitial fluid by avid cellular uptake; and the capacity of adjuvant particles to migrate and slowly accumulate in lymphoid organs and the brain, a phenomenon documented in animal models and resulting from MCP1/CCL2-dependant translocation of adjuvant-loaded monocyte-lineage cells (Trojan horse phenomenon). These novel insights strongly suggest that serious re-evaluation of long-term aluminum adjuvant phamacokinetics and safety should be carried out.

Objectives To report a patient with systemic ANCA-associated vasculitis, under maintenance treatment, who had persistent microscopic hematuria and developed recurrent pelvic pain due to Corynebacterium urealyticum encrusting cystitis. The relevant literature on this infection is reviewed. Methods Descriptive case report and a review of the literature (PubMed search). Results A 39-year-old woman on maintenance therapy for systemic ANCA-associated vasculitis, diagnosed 10 months earlier and with persistent microscopic hematuria, developed recurrent pelvic pain. She had received several immunosuppressants (including cyclophosphamide and rituximab) since the onset of her vasculitis, as well as cycles of broad-spectrum antibiotics during the acute initial phase of her disease. Computerized tomography of the pelvis and cystoscopy showed several encrusted calcifications in the bladder mucosa, and, finally, urine culture (selective media) led to the diagnosis of C. urealyticum infection. Most of the bladder-encrusted stones were removed during cystoscopy and daily intramuscular teicoplanin injections were given for 14 days. Her symptoms disappeared rapidly and completely. On reviewing the literature, immunosuppression, previous broad-spectrum antibiotics, urogenital alkaline pH, and prolonged bladder catheterization are predisposing factors for this rare infection. C. urealyticum encrusting cystitis has been reported in patients with systemic diseases but not yet in ANCA-associated vasculitis. Outcome is almost always good under adequate antibiotic therapy, mainly glycopeptides. Conclusion Physicians should be aware of this unusual but potentially emerging infectious complication that can be challenging in ANCA-associated vasculitis, because the urinary tract can be affected by the vasculitis or as a complication of previous cyclophosphamide therapy.

Retroperitoneal fibrosis has been reported in several patients with Wegener granulomatosis (WG), but only three isolated cases of dorsal prevertebral lesions, closely resembling fibrosing mediastinitis, have been published so far. We describe four new WG patients (two men, two women), 49-59 years old at diagnosis, with dorsal prevertebral lesions, mainly right-sided, and with adjacent pleural thickening in two. These lesions were detected on computed-tomography scans at diagnosis in two patients, and occurred later in the two others. Only one of them had mild back pain. Two patients' lesions were biopsied, revealing granulomatous inflammation. In one patient, the lesion regressed under WG treatment. Lesion size did not change in the remainings. Intralesional calcifications appeared in two. None of the patients had local bone erosion, vascular or neurological complications. These prevertebral lesions might represent a dorsal form of retroperitoneal fibrosis in WG, but usually with a more benign presentation and course. WG should be included in the differential diagnosis of fibrosing mediastinitis (with tuberculosis, neoplastic diseases, sarcoidosis, histiocytosis and inflammatory pseudotumor), which may have a similar radiological appearance.

Resume La survenue d’une fibrose retroperitoneale a ete rapportee chez plusieurs patients atteints de granulomatose de Wegener (GW), mais seuls trois cas isoles de lesions dorsales prevertebrales, ressemblant fortement a une mediastinite fibrosante, ont ete publies a ce jour. Nous rapportons quatre nouveaux cas de patients atteints de GW (deux hommes, deux femmes), âges de 49 a 59 ans au moment du diagnostic, presentant des lesions dorsales prevertebrales, localisees principalement a droite, associees a un epaississement de la plevre dans deux cas. Ces lesions ont ete detectees sur le scanner realise au moment du diagnostic chez deux patients et sont survenues plus tard chez les deux autres. Seul un des patients avait des rachialgies moderees. Deux patients ont eu une biopsie qui a mis en evidence une inflammation granulomateuse. Chez un patient, la lesion a regresse sous traitement de la GW. La taille des lesions n’a pas diminue chez les autres patients. Des calcifications intralesionnelles sont apparues dans deux cas. Aucun des patients n’a eu d’erosion osseuse locale, de complications vasculaires ou neurologiques. Ces lesions prevertebrales pourraient representer une forme dorsale de fibrose retroperitoneale au cours de la GW, mais avec une presentation et une evolution en general moins severe. La GW doit etre evoquee dans le diagnostic differentiel de mediastinite fibrosante (avec la tuberculose, les neoplasies, la sarcoidose, l’histiocytose et les pseudotumeurs inflammatoires) qui peut avoir une presentation radiologique similaire.

Background and objectives: Sarcoidosis is a multisystem disorder of unknown etiology. The outcome of renal transplantation on patients with sarcoidosis is not well known. A few case reports have described recurrence of sarcoidosis after transplant. Here, we report for the first time results and outcome of renal transplantation in a series of patients with sarcoidosis. Design, setting, participants, & measurements: Eighteen patients with sarcoidosis who underwent renal transplantation were identified retrospectively in eight French renal transplantation departments. Patient medical charts, demographics, and the outcome of renal transplantation were reviewed. Results: Initial renal disease was related to sarcoidosis in 10 patients. At the end of the follow-up (median, 42 months), patient and death-censored graft survival were 94.4% and the mean GFR was 60 ml/min per 1.73 m 2 . Five patients (27%) experienced recurrence of sarcoidosis including extra-renal involvement in two patients and renal involvement in three patients. Median GFR was lower in the group of patients with renal recurrence compared with that of the entire cohort: 31 ml/min per 1.73 m 2 . Recurrence occurred shortly after transplantation (median period, 13 months). Risk factors for recurrence included primary renal disease related to sarcoidosis and a shorter delay between the last episode of sarcoidosis and renal transplantation. Conclusions: Our results indicate that renal transplantation may be carried out safely in transplant candidates with sarcoidosis. Recurrence is not rare and is likely to affect graft outcome. These results fully justify a specific clinical and histologic monitoring mainly during the early posttransplant period.

The anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody is specifically associated with dermatomyositis (DM). Nevertheless, anti-MDA5(+)-patients experience characteristic symptoms distinct from classic DM, including severe signs of extramuscular involvement; however, the clinical signs of myopathy are mild or even absent. The morphological and immunological features are not yet described in adulthood. Data concerning the pathophysiology of anti-MDA5 DM are sparse; however, the importance of the interferon (IFN) type I pathway involved in DM has been shown. Our aim was to define morphological alterations of the skeletal muscle and the intrinsic immune response of anti-MDA5-positive DM patients. Immunohistological and RT-PCR analysis of muscle biopsy specimens from anti-MDA5 and classic DM were compared. Those with anti-MDA5 DM did not present the classic features of perifascicular fiber atrophy and major histocompatibility complex class I expression. They did not show significant signs of capillary loss; tubuloreticular formations were observed less frequently. Inflammation was focal, clustering around single vessels but significantly less intense. Expression of IFN-stimulated genes was up-regulated in anti-MDA5 DM; however, the IFN score was significantly lower. Characteristic features were observed in anti-MDA5 DM and not in classic DM patients. Only anti-MDA5 DM showed numerous nitric oxide synthase 2-positive muscle fibers with sarcoplasmic colocalization of markers of regeneration and cell stress. Anti-MDA5-positive patients demonstrate a morphological pattern distinct from classic DM.

Patients with renal failure who are being treated with dialysis frequently develop neuromuscular manifestations. Renal failure-associated calciphylaxis, also termed calcific uremic arteriolopathy (CUA), is a life-threatening condition usually observed in patients with end-stage renal disease on chronic dialysis or after renal transplantation.We describe a hemodialyzed patient who presented with rapidly progressive unexplained systemic vasculopathy, muscle atrophy, and proximal weakness, that unexpectedly proved to be caused by calciphylaxis.Quadriceps muscle biopsy disclosed diffuse vascular calcific deposits on medium- and small-sized vessels, characteristic of CUA. Other changes included ischemic myopathy, focal intracellular calcium accumulation within myofibers, and calcium deposits in endomysial capillaries associated with marked complement activation and C5b9 formation.There are only a few descriptions of muscle involvement in the context of CUA, a condition with a prognosis that depends on early diagnosis and treatment. This report underscores the usefulness of muscle biopsy in the diagnosis of systemic calciphylaxis. Muscle Nerve 56: 529-533, 2017.

OBJECTIVE Outcome of JDM is highly heterogeneous. Our objective was to determine clinical and muscle biopsy features associated with poor outcome and response to treatment. METHODS Clinical data and muscle biopsy were obtained from a monocentric cohort of 29 patients. Clinical subgroups were defined by latent class model analysis of initial and follow-up parameters. Myopathological features were analysed using validated scores. Capillary loss was determined on reconstructions of transversal sections and assessed in the different age groups to take into account variations of muscle capillarization during post-natal development. Regression models were used to identify initial predictors of therapeutic response. RESULTS Two distinct homogeneous subgroups of patients were identified according to clinical severity and pathological findings. The smallest group of patients (7/29) presented with severe JDM. Compared with the other group (22/29), patients had more severe muscle weakness at disease onset, low remission rate at 12 months, frequent subcutaneous limb oedema or gastrointestinal (GI) involvement and higher myopathological scores (capillary dropout, perifascicular necrosis/regeneration, fibres with internal myonuclei and fibrosis subscores). Relevance of capillary dropout to JDM severity was substantiated by age-based analysis, confirming its major role in JDM pathophysiology. Most of these manifestations could be related to vasculopathy (limb oedema, GI involvement, capillary dropout). Furthermore, Childhood Myositis Assessment Scale

Background Macrophagic myofasciitis (MMF) is characterized by abnormal long-term persistence of aluminum hydroxide within macrophages at the site of previous immunization. Patients present with diffuse arthromyalgias, chronic fatigue, and cognitive dysfunction. The aim of this study was to characterize brain PET metabolic abnormalities in patients with aluminum hydroxide adjuvant-induced macrophagic myofasciitis, and relation with cognitive dysfunction. Methods FDG-PET brain imaging and a comprehensive battery of neuropsychological tests were performed in 100 consecutive MMF patients (mean age, 45.9 ± 11.8 y; women, 74%) followed in our Reference Center for Rare Neuromuscular Diseases. Images were analyzed using statistical parametric mapping (SPM12). Using ANCOVA analysis, all FDG-PET brain images of MMF patients were compared to normal reference samples from 44 healthy subjects matched for age ( p = 0.87) and gender ( p = 0.88) with the whole population of patients (mean age, 45.4 ± 16 y; women, 73%). All results were collected at a p -value k ≥ 200 voxels (corrected for cluster volume) with adjustment for age and gender. The neuropsychological assessment identified four categories of patients with: (i) no significant cognitive impairment ( n = 42); (ii) frontal sub-cortical (FSC) dysfunction ( n = 29); (iii) papezian dysfunction ( n = 22); and (iv) callosal disconnection ( n = 7). Results In comparison with healthy subjects, ANCOVA analysis of the whole population of patients with MMF exhibited a pattern of hypometabolism ( p Conclusions Our study identified a cerebral glucose metabolic biomarker in patients with long-lasting aluminum hydroxide-induced MMF. The pattern appeared mostly marked in MMF patients with FSC dysfunction.

Preventive treatment of focal and segmental glomerulosclerosis (FSGS) allograft recurrence in high risk recipients having a prior history of graft loss caused by FSGS recurrence is still a challenging question. We retrospectively identified four patients who underwent a second renal transplantation because of recurrent FSGS and who received Rituximab therapy as a prophylactic treatment. Loss of their first allograft was directly related to an early (3 months) recurrence of FSGS that was either resistant to plasmapheresis therapy in two cases or had escaped to this therapeutic management in the two others. After the second renal transplantation, all patients were free of FSGS recurrence during follow-ups that were between 12 and 54 months long. These preliminary results demonstrate for the first time that Rituximab therapy may constitute an attractive prophylactic option for patients being considered for a second renal transplantation because of recurrent FSGS in their first graft.

Les myopathies inflammatoires et dysimmunitaires (MID) idiopathiques sont divisees en trois principaux groupes sur la base de criteres morphologiques et immunopathologiques : (i) polymyosite (PM) et myosite a inclusions (IBM), (ii) dermatomyosite (DM), et (iii) myopathie necrosante auto-immune. Les MID peuvent egalement s’integrer dans le cadre d’une connectivite ou s’associer a une atteinte systemique extra-musculaire multi-systemique (myosite de chevauchement), comme dans le cas des patients avec auto-anticorps anti-synthetases. Nous avons montre que la myopathie associee aux anticorps anti-synthetases etait caracterisee par une expression myocytaire perifasciculaire d’HLA-DR associee a des signes d’activation du complement avec formation de C5b-9 myocytaire. Ce patron immunopathologique est different de ceux observes dans les autres types de MID et constitue donc un biomarqueur distinctif de myopathie anti-synthetase (Acta Neuropathol Commun 2014;2:154). Nous avons evalue la valeur diagnostique de l’expression myocytaire d’HLA-DR sur 160 biopsies musculaires. Une expression myocytaire d’HLA-DR etait observee dans 13/160 cas (8 %), de type perifasciculaire (7/13) ou multifocale (6/13). Les principaux diagnostics relies a l’expression d’HLA-DR etaient la myosite de chevauchement (5/13, perifasciculaire 4/5) et la myosite a inclusion (4/13, multifocal). Ces resultats confirment l’existence d’un patron immunopathologique caracteristique des myosites de chevauchement caracterise par l’expression myocytaire perifasciculaire d’HLA-DR.

Background. Henoch-Schonlein Purpura nephropathy (HSPN) recurrence in renal transplant recipients (RTRs) has been reported in 35% of patients, leading in 11% of these patients to graft loss at 5 years. However, its true incidence is unknown. The aim of this study was to investigate this recurrence incidence using routine allograft biopsies (RBs). Methods. All RTRs with biopsy-proven HSP initial nephropathy were included (13 RTRs and 18 renal transplantations). At transplantation, the median age was 34 years, and 85% of RTRs were men. Overall, we analyzed 66 RBs that were routinely performed at 3 and 12 months after RT and when clinically indicated. Histologic recurrence was defined as the presence of IgA deposits within the mesangium and along the glomerular capillary walls. Results. After a median follow-up of 83 months (range, 13–232 months; interquartile range, 26–235 months), histologic recurrence was detected in 69% of patients and in 61% of grafts after a mean period of 24 months (range, 1–156 months). Clinical or biological signs were absent in all but one. Patient survival was 92.8%. Graft loss occurred in five cases, never were related to recurrence. At the last follow-up, the mean glomerular filtration rate was 48±14.2 mL/min/1.73 m2; in patients with and without recurrence, the mean rates were 52.1±17.5 and 42.4±5.3 mL/min/1.73 m2, respectively (P=0.27). Conclusion. Histologic recurrence of HSPN after RT is frequently observed on routine RBs but is not associated with clinical consequences. The short-term prognosis of recurrence is good, but its long-term prognosis remains to be determined.

The anti-MDA5 auto-antibody (Ab) is specifically associated with a subgroup of dermatomyositis patients. Patients suffer from mainly extramuscular involvement (lung and skin) whereas clinical signs of myopathy are rather mild or absent. Although extra muscular lesions are well described, there are no reports about the affection of the muscle in terms of morphology and immunology. To describe the histological pattern of the skeletal muscle and the intrinsic immune response. Immunohistochemical analysis and molecular testing of a comprehensive panel of mediators involved in the immune response were performed by quantitative PCR (n = 10). Histological analysis were performed using imageJ software on digitally completely scanned slides. Results are compare to patients with classical dermatomyositis (cDM) based on ENMC criteria ( n = 7). Only 6 patients had a muscular deficit (the mean MRC score of the weakest muscular group was 4.5 ± 0.5) and CK level was normal in 6 patients (mean CK level was 498 ± 809 I.U/l). Histological analysis showed that patients do not present the classical feature of perifascicular fiber atrophy. All, but one had inflammation (focal and located in perivascular regions). Compared to cDM patients inflammatory infiltrates were significantly less intense (CD45 + cells 35.8 ± 28 vs. 5.9 ± 7.6 cells/mm 2 ; p p p = 0.05), frequency of enlarged capillaries however is increased (14 ± 6.8% vs. 5.8 ± 3.3, p

Objectives To assess the value of major histocompatibility complex (MHC) class II antigen (HLA-DR) expression to distinguish anti-synthetase myopathy (ASM) from dermatomyositis (DM). Methods Muscle biopsies from patients with ASM (n = 33), DM without anti-synthetase antibodies (ASAb) (n = 17), and normal muscle biopsy (n = 10) were first reviewed. ASAb included anti-Jo1 (26/33), anti-PL12 (4/33), anti-PL7 (2/33), and anti-EJ (1/33). Immunohistochemistry was performed for MHC-I/HLA-ABC, MHC-II/HLA-DR, membrane attack complex (C5b-9), neural cell adhesion molecule (NCAM)/CD56 expression, and inflammatory cell subsets. Twenty-four ASM and 12 DM patients from another center were added for HLA-DR evaluation. Results Ubiquitous myofiber HLA-ABC expression was equally observed in ASM and DM (93.9% vs 100%, NS). In contrast, myofiber HLA-DR expression was found in 27/33 (81.8%) ASM (anti-Jo1: 23/26, 88.5%; others: 5/7, 71.4%) vs 4/17 (23.5%) DM patients (p