Large-vessel involvement in ANCA-associated vasculitis: A multicenter case-control study.

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) primarily affects small vessels. Large-vessel involvement (LVI) is rare. We aimed to describe the characteristics of LVI, to identify associated risk factors, and to describe its therapeutic management. METHODS: This multicenter case-control (1:2) study included patients with AAV according to the ACR/EULAR classification and LVI as defined by the Chapel Hill nomenclature, together with controls matched for age, sex, and AAV type. RESULTS: We included 26 patients, 15 (58 %) of whom were men, with a mean age of 56.0 ± 17.1 years. The patients had granulomatosis with polyangiitis (n = 20), or microscopic polyangiitis (n = 6). The affected vessels included the aorta (n = 18; 69 %) supra-aortic trunks (n = 9; 35 %), lower-limb arteries (n = 5; 19 %), mesenteric arteries (n = 5; 19 %), renal arteries (n = 4; 15 %), and upper-limb arteries (n = 2; 8 %). Imaging showed wall thickening (n = 10; 38 %), perivascular inflammation (n = 8; 31 %), aneurysms (n = 5; 19 %), and stenosis (n = 4; 15 %). Comparisons with the control group revealed that LVI was significantly associated with neurological manifestations (OR=3.23 [95 % CI: 1.11-10.01, p = 0.03]), but not with cardiovascular risk factors (OR=0.70 [95 % CI: 0.23-2.21, p = 0.60]), or AAV relapse (OR=2.01 [95 % CI: 0.70-5.88, p = 0.16]). All patients received corticosteroids, in combination with an immunosuppressant in 24 (92 %), mostly cyclophosphamide (n = 10, 38 %) or rituximab (n = 9, 35 %). CONCLUSION: Regardless of distinctions based on vessel size, clinicians should consider LVI as a potential manifestation of AAV, with the aorta commonly affected. The risk of developing LVI appears to be greater for clinical phenotypes of AAV with neurological involvement. Standard AAV treatment can be used to manage LVI.

Craniofacial fibrous dysplasia: A 10-case series.

OBJECTIVES: Fibrous dysplasia of bone is a rare sporadic benign congenital condition in which normal cancellous bone is replaced by fibro-osseous tissue with immature osteogenesis. Sarcomatous transformation is exceptional. Lesions may involve one bone (monostotic) or several (polyostotic). Fibrous dysplasia may be associated with café-au-lait skin macules and endocrinopathy in McCune-Albright syndrome, or with myxoma in Mazabraud's syndrome. METHODS: We report ten cases of patients followed up for craniofacial fibrous dysplasia in our center between 2010 and 2015. RESULTS: Mean age was 43 years (range, 10-72 years). Clinical symptoms comprised headache (n=3) and sensorineural disorder: recurrent anterior uveitis (n=1), visual acuity loss, epiphora and vestibular syndrome (n=1), and hearing loss (n=1). All cases were monostotic. The sphenoid bone was most commonly involved (n=5), followed by the ethmoid (n=1), frontal (n=1), fronto-ethmoid (n=1), temporal (n=1) and fronto-ethmoido-sphenoid (n=1) bones. Five patients were treated with intravenous pamidronate, a bisphosphonate: evolution was favorable for 3 of them at 1-6 months after treatment initiation, with resolution of headache or vestibular syndrome; the other 2 patients were stable. Two patients were operated on. CONCLUSION: Diagnosis of craniofacial fibrous dysplasia should be considered in case of headache, neuralgia, sensory disorder, functional disorder or infectious ENT complications. A medico-surgical approach is useful for these patients.

[Craniofacial fibrous dysplasia]. / La dysplasie fibreuse osseuse cranio-faciale.

Fibrous dysplasia of bone is a benign, uncommon, sporadic, congenital skeletal disorder resulting in deformity. This disease arises from activating somatic mutation in GNAS which encodes the α subunit of the G stimulatory protein associated with proliferation of undifferentiated osteogenic cells resulting in marrow fibrosis, abnormal matrix production, and stimulation of osteoclastic resorption upon overproduction of IL-6 observed in dysplastic cells. Fibrous dysplasia may be monostotic or polyostotic. This mutation affecting many tissues, café au lait skin macules and endocrinopathies (precocious puberty, hyperthyroidism, growth hormone excess, Cushing syndrome) may be associated in McCune-Albright syndrome, but also myxoma in Mazabraud syndrome or phosphate diabetes. Diagnosis of craniofacial fibrous dysplasia should be considered in the presence of headache, neuralgia, sensory disorders (vision, hearing, balance, smelling), functional disorders (nasal obstruction, nasolacrimal duct obstruction, non-matching occlusion), infectious complications (sinusitis, otitis, mastoiditis). Such symptoms should lead to perform craniofacial CT scan completed with MRI. Bone biopsy is not systematic. Surgical treatment is discussed in cases of nervous complication, facial deformity or active lesions. In case of pain resistant to conventional analgesics, intravenous bisphosphonates can be proposed. In non-responder patients, several case reports suggest the efficacy of a monoclonal antibody directed against the IL-6 receptor which requires to be confirmed by randomized studies.

[Natural history of portal cavernoma without liver disease. A single centre retrospective study of 32 cases]. / Évolution naturelle des cavernomes portaux non liés à une hépatopathie. Étude rétrospective monocentrique de 32 observations.

PURPOSE: Portal cavernoma follows a chronic occlusion of the portal vein. The long-term consequences of portal cavernoma are not well known. The objective of this study was to report the aetiology of the portal cavernoma and its natural course after excluding liver diseases causes. METHODOLOGY: A single centre retrospective study based on the data collected from the radiology department of the Clermont-Ferrand hospital was conducted from 2000 to 2011. All the patients for whom an imagery found a portal cavernoma have been looked for excluding the patients having a liver disease whatever the aetiology and the Budd-Chiari syndrome. RESULTS: Thirty-two cases (18 women and 14 men) were selected. The mean age at diagnosis was 54.2 years and the mean follow-up period was 5.4 years. The discovery of a portal cavernoma was incidental for 8 cases. An aetiology was found for 24 cases: it was an haematological aetiology in 15 cases (10 myeloproliferative syndromes, 2 antiphospholid syndromes, 1 thalassemia major, 1 hyperhomocysteinemia, 1 prothrombin gene mutation), a general aetiology in 2 cases (1 coeliac disease, 1 pancreatic neoplasia), and a local inflammation in 7 cases. A dysmorphic aspect of the liver was noticed on medical imaging for 11 out of the 32 cases. A liver biopsy was performed in 4 patients and was normal for all of them. Sixteen patients developed oesophageal varices, 4 patients developed ascites, 3 developed asymptomatic biliary compression by the portal cavernoma, and the patient who had been followed for the longest time (15 years) developed an encephalopathy. CONCLUSION: In addition to its underlying etiology, the prognosis of portal is mainly related to the occurrence of oesophageal varices that may develop during the follow-up of the patients.

Determinants of hydroxychloroquine blood concentration variations in systemic lupus erythematosus.

OBJECTIVE: Blood concentrations of hydroxychloroquine (HCQ) vary widely among patients with systemic lupus erythematosus (SLE). A pharmacokinetic/pharmacodynamic relationship has been found in different situations, and a very low blood concentration of HCQ is a simple marker of nonadherence to treatment. Therefore, interest in blood HCQ concentration measurement has increased, but little is known about factors that influence blood HCQ concentration variability. This study was undertaken to analyze determinants of blood HCQ concentrations. METHODS: We conducted a retrospective analysis of patient data, including data from the Plaquenil Lupus Systemic (PLUS) study, to determine the association of epidemiologic, clinical, and biologic factors with blood HCQ concentrations. Data for nonadherent patients (blood HCQ concentration <200 ng/ml) were excluded. RESULTS: To examine homogeneous pharmacologic data, we restricted the analyses of the PLUS data to the 509 SLE patients receiving 400 mg/day. We found no association of ethnicity or smoking with blood HCQ concentrations and no pharmacokinetic drug-drug interaction with antacids or with inhibitors or inducers of cytochrome P450 enzymes. On multivariate analysis, high body mass index (P = 0.008), no treatment with corticosteroids (P = 0.04), increased time between the last tablet intake and measurement of blood HCQ concentrations (P = 0.017), low platelet count (P < 0.001), low neutrophil count (P < 0.001), and high estimated creatinine clearance (P < 0.001) were associated with low blood HCQ concentrations. In 22 SLE patients with chronic renal insufficiency (median serum creatinine clearance 52 ml/minute [range 23-58 ml/minute]) who received 400 mg/day HCQ, the median blood HCQ concentration was significantly higher than that in the 509 patients from the PLUS study (1,338 ng/ml [range 504-2,229 ng/ml] versus 917 ng/ml [range 208-3316 ng/ml]) (P < 0.001). CONCLUSION: We provide a comprehensive analysis of determinants of blood HCQ concentrations. Because this measurement is increasingly being used, these data might be useful for clinicians.

Systemic lupus erythematosus-associated acute transverse myelitis: manifestations, treatments, outcomes, and prognostic factors in 20 patients.

BACKGROUND: Transverse myelitis is a rare complication of systemic lupus erythematosus (SLE). This retrospective multicentre study identifies the prognostic factors in a relatively large patient series. PATIENTS AND METHODS: Twenty patients fulfilled the SLE criteria of the ACR classification and the Transverse Myelitis Consortium Working Group. A severe neurological flare was defined as muscle strength grade <3/5 in more than half the muscle groups at the motor neurological level. Inability to run or another significant ambulation-unrelated disability was considered as 'unfavourable neurological outcome'. RESULTS: Myelitis was the first SLE symptom in 12 patients; in the eight others, it occurred 8.6 years (median delay) after SLE onset. Eleven patients presented severe neurological impairments. The treatment included corticosteroids in all patients associated with intravenous cyclophosphamide in 11 and/or hydroxychloroquine in 14. Unfavourable outcomes were observed in 53% of the patients at six months and in 28% at end of follow-up (median: 5.9 years). An initial severe neurological impairment and no cyclophosphamide use were associated with unfavourable neurological outcomes at six months and at end of follow-up, respectively. CONCLUSION: Transverse myelitis may reveal SLE or occur more than 10 years after SLE diagnosis. The initial severity of the neurological flare (with paraplegia) is the main prognostic marker. The study provides arguments for cyclophosphamide use.

[The myeloproliferative neoplasms-related glomerulopathy]. / Les glomérulopathies associées aux néoplasies myéloprolifératives.

PURPOSE: Myeloproliferative neoplasms (MPN) are hematological disorders characterized by clonal expansion of one or more medullary lines. Renal complications are rare, chiefly as acute renal failure. Glomerular involvement is exceptional METHODS: We report on a retrospective multicenter case series of eight patients who presented with a glomerulopathy (GP) associated with MPN RESULTS: All GP were revealed by a major proteinuria frequently associated with nephrotic syndrome and oedema. Histology was mainly characterized by lesions of focal segmental glomerulosclerosis associated with increased mesangial cellularity. The pathophysiology is still unclear but platelet-derived growth factor (PDGF) and transforming growth factor-ß (TGF-ß), which play a central role in the MPN may be involved. A majority of patients developed chronic renal failure despite of a therapy intended to block the renin-angiotensin system CONCLUSION: Monitoring of proteinuria during the follow-up of MPN would allow earlier diagnosis of renal involvement. Further studies on a larger scale are needed to specify the pathophysiological mechanisms involved and the management of these complications.

[Preauricular lymphadenopathy related to Bartonella henselae]. / Adénopathies prétragiennes liées à Bartonella henselae.

INTRODUCTION: Cat scratch disease is characterized by adenitis with usually positive outcome. We reported two cases of cat scratch disease with preauricular involvement occurring in immunocompetent patients. OBSERVATIONS: Observation 1: a 28-year-old man had a recent onset of left cervical swelling, with a peripheral facial paralysis and liver cytolysis. Serologies for EBV, viral hepatitis, CMV, HIV and toxoplasma were negative. Node excision biopsy suggested granulomatous lymphadenitis and Bartonella henselae PCR on lymph node was positive. With doxycyclin for 3 months, associated with rifampicin for 15 days, abnormal liver function disappeared and facial paralysis improved. Observation 2: a 17-year-old man had parotid swelling associated with right posterior cervical lymphadenopathies associated with fever and profuse sweating. A large right preauricular lymphadenopathy with necrotic remodeling was visible on the CT-scan. Lymph fluid B. henselae PCR was positive. Positive outcome occurs after surgical drainage and short azithromycin treatment. CONCLUSION: Physicians should be aware of the rare preauricular localization of cat scratch disease and ask for contact with a cat. Parotid tumor localization, lymphoma or tuberculosis should be ruled out. Diagnosis is based on the B. henselae PCR. Outcome is often spontaneously positive but surgical treatment may be required.

[Recurrent pericarditis related to primary pericardial malignant mesothelioma]. / Péricardite récidivante : traquer le mésotheliome péricardique primitif.

INTRODUCTION: Most of recurrent pericarditis are idiopathic and only 15 to 20% have a specific diagnosis. Primary pericardial mesothelioma is a rare cause of recurrent pericarditis. Diagnosis can be challenging and antedates patient's death in only 10 to 20% of cases. Histology of mesothelioma and immunohistochemistry are mandatory for the diagnosis. Median of survival before using pemetrexed was about 6 months after diagnosis. CASE REPORT: We report the history of a 64-year-old woman for which repeated biopsy for recurrent pericarditis was necessary to diagnose a primary pericardial mesothelioma. The first biopsy had only found mesothelial hyperplasia. CONCLUSION: This case report highlights the necessity of repeat pericardial biopsy in the case of adverse outcome.

[100 essential drugs. An internal medicine approach]. / Les 100 médicaments essentiels. Une approche de médecine interne.

PURPOSE: Up to 4600 drugs in about 15,000 pharmaceutical forms are available in France which may be a source of misuse with increased occurrence of side effects and costs. While the World Health Organization is encouraging each developed country to work out its own list of essential drugs. The list provided in 2008 by the French Office for the safety of health products has had so far limited impact on practice, so it became obvious to a group of internists to work out a "wise list" of 100 essential medicines covering 95% of the disorders observed in France. METHODS: In June 2011, 10 internists agreed to each provide a list of 100 essential medicines, according to individual experience. In December 2011, a meeting of the participants provided a list as initial consensus and mandated five among them to make proposals for those areas neglected by too many participants or in which needless dispersion of medicines was stated. After internet-facilitated exchanges, an additional list was validated in mild-January 2012. RESULTS: Fifty-four drugs were included in the list of initial consensus (including nine selected by all 10 participants), and 46 in the additional list. So the final "wise list" included 100 drugs. In June 2012, 56 of these drugs were available as generics. This list was compared to those lists set out by five countries in the European Union. CONCLUSION: Generating such a list is feasible. Undoubtedly still non-comprehensive, this list will benefit from the expertise of 14 general practitioners who are currently working out a similar list across France. The final list will be submitted for validation by the French associations of generalist teachers and Internists.

Is IgG4-Related Disease a Cause of Xerostomia? A Cohort Study of 60 Patients.

Objective. Immunoglobulin-G4-(IgG4-) related disease (IgG4 RD) is a fibrosing process characterized by a significant infiltration of IgG4-secreting plasma cells. IgG4 RD can affect almost all organs including salivary glands. Whether IgG4 RD plays a role in the development of sicca syndrome and particularly dry mouth syndrome remains to be investigated. Methods. We conducted a monocentric cohort study for two years to search for IgG4 RD features in patients with dry mouth syndrome using immunostainings of labial salivary gland specimens with anti-IgG4 antibody. Results. Among 60 patients presenting with dry mouth syndrome who underwent labial salivary gland biopsy, 18 showed positive immunostaining with the anti-IgG4 antibody including 4 patients with typical systemic IgG4 RD. Five also fulfilled criteria for Sjögren's syndrome. Conclusion. These findings suggest that clinical forms of IgG4 RD salivary involvement without salivary swelling may occur. This salivary involvement is probably overlooked in everyday practice and could represent a mild form of IgG4 RD.

[Mesenteric panniculitis]. / Panniculite mésentérique.

Mesenteric panniculitis is a nonspecific inflammatory process affecting the fatty tissue at the root of the mesentery. This term is also used to describe the clinical and imaging findings in this disorder. Mesenteric panniculitis can be a misleading term: it is commonly misused to design an increased density of the mesentery without prejudice regarding the etiology. Pain is the main clinical symptom. Half of the patients are asymptomatic. There is a palpable mass in half of cases. Laboratory tests sometimes reveal an acute phase reaction of varying intensity. Mesenteric panniculitis is suspected when CT scan shows increased density of the mesenteric fat. Nevertheless, only histological examination could establish the diagnosis. Histologic examination may reveal various stages: lipodystrophy (the first stage when fat necrosis is predominant), mesenteric panniculitis (a majority of infiltrating lymphocytes), sclerosing mesenteritis (the end stage when fibrosis is predominant). Histopathologic differential diagnoses are lymphomas, lipomas, liposarcomas that can mimic mesenteric panniculitis on CT scan. Mesenteric panniculitis is associated with various diseases, especially with intra-abdominal inflammatory process. It also can be idiopathic. Rare complications can occur with vascular or digestive tract compressions. Empirical treatment is only useful in symptomatic patients. Colchicine, corticosteroids or immunosuppressive agents can be used. The only interest of surgery is the histological confirmation of the diagnosis. A better understanding of the pathophysiology of the immunoregulatory functions of adipose tissue will improve mesenteric panniculitis management.

[Pituitary metastasis presenting as diabetes insipidus: a report of four cases and literature review]. / Diabète insipide révélateur de métastases hypophysaires : quatre observations et revue de la littérature.

INTRODUCTION: Pituitary metastases are a rare cause of central diabetes insipidus and usually complicate advanced cancers. CASE REPORTS: We report four cases in which diabetes insipidus revealed a metastatic stage of a lung (two cases) or a breast (two cases) cancer. One patient presented with a panhypopituitarism, three had diabetes insipidus including one with corticotroph insufficiency. In one case, the cerebrospinal fluid analysis showed a lymphocytic meningitis. On brain magnetic resonance imaging there was an absence of high intensity signal in the posterior pituitary lobe (one case) or an infiltration of the posterior lobe (three cases). CONCLUSION: Breast and lung malignancies are the most frequent causes of metastasis of the pituitary gland. In most cases there are often other metastatic locations; however insipidus diabetes can reveal the metastatic stage of the cancer. A pituitary biopsy may be necessary to obtain the diagnosis.

[Tracheopathia osteoplastica]. / Trachéopathie ossifiante.

OBJECTIVES: Report a case of tracheopathia osteoplastica and describe from a literature analysis the main clinical, radiological, and therapeutic features of this rare disease based on literature review. MATERIAL AND METHODS: A 74-year-old patient suffering from a nasal polyposis that had been repeatedly operated was admitted for surgery of the frontal sinus. The day of surgery, the difficult intubation required a laryngotracheoscopy, which found a dystrophic trachea, with a sprinkling of whitish nodules, and hard swelling. The pathologic exams of a large biopsy specimen using a rigid bronchoscopy provided the diagnosis of tracheopathia osteoplastic. A complementary workup to search for the etiology was undertaken. The risk and the difficulty of the intubation led to suspending the surgery. RESULTS: The CT scan as well as the histological, bacteriological, and immunological tests showed nothing specific. The etiopathogenic hypothesis was the association of chronic disease of the upper airways such as the ozena or the chronic inflammation of the respiratory tract, an endocrine factor, dermatomyositis, exposure to toxic substances such as silica, or tracheobronchial amyloidosis. The bronchial microbiology test is positive in more than 50% of patients, and often Klebsiella ozaenae or Pseudomonas aeruginosa is found. CONCLUSION: Tracheopathia osteoplastica is a rare tumor, with unknown etiology and physiopathology. The discovery is most often incidental. Progession is slow and it does not compromise the vital prognosis. The treatment is symptomatic. Few surgical tracheal operations are described in the literature.

[Intra-alveolar haemorrhage without renal damage as the initial presenting feature of Goodpasture's syndrome: case report and review of literature]. / Hémorragie intra-alvéolaire isolée révélant un syndrome de Goodpasture sans atteinte rénale : à propos d'une observation et revue de la littérature.

Isolated pulmonary involvement in Goodpasture's syndrome is exceptionally described. We report a 36-year-old woman with pulmonary haemorrhage and review 28 additional cases of the literature. In fact, these patients had often mild urine abnormalities and constant glomerular lesions. Antiglomerular basement membrane antibodies testing should be systematically ordered in patients presenting with alveolar haemorrhage. Goodpasture's syndrome without renal abnormality could be an early stage of the disease with a better prognosis.

[Lingual tuberculosis revealing disseminated tuberculosis]. / Tuberculose disséminée révélée par une localisation linguale.

INTRODUCTION: Tuberculous lesions of the oral cavity are uncommon. Most of cases are secondary to pulmonary disease and the primary form is rare. EXEGESIS: We report the case of a 64 year-old man, smoker, presenting a chronic ulcer of the tongue, with anorexia and important weight loss. The biopsy of this ulcer showed granulomatous inflammation and Langhans type giant cells, without necrosis. Ziehl-Nielsen stain was negative. Pulmonary lesions were subsequently detected (chest X-ray, CT-scan) and the disseminated tuberculosis was confirmed by a positive culture with acid-fast bacilli in urine, blood, and pulmonary sample. Antituberculosis treatment resulted in the complete resolution of the oral lesion. CONCLUSION: Biopsy for histopathological diagnosis, acid-fast stains and culture, is essential to determine the exact nature of chronic oral ulceration to distinguish between oral malignancy, infectious (syphilis), traumatic, or aphthous ulcers. Tuberculosis of the tongue is a difficult diagnosis. However it should be searched for because treatment usually results in a rapid recovery.

[Rapid diagnosis of rotavirus infections: comparative prospective study of two techniques for antigen detection in stool]. / Diagnostic rapide des infections à rotavirus: étude prospective comparative de deux techniques de détection d'antigènes dans les selles.

The ability of two commercially available diagnosis rapid assays in detecting rotavirus antigen was compared in a prospective study conducted from September 2002 to May 2003. Five hundred and twelve faecal specimens were studied by IDEIA Rotavirus enzyme immunoassay test (EIA) and Diarlex MB immunochromatographic test (ICG). Specimens giving discrepant results were examined by electron microscopy (EM) and clinical data reconsidered. Out of 512 stool specimens, 155 (30.3%) were positive and 332 (64.8%) negative with the two assays. Discrepant results were obtained for 25 (4.88%) specimens (24 children, 1 adult), with EIA giving more positive results. The retrospective examination by EM, possible for fifteen stools on the 25 that gave discrepant results, confirmed the presence of rotavirus in 7/14 stools which were positive only by EIA and in the stool specimen that was found positive only by ICG. The 25 clinical observations re-examination showed the presence of GEA signs in all cases. The statistical analysis shows an excellent concordance between the EIA and the ICG tests (kappa = 0.89, IC(95%) = [0.85-0.93]) in spite of the underestimation of ICG test in comparison with EIA test (P < 0.0001).

[Pancreatic involvement in Wegener's granulomatosis: a rare and difficult diagnosis]. / Les atteintes pancréatiques au cours de la granulomatose de Wegener: une localisation rare et un diagnostic difficile.

INTRODUCTION: Pancreatic involvement in the course of wegener's granulomatosis is rarely reported. EXEGESIS: We report a case presenting as a pancreatic tumorlike lesion. We also discuss six further cases from the medical literature. Two of them had a tumorlike lesion, three had acute pancreatitis and the last had exocrine pancreatic insufficiency. CONCLUSION: Treatment, association of corticoid and cyclophosphamide, is efficient if it is started quickly. So we think that this unusual manifestation of Wegener's granulomatosis should be recognized.