Quality of life in systemic lupus erythematosus: description in a cohort of French patients and association with blood hydroxychloroquine levels.

OBJECTIVES: Benefits of hydroxychloroquine (HCQ) use on physician reported outcomes are well documented in systemic lupus erythematosus (SLE). We assess for the first time the association and predictive value of blood HCQ levels towards health-related quality of life (HRQOL) in SLE. METHODS: Data from the PLUS study (a randomized, double-blind, placebo-controlled, multicentre study) were utilized. Blood HCQ levels were quantified by high-performance liquid chromatography along with HRQOL assessments (Medical Outcomes Study-SF-36) at baseline (V1) and month 7 (V2). RESULTS: 166 SLE patients' data were analysed. Mean (SD) age and disease duration were 44.4 (10.7) and 9.3 (6.8) years. Eighty-seven per cent were women. Mean (SD, median, IQR) HCQ concentrations in the blood at V1 were 660 (314, 615, 424) ng/ml and increased to 1020 (632, 906, 781) ng/ml at V2 (mean difference 366 units, 95% confidence interval -472 to -260, p < 0.001). No significant correlations between HCQ concentrations with HRQOL domains at V1 or V2 were noted. There were no differences in HRQOL stratified by HCQ concentrations. HCQ concentrations at V1 or changes in HCQ concentration (V2-V1) were not predictive of HRQOL at V2 or changes in HRQOL (V2-V1). CONCLUSIONS: No association of HCQ concentrations with current or longitudinal HRQOL were found in SLE.

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.

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.

[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.

[Abdominal manifestations of Henoch-Schönlein purpura in adults. A retrospective study of 23 cases]. / Atteintes digestives du purpura rhumatoïde de l'adulte. Etude d'une série rétrospective de 23 patients.

INTRODUCTION: Gastrointestinal manifestations of Henoch-Schönlein purpura (HSP) in adults may be severe. Data about treatment are controversial and the outcome is seldom described. METHODS: Twenty-three patients with gastrointestinal manifestations of HSP (ACR criteria) were retrospectively studied. We proposed to use clinical and radiological (CT scan) severity scores to assess the usefulness and the efficacy of corticosteroid therapy. RESULTS: Age at onset ranged from 16 to 80 years (median 39). Gastrointestinal manifestations included abdominal pain (96%), vomiting (52%), gastrointestinal bleeding (39%), diarrhoea (13%) and intestinal obstruction (9%). Scores of disease clinical severity were calculated in 21 patients. Fourteen, three and four had severe, intermediate and mild disease, respectively. Ten patients in the group with severe clinical involvement underwent CT scan that showed severe radiological involvement (parietal thickening of several bowel loops of the same segment or several segments with ileal involvement). Eleven patients out of 14 with clinically severe disease were given corticosteroids. Two patients out of three with intermediate and three patients out of four with mild scores also received corticosteroids. The others received supportive care. In-patients with severe clinical scores, gastrointestinal symptoms improved within 2 days when they were given corticosteroids and within 12.3 days without corticosteroids (p<0.0002). No side effect was observed with steroid therapy. CONCLUSION: These results suggest that corticosteroids may reduce abdominal symptoms of HSP in adults with clinically severe disease. They are safe when CT scan is performed.

[Nephrotic syndrome: don't forget to search for hypothyroidism]. / Syndrome néphrotique: penser à rechercher une hypothyroïdie associée.

INTRODUCTION: If abnormal thyroid function indices have been reported in patients with nephrotic syndrome, hypothyroidism is exceptional. EXEGESIS: We report three adult patients (1, 2, 3) with hypothyroidism associated with nephrotic syndrome (minimal change glomerulonephritis [1], idiopathic membranous nephropathy stage I [2], stage II [3]). Glomerulopathy treatment and thyroid hormone replacement therapy were both initiated. Low replacement (1, 2) was sufficient when proteinuria decreased. It was higher when nephrotic syndrome was uncontrolled (3). CONCLUSION: Excessive thyroxine-binding protein and thyroxine urinary loss generate low rate of free thyroxine and elevated TSH. Systematic thyroid hormonal test is necessary if nephrotic syndrome is severe and prolonged.

[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.

[Nitrofurantoin-induced lung disease: about two cases]. / Pneumopathie à la nitrofurantoïne: à propos de deux observations.

INTRODUCTION: Nitrofurantoin is commonly used in the treatment of urinary tract infection and may cause a potential severe complication: interstitial lung diseases. CASE REPORT: A 78-year-old and an 87-year-old woman treated with nitrofurantoin since respectively 10 months and 6 years developed cough and dyspnea. Antibiotics were ineffective and interstitial lung disease was found. Nitrofurantoin's stopping allowed a clinical and radiological improvement. CONCLUSION: A good medical supervision is important when nitrofurantoin is prescribed for a long time. The treatment has to be stopped when respiratory symptoms appear to allow an improvement of the symptoms.

[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.

[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.

[Salivary involvement in IgG4-related multifocal fibrosclerosing disease]. / Manifestations salivaires dans la Maladie Fibrosclérosante Multiple à IgG4.

OBJECTIVES: To report a case of IgG4-related multifocal fibrosclerosis, revealed by a multifocal salivary involvement. MATERIAL AND METHODS: A 59-year-old man, with chronic pancreatitis, was managed for fibrotic involvement of the 2 submaxillary glands and the 2 parotids. Clinical, radiological, and histologic features were retrospectively studied. RESULTS: Pathological features of submandibular gland revealed a chronic sclerosing sialadenitis. Retroperitoneal fibrosis in computed tomography and high rate of IgG4 are objectived. The diagnosis of IgG4-related multifocal fibrosclerosis is evoked. The patient's state improved with corticosteroid therapy. CONCLUSION: Salivary involvement in IgG4-related multifocal fibrosclerosis must be recognized in salivary medical pathology.

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.

[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.

[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.

Susac syndrome.

Susac syndrome is an occlusive arteriolar disease that provokes infarcts in the cochlea, retina, and brain of young subjects, mostly women. Its cause is unknown. Some infarcts may be asymptomatic and only revealed by ancillary investigation: 1) audiogram that shows bilateral sensorineural hearing loss predominating on low frequencies, 2) funduscopy and fluorescein retinal angiography demonstrating bilateral distal branch retinal artery occlusions, and 3) brain MRI T2-weighted images disclosing small multifocal hyperintensities in white and gray matter. Treatment options are not codified, ranging from antithrombotic drugs to immunomodulatory therapy. Course is self-limited after an active fluctuating phase. Dementia, blindness, and deafness are rare late sequelae, and half of patients return to normal life.

Lupus and pulmonary nodules consistent with bronchiolitis obliterans organizing pneumonia induced by carbamazepine.

Carbamazepine-induced lupus is uncommon; its frequency is less than 0.001% of the cases of lupus treated. Herein we describe a 52-year-old woman who had development of facial erythema, arthralgia, dyspnea, and multiple pulmonary rounded masses and nodules while she was taking carbamazepine for epilepsy. Pulmonary histologic examination showed bronchiolitis obliterans organizing pneumonia. Antinuclear antibodies and antihistone antibodies were present without antibodies to double-stranded DNA. Thirteen months after carbamazepine had been withdrawn, all symptoms had disappeared without the use of anti-inflammatory drugs. Even though pulmonary involvement is possible during carbamazepine treatment, to our knowledge, bronchiolitis obliterans organizing pneumonia on its own or associated with carbamazepine-induced lupus has not been previously described.

A comparison of the effects of vitamin B12 and aspirin in three experimental pain models in rats and mice.

The effects of vitamin B12 are compared to those of aspirin and 0.9% saline in three different experimental pain models in rats and mice; an electric shock test, the hot-plate test, and the phenylbenzoquinone writhing test. Neither cyanocobalamin nor hydroxocobalamin showed any antinociceptive activity in any of the three tests at any of the doses used, whether the drug was administered as a single injection or as a series of daily injections lasting 7 days. These results run counter to those of clinical trials in man, though close scrutiny of the experimental procedures used in these trials often reveals a lack of rigor which casts doubts on their validity. This consideration, together with the negative findings reported here, suggests that the clinical use of vitamin B12 as an analgesic may be inappropriate.