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.

Rituximab prescription patterns and efficacy in the induction treatment of ANCA-Associated Vasculitis in a Belgian multicenter cohort.

Introduction: The RAVE trial has revolutionized induction treatment of anti-neutrophil cytoplasmic antibodies (ANCA)-Associated Vasculitis (AAV)by demonstrating the non-inferiority of rituximab (RTX) compared with cyclophosphamide.Objectives: We studied AAV patients' characteristics, RTX prescription practices and efficacy in AAV induction treatment in four Belgian university hospitals. The patient population, selected according to the Belgian reimbursement criteria, was relatively homogeneous and comparable to the one of RAVE trial.Methods: 57 patients, receiving RTX as AAV induction therapyfrom May 2014 to June 2017 were enrolled in an observational retrospective multicenter trial involving four Belgian university hospitals. We focused on the type of AAV, ANCA specificity, prescriber's specialty, used reimbursement criteria, organ involvements, severity of the flares and finally RTX efficacy in AAV induction treatment by considering the RAVE primary (complete remission without prednisone) and secondary (complete remission with prednisone <10 mg) outcomes at 6, 12, 18 and 24 months.Results: 66.7% of the patients reached complete remission with prednisone <10 mg at 6 months, 55.3% at 12 months, 40% at 18 months and 25% at 24 months. The rates of complete remission without steroids were very low at 6, 12, 18 and 24 months. The rates of relapses were high between 18 and 24 months. Conclusions: Our results confirm those of RAVE regarding complete remission rates with prednisone <10 mg/day, in a 'real-life' cohort of patients selected according to data of RAVE trial. The high prevalence of relapses - especially after 18 months - underlines the need to optimize maintenance treatment after an induction treatment with RTX..

[Study of diagnostic value of natremia in a cohort of patients with hypercalcemia]. / Etude de la valeur diagnostique de la natrémie dans une cohorte de patients hypercalcémiques.

INTRODUCTION: Hypercalcemia is a common pathological condition in clinical practice. The two most common causes are primary hyperparathyroidism and cancer. SIADH is often encountered in cancer cases and is the most common cause of hyponatremia. The aim of this study is to evaluate serum sodium levels in a cohort of patients with hypercalcemia and consider its predictive value in determining the origin of this hypercalcemia. MATERIALS AND METHODS: We performed a retrospective study on a series of 15.284 blood tests among adult patients with hypercalcemia. After selection, the study population had 151 patients. We studied mainly serum sodium and etiology of hypercalcemia in our population. RESULTS: We observed a statistically significant association between the presence of hyponatremia and the neoplastic etiology of hypercalcemia. This association persisted after exclusion of patients under treatment with loop diuretics. Conversely, there was no association between hypernatremia and cancer-related hypercalcemia. Among 151 patients with hypercalcemia, 16 presented hyponatremia and 7 with hypernatremia. SIADH was the main cause of hyponatremia. We performed univariate and multivariate logistic regression showing the association between the presence of cancer and the presence of hyponatremia. CONCLUSION: Our study shows that there is an association between the presence of hyponatremia and neoplastic origin of hypercalcemia. Besides, the association described between hyponatremia and cancer is not faulted by the presence of hypercalcemia, a potential cause of acquired nephrogenic diabetes insipidus.

INTRODUCTION: L'hypercalcémie est une condition pathologique courante en pratique clinique. Les deux causes les plus fréquentes sont l'hyperparathyroïdie primaire et le cancer. Le syndrome de sécrétion inappropriée de l'hormone antidiurétique (SIADH) est souvent rencontré dans les cas de cancer, et constitue la cause la plus fréquente d'hyponatrémie. Le but de cette étude est d'évaluer la natrémie dans une cohorte de patients atteints d'hypercalcémie et d'apprécier sa valeur prédictive dans la détermination de l'origine de cette hypercalcémie. Matériel et méthode : Nous avons réalisé une étude rétrospective sur une série de 15.284 analyses sanguines chez des patients adultes hypercalcémiques. Après sélection, la population de l'étude comptait 151 patients. Nous avons étudié principalement la natrémie et l'étiologie de l'hypercalcémie au sein de notre population. Résultats : Nous avons observé une association statistiquement significative entre la présence d'une hyponatrémie et l'étiologie néoplasique de l'hypercalcémie. Cette association persistait après l'exclusion des patients sous traitement par diurétiques de l'anse. Par contre, il n'existait pas d'association entre l'hypernatrémie et l'origine cancéreuse de l'hypercalcémie. Sur 151 patients hypercalcémiques, 16 étaient hyponatrémiques et 7 étaient hypernatrémiques. Un SIADH représentait la cause principale des cas d'hyponatrémie. Nous avons réalisé une régression logistique uni- et multivariée montrant l'association entre l'existence d'un cancer et la présence d'une hyponatrémie. CONCLUSION: Notre étude montre qu'il existe une association entre la présence d'une hyponatrémie et l'étiologie néoplasique de l'hypercalcémie. Par ailleurs, l'association classiquement décrite entre hyponatrémie et cancer n'est pas prise en défaut par la présence d'une hypercalcémie, cause potentielle de diabète insipide néphrogénique acquis.

Mild water restriction with or without urea for the longterm treatment of syndrome of inappropriate antidiuretic hormone secretion (SIADH): Can urine osmolality help the choice?

BACKGROUND: Treatment options for chronic SIADH include water restriction (WR) and urea. The usefulness of urine osmolality to guide the choice of the treatment option is not clearly defined. We hypothesized that urine osmolality can indicate whether treatment with mild water restriction alone could be successful. METHODS: Retrospective Review of clinical and biochemical (blood and urine) data of patients with chronic SIADH treated for at least one year with mild WR (1.5-2l/day) either with or without urea. RESULTS: Twenty nine patients were included. Nine patients were treated by mild WR. Mean serum sodium (SNa) and mean Uosm were 129±2mEq/l and 274±78mOsm/kgH2O respectively before WR, and increased to 138.5±3mEq/l and 505±87mOsm/kgH2O (P<0.001). Eight patients were treated with mild WR and 15g urea daily, the SNa and Uosm before treatment were 127.5±3mEq/l and 340±100mOsm/kgH2O respectively and increased to 136.5±1mEq/l and 490±151mOsm/kgH2O (P<0.001). Four of the eight patients had a permanent low solute intake which contributed to hyponatremia. Twelve patients needed 30g urea daily combined with mild WR. The SNa and Uosm were respectively 126±2mEq/l and 595±176mOsm/kgH2O and increased to 136.5±2mEq/l and 698±157mOsm/kgH2O (P<0.05). Uosm increased in most of the treated patients. CONCLUSIONS: About 30% of patients could be treated by moderate WR alone. All these patients presented an initial urine osmolality lower than 400mOsm/kgH2O.

Hyponatremia at the Emergency Department: a case-control study.

BACKGROUND: Hyponatremia (HNA) is a common electrolyte disturbance associated with morbidity and mortality. The aim of this study was to assess incidence and prognosis value of HNA in the Emergency Department (ED). METHODS: A retrospective observational case-control study has been conducted in the ED during 10 months. Control patients (Na 135-145 mmol/L) were matched, in a 1:1 ratio, on age, gender and month of ED admission with hyponatremic patients (Na<130 mmol/L). RESULTS: Two hundred fifty-six patients (2.4% of patients with a blood analysis) had HNA among which 166 were matched with 166 normonatremic controls. HNA patients had more often a history of asthma/chronic obstructive pulmonary disease (P=0.002) and solid tumors (P=0.001), received more diuretics (P=0.026), and presented more often with vomiting (P=0.034). Admission to the hospital or to the ICU was more frequent in HNA patients (89% vs. 52%, P<0.001; 13% vs. 3%, P=0.003, respectively). Patients with HNA presented more frequently at least one complication (digestive, septic, respiratory, renal, and cardiovascular) during their hospital/ICU stay (40% vs. 4%, P<0.001). Mortality rate was higher in HNA than in controls (10% vs. 3%, P=0.021). The multivariable conditional logistic regression analysis showed an independent association of HNA with solid tumors (OR=4.12; 95% CI: 1.68 to 10.1) and hospital death (OR=2.90; 95% CI: 1.03 to 8.17). CONCLUSION: HNA was present in 2.4% of patients with a blood analysis and was associated independently with solid tumors and hospital death.

Long-term treatment of hyponatremic patients with nephrogenic syndrome of inappropriate antidiuresis: personal experience and review of published case reports.

BACKGROUND: Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a disorder of water balance linked to gain-of-function mutation of arginine vasopressin receptor type 2 (AVPR2) resulting in free water reabsorption and episodes of hyponatremia. AIMS: To review the long-term treatment of NSIAD. METHODS: In the first part of this paper, we report 3 cases of male patients presenting with hyponatremia due to NSIAD. The second part consists of a comprehensive review of all published case reports. RESULTS: In our experience, long-term fluid restriction (FR) and treatment with low doses of urea are efficient and well tolerated. Episodic intake of urea seems sufficient in some patients. Treatment data were available for 13 of the 16 hyponatremic patients reported in the literature. Each of these 13 patients had regulated fluid intake. Six of the patients received urea with no reported failure to correct hyponatremia and 5 received NaCl supplementation with varying efficacy. The AVPR2 antagonists tolvaptan and satavaptan (prescribed before the diagnosis of NSIAD was made) showed no efficacy in 1 patient. CONCLUSIONS: NSIAD is quite easy to treat with FR and urea in adults as well as in children, with good compliance and efficacy. Of note, FR is well tolerated, suggesting that NSIAD may differ from other causes of syndrome of inappropriate antidiuretic hormone secretion by reduction of thirst intensity due to lower levels of AVP (which stimulates thirst). In eventual refractory cases, furosemide (associated with NaCl supplementation) would represent a valuable therapeutic option by analogy of its efficacy in syndrome of inappropriate antidiuretic hormone secretion.

Relapse of a renal inflammatory pseudotumour associated with Wegener's granulomatosis.

We report the case of a 32-year-old patient with Wegener's granulomatosis (WG) associated with a (biopsy - proven) renal inflammatory pseudotumour (IPT) of the left kidney treated by a partial nephrectomy, glucocorticoids and immunosuppressive drugs, in whom a relapse of renal IPT was found 6 years after the diagnosis of the first IPT. The originality of this observation lies in the fact that a relapse of IPT has never been described and also in the fact that complete regression of the IPT relapse was obtained with immunosuppressive treatment, while renal IPTs are currently treated by total or partial resection of the kidney. Finally, we discuss the potential benefits of an integrated 18fluorodeoxyglucose PET/CT for the follow-up of WG, since this imaging technique contributed to the management of the present case.

[Acute pericarditis in a sclerodermic patient at the 27th week of pregnancy]. / Péricardite aiguë chez une patiente sclérodermique survenue à la 27ème semaine de grossesse.

A 31-year-old women with a limited cutaneous form of systemic sclerosis (ISSc), developed chest pain at the 27th week of pregnancy, with electric pathognomonic signs of pericarditis. As there was no evidence of another etiology than ISSc, (oral) aspirin and (oral) prednisolone were successively administered and the patient's condition improved rapidly.

Inefficacy of intravenous immunoglobulins and infliximab in Degos' disease.

We report the case of a 60-year-old man who presented with sudden visual loss, a history of postprandial abdominal pain, malabsorption, and skin lesions typical of systemic Degos' disease. Despite anti-aggregants and prednisone the patient's status did not improve. On the basis of the hypothetical dysimmune origin of this disease, we attempted treatment with intravenous immunoglobulins, without success. We then administered infliximab (Remicade), but 2 months after the third injection the patient developed mesenteric infarction and died. We therefore believe that both intravenous immunoglobulins and antiTNFalpha are ineffective for the treatment of Degos' disease.

An atypical case of Whipple's disease: case report and review of the literature.

We report the case of a 57-year-old man, presenting with bilateral panuveitis, bilateral sacroiliitis, intermittent pyrexia and a pulmonary nodule. The patient had been under immunosuppressive treatment for 2 years for Behçet's disease. However, he did not fulfill the diagnostic criteria of Behçet's disease. Blood analysis showed a very high C reactive protein (CRP at 34 mg/dl). In view of severe intra-ocular inflammation, the anterior chamber was punctured. Polymerase chain reaction (PCR) on the aqueous humour and on the blood revealed the presence of Tropheryma whippelii DNA, an agent responsible for Whipple's disease. The patient was treated with ceftriaxone followed by trimethoprim-sulfamethoxazol for 1 year with good clinical and biological evolution. This case illustrates the difficulty to diagnose an atypical Whipple's disease. In cases of uveitis with atypical signs and/or not responding to the treatment, the internist must consider to perform an analysis of the ocular fluids.

Wegener's granulomatosis overlapping with Takayasu's arteritis revealed by FDG-PET scan.

We report the case of a 23-year-old woman who initially presented with Wegener's granulomatosis (WG) limited to the lungs, diagnosed on the basis of a biopsy of an upper left lobe nodule and elevated ANCA titers. Remission occurred under treatment with methylprednisolone and intravenous immunoglobulins. Later in the course of the disease, findings highly suggestive of Takayasu's arteritis (TA) appeared: murmur at the level of the left subclavian artery, thickening of the arterial wall of the aorta and pulmonary arteries on tomodensidometry, and abnormal uptake of the aortic arch and ascending aorta on FDG-PET scan. This latter exam also showed an increased uptake of an already known pulmonary nodule, due to WG. Although five cases of WG occurring together with TA have previously been reported, this is the only one in which TA was revealed by FDG-PET scan. In the specific setting of overlapping vasculitides, FDG-PET scan may be helpful in simultaneously evaluating the activity of the two diseases.

Wegener's granulomatosis masquerading as a renal cancer: a case report and review of the literature.

A 32 year-old man presented with sinusitis, proteinuria, mononeuritis multiplex, very increased acute phase proteins. Anti-PR3 ANCA were detected and Wegener's granulomatosis (WG) was diagnosed. As abdominal tomodensitometry detected a tumoral process of the left kidney, a paraneoplastic vasculitis associated with a renal cancer was suspected. Biopsy of the mass showed fibrosis, inflammatory infiltrates and necrotizing granulomas. No malignant cells were detected. The outcome was favourable after administration of methylprednisolone and cyclophosphamide. Characteristics of the nine previously reported renal inflammatory pseudotumors associated with WG are discussed.

Anti-pm/scl antibodies in connective tissue disease: Clinical and biological assessment of 14 patients.

INTRODUCTION: Anti-PM/Scl antibodies (Anti-PM/Scl) represent a rarely encountered type of antinuclear antibodies. They have mainly been reported in association with idiopathic inflammatory myositis - systemic sclerosis overlap syndromes (also called scleromyositis or sclerodermatomyositis) but also with polymyositis, dermatomyositis and systemic sclerosis without features of overlap syndromes. Studies concerning characteristics of patients with anti-PM/SCl are rare and include small numbers of patients. PATIENTS AND METHODS: Retrospective review of clinical and biological characteristics of 14 patients with anti-PM/Scl in two University Hospitals: one in Belgium (Erasme Hospital, Bruxelles) and one in France (Hautepierre Hospital, Strasbourg). RESULTS: Seven patients were identified in Erasme and 7 in Strasbourg: 5 with systemic sclerosis-(dermato)myositis overlap syndromes, 4 with dermatomyositis, 1 with polymyositis, 3 with systemic sclerosis, 1 with primary Sjögren's syndrome. The most frequently observed clinical characteristics (85% of patients) were: pulmonary interstitial disease and arthralgia or arthritis. No patient of our series died or developed cancer (mean follow-up:6.1 years). CONCLUSIONS: Our study failed to identify an homogeneous clinical pattern in patients with anti-PM/Scl, except for 2 characteristics shared by 85% of the patients. This lack of homogeneity is in agreement with preceding literature. We confirm the favourable prognosis associated with the presence of anti-PM/Scl, despite the high incidence of interstitial pulmonary disease. The absence of cancer associated with presence of anti-PM/Scl represents a partial explanation. Finally, we report herein the second case of primary Sjögren's syndrome associated with anti-PM/Scl.

Primary Sjögren's syndrome associated with pneumatosis cystoides coli.

We report the case of a 43-year-old woman with primary Sjögren's syndrome, according to Americano-European criteria. Eighteen months after the diagnosis, the patient presented pneumatosis cystoides coli (PCC), which resolved with medical treatment consisting of diet and cisapride. Four years after this episode, the patient has not developed clinical features of another systemic inflammatory rheumatic disease and PCC has not relapsed. To the best of our knowledge, the association between primary Sjögren' syndrome and PCC has never been reported. Physiopathology and treatment of PCC are discussed.