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Pulmonary Artery Involvement and Associated Lung Disease in Behçet Disease: A Series of 47 Patients.

Medicine (Baltimore). 2011 Dec 29;

Authors: Seyahi E, Melikoglu M, Akman C, Hamuryudan V, Ozer H, Hatemi G, Yurdakul S, Tuzun H, Oz B, Yazici H

Abstract

ABSTRACT: Pulmonary artery aneurysms (PAAs) are well known causes of mortality and morbidity in Behçet disease (BD). However, pulmonary artery involvement in BD is not limited to PAA; the other main type of pulmonary artery involvement is pulmonary artery thrombus (PAT), with or without associated PAA. In addition, other types of lung disease like nodules and cavities in the lung parenchyma are frequently associated with pulmonary artery involvement, and can be misinterpreted as being due to infection. We surveyed the clinical, radiologic, and laboratory characteristics and outcome of 47 BD patients with pulmonary artery involvement and the associated findings, all seen and followed at a single dedicated tertiary care center.We identified 47 (41 male, 6 female) patients in whom pulmonary artery involvement was diagnosed, who were registered in the multidisciplinary clinic at Cerrahpasa Medical Faculty between January 2000 and December 2007. Mean age at diagnosis was 29 ± 8 years, and mean disease duration to the onset of pulmonary artery involvement was 3.6 ± 4.8 years. Hemoptysis was the most common presenting symptom (79%) followed by cough, fever, dyspnea, and pleuritic chest pain. Thirty-four of 47 patients (72%) presented with PAA, including 8 with associated PAT. The remaining 13 patients (28%) had isolated PAT. Patients with isolated PAT in general have clinical features similar to patients with PAA. However, hemoptysis was less frequent and voluminous in patients with isolated PAT. Most (91%) of the patients had active disease outside the lungs when they presented with pulmonary artery involvement.Forty (85%) patients had nodules and 6 (13%) had cavities when first seen. Peripheral venous thrombosis was present in 36 of 47 (77%) patients, and intracardiac thrombi in 12 of the 36 (33%) patients. Nodules, cavities, and intracardiac thrombi were mainly present in the acute stages of pulmonary artery involvement.Pulmonary artery involvement is usually multiple, and involves mostly descending branches of the pulmonary artery. Pulmonary artery involvement may disappear, but arterial stenosis or occlusions usually develop at the same location. After a mean follow-up of 7 years, 12 of 47 (26%) patients were dead; patients with larger aneurysms were more likely to die. Sixteen of 47 (34%) patients were symptom free, and the remaining 40% had mild dyspnea (13/47) and/or small bouts of hemoptysis (8/47).Pulmonary artery pressure may be elevated, and may indicate a poor prognosis. Mediastinal lymphadenopathy and mild pleural and pericardial effusions may also be observed. Corticosteroids and immunosuppressive agents are the mainstays of treatment; however, refractory cases may require embolization, lobectomy, cavitectomy, and decortication.

PMID: 22210555 [PubMed - as supplied by publisher]

Rituximab for the Treatment of IgG4-Related Disease: Lessons From 10 Consecutive Patients.

Medicine (Baltimore). 2011 Dec 29;

Authors: Khosroshahi A, Carruthers MN, Deshpande V, Unizony S, Bloch DB, Stone JH

Abstract

ABSTRACT: Patients with IgG4-related disease (IgG4-RD) typically have elevated serum concentrations of IgG4 and share histopathologic features that are similar across affected organ(s). IgG4-RD patients frequently require prolonged treatment with glucocorticoids and are often unable to taper these medications. Traditional disease-modifying antirheumatic drugs (DMARDs) are generally ineffective. We assessed the clinical and serologic responses to B lymphocyte depletion therapy in 10 consecutive patients with steroid- and DMARD-refractory IgG4-RD.Ten patients with IgG4-RD were treated with rituximab (RTX) (2 infusions of 1000 mg, 15 days apart). Clinical improvement was assessed by monitoring the patient’s ability to taper prednisone to discontinuation and to stop DMARDs; by serial measurements of total IgG and IgG subclasses; and by follow-up radiologic assessments guided by the patient’s particular pattern of organ involvement. We also developed and retrospectively applied the IgG4-RD Disease Activity Index and Flare Tool.Organ involvement included the pancreas, biliary tree, aorta, salivary glands (submandibular and parotid), lacrimal glands, lymph nodes, thyroid gland, and retroperitoneum. Nine of 10 patients demonstrated striking clinical improvement within 1 month of starting RTX. One patient with advanced thyroid fibrosis associated with Riedel thyroiditis and a history of disease in multiple other organ systems did not have improvement in the thyroid gland, but the disease did not progress to involve new organs. All 10 patients were able to discontinue prednisone and DMARDs following RTX therapy. Significant decreases in IgG concentrations were observed for the IgG4 subclass only. Four patients were re-treated with RTX after 6 months because of either symptom recurrence and increasing IgG4 concentration at the time of peripheral B cell reconstitution (n = 2) or because of physician discretion (n = 2). Repeated courses of RTX maintained their effectiveness and resulted in further decreases in IgG4 concentrations. In patients who had an increased IgG4 concentration at the time of presentation, the level of serum IgG4 appeared to be a reliable measure of disease activity.IgG4-RD is an idiopathic, multiorgan inflammatory disease in which diverse organ manifestations are linked by characteristic histopathologic and immunohistochemical features. Treatment with RTX led to prompt clinical and serologic improvement in refractory IgG4-RD in all patients with active inflammation. Serial treatments with RTX may lead to progressive declines in serum IgG4 concentrations and better disease control. Serum IgG4 concentrations may remain low, and clinical disease activity may remain quiescent even after B cell reconstitution in a significant proportion of patients.

PMID: 22210556 [PubMed - as supplied by publisher]

Prognosis and Outcome of Non-Hodgkin Lymphoma in Primary Sjögren Syndrome.

Medicine (Baltimore). 2011 Dec 22;

Authors: Voulgarelis M, Ziakas PD, Papageorgiou A, Baimpa E, Tzioufas AG, Moutsopoulos HM

Abstract

ABSTRACT: Sjögren syndrome (SS) has been associated with the development of non-Hodgkin lymphoma (NHL). From a cohort of 584 SS patients followed in our department from 1980 to 2010, we retrospectively analyzed 53 consecutive NHL cases. Considerations included histologic type, clinical manifestation and NHL staging, treatment, response rate and overall survival (OS), event-free survival (EFS), and standardized mortality ratio (SMR).Mucosa-associated lymphoid tissue (MALT) lymphomas constituted the majority (59%) of NHL subtypes, followed by nodal marginal zone lymphomas (NMZLs) (15%) and diffuse large B-cell lymphomas (DLBCLs) (15%). Six lymphoma patients died during the median follow-up of 40.8 months. The corresponding age/sex-adjusted SMR of SS with and without NHLs versus the general population was 3.25 (95% confidence interval [CI] 1.32-6.76) and 1.08 (95% CI, 0.79-1.45), respectively. A “watch and wait” policy was adopted for 9 patients with asymptomatic localized salivary MALT lymphomas. Eight patients with limited-stage MALT lymphomas and extraglandular manifestations were treated with rituximab. Ten MALT lymphoma patients with disseminated disease received chemotherapy with or without rituximab. The 3-year OS and EFS in patients with MALT lymphomas was 97% and 78%, respectively. Rituximab plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) was the chosen therapeutic intervention for patients with DLBCLs. A successful outcome was recorded for this group, with 100% OS and EFS at 3 years. Patients with NMZLs had a less favorable outcome, with a 3-year OS of 80% and EFS of 53%. Our results describe the course and prognosis of SS-associated NHL and highlight the need for a risk-stratified treatment approach.

PMID: 22198497 [PubMed - as supplied by publisher]

Long-Term Outcome of Arterial Lesions in Behçet Disease: A Series of 101 Patients.

Medicine (Baltimore). 2011 Dec 22;

Authors: Saadoun D, Asli B, Wechsler B, Houman H, Geri G, Desseaux K, Piette JC, Huong DL, Amoura Z, Salem TB, Cluzel P, Koskas F, Resche-Rigon M, Cacoub P

Abstract

ABSTRACT: The vasculitis of Behçet disease (BD) is distinctive because of involvement of both arteries and veins of all sizes. The concept of vasculo-Behçet disease has been adopted for cases in which vascular manifestations are present and often dominate the clinical features. While venous manifestations are frequent and have been reported in many publications, data regarding arterial lesions in patients with BD are rare and often isolated. In this study, we report the main characteristics, treatment, and long-term outcome of 101 patients with arterial lesions among a cohort of 820 (12.3%) BD patients. Factors that affect prognosis were assessed by multivariate analysis. There were 93 (91.2%) male patients; the median (Q1-Q3) age at diagnosis of BD was 33 (27-41) years. Arterial lesions included aneurysms (47.3%), occlusions (36.5%), stenosis (13.5%), and aortitis (2.7%). Lesions mainly involved the aorta (n = 25) and femoral (n = 23) and pulmonary (n = 21) arteries. Patients with arterial lesions were more frequently male (91.2% vs. 62.4%, respectively; p = 0.017) and had higher rates of venous involvement (80.4% vs. 29.8%, respectively; p < 0.001) compared to patients without arterial manifestations. Thirty-nine (38.6%) patients achieved complete remission. In multivariate analysis, the presence of venous involvement (odds ratio [OR], 0.29; 95% confidence interval [CI], 0.08-1.11) and arterial occlusive lesions (OR, 0.13; 95% CI, 0.01-1.25) were negatively associated with complete remission. The use of immunosuppressants (OR, 3.38; 95% CI, 0.87-13.23) was associated with the occurrence of complete remission. The 20-year survival rate was significantly lower in BD patients with arterial involvement than in those without arterial lesions (73% vs. 89%, respectively; p < 0.0001). In conclusion, the long-term outcome of arterial lesions in BD is poor, especially in the case of occlusive lesions and associated venous involvement. The use of immunosuppressants improved the prognosis.

PMID: 22198498 [PubMed - as supplied by publisher]

Methicillin-Resistant Staphylococcus aureus Meningitis in Adults: A Multicenter Study of 86 Cases.

Medicine (Baltimore). 2011 Dec 22;

Authors: Pintado V, Pazos R, Jiménez-Mejías ME, Rodríguez-Guardado A, Gil A, García-Lechuz JM, Cabellos C, Chaves F, Domingo P, Ramos A, Pérez-Cecilia E, Domingo D

Abstract

ABSTRACT: Methicillin-resistant Staphylococcus aureus (MRSA) meningitis is an uncommon disease, and little is known about its epidemiology, clinical features, therapy, and outcome. We performed a multicenter retrospective study of MRSA meningitis in adults. Eighty-six adult patients were included and the following data were obtained: underlying diseases, clinical presentation, analytical and microbiologic data, response to therapy, and outcome.There were 56 men (65%) and the mean age was 51.5 years; 54 of them (63%) had severe comorbidities. There were 78 cases of postoperative meningitis and 8 of spontaneous meningitis. The infection was nosocomial in 93% (80/86) of the cases. Among the 78 patients with postoperative meningitis, the most common predisposing conditions were cerebrospinal fluid (CSF) devices (74%), neurosurgery (45%), CSF leakage (17%), and head trauma (12%). Most patients had fever (89%), altered mental status (68%), headache (40%), and meningeal signs (29%). The most common CSF findings were pleocytosis (90%), elevated protein level (77%), and hypoglycorrhachia (30%). CSF Gram stain and blood cultures were positive in 49% (32/65) and 36% (16/45) of cases, respectively. An associated MRSA infection and polymicrobial meningitis appeared in 33% (28/86) and 23% (20/86) of cases, respectively. Antimicrobial therapy was given to 84 patients. Most of them received vancomycin (92%) either as monotherapy (64%) or in combination with other antibiotics (28%), for a median of 18 days. Overall 30-day mortality was 31% (27/86). Multivariate study identified 2 independent factors associated with mortality: spontaneous meningitis (odds ratio [OR], 21.4; 95% confidence interval [CI], 2.3-195.4; p = 0.007), and coma (OR, 9.7; 95% CI, 2.2-42.3; p = 0.002).In conclusion, MRSA is a relatively uncommon but serious disease. Although most cases are nosocomial infections appearing in neurosurgical patients, spontaneous meningitis may present as a community-onset infection in patients with severe comorbidities requiring frequent contact with the health care system. Most patients have a favorable response to vancomycin, but the beneficial effect of combined and intraventricular therapy, or alternative drugs, remains unclear. MRSA meningitis is associated with a high mortality, and the presence of spontaneous infection and coma are the most important prognostic factors.

PMID: 22198499 [PubMed - as supplied by publisher]

Spectrum of Cardiac Lesions in Behçet Disease: A Series of 52 Patients and Review of the Literature.

Medicine (Baltimore). 2011 Dec 22;

Authors: Geri G, Wechsler B, Thi Huong DL, Isnard R, Piette JC, Amoura Z, Resche-Rigon M, Cacoub P, Saadoun D

Abstract

ABSTRACT: Cardiac abnormalities in patients with Behçet disease (BD) include pericarditis, myocarditis, endocarditis with valvular regurgitation, intracardiac thrombosis, endomyocardial fibrosis, coronary arteritis with or without myocardial infarction, and aneurysms of the coronary arteries or sinus of Valsalva. Data regarding the clinical spectrum, prevalence, and outcome of cardiac lesions in BD are lacking. In this study, we report the main characteristics, treatment, and long-term outcomes of 52 patients with cardiac lesions from a cohort of 807 (6%) BD patients. Forty-five (86.5%) patients were male, with a mean (±SD) age at BD diagnosis of 29.3 ± 10.3 years.Cardiac involvement was the first feature of BD in 17 (32.7%) patients. Cardiac lesions included pericarditis (n = 20; 38.5%), endocarditis (mostly aortic insufficiency) (n = 14; 26.9%), intracardiac thrombosis (n = 10; 19.2%), myocardial infarction (n = 9; 17.3%), endomyocardial fibrosis (n = 4; 7.7%) and myocardial aneurysm (n = 1; 1.9%). Patients with cardiac involvement were more frequently male (86.5% vs. 64.9%; p < 0.01) and had more arterial (42.3% vs. 11.1%; p < 0.01) and venous lesions (59.6% vs. 35.8%; p < 0.01) compared to those without cardiac manifestations. Factors associated with complete remission of cardiac involvement were treatment regimens with oral anticoagulants, immunosuppressants, and colchicine. The 5-year survival rate was 83.6% and 95.8% (p = 0.03) in BD patients with and without cardiac involvement, respectively. After a median (Q1-Q3) follow-up of 3.0 (1.75-4.2) years, 8 patients had died, in 3 cases directly related to cardiac involvement.In conclusion, cardiac lesions affected 6% of our large cohort of BD patients. The prognosis of cardiac involvement in BD is poor and improves with oral anticoagulation, immunosuppressive therapy, and colchicine.

PMID: 22198500 [PubMed - as supplied by publisher]

IgG4-Related Systemic Disease: Features and Treatment Response in a French Cohort: Results of a Multicenter Registry.

Medicine (Baltimore). 2011 Dec 22;

Authors: Ebbo M, Daniel L, Pavic M, Sève P, Hamidou M, Andres E, Burtey S, Chiche L, Serratrice J, Longy-Boursier M, Ruivard M, Haroche J, Godeau B, Beucher AB, Berthelot JM, Papo T, Pennaforte JL, Benyamine A, Jourde N, Landron C, Roblot P, Moranne O, Silvain C, Granel B, Bernard F, Veit V, Mazodier K, Bernit E, Rousset H, Boucraut J, Boffa JJ, Weiller PJ, Kaplanski G, Aucouturier P, Harlé JR, Schleinitz N

Abstract

ABSTRACT: IgG4-related systemic disease is now recognized as a systemic disease that may affect various organs. The diagnosis is usually made in patients who present with elevated IgG4 in serum and tissue infiltration of diseased organs by numerous IgG4+ plasma cells, in the absence of validated diagnosis criteria. We report the clinical, laboratory, and histologic characteristics of 25 patients from a French nationwide cohort. We also report the treatment outcome and show that despite the efficacy of corticosteroids, a second-line treatment is frequently necessary. The clinical findings in our patients are not different from the results of previous reports from Eastern countries. Our laboratory and histologic findings, however, suggest, at least in some patients, a more broad polyclonal B cell activation than the skewed IgG4 switch previously reported. These observations strongly suggest the implication of a T-cell dependent B-cell polyclonal activation in IgG4-related systemic disease, probably at least in part under the control of T helper follicular cells.

PMID: 22198501 [PubMed - as supplied by publisher]

Clinical and Laboratory Factors Associated With the Severity of Proliferative Sickle Cell Retinopathy in Patients With Sickle Cell Hemoglobin C (SC) and Homozygous Sickle Cell (SS) Disease.

Medicine (Baltimore). 2011 Oct 25;

Authors: Leveziel N, Bastuji-Garin S, Lalloum F, Querques G, Benlian P, Binaghi M, Coscas G, Soubrane G, Bachir D, Galactéros F, Souied EH

Abstract

Proliferative sickle cell retinopathy (PSCR) is the most frequent vision-threatening complication of sickle cell disease (SCD). We investigated the relationship between the severity of sickle cell retinopathy in heterozygous (SC) or homozygous (SS) adult SCD patients and the clinical and laboratory data obtained during visits to a national SCD referral center. This retrospective longitudinal analysis included 942 SCD patients (313 patients with SC and 629 with SS disease) with ophthalmologic evaluations who were followed over a 19-year period by a multidisciplinary team in a referral center. PSCR was graded using the Goldberg classification. We identified patient and SCD characteristics associated with sickle cell retinopathy severity using multinomial logistic-regression models. Multivariate analysis associated severe PSCR forms (stages III-V) with older age (p = 0.032), pulmonary involvement (documented pulmonary hypertension with pulmonary arterial pressure ≥40 mm Hg, restrictive syndrome >20%, or previous history of pulmonary embolism diagnosed by vascular imaging) (p = 0.029), deafness or tinnitus (p = 0.026), and no history of osteomyelitis (p = 0.013) for SC patients; and with older age (p < 0.001), male sex (p = 0.003), and acute pyelonephritis (p = 0.04) for SS patients. The model of severe PSCR versus no PSCR showed good calibration and discrimination for SC and SS patients. Awareness of the clinical and laboratory factors significantly associated with severe PSCR in patients with SC or SS SCD may contribute to improved preventive strategies.

PMID: 22033449 [PubMed - as supplied by publisher]

Fibrosing Mediastinitis: Clinical Presentation, Therapeutic Outcomes, and Adaptive Immune Response.

Medicine (Baltimore). 2011 Oct 25;

Authors: Peikert T, Colby TV, Midthun DE, Pairolero PC, Edell ES, Schroeder DR, Specks U

Abstract

Fibrosing mediastinitis (FM) is a rare disorder characterized by the invasive proliferation of fibrous tissue within the mediastinum. FM frequently results in the compression of vital mediastinal structures and has been associated with substantial morbidity and mortality. Its pathogenesis remains unknown. However, in North America most cases are thought to represent an immune-mediated hypersensitivity response to Histoplasma capsulatum infection.To characterize the clinical disease spectrum, natural disease progression, responses to therapy, and overall survival, we retrospectively analyzed all 80 consecutive patients with a diagnosis of FM evaluated at Mayo Clinic, Rochester, MN, from 1998 to 2007. Furthermore, we characterized the adaptive immune response in 15 representative patients by immunohistochemistry.The majority of patients presented with nonspecific respiratory symptoms due to the compression of mediastinal broncho-vascular structures. Chest radiographic imaging most frequently revealed localized, invasive, and frequently calcified right-sided mediastinal masses. Most patients had radiographic or serologic evidence of previous histoplasmosis.In contrast to earlier reports summarizing previously reported FM cases, the clinical course of our patients appeared to be more benign and less progressive. The overall survival was similar to that of age-matched controls. There were only 5 deaths, 2 of which were attributed to FM. These differences may reflect publication bias associated with the preferential reporting of more severely affected FM patients in the medical literature, as well as the more inclusive case definition used in our consecutive case series.Surgical and nonsurgical interventions effectively relieved symptoms caused by the compression of mediastinal vascular structures in these carefully selected patients. In contrast, antifungal and antiinflammatory agents appeared ineffective. Histologic examination and immunostaining revealed mixed inflammatory infiltrates consistent with a fibroinflammatory tissue response in these histoplasmosis-associated FM cases. The immune cell infiltrates included large numbers of CD20-positive B lymphocytes. As B lymphocytes may contribute to the pathogenesis of the disease, therapeutic B-cell depletion should be investigated as a therapeutic strategy for FM.

PMID: 22033450 [PubMed - as supplied by publisher]

Hepatitis B Virus (HBV) Reactivation in Patients Receiving Tumor Necrosis Factor (TNF)-Targeted Therapy: Analysis of 257 Cases.

Medicine (Baltimore). 2011 Oct 25;

Authors: Pérez-Alvarez R, Díaz-Lagares C, García-Hernández F, Lopez-Roses L, Brito-Zerón P, Pérez-de-Lis M, Retamozo S, Bové A, Bosch X, Sanchez-Tapias JM, Forns X, Ramos-Casals M,

Abstract

The emergence of tumor necrosis factor-α (TNF-α)-targeted therapies as a key therapeutic option for patients with rheumatic, digestive, and dermatologic autoimmune diseases has been associated with increasing reports of liver damage in patients with hepatitis B virus (HBV) infection. We studied the current evidence on the use of anti-TNF agents in patients with HBV through a systematic analysis of cases reported in the MEDLINE and EMBASE databases using the MeSH term “hepatitis B virus” combined with the terms “infliximab,” “etanercept,” “adalimumab,” “certolizumab,” “golimumab,” and “anti-TNF agents,” and summarize the results here. We analyzed 257 patients with positive HBV markers who received anti-TNF therapy (255 identified in the search strategy and 2 new cases), 89 HBsAg+ carriers, and 168 anti-HBc+ persons. HBV reactivation was reported in 35 (39%) HBsAg+ carriers. The percentage of reactivation was higher in patients previously treated with immunosuppressive agents (96% vs. 70%, p = 0.033) and lower in those who received antiviral prophylaxis (23% vs. 62%, p = 0.003). Acute liver failure was reported in 5 patients, 4 of whom died. Infliximab was associated with a higher rate of induced liver disease (raised transaminase levels, clinical signs, viral reactivation, and acute liver failure) compared with etanercept. In anti-HBc+ persons, reactivation was reported in 9 (5%) cases, including 1 patient who died due to fulminant liver failure.In summary, our search of the current evidence identified 257 reported HBV+ patients treated with anti-TNF agents, with a significant percentage of liver damage in HBsAg+ carriers, including raised transaminase levels (42%), signs and symptoms of liver disease (16%), reappearance of serum HBV-DNA (39%), and death related to liver failure (5%). The rate of reactivation in anti-HBc+ persons was 7-fold lower than in HBsAg+ carriers. The increasing number of reported cases of HBV reactivation following TNF-targeted therapies and the associated morbidity and mortality demand specific preventive strategies.

PMID: 22033451 [PubMed - as supplied by publisher]