Pulmonary embolism versus pulmonary vasculitis in Hughes-Stovin syndrome: Characteristic computed tomography pulmonary angiographic findings and diagnostic and therapeutic implications. HSS International Study Group.

BACKGROUND AND AIM: Hughes-Stovin syndrome (HSS) is a rare systemic vasculitis with widespread venous/arterial thrombosis and pulmonary vasculitis. Distinguishing between pulmonary embolism (PE) and in-situ thrombosis in the early stages of HSS is challenging. The aim of the study is to compare clinical, laboratory, and computed tomography pulmonary angiography (CTPA) characteristics in patients diagnosed with PE versus those with HSS. METHODS: This retrospective study included 40 HSS patients with complete CTPA studies available, previously published by the HSS study group, and 50 patients diagnosed with PE from a single center. Demographics, clinical and laboratory findings, vascular thrombotic events, were compared between both groups. The CTPA findings were reviewed, with emphasis on the distribution, adherence to the mural wall, pulmonary infarction, ground glass opacification, and intra-alveolar hemorrhage. Pulmonary artery aneurysms (PAAs) in HSS were assessed and classified. RESULTS: The mean age of HSS patients was 35 ± 12.3 years, in PE 58.4 ± 17 (p < 0.0001). Among PE 39(78 %) had co-morbidities, among HSS none. In contrast to PE, in HSS both major venous and arterial thrombotic events are seen.. Various patterns of PAAs were observed in the HSS group, which were entirely absent in PE. Parenchymal hemorrhage was also more frequent in HSS compared to PE (P < 0.001). CONCLUSION: Major vascular thrombosis with arterial aneurysms formation are characteristic of HSS. PE typically appear loosely-adherent and mobile whereas "in-situ thrombosis" seen in HSS is tightly-adherent to the mural wall. Mural wall enhancement and PAAs are distinctive pulmonary findings in HSS. The latter findings have significant therapeutic ramifications.

Autoimmune diseases and myelodysplastic syndromes.

Autoimmune diseases (ADs) and myelodysplastic syndrome (MDS) may be associated in approximately 10-20% of cases. Although this association has been well recognized, it is not always easily diagnosed. The exact physiopathological mechanism involved has yet to be determined but seems to be multifactorial. The therapeutic decision is not well codified and often represents a challenge. But overall, glucocorticosteroids have generally proven to be effective at the expense of a high incidence of dependence and relapse. This review aims to summarize and analyze all aspects of this association to provide an overview for practitioners and clinicians. A scientific search in databases (PubMed, Scopus, Web of Science, Google Scholar) was conducted using a combination of key words such as autoimmune diseases, myelodysplastic syndromes, and association. Articles from 1992 to 2022 were considered and relevant data were collected and summarized to provide a coherent detailed overview of the coexistence of ADs and MDS.

Radiological predictive remission factors of pulmonary involvement in systemic sarcoidosis: a computed tomography scan study.

INTRODUCTION: As little is known about the prognostic value of CT scan findings at onset in patients presenting with sarcoidosis, we aimed to identify factors independently associated with radiological remission of pulmonary involvement in systemic sarcoidosis on CT scan findings. METHODS: We conducted a retrospective descriptive and analytic study of patients with a biopsy proven systemic sarcoidosis. We compared patients on radiological remission (group 1) to those on stabilization or progression (group 2). Multivariate analysis of variables significantly associated with radiological remission in univariate analysis was performed using binary logistic regression. RESULTS: Out of 65 records of systemic sarcoidosis, 43 were analyzed. 18.6% where male and 81.6% female with a sex-ratio of 0.22 and a mean age at diagnosis of 47.2 ±13.6 years. We found atypical lesions in CT scan findings in 16 patients (37.2%). Comparative pulmonary CT scan findings at admission and at 12 months follow-up revealed 13 patients (30.2%) in remission (group1) and 30 patients in radiological stabilization or progression (group 2). On multivariate analysis, lymphopenia, calcifications, and typical CT scan findings at presentation were predictive factors of remission of pulmonary involvement in systemic sarcoidosis (aOR=27.57; 95%IC=2.67-284.63; p=0.005) (aOR= 37.2; 95%IC= 2.08-663.89; p= 0.014) (aOR=47.1; 95%IC= 1.79-1238.7; p=0.021) respectively. CONCLUSION: In patients with systemic sarcoidosis with no lymphopenia at onset or calcifications or typical CT scan findings at presentation, we suggest a close follow-up as well as an intensive treatment.

Pulmonary vasculitis in Behçet's disease: reference atlas computed tomography pulmonary angiography (CTPA) findings and risk assessment-management proposal.

BACKGROUND AND AIM:  Pulmonary artery aneurysms (PAAs) are the most well-defined type of pulmonary vascular complication in Behçet's disease (BD).The aim of this study is to analyze which CT pulmonary angiography (CTPA) signs are associated with serious morbidity and mortality. METHODS: The study included 42 BD patients with pulmonary vascular complications. All patients' medical records were reviewed retrospectively in terms of demographics, disease characteristics, laboratory investigations, pulmonary manifestations, arterial and/or venous thrombosis and CTPA vascular and parenchymal findings. RESULTS: Deep venous thrombosis was observed in 31(73.8%) patients, arterial thrombosis in 13(31%), peripheral arterial aneurysms in 12(286%), haemoptysis in 38 (90.5%), and fatal haemoptysis in 8(19 %) patients. CTPA revealed: in situ thrombosis in 14(33.3%) patients, true stable PAAs in 13(31), true unstable PAAs in 11(26.2%), stable pulmonary artery pseudoaneurysms (PAPs) in 7(16.7%), unstable PAPs in 17(40.5%), the latter were associated with perianeurysmal leaking in 26(61.9%) and bronchial indentation in 19(45.2%).In regression analysis, fatal outcomes were associated with age in years (p=0.035), arterial thrombosis (p=0.025), peripheral arterial aneurysms (p=0.010), intracardiac thrombosis (p=0.026) and positively associated with haemoptysis severity (p<0.001). CONCLUSION: Peripheral arterial thrombosis and/or aneurysms, intracardiac thrombosis and haemoptysis severity are predictor of fatal outcomes in BD pulmonary vasculitis. PAPs with perianeurysmal alveolar haemorrhage and/or bronchial indentation are serious CTPA signs that require prompt identification and aggressive treatment. PAPs are a more serious aneurysmal pattern than true PAAs because they are a contained rupture of a PA branch in the context of pulmonary vasculitis.

Simultaneous testicle and epididymis vasculitis revealing granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA) is a systemic necrotizing granulomatous vasculitis, which predominantly affects small-sized blood vessels. We aimed to report a case of GPA involving testicles and epididymis taken for malignancy. A 75-year-old patient was admitted for a painful left testicular mass. There was no extra urogenital manifestations on examination and the workup was unremarkable. Histological findings after orchidectomy revealed granulomatous inflammation of the testis and epididymis with fibrinoid necrosis and necrotic vasculitis consisting with the diagnosis of GPA. Further investigations regarding ear, nose, throat, pulmonary, and renal involvement were negative. Proteinase 3 antineutrophil cytoplasmic antibodies (PR3-ANCA) test was negative. Furthermore, infectious diseases especially tuberculosis were ruled out. Based on histopathological findings, limited GPA was diagnosed. The patient was treated with methotrexate and prednisone with good outcome. There was no relapse after 1 year of follow-up. Isolated urogenital involvement may occur at the onset of GPA and can be taken for malignancy. Histopathological findings are the gold standard for the diagnosis. Treatment is based on steroids and immunosuppressive drugs.

Clinical presentation, radiological findings and treatment options in Hughes-Stovin syndrome.

Hughes-Stovin syndrome is a rare disease characterized by thrombophlebitis associated with arterial or bronchial aneurysms. Even though it was described first in 1911, it is scarcely reported in the literature. Hughes-Stovin syndrome diagnosis is based on clinical manifestations as well as radiological findings. There are no validated criteria or specific laboratory findings to confirm the diagnosis. Computed tomography pulmonary angiography remains the gold standard for the diagnosis and follow-up of radiological findings, as they were recently described in a critical analysis of the largest cohort in the literature. The aim of this review is to draw attention to this rare but potentially fatal disease and to discuss its therapeutic options.

Pulmonary vasculitis in Hughes-Stovin syndrome (HSS): a reference atlas and computed tomography pulmonary angiography guide-a report by the HSS International Study Group.

INTRODUCTION: Hughes-Stovin syndrome (HSS) is a systemic vasculitis characterized by widespread venous/arterial thrombosis and pulmonary artery aneurysms (PAAs), which is associated with serious morbidity and mortality. All fatalities reported in HSS resulted from unpredictable fatal suffocating hemoptysis. Therefore, it is necessary to recognize pulmonary complications at an early stage of the disease. OBJECTIVES: The aims of this study are to develop a reference atlas of images depicting the characteristic features of HSS by computed tomography pulmonary angiography (CTPA). To make a guide for physicians by developing a classification of PAAs according to the severity and risk of complications associated with each distinct lesion type. METHODS: The Members of the HSS International Study Group (HSSISG) collected 42 cases, with high-quality CTPA images in one radiology station and made reconstructions from the source images. These detailed CTPA studies were reviewed for final image selection and approved by HSSISG board members. We classified these findings according to the clinical course of the patients. RESULTS: This atlas describes the CTPA images that best define the wide spectrum of pulmonary vasculitis observed in HSS. Pulmonary aneurysms were classified into six radiographic patterns: from true stable PAA with adherent in-situ thrombosis to unstable leaking PAA, BAA and/or PAP with loss of aneurysmal wall definition (most prone to rupture), also CTPA images demonstrating right ventricular strain and intracardiac thrombosis. CONCLUSION: The HSSISG reference atlas is a guide for physicians regarding the CTPA radiological findings, essential for early diagnosis and management of HSS-related pulmonary vasculitis. Key Points • The Hughes-Stovin syndrome (HSS) is a systemic vasculitis characterized by extensive vascular thrombosis and pulmonary artery aneurysms (PAAs) that can lead to significant morbidity and mortality. • All fatalities reported in HSS were related to unpredictable massive hemoptysis; therefore, it is critical to recognize pulmonary complications at an early stage of the disease. • The HSS International Study Group reference atlas  classifies pulmonary vasculitis in HSS at 6 different stages of the disease process and defines the different radiological patterns of pulmonary vasculitis notably pulmonary artery aneurysms, as detected by computed tomography pulmonary angiography (CTPA). • The main aim of the classification is to make a guide for physicians about this rare syndrome. Such a scheme has never been reached before since the first description of the syndrome by Hughes and Stovin since 1959. This classification will form the basis for future recommendations regarding diagnosis and treatment of this syndrome.

Predictive echocardiographic factors of severe obstructive sleep apnea.

INTRODUCTION: obstructive sleep apnea (OSA) is a common chronic pulmonary disease, characterized by repetitive collapse of the upper respiratory airways, leading to oxygen desaturation. This condition is recognized to be associated with cardiovascular disease. Several studies have shown the effects of OSA on both geometry and cardiac function, with conflicting results. We aimed to investigate the relationship between echocardiographic abnormalities and the severity of OSA. METHODS: this is a cross-sectional single center study including patients, without any cardiovascular or pulmonary comorbidities, with polygraphy proven OSA. All participants underwent a detailed transthoracic echocardiography (TTE). RESULTS: a total of 93 patients were included in the study, with 62.2% (n=56) females. According to the apnea hypopnea index (AHI), patients were divided into two groups: mild to moderate OSA (5≤ AHI< 30/H) and severe OSA (AHI≥ 30/H). There were no differences in baseline characteristics between the two groups. The assessment of echocardiographic parameters demonstrated that severe OSA have a higher left ventricular end-systolic (LVES) (47.6±7.2 VS 46.2±4.7), left ventricular end-diastolic (LVED) (31.3±6.2 VS 28.9±4.5) diameters and interventricular septum (IVS) thickness (12.7±2.4 VS11.7±2.5) diameters rather than mild to moderate OSA without a significant difference between the two groups. Furthermore, severe OSA patients had lower mean value of left ventricular ejection fraction (LVEF) and fractional shortening (FS) equal to 62.1±9.7 and 32.5±6.3 respectively. The difference between the two groups was not statistically significant. However, a significant association was shown between severity of OSA and left ventricular (LV) diastolic dysfunction, right ventricular internal diameter (RVID) and systolic pulmonary artery pressure (sPAP), with p=0.05, p=0.05 and p= 0.03 respectively. The RVID was also independently associated to the severity of the OSA (aOR 1.33, 95%CI: 0.99-1.79; p=0.05). CONCLUSION: using bidimensional echocardiography showed a relationship between severe OSA and right ventricular parameters (diastolic dysfunction and RVID) and sPAP.

A critical analysis of 57 cases of Hughes-Stovin syndrome (HSS). A report by the HSS International Study Group (HSSISG).

BACKGROUND: Hughes-Stovin syndrome (HSS) is a systemic disease characterized by widespread vascular thrombosis and pulmonary vasculitis with serious morbidity and mortality. The HSS International Study Group is a multidisciplinary taskforce aiming to study HSS, in order to generate consensus recommendations regarding diagnosis and treatment. METHODS: We included 57 published cases of HSS (43 males) and collected data regarding: clinical presentation, associated complications, hemoptysis severity, laboratory and computed tomography pulmonary angiography (CTPA) findings, treatment modalities and cause of death. RESULTS: At initial presentation, DVT was observed in 29(33.3 %), thrombophlebitis in 3(5.3%), hemoptysis in 24(42.1%), and diplopia and seizures in 1 patient each. During the course of disease, DVT occurred in 48(84.2%) patients, and superficial thrombophlebitis was observed in 29(50.9%). Hemoptysis occurred in 53(93.0%) patients and was fatal in 12(21.1%). Pulmonary artery (PA) aneurysms (PAAs) were bilateral in 53(93%) patients. PAA were located within the main PA in 11(19.3%), lobar in 50(87.7%), interlobar in 13(22.8%) and segmental in 42(73.7%). Fatal outcomes were more common in patients with inferior vena cava thrombosis (p = 0.039) and ruptured PAAs (p < 0.001). Death was less common in patients treated with corticosteroids (p < 0.001), cyclophosphamide (p < 0.008), azathioprine (p < 0.008), combined immune modulators (p < 0.001). No patients had uveitis; 6(10.5%) had genital ulcers and 11(19.3%) had oral ulcers. CONCLUSIONS: HSS may lead to serious morbidity and mortality if left untreated. PAAs, adherent in-situ thrombosis and aneurysmal wall enhancement are characteristic CTPA signs of HSS pulmonary vasculitis. Combined immune modulators contribute to favorable outcomes.

Simulation Based Learning in internal medicine students.

INTRODUCTION: Few experiences have been reported in simulation-based learning (SBL) in internal medicine. AIM: To assess the SBL impact in internal medicine learning on learners' perception, knowledge acquisition, and cognitive and communication skills evaluation. METHODS: A prospective observational study conducted in the Simulation Center at the Faculty of Medicine of Monastir between November 2018 and March 2019. High fidelity sessions were intended for lupus flare diagnosis and a standardized patient session for therapeutic education of patients on antivitamin K treatment. RESULTS: A total of 118 third-year undergraduate medical learners split into 9 groups attended 9 SBL sessions. Regarding learners' perception, gain in communication was felt among 117 learners (99.1%) and gain in confidence among 116 of them (98.3%). As for SBL impact on knowledge acquisition, the overall median pre and post-test scores were 5.76 / 10 (4.61-6.92) and 7.69 / 10 (6.92-9.23) respectively (p = 10-3). The median overall improvement score was 2.3(0.76-3.07). Assessing learners' skills made it possible to highlight certain learners' shortcomings which we focused on during debriefing. CONCLUSION: According to the current study, SBL was associated with a high level of learners' satisfaction and was effective in optimizing knowledge and communication in lupus flare diagnosis and antivitamin K management.

Acute lymphoblastic leukemia relapse presenting as retinal vasculitis.

Retinal vasculitis may occur as an isolated manifestation of acute lymphoblastic leukemia (ALL) relapse and precede central nervous involvement. Therefore, a high index of suspicion and repeated ocular and neurological evaluations are essential for early diagnosis and prompt appropriate treatment to save life and sight.

Changing pattern of clinical manifestations of Behçet's disease in Tunisia: comparison between two decades.

OBJECTIVES: To investigate the changes over time in extraocular and ocular manifestations of Behçet's disease (BD) in Tunisian patients. MATERIAL AND METHODS: Retrospective study of 246 patients divided into two groups: group 1 (147 patients examined from 1995 to 2005) and group 2 (99 patients examined from 2006 to 2017). RESULTS: Active or scarred genital ulcers observed by physician at presentation were significantly less frequent in group 2 (47.2% vs. 29.6%; p = 0.007), as were articular involvement (50.3% vs. 34.7%; p = 0.016) and erythema nodosum (18.4% vs. 8.1%; p = 0.024). One hundred-seven patients (43.5%) developed ocular manifestations during the 23-year study period. Intermediate uveitis was significantly more frequent in group 2 than in group 1 (11.7% vs. 28.4%; p = 0.003), and posterior uveitis less frequent in group 2 than in group 1 (34.2% vs. 19.7%; p = 0.016). Patients from group 2 were more likely to have macular edema (19.8% vs. 45.6%; p = 0.001). However, better visual prognosis, with a lower rate of legal blindness, was noted in group 2. CONCLUSIONS: Changes over time included a decrease in the rate of articular involvement and cutaneous involvement. There was an increase in the rate of intermediate uveitis and a decrease in the rate of posterior uveitis over time. Despite an increase in the rate of macular edema, there was an improvement in visual prognosis, with less legal blindness over time.

Panuveitis revealing Melkersson Rosenthal syndrome: a case report.

AIM: To describe a case of panuveitis revealing Melkersson Rosenthal syndrome (MRS). CASE REPORT:   A 35-year-old female with a history of bilateral chronic idiopathic panuveitis was referred for work up. On examination, her visual acuity was 3/10 in the right eye and limited to hand motion in the left eye. Slit lamp examination revealed posterior synechiae and vitritis more severe in the left eye. Fundus examination showed bilateral vascular sheathing with no retinitis or choroiditis. Fluorescein angiography revealed bilateral occlusive retinal vasculitis. A careful questioning of the patient revealed the history of relapsing facial paralysis with palpebral edema. The work up ruled out an underlying infectious disease, especially ocular tuberculosis. Examination of the internist revealed a cheilitis and a fissured tongue. The diagnosis of MRS was made and the patient was treated with systemic corticosteroids and scatter laser treatment of retinal nonperfusion areas. CONCLUSION: MRS is a rare disorder. Ocular involvement, especially uveitis, is uncommon. Clinicians should be aware of this syndrome to avoid misdiagnosis and extensive work up.

A Case of Behçet Disease Myocarditis Documented Using Cardiac Magnetic Resonance Imaging.

Acute myocarditis is extremely rare in patients with Behçet disease. Here we report a case of a 32-year-old man with a history of oral ulcerations who was admitted for fever and chest pain. On examination, he had bipolar ulcers with pseudofolliculitis and a positive pathergy test. Electrocardiogram and transthoracic echocardiography were normal. Cardiac magnetic resonance imaging revealed left ventricular inferior and lateral wall late gadolinium enhancement. A diagnosis of acute myocarditis revealing Behçet disease was made, and the patient was treated with colchicine and pulses of methylprednisolone, and cyclophosphamide. A 7-month follow-up magnetic resonance image showed a substantial decrease in the late gadolinium enhancement area.

Cardio-metabolic risk factors in Tunisia: state of the art.

Cardiometabolic risk factors in Tunisia are growing fast. The main risk factor is metabolic syndrome which is a global health issue in both developing and developed countries. It is resulting from a new phase of epidemiological transition characterised by ageing and an increase in non-communicable diseases. It is common in both genders with some disparities between urban and rural regions, educational levels and social classes. Hypertension and diabetes are also additional risk factors predicting alarming mortality rates. We propose here a review of the determinants of metabolic syndrome in Tunisia and the overall cardiometabolic risk factors.

Myxedema coma: four patients diagnosed at the Internal Medicine Department of the Dr. Negrin University Hospital in Spain.

Myxedema coma is a rare complication of hypothyroidism. Clinical examination may reveal hypotension, bradycardia, and hypothermia. Laboratory tests may show hyponatremia, lipid disorders, and elevations of creatine kinase, liver, and cardiac enzymes. We describe four cases diagnosed in our hospital during the period 1999-2017. The patients were related to amiodarone treatment, noncompliance with hormone replacement therapy, or a new diagnosis of hypothyroidism. Intravenous hormone replacement therapy was effective in three of the cases and one died. The outcome of this disease may be fatal as seen in one of our cases.

Update on Autoimmune Diseases Pathogenesis.

BACKGROUND: Autoimmune diseases result from the interplay of cellular effectors like T and B cells, regulatory cells in addition to molecular factors like cytokines and regulatory molecules. METHODS: Different electronic databases were searched in a non-systematic way to find out the literature of interest. RESULTS: Pathogenesis of autoimmune diseases involves typical factors such as genetic background including HLA and non HLA system genes, environmental factors such as infectious agents and inflammatory cells mainly T and B lymphocytes abnormally activated leading to immune dysfunction. Other recently reported less typical factors such as micro-RNAs, circular RNAs, myeloperoxidase, vimentine and microbiome dysbiosis seem to be potential target therapies. CONCLUSION: We aimed in this manuscript to review common factors in the pathogenesis of autoimmune diseases.

[Nutcracker syndrome]. / Síndrome del cascanueces.

Nutcracker syndrome is a vascular anomaly consisting in the compression of the left renal vein between the superior mesenteric artery and the aorta. Clinical features in nutcracker syndrome include pelvic pain, flank pain, haematuria, gonadal varices or simply asymptomatic. We are presenting two cases, one of them with macroscopic haematuria and flank pain and the other was studied for hypertension but with previous antecedents of left renal vein embolization in the setting of varicocele. We discuss the clinical presentation as well as diagnostic and therapeutic aspects related to this syndrome.

El síndrome del cascanueces es una anomalía vascular en la que se comprime la vena renal izquierda a su paso entre la unión de la aorta y la arteria mesentérica superior, debido a un ángulo muy cerrado entre ambas arterias. Clínicamente puede presentarse como hematuria macro o microscópica, dolor episódico en flanco izquierdo, dolor pélvico, várices gonadales o simplemente cursar de forma asintomática. Presentamos dos casos clínicos, uno de ellos con dolor abdominal tipo cólico nefrítico y hematuria macroscópica y otro estudiado por hipertensión pero con antecedentes de embolización de la vena renal izquierda por varicocele izquierdo. Discutimos los aspectos clínicos, diagnósticos y terapéuticos de este síndrome.

Cognitive Function in Primary Sjögren's Syndrome: A Systematic Review.

BACKGROUND: Cognitive disorders are reported to be common in patients with primary Sjogren's syndrome (pSS). In some cases, they are the first clinical manifestation, preceding the diagnosis of pSS by two years on average. AIM: A systematic review was conducted to explore cognitive impairment in pSS, with reference to diagnostic methods and their relationship with laboratory data and clinical manifestations. MATERIALS AND METHODS: According to the PRISMA 2009 checklist, we carried out a comprehensive literature search in the three main bibliographic databases: MEDLINE, EMBASE, and PsycINFO (NICE HDAS interface). The following main search terms were used: primary Sjogren syndrome, neurological manifestations, fatigue, cognitive functions, psychiatric manifestations, mild cognitive impairment, dementia, and neurocognitive disorder. The search was made on 14 September, 2018. References from all selected studies were also examined. Inclusion criteria were: all studies and case-reports published in any language from 2002 that assessed the association of pSS (according to classification criteria proposed by the 2002 American/European collaborative group (AECG)) with all types of cognitive impairment (including dementia). Exclusion criteria were: reviews, abstracts, secondary Sjögren's syndrome (SS), and all articles in which other classification criteria were used. RESULTS: The initial search yielded 352 articles, of which 253 were excluded based on the title and abstract review. A total of 54 articles underwent a full-length review, and 32 articles were excluded. Data were extracted from 18 studies and three case-reports involving a total of 6196 participants. In most cases, cognitive dysfunction was a brain fog or a mild cognitive impairment (MCI). Occasionally, an autoimmune dementia was present. The relationship between pSS and degenerative dementias, such as Alzheimer's disease (AD), was a controversial issue, even if some investigators hypothesized that pSS could be a risk factor. Several unmet needs were highlighted. First, some of the included studies had not reported the severity of pSS; hence, few correlations between disease severity and cognitive function were possible. Secondly, the evaluation of the pathogenetic role of comorbid diseases was often absent. The lack of information on the type of dementia represented a third critical point in the majority of the included studies. CONCLUSIONS: This systematic review confirmed that adequate studies on cognitive function in pSS are scarce, mostly performed on small-sized samples, and often conflicting. The routine assessment of cognitive function in patients with pSS seems advisable and it will help to elucidate some of the unmet needs highlighted by this review in future appropriately designed studies.