A rare case report of polyangiitis overlap syndrome: granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is a systemic ANCA-associated vasculitis characterized by necrotizing granulomatous inflammation and a predilection for the upper and lower respiratory tract. Eosinophilic granulomatosis with polyangiitis (EGPA) is also a systemic ANCA-associated vasculitis, but EGPA is characterized by eosinophilic as well as granulomatous inflammation and is more commonly associated with asthma and eosinophilia. Polyangiitis overlap syndrome is defined as systemic vasculitis that does not fit precisely into a single category of classical vasculitis classification and/or overlaps with more than one category. Several polyangiitis overlap syndromes have been identified, however, there are very few case reports of an overlap syndrome involving both GPA and EGPA in the medical literature. CASE PRESENTATION: We conducted a PUBMED literature review using key words 'granulomatosis with polyangiitis,' 'Wegener's,' 'GPA,' 'eosinophilic granulomatosis with polyangiitis,' 'Churg-Strauss,' 'EGPA,' 'overlap syndrome,' 'Wegener's with eosinophilia,' and 'GPA with eosinophilia' in English only journals from 1986 to 2017. Relevant case reports and review articles of overlap syndromes of GPA and EGPA were identified. We aim to report a unique case of GPA and EGPA overlap syndrome and review the cases that have been previously described. Between 1986 and 2017, we identified 15 cases that represent an overlap syndrome with compelling features of both GPA and EGPA. Patients ranged in age between 21 and 78. Of those whose gender was identified, 80 % of the patients were female. All cases described involved the lungs, 60 % reported sinus involvement, and more than 50 % displayed renal involvement. An overwhelming majority of patients were positive for c-ANCA and demonstrated eosinophilia (peripheral blood or tissue eosinophilia). A preponderance of the cases described were treated with systemic corticosteroids combined with an immunosuppressive/cytotoxic agents. CONCLUSION: To our knowledge, there have been very few cases reported of an overlap syndrome of GPA and EGPA. Identification of patients with a polyangiitis overlap syndrome of GPA and EGPA is imperative as prognosis, longitudinal management and treatment modalities may differ between these entities.

Transcriptomic Profiling of Peripheral B Cells in Antibody Positive Sjogren's Patients Reveals Interferon Signature.

BACKGROUND: Sjögren's disease (SjD) is a common systemic autoimmune disease that affects mainly women. Key pathologic features include the infiltration of exocrine glands by lymphocytes and the activation of B lymphocytes with the production of autoantibodies. We aimed to analyze the transcriptome of circulating B cells from patients with SJD and healthy controls to decipher the B-cell-specific contribution to SJD. METHODS: RNA from peripheral blood B cells of five untreated female patients with SjD and positive ANA, positive anti-SSA (both Ro-52 and Ro-60), positive anti-SSB and positive rheumatoid-factor, and five healthy controls was subjected to whole-transcriptome sequencing. A false discovery rate of < 0.1 was applied to define differentially expressed genes (DEG). RESULTS: RNA-sequencing identified 56 up and 23 down DEG. Hierarchal clustering showed a clear separation between the two groups. Ingenuity pathway analysis revealed that these genes may play a role in interferon signaling, chronic mycobacterial infection, and transformation to myeloproliferative disorders. CONCLUSIONS: We found upregulated expression of type-I and type-II interferon (IFN)-induced genes, as well as genes that may contribute to other concomitant conditions, including infections and a higher risk of myeloproliferative disorders. This adds insight into the autoimmune process and suggests potential targets for future functional and prognostic studies.

Manifestations and management of Sjögren's disease.

Sjögren's disease is a heterogeneous autoimmune disorder that may be associated with systemic manifestations such as pulmonary or articular involvement. Systemic complications have prognostic implications and need to be identified and managed in a timely manner. Treatment should be tailored to the type and severity of organ involvement, ideally based on multidisciplinary evaluation.

Diagnosis and Management of Interstitial Lung Disease in Patients with Connective Tissue Diseases.

Interstitial lung disease (ILD) associated with connective tissue diseases (CTDs) is highly heterogeneous in its clinical presentation and course. The diagnosis and management of CTD-ILD require a multidisciplinary approach involving, at minimum, a rheumatologist, a pulmonologist, and a radiologist. Close monitoring of patients with CTD-ILD is important to enable early detection of disease progression and inform decisions regarding the initiation or escalation of pharmacotherapy. In the absence of guidelines regarding how CTD-ILDs should be treated, clinicians face difficult decisions on when to use immunosuppressant and anti-fibrotic therapies. The importance of a multidisciplinary and individualized approach to the diagnosis and management of CTD-ILD is highlighted in the three case studies that we describe in this article.

A 56-Year-Old Man With Emphysema, Rash, and Arthralgia.

CASE PRESENTATION: A 56-year-old man presented to the pulmonary clinic with dyspnea and hypoxemia on exertion. He was an avid biker and skier who had noticed a significant decrease in high-level physical activity over the past 3 years. He reported dyspnea, desaturations at altitudes higher than 9,000 feet, dry cough, tachycardia, and palpitations with exercise. Review of systems was also notable for gluten-intolerance, Raynaud's phenomenon, recurrent skin lesions and joint swelling, pain, and stiffness in the areas overlying the jaw, wrists, knees, and ankles (after capsaicin exposure). He denied fever, chills, anorexia, weight loss, hair loss, ocular symptoms, jaw claudication, chest pain, or lower extremity swelling. He had a five pack-year smoking history, no history of prematurity, childhood asthma, recurrent infections, or environmental and occupational exposure. Based on pulmonary function tests from an outside provider, he had received a diagnosis of exercise-induced asthma and had been prescribed an albuterol inhaler to use on an as-needed basis, which failed to improve his symptoms. He was later prescribed a mometasone-formoterol inhaler, still with no symptomatic improvement.

Trends in systemic sclerosis and systemic sclerosis-related pulmonary arterial hypertension mortality in the USA.

There are limited data nationwide on the burden of systemic sclerosis (SSc)-related mortality. We aimed to determine recent trends in SSc and SSc-related pulmonary arterial hypertension (PAH) mortality overall and across population subgroups. Using death certificate data from the National Center for Health Statistics, we computed the age-adjusted mortality rates of SSc and SSc-SSc-PAH, a lethal prevailing complication, across demographic groups, geographic regions and comorbid cardiorespiratory conditions, and used Joinpoint regression analysis to calculate the average annual percentage change (APC) in mortality. From 2003 to 2016, 25 175 death records contained a code for SSc. Decedents were predominantly female (81%) and white (73%), with an average age of 66±14 years. The age-adjusted mortality rate decreased by 3% per year from 6.6 in 2003 to 4.3 per 1 000 000 population in 2016. Also, a decreasing trend was found when SSc was stratified by age, sex, race and geographic region. The prevalence of PAH was 23%. The odds of PAH were highest in female and black decedents, and in decedents with concomitant pulmonary embolism, cardiomyopathy and interstitial lung disease (ILD). SSc-PAH mortality remained stable from 2003 to 2008 then decreased by 3% per year from 2008 to 2016. In decedents with SSc-PAH, among all concomitant comorbidities, the mortality rate associated with ILD had the highest increase (average APC 6%, 95% CI 2%-10%). The mortality rate from SSc decreased from 2003 to 2016. Decreases in mortality rates were similar across demographic groups and geographic regions. SSc-PAH-related mortality remained stable. The death rate for SSc-ILD and concomitant PAH increased during this period.

New developments in osteoarthritis. Sex differences in magnetic resonance imaging-based biomarkers and in those of joint metabolism.

Sex differences in the prevalence, incidence, and severity of osteoarthritis (OA) have long been known. Some differences in the evaluation of this issue across studies may be related to differences in study design, sampling, study size, study populations, targeted joint sites, and definitions of OA. This report highlights recent studies of sex differences in individual joint components imaged by magnetic resonance imaging and in systemic biomarkers of joint metabolism. Particularly important are those studies that examine this issue in young unaffected adults and children before the development of disease. Despite some variation across studies, women appear for the most part to have a thinner and more reduced volume of cartilage in the knee than men, and this may occur from early childhood. It is not clear whether women have a more accelerated rate of cartilage volume loss than men. Few data exist on sex differences in systemic biomarkers of joint metabolism. In these studies, it is critically important to characterize the total body burden of OA and the presence of comorbid conditions likely to influence a given biomarker. Lastly, future research should dovetail studies of sex differences in imaging and biochemical biomarkers with genetics to maximize insight into the mechanisms behind observed sex differences.