Clinical Characteristics of EGPA Patients in Comparison to GPA Subgroup with Increased Blood Eosinophilia from POLVAS Registry.

Objective: To characterize the eosinophilic granulomatosis with polyangiitis (EGPA) population from the POLVAS registry depending on ANCA status and diagnosis onset, including their comparison with the granulomatosis with polyangiitis (GPA) subset with elevated blood eosinophilia (min. 400/µl) (GPA HE) to develop a differentiating strategy. Methods: A retrospective analysis of the POLVAS registry. Results: The EGPA group comprised 111 patients. The ANCA-positive subset (n = 45 [40.54%]) did not differ from the ANCA-negative one in clinics. Nevertheless, cardiovascular manifestations were more common in ANCA-negative patients than in those with anti-myeloperoxidase (MPO) antibodies (46.97% vs. 26.92%, p = 0.045). Patients diagnosed before 2012 (n = 70 [63.06%]) were younger (median 41 vs. 49 years, p < 0.01), had higher blood eosinophilia at diagnosis (median 4,946 vs. 3,200/µl, p < 0.01), and more often ear/nose/throat (ENT) and cardiovascular involvement. GPA HE comprised 42 (13.00%) out of 323 GPA cases with reported blood eosinophil count. Both GPA subsets had a lower prevalence of respiratory, cardiovascular, and neurologic manifestations but more often renal and ocular involvement than EGPA. EGPA also had cutaneous and gastrointestinal signs more often than GPA with normal blood eosinophilia (GPA NE) but not GPA HE. The model differentiating EGPA from GPA HE, using ANCA status and clinical manifestations, had an AUC of 0.92, sensitivity of 96%, and specificity of 95%. Conclusion: Cardiovascular symptoms were more prevalent in the ANCA-negative subset than in the MPO-ANCA-positive one. Since EGPA and GPE HE share similarities in clinics, diagnostic misleading may result in an inappropriate therapeutic approach. Further studies are needed to optimize their differentiation and tailored therapy, including biologics.

Influence of smoking on disease activity and prognosis of antineutrophil cytoplasmic antibody-associated vasculitis: a retrospective cohort study.

INTRODUCTION: Antineutrophil cytoplasmic antibody-associated vasculitides (AAV) are a group of autoimmune diseases characterized by inflammation of small blood vessels. Smoking is a potential trigger for such diseases, however, its link with AAV remains controversial. OBJECTIVES: The aim of this study was to analyze the link between AAV and smoking based on clinical characteristics, disease activity, and mortality. METHODS: This retrospective study included 223 AAV patients. Their smoking status was assessed at diagnosis and they were classified as ever smokers (ESs), including current or past smokers, and never smokers (NSs). Information regarding clinical presentation, the disease activity, immunosuppressive therapy, and survival was collected. RESULTS: The ESs had similar organ involvement to the NSs, except for significantly greater frequency of renal replacement therapy (31% vs 14%; P = 0.003). Median (interquartile range [IQR]) time from symptom onset to diagnosis was significantly shorter in the ESs than the NSs (4 [2-9.5] vs 6 [3-13] months; P = 0.03), with significantly higher mean (SD) value of the Birmingham Vasculitis Activity Score version 3 (19.5 [7.93] vs 17.25 [8.05]; P = 0.04). The ESs were more likely to receive cyclophosphamide therapy (P = 0.03), and had significantly higher morality than the NSs (hazard ratio, 2.89; 95% CI, 1.47-5.72; P = 0.002). There were no significant differences between the current and past smokers. The multivariable Cox proportional regression analysis found ever smoking and male sex to be independent predictors of mortality in AAV patients. CONCLUSION: Ever smoking is associated with increased AAV activity and more frequent renal replacement therapy and immunosuppressive treatment, resulting in a poorer survival prognosis in AAV patients. Future multicenter studies are required to further characterize the clinical, biological, and prognostic impact of smoking on AAV.

Respiratory involvement in antineutrophil cytoplasmic antibody-associated vasculitides: a retrospective study based on POLVAS registry.

OBJECTIVES: The study aimed to characterise the Polish population of (ANCA)-associated vasculitides (AAV) with respiratory involvement (RI), in comparison to the subgroup without lung manifestations and the other cohorts. METHODS: Retrospective analysis of the Polish population of AAV with RI was conducted, based on data from the POLVAS registry. Standard descriptive statistics, χ2 test, and Mann-Whitney U test were used to perform comparisons. RESULTS: Among 461 cases qualified to this study, there were 316 cases with RI (68.5%), 206 with granulomatosis with polyangiitis (GPA) (65.2%), 80 with eosinophilic granulomatosis with polyangiitis (EGPA) (25.3%) and 30 with microscopic polyangiitis (MPA) (9.5%). Proportion of RI in GPA, MPA, and EGPA accounted for 67.8%; 40.0%; 97.6%, respectively. The number of relapses was higher in the RI group (median 1.0 vs. 0.0; p=0.01). In the subgroup of combined GPA and MPA with RI, the trends toward higher proportion of deaths (11.7% vs. 5.7%; p=0.07), relapses requiring hospitalisation (52.2% vs. 42.4%, p=0.07) and relapses requiring admission to the intensive care unit (5.6% vs. 1.4%, p=0.09) were observed, median maximal concentration of CRP was higher (46 vs. 25 mg/l; p=0.01) and more aggressive treatment was administered. CONCLUSIONS: Prevalence of RI in the Polish population of AAV is similar to the values reported in the literature, however, the proportion observed in GPA is closer to those presented in Asian than Western European cohorts. RI seems to be associated with a more severe course of disease and its presence prompts more aggressive treatment.

Association of antineutrophil cytoplasmic antibody (ANCA) specificity with demographic and clinical characteristics of patients with ANCA­associated vasculitides.

INTRODUCTION: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by the presence of proteinase­3 (PR3) or myeloperoxidase (MPO) ANCA. In over 90% of cases, PR3­ANCA is associated with granulomatosis with polyangiitis (GPA). However, it is also rarely found in microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). On the other hand, MPO­ANCA being characteristic of MPA (>90% of cases), is also found in about 40% of EGPA and 5% of GPA patients. On the ground of this overlap, clinical importance of ANCA specificity identification has been questioned. OBJECTIVES: In this study, we analyzed the clinical and demographic characteristics of AAV subgroups identified by ANCA serotype. PATIENTS AND METHODS: We conducted a multicenter study of AAV patients (417 GPA, 106 MPA, 102 EGPA; diagnosed between 1990 and 2016), included in the POLVAS registry. The data were systematically collected according to a standardized protocol. RESULTS: In the ANCA-positive group (anti­MPO, anti­PR3) a male-to-female ratio was 1:1, whereas in the ANCA-negative group it was 1:2, regardless of AAV diagnosis. Anti­MPO antibodies were present in significantly older patients. Patients with MPO+GPA and MPO+EGPA were older than those with corresponding ANCA­negative GPA and EGPA as well as PR3+AAV. Moreover, ANCA­negative AAV was characterized by a low risk of end­stage kidney disease and death. CONCLUSIONS: The presence and specificity of ANCA in AAV patients are related to sex and age, determine their organ involvement and influence mortality as previously shown. Patients with MPO­ANCA-positive AAV constitute a clinically homogeneous group, whereas PR3­ANCA-positive patients are much more clinically heterogeneous. ANCA-negative AAV patients are characterized by better prognosis. Thus, ANCA identification is an indispensable element and should not be omitted in establishing AAV diagnosis.

Long-lasting severe knee pain in a SLE patient after renal transplantation: what is the reason? A case report and literature review.

Musculo-skeletal complaints in a patient suffering from systemic lupus, with co-existing chronic renal failure, undergoing immunosuppressive treatment after kidney transplantation, can have a varied etiology. The aim of this work was to present a case based review of differential diagnosis of knee pain in such a patient. A literature search was carried out using MEDLINE/PubMed, Google Scholar and EBSCO, with no time limit. We undertook a systematic review of the literature published in English, limited to full-text publications of original articles, letters to the editor, and case reports in peer-reviewed journals, for a discussion and analysis of studies reporting arthralgia in patients with lupus after kidney transplantation. We present a case report of a 45-year-old woman with lupus nephritis, after kidney transplantation, who started to complain of increasing pain in the knees, most pronounced at night and after physical activity approximately 2 years after transplantation. Extensive causal diagnostics were carried out, which revealed bilateral extensive regions of bone infarction in the femur and tibia, chondropathy, degenerative changes of medial meniscuses in the body and posterior horn as well as chondromalacia of the patella. Establishing the right diagnosis is crucial for implementing appropriate treatment.

Prevalence of fibromyalgia in medical students and its association with lifestyle factors - a cross-sectional study.

OBJECTIVES: Fibromyalgia (FM) is a chronic widespread pain syndrome, known to be associated with several other symptoms. Chronic stress is suspected to be a contributing factor in the pathogenesis of FM. It is known that medical students are under a constant state of stress originating from personal and social expectations. The aim of the study was to assess the prevalence of FM in this population and identify lifestyle parameters influencing FM severity. MATERIAL AND METHODS: An online survey of first- and final-year medical students was conducted using the ACR modified 2016 criteria and FANTASTIC checklist. The survey acquired demographic information such as age, gender, year, and division of studies. A subgroup analysis based on gender, year of studies, and division of studies was performed. RESULTS: 439 medical students (71% females) completed the survey. The overall prevalence of FM in our cohort was 10.48%. The ratio of females to males was 3 : 1. A significant negative correlation between better quality of lifestyle and worse FM severity was observed in all subgroups. The "insight", "sleep and stress", "behavior" and "career" domains of lifestyle were found to have a significant negative correlation with FM severity on univariate analysis. CONCLUSIONS: The prevalence of FM in medical students seems to be considerably higher than in the general population. Chronic stress levels, sleep problems, social support, and behavior seem to be the major factors influencing FM severity in this population. Our findings suggest that medical students must be considered a "high-risk" group for FM, and hence must be identified, educated, and managed accordingly. It is, therefore, important for medical universities to implement programs educating students about FM, the importance of a healthy lifestyle, and stress coping strategies, while also making systemic changes to curb stressors in medical training.

Subphenotypes of ANCA-associated vasculitis identified by latent class analysis.

OBJECTIVES: ANCA-associated vasculitides (AAV) are a heterogeneous group of rare diseases with unknown aetiology and the clinical spectrum ranging from life-threatening systemic disease, through single organ involvement to minor isolated skin changes. Thus, there is an unmet need for phenotype identification, especially among patients with granulomatosis with polyangiitis (GPA). Patients with microscopic polyangiitis (MPA) seem to be clinically much more uniform. Recently, three subcategories of AAV have been proposed and described as non-severe AAV, severe PR3-AAV, and severe MPO-AAV. METHODS: In line with these attempts, we decided to use an unbiased approach offered by latent class analysis (LCA) to subcategorise GPA and MPA in a large cohort of Polish AAV patients included in a multicentre POLVAS registry. RESULTS: LCA of our AAV group identified a four-class model of AAV, including previously proposed three subphenotypes and revealing a fourth (previously not described) clinically relevant subphenotype. This new subphenotype includes only GPA patients, usually diagnosed at a younger age as compared to other groups, and characterised by multiorgan involvement, high relapse rate, relatively high risk of death, but no end-stage kidney disease. CONCLUSIONS: Based on multiple clinical and serological variables, LCA methodology identified 4-class model of AAV. This newly described fourth class of AAV may be of clinical relevance and may require prompt diagnosis and aggressive treatment due to the multiorgan involvement, high risk of relapse and marked mortality among these relatively young GPA subjects.

New lung mass in a patient with granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA) is a potentially lethal ANCA-associated small-vessel vasculitis characterized by a typical triad of upper respiratory tract, lung, and kidney involvement. Lung involvement in GPA occurs in 25-80% of cases. The most common radiographic and computed tomography (CT) abnormalities of pulmonary GPA are lung nodules and masses, very often multiple and with cavitation. As there are various clinical presentations, the diagnosis of GPA can be challenging, and the illness is difficult to distinguish from other diseases such as infection or malignancy. Following the improved survival rates in patients with GPA, there is accumulating evidence to suggest an increased occurrence of different types of cancer. Exposure to cyclophosphamide seems to be one of its main causes. We present the case of a patient with chronic GPA who was hospitalized owing to a new infiltrate in the lung, suggesting relapse of the disease, and finally diagnosed with small cell lung cancer. Data regarding lung cancer in GPA patients are limited. While there are some case reports and short case series in the literature, there are no detailed data regarding an association between CYC exposure and lung cancer development in vasculitis. It is necessary to consider the causes of pulmonary masses other than a GPA relapse. Bronchoscopy with biopsy and histopathological examination are crucial in proper differential diagnosis. GPA patients require long-term follow-up to monitor for the development of complications during treatment.

Treatment and its side effects in ANCA-associated vasculitides - Study based on POLVAS registry data.

PURPOSE: The aim of this study is to present the treatment modalities and associated side effects in a Polish nation-wide ANCA-associated vasculitides (AAV) patients' cohort. MATERIALS AND METHODS: Retrospective analysis of patients diagnosed with AAV between 1990 and 2016, included in the POLVAS registry was performed. Standard descriptive statistic methods were used with an emphasis on the treatment modalities. RESULTS: There were 625 patients diagnosed with AAV included in this study: 417 cases of granulomatosis with polyangiitis (GPA; 66.7%), 106 cases of microscopic polyangiitis (MPA; 17.0%) and 102 cases of eosinophilic granulomatosis with polyangiitis (EGPA; 16.3%). The mean age at the date of diagnosis was 50.4 (±15.7) years and the median observational period amounted to 4.0 (2.0-8.0) years. Glucocorticosteroids (GCs) were the medicaments most frequently used for remission induction (593/622; 95.3%), followed by cyclophosphamide (487/622; 78.3%), rituximab (44/622; 7.1%), and methotrexate (39/622; 6.3%). GCs were also most frequently administered for maintenance therapy (499/592; 84.3%), followed by azathioprine (224/592; 37.8%), methotrexate (136/592; 23.0%) and mycophenolate mofetil (99/592; 16.7%). The median cumulative doses of cyclophosphamide and rituximab equalled 7.99 g (4.18-14.0) and 2000 mg (1500-2800), respectively. The most commonly observed adverse events included: infections - 214/551 cases (38.8%), which were associated with the time of observation (OR = 1.05; 95% CI 1.01-1.10), the use of GCs intravenous pulses (OR = 2.76; 95% CI 1.68-4.54) and need for haemodialysis (OR = 1.73; 95% CI 1.10-2.71). CONCLUSIONS: Polish patients with AAV were predominantly treated according to appropriate guidelines. The most frequent adverse events were typical for usually administered immunosuppressive treatment.

Utility of lung ultrasound in ANCA-associated vasculitis with lung involvement.

INTRODUCTION: Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are forms of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). AAV most commonly affects the upper and lower respiratory tract as well as the kidneys. The first symptoms are often nonspecific, requiring careful differential diagnosis with infections and malignancies. MATERIALS AND METHODS: We analyzed the clinical and radiological data of 38 patients (20 females and 18 males) diagnosed with ANCA-associated vasculitis. Lung involvement was observed in 29 cases. Lung ultrasound (LUS) was performed on 21 patients from the study group and compared to chest CT. For 7 patients the examination was conducted repeatedly. RESULTS: In total, 35 LUS and CT examinations were performed, revealing the following lesions: nodules, infiltrates with and without features of disintegration, caves (n = 17), diffuse alveolar hemorrhage (n = 3), and features of interstitial lung disease (ILD) with pulmonary fibrosis (PF) (n = 11). In 2 cases LUS and CT were negative. In 4 cases LUS was negative, despite a positive CT result. CONCLUSIONS: Both in CT and LUS, images of pulmonary lesions were consistent though highly variable. Therefore, further studies are required for a larger group of patients.

Hypertrophic pachymeningitis as an important neurological complication of granulomatosis with polyangiitis.

Headache is a common symptom in patients with granulomatosis with polyangiitis (GPA) mainly due to chronic sinusitis or orbital disease. Meningeal involvement may thus remain unrecognized for a long time. This can lead to a significant delay in accurate diagnosis, serious local damage of the central nervous system and high relapse rates. New diagnostic techniques such as contrast MRI allow one to identify inflammation of the dura mater in the course of GPA more frequently. The objective of this article is to characterize hypertrophic pachymeningitis (HP) in patients with GPA and report diagnostic difficulties associated with this complication.

Relapsing granulomatosis with polyangiitis with severe lung and upper respiratory tract involvement successfully treated with rituximab.

Granulomatosis with polyangiitis (GPA) is a chronic, relapsing, primary systemic small vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies. The disease is characterised by the involvement of various organs. The relapse rate rises from about 20% at 12 months to about 60% at 5 years. The combination of glucocorticoids and cyclophosphamide remains the standard therapy for patients with generalised GPA; nevertheless, some patients do not respond satisfactorily to this treatment. According to EULAR-EDTA recommendations for the management of ANCA-associated vasculitis, RTX should be considered for remission-induction of new-onset as well as major relapse of organ-threatening or life-threatening GPA. Here we present a 35-year-old patient with relapsing GPA successfully treated with RTX. We also highlight the infectious complications of immunosuppressive treatment.

Hepatic involvement in granulomatosis with polyangiitis - diagnostic difficulties.

We report the case of a 57-year-old Caucasian man who presented with dry cough, haemoptysis, fever, lung nodules, erythrocyturia, and acute hepatitis. After a lung biopsy, the patient was diagnosed with granulomatosis with polyangiitis. The diagnosis was supported by the presence of anti-proteinase-3 anti-neutrophil cytoplasmic antibodies. The most common causes of liver damage are excluded. The patient was treated with prednisone and cyclophosphamide, which resulted in remission of chest CT findings and improvement in liver function tests. During the flare, new lung infiltrations as well as elevation of liver enzymes were present. Treatment with rituximab resulted in complete clinical and radiological remission and normalisation of liver function tests. What makes this case worth reporting is the rare liver involvement in the GPA. After exclusion of coexistence of autoimmune liver disease and drug-induced liver lesion, organ involvement was supported by the reversion of abnormal LFT after the immunosuppression of GPA.

The usefulness of histopathological examinations of non-renal biopsies in the diagnosis of granulomatosis with polyangiitis.

INTRODUCTION: Granulomatosis with polyangiitis (GPA) is a rare, ANCA-associated, systemic disease characterized by necrotizing small and medium vessel vasculitis of unknown etiology associated with granulomatous inflammation affecting the renal, pulmonary, upper airways, ocular systems and other tissues. Histological proof of the granulomatosis with polyangiitis (GPA) can be obtained by biopsy of clinically involved sites. The main purpose of this study was to examine histopathological changes in non-renal biopsies from patients with established diagnosis of GPA and evaluated the histological confirmation at diagnosis of this disease. MATERIAL AND METHODS: A retrospective analysis was performed in patients with GPA diagnosed and treated in clinics of the University Clinical Center (UCK) in Gdansk in 1988-2009. RESULTS: In the analyzed group of GPA patients the histopathological examination of biopsies taken from involved tissues (except kidney) was performed in 60% of patients. Thirty-six out of 93 biopsies (39%) were diagnosed as typical of GPA, 10 (10.7%) were suggestive and 51 (54.8%) were non-specific. Considering all biopsies, the diagnosis was confirmed in 24 patients (57% of patients in whom biopsies were taken). Epitheloid cell granulomas were present in 33 biopsies (43%), characteristic necrosis in 27 biopsies (35%), small vessel vasculitis in 18 biopsies (23%), while multinucleated giant cells were identified only in 9 biopsies (12%). CONCLUSIONS: Histopathological examination of the affected tissues remains the gold standard of the diagnosis of GPA. Its usefulness increases, particularly in ANCA-negative patients, in the initial phase of the disease, or in patients with atypical clinical presentation. In many cases, it is necessary to repeat biopsy to establish the diagnosis. The role of the histopathological examination seems to be particularly important when ANCA is negative or clinical symptoms are atypical of GPA.

Clinical characteristics of patients with anti-TIF1-γ antibodies.

OBJECTIVES: Inflammatory myopathies are a group of idiopathic, heterogeneous systemic diseases affecting predominantly skeletal muscles, though they can also involve the skin and internal organs. The association between cancer and idiopathic inflammatory myopathies, particularly dermatomyositis, which is termed cancer-associated myositis (CAM), has been reported in the medical literature. A newly described autoantibody to a 155-kDa nuclear protein, identified as transcription intermediary factor 1-gamma (TIF1-γ), has proven useful for cancer screening in patients with dermatomyositis. MATERIAL AND METHODS: Based on our database of laboratory results, between November 2014 and January 2016, we found 80 patients with a positive autoimmune inflammatory myopathy immunoblot profile. RESULTS: Eleven of 80 patients revealed the presence of anti-TIF1-γ antibodies: 8 women and 3 men with average age 54.2 years. Dermatomyositis (DM) was diagnosed in 6 cases, polymyositis in 1 case, myositis limited to ocular muscles and rhabdomyolysis in 1 case each, and undifferentiated connective tissue disease in 2 cases. Neoplasm was found in 4 cases. All of those patients had DM. The average time between DM and diagnosis of neoplasm was 7.5 months (from 1 to 18 months). CONCLUSIONS: The association between cancer and idiopathic inflammatory myopathies, particularly DM, is well known, and cancer screening should be obligatory in such patients. So far there is no consensus as to the method or frequency with which patients with an idiopathic inflammatory myopathy should be tested to rule out neoplasm. Detection of anti-TIF1-γ antibodies in patients with DM gives the clinicians the very important suggestion of CAM. It seems reasonable that these patients should have more detailed and often repeated differential diagnostics.

Gastrointestinal tract involvement in granulomatosis with polyangiitis.

INTRODUCTION: Granulomatosis with polyangiitis (GPA) is a necrotising vasculitis of small arteries and veins. In its classical manifestation GPA affects the upper and lower respiratory tract and kidneys. However, other organs, including those of the gastrointestinal tract, may be affected as well. AIM: To present the clinical manifestations of gastrointestinal tract involvement in patients with GPA. MATERIAL AND METHODS: We analysed case records of 34 patients with GPA treated in the Department of Nephrology, Transplantology, and Internal Medicine of the Medical University of Gdansk from 1991 to 2009. RESULTS: In 9 of 34 patients, 2 men and 7 women, aged 18 to 74 years, gastrointestinal complications were observed in the course of GPA. In two of them a localised and in seven a generalised type of GPA was diagnosed. The main symptoms relating to gastrointestinal tract were: oral mucosa ulcerations, gum mucosa hypertrophy, dyspepsia, vomiting, stomachache, gastrointestinal haemorrhage, diarrhoea, and symptoms of gastrointestinal tract perforation. Two patients required urgent surgical treatment. In 2 of the 5 patients who developed gastrointestinal bleeding, it was the direct cause of death. The histopathological confirmation of specificity of changes in gastrointestinal tract was established only in 2 cases. Tissue samples collected during endoscopy usually revealed only nonspecific inflammation or the presence of ulcers. CONCLUSIONS: Therapeutic strategies accepted for GPA treatment are effective in treating patients with gastrointestinal involvement in the course of the disease. Some complications require surgical intervention.

Infectious complication or exacerbation of granulomatosis with polyangiitis?

Granulomatosis with polyangiitis (GPA) is a primary, systemic small vessel vasculitis. The respiratory tract is typically involved in the course of the disease. Abnormalities on the chest radiograph are noted in more than 70% patients at some point during their disease history. In some clinical situations it is difficult to distinguish whether symptoms result from the underlying disease or are a symptom of infection. In these clinical situations, chest computed tomography (CT) can be very useful. We present a patient with GPA localized mainly in the respiratory tract with sudden deterioration of the general state and new abnormalities revealed in the CT of the chest.