Co-existence of ANCA-associated vasculitides with immune-mediated diseases: a single-center observational study.

BACKGROUND: Antineutrophil cytoplasmic antibody-associated vasculitides (AAV) is a group of systemic necrotizing small vessel autoimmune diseases, with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) being the two most common. The co-existence of AAV with different immune-mediated diseases (autoimmune disesases - AID) might affect the clinical presentation of the primary disease. The purpose of the study was to assess the co-existence of AAV with AID and to investigate whether it affects the characteristics and the course of AAV. METHODS: A retrospective single-center study was performed to identify patients with a diagnosis of MPA or GPA and concomitant AID, and to investigate their clinical features and characteristics. The group consisted of consecutive unselected AAV patients treated at a large university-based hospital, since 1988 with follow-up until 2022. RESULTS: Among 284 patients diagnosed either with GPA (232) or MPA (52), 40 (14,1%) had co-existing AIDs. The most frequent were: Hashimoto thyroiditis (16 cases), rheumatoid arthritis (8 cases), followed by psoriasis (6 cases), pernicious anemia (3 cases), and alopecia (3 cases). Patients with autoimmune comorbidities had a significantly longer time between the onset of symptoms and the diagnosis (26 vs. 11 months, p < 0.001). Laryngeal involvement (20.0% vs. 9.0%, p = 0,05), peripheral nervous system disorders (35.0% vs. 13.9%, p < 0.001), and neoplasms (20.0% vs. 8.6%, p = 0,044) were more common in patients with AID comorbidities, compared to subjects without AID. In contrast, renal involvement (45.0% vs. 70.9%, p = 0.001) and nodular lung lesions (27.5% vs. 47.5%, p = 0.044) were significantly less frequent in patients with co-morbidities. Following EUVAS criteria, patients with autoimmune co-morbidities had a generalized form of the disease without organ involvement (52.5% vs. 27.2%, p = 0.007), while the others had a higher percentage of generalized form with organ involvement (38.3% vs. 20.0%, p = 0.007). CONCLUSIONS: The coexistence of AAV with different autoimmune diseases is not common, but it might affect the clinical course of the disease. Polyautoimmunity prolonged the time to diagnosis, but the AAV course seemed to be milder. Particular attention should be paid to the increased risk of cancer in these patients. It also seems reasonable that AAV patients should receive a serological screening to exclude the development of overlapping diseases.

Rat bite fever mimicking ANCA-associated vasculitis.

Rat bite fever (RBF) is a rare infectious zoonotic disease caused by two bacterial species: the Gram-negative rod Streptobacillus moniliformis and the Gram-negative coiled rod Spirillum minus. The association between RBF and skin vasculitis and arthritis has been observed. The aim of this paper was to present a case of rat-bite fever with symptoms of skin vasculitis and arthritis, associated with high titers of ANCA antibodies and anti-endothelial cell antibodies suggestive of primary vasculitis. The patient was successfully treated with antibiotics and non-steroidal anti-inflammatory drugs, leading to significant improvement. Based on the presented case, we discuss the differential diagnosis of the signs and the role of infection in the induction of ANCA antibodies. We reviewed the English language literature for cases of RBF presenting with symptoms of vasculitis and/or antibody presence. A literature review was performed in PubMed and Google using the keywords "rat bite fever" AND "vasculitis", "systemic vasculitis", "ANCA", "antiendothelial antibodies". No cases of rat-bite fever with the presence of ANCA antibodies or AECA antibodies in its course have been described thus far. Rat bite fever is a rare disease with nonspecific symptoms. In its course, general weakness, intermittent fever, leukocytoclastic vasculitis, and arthritis are reported. To our knowledge, this is the first reported case of ANCA positivity associated with RBF.

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.

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.

Self-limiting COVID-19-associated Kikuchi-Fujimoto disease with heart involvement: case-based review.

BACKGROUND: The association between COVID-19 infection and the development of autoimmune diseases is currently unknown, but there are already reports presenting induction of different autoantibodies by SARS-CoV-2 infection. Kikuchi-Fuimoto disease (KFD) as a form of histiocytic necrotizing lymphadenitis of unknown origin. OBJECTIVE: Here we present a rare case of KFD with heart involvement after COVID-19 infection. To our best knowledge only a few cases of COVID-19-associated KFD were published so far. Based on presented case, we summarize the clinical course of KFD and its association with autoimmune diseases, as well we discuss the potential causes of perimyocarditis in this case. METHODS: We reviewed the literature regarding cases of "Kikuchi-Fujimoto disease (KFD)" and "COVID-19" and then "KFD" and "heart" or "myocarditis" by searching medical journal databases written in English in PubMed and Google Scholar. RESULTS: Only two cases of KFD after COVID infection have been described so far. CONCLUSION: SARS-CoV-2 infection can also be a new, potential causative agent of developing KFD.

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.

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.

Peripheral neuropathy and health-related quality of life in patients with primary Sjögren's syndrome: a preliminary report.

Sjögren's syndrome (SS) is a chronic autoimmune disease with a wide spectrum of possible organ involvement. Peripheral (PNS) and central nervous system (CNS)-related symptoms may occur in the course of the disease. The aim of this study was to compare the health-related quality of life (HR-QOL) in SS patients with and without peripheral neuropathy. The study involved 50 patients with primary Sjögren's syndrome (pSS). All patients underwent neurological clinical examination followed by nerve conduction studies (NCS) and rheumatological examination. Thirty-six-item Short Form Health Survey (SF-36) was used for evaluating HR-QOL. To assess pSS activity, the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) and EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) were used. For the assessment of clinical disability due to peripheral neuropathy, the Overall Disability Sum Score scale (ODSS) was used. Additional evaluation of pain was performed with the use of the Visual Analogue Scale (VAS) and a semistructured interview. Twenty-three (46%) patients were diagnosed with peripheral neuropathy. The most common PNS manifestation was sensorimotor neuropathy (47%). Neurological symptoms preceded the diagnosis of pSS in eight patients. The following domains of the SF-36 form were significantly lower scored by patients with peripheral nervous system involvement: role-physical [0 (0-100) vs. 75 (0-100)], role-emotional [67 (0-100) vs. 100 (0-100)], vitality [40 (10-70) vs. 50 (20-75)], bodily pain [45 (10-75) vs. 55 (0-100)], and general health [20 (5-50) vs. 30 (0-50)] (p ≤ 0.05). Our study showed that peripheral neuropathy was a common organ-specific complication in SS patients. In pSS patients, coexisting neurological involvement with symptoms such as pain and physical disability may be responsible for diminished HR-QOL.

Rheumatoid arthritis with pachymeningitis - a case presentation and review of the literature.

Rheumatoid meningitis (RM) is a rare central nervous system (CNS) manifestation of rheumatoid arthritis (RA) with a wide spectrum of symptoms. We present a review of the literature with a rare illustrative case of a 61-year-old man with a history of seropositive rheumatoid arthritis (RA) who presented headaches, stroke-like symptoms and seizures. MRI revealed the leptomeningeal enhancement in the right hemisphere. As cerebromeningeal fluid showed increased level of protein and was positive for Candida mannan, the initial clinical diagnosis was fungal meningitis. Despite the antifungal treatment the patient's clinical condition did not improve. Detailed laboratory, radiologic and histopathological diagnostics enabled the diagnosis of RM. In conclusion is worth to highlight that presentation of RM is variable and complex, diagnosing it is a big dilemma which is why it must be considered in the differential in a patient with long-standing seropositive RA.

The clinical phenotype associated with antisynthetase autoantibodies.

OBJECTIVES: Specific systemic autoimmune syndrome characterized by inflammatory myopathy, arthritis or arthralgias, interstitial lung disease (ILD), fever, Raynaud's phenomenon, and mechanic's hands is called antisynthetase syndrome (AS). The aim of this study was to assess the clinical spectrum associated with presence of aminoacyl-transfer RNA synthetase autoantibodies (ASA). MATERIAL AND METHODS: A total of 305 patients with presence of myositis-specific autoantibodies were identified in the database of immunological tests performed in the Clinical Immunology and Transplantology Unit, Medical University of Gdansk between January 2011 and March 2016. In 110 patients (36%) ASA were detected. The detailed analysis included 50 patients with ASA for whom full clinical data were available. RESULTS: The incidence of specific ASA in the analyzed group was: Jo-1 46% (23 patients), PL-12 32% (16 patients), PL-7 16% (8 patients), OJ 12% (6 patients), EJ 6% (3 patients). In 10% (5 patients) there was coexistence of at least one ASA, and in another 5 patients there was coexistence of ASA with other antibodies specific for myositis (MSA). In the analyzed group of patients 11 (22%) satisfied the Bohan and Peter criteria for dermatomyositis, 1 for polymyositis. In 5 patients (10%) based on clinical presentation and ASA presence the AS was recognized. Another 3 patients met the criteria of the overlap syndrome polymyositis respectively with systemic lupus, rheumatoid arthritis, and scleroderma. In 5 patients undifferentiated connective tissue disease was diagnosed, and 14 consecutive patients were diagnosed with other connective tissue diseases, while 12 patients did not receive a definitive diagnosis. CONCLUSIONS: The clinical presentation of patients with the presence of ASA is varied. Their presence indicates not only idiopathic inflammatory myopathies, but also non-specifically other disease entities. These patients require observation for the development of idiopathic inflammatory myopathy, and ILD.

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.

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.

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.

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.