Unveiling cancer risk in ANCA-associated vasculitis: result from the Turkish Vasculitis Study Group (TRVaS).

To investigate cancer incidence in patients with ANCA-associated vasculitis (AAV), compare it with the age/sex-specific cancer risk of the Turkish population, and explore independent risk factors associated with cancer. This multicenter, incidence case-control study was conducted using the TRVaS registry. AAV patients without cancer history before AAV diagnosis were included. Demographic and AAV-related data of patients with and without an incident cancer were compared. Standardized cancer incidence rates were calculated using age-/sex-specific 2017 Turkish National Cancer Registry data for cancers (excluding non-melanoma skin cancers). Cox regression was performed to find factors related to incident cancers in AAV patients. Of 461 AAV patients (236 [51.2%] male), 19 had incident cancers after 2022.8 patient-years follow-up. Median (IQR) disease duration was 3.4 (5.5) years, and 58 (12.6%) patients died [7 with cancer and one without cancer (log-rank, p = 0.04)]. Cancer-diagnosed patients were older, mostly male, and more likely to have anti-PR3-ANCA positivity. The cumulative cyclophosphamide dose was similar in patients with and without cancer. Overall cancer risk in AAV was 2.1 (SIR) ((1.3-3.2), p = 0.004); lung and head-neck [primary target sites for AAV] cancers were the most common. In Cox regression, male sex and ≥ 60 years of age at AAV diagnosis were associated with increased cancer risk, while receiving rituximab was associated with decreased cancer risk. Cancer risk was 2.1 times higher in AAV patients than the age-/sex-specific cancer risk of the Turkish population population, despite a high rate of rituximab use and lower dose of cyclophosphamide doses. Vigilance in cancer screening for AAV patients covering lung, genitourinary, and head-neck regions, particularly in males and the elderly, is vital.

Clinical Characteristics and Outcomes of Polyarteritis Nodosa: An International Study.

OBJECTIVE: We describe the demographics, clinical features, disease course, and survival of polyarteritis nodosa (PAN) through an international collaboration (GLOBAL-PAN). METHODS: Patients with PAN were recruited between 1990 and 2020 from observational cohorts of nine countries across Europe, Japan, and North America. Eligibility was retrospectively defined using the European Medicines Agency classification algorithm. Patients with PAN related to hepatitis B virus (n = 12) and two monogenic diseases mimicking PAN, deficiency of adenosine deaminase 2 enzyme (n = 16) or familial Mediterranean fever (n = 11), were excluded. Data regarding organ involvement, relapse, disease-related damage, and survival were analyzed. RESULTS: Three hundred fifty-eight patients (female:male ratio 174:184), including those with systemic PAN (sPAN, n = 282) and cutaneous PAN (n = 76), were included. Twenty-five were pediatric onset. Mean ± SD age at diagnosis was 44.3 ± 18.1 years. Constitutional symptoms (71.5%), cutaneous involvement (70.5%), musculoskeletal findings (69.1%), and neurologic features (48.0%) were common manifestations. Among patients with sPAN, gastrointestinal involvement and proteinuria over 400 mg/day were reported in 52.2% and 11.2%, respectively. During a median (interquartile range) 59.6 (99.5) months of follow-up, relapse occurred in 48.5% of patients. One, 5- and 10-year survival rates for sPAN were 97.1%, 94.0%, and 89.0%, respectively. Predictors of death for sPAN included age ≥65 years at diagnosis, serum creatinine at diagnosis >140 µmol/L, gastrointestinal manifestations, and central nervous system (CNS) involvement. CONCLUSION: The spectrum of PAN remains a complex, multifaceted disease. Relapse is common. Age ≥65 years and serum creatinine >140 µmol/L at diagnosis, as well as gastrointestinal and CNS involvement, are independent predictors of death in sPAN.

IgG4-related pachymeningitis-Long term follow up and outcome of six patients.

OBJECTIVE: Our understanding of IgG4-RD and pachymeningitis has grown substantially, but the optimal approach for diagnosis, management, and long-term outcomes is still an area of uncertainty. METHODS: HUVAC is a database for IgG4-RD patients, this database was retrospectively evaluated for pachymeningeal disease. Demographic, clinical, serological, imaging, histopathological data, and treatment details were re-interpreted in patients with pachymeningitis. RESULTS: Among 97 patients with IgG4-RD, 6 (6.2%) had pachymeningitis. None of these patients had extracranial features, and also, in most of the patients, serum IgG4 levels were normal. Tentorium cerebelli and transverse sinus dura were the most commonly involved in the posterior fossa. During 18 months of median follow-up on steroid+-rituximab, none of them relapsed as pachymeningitis. CONCLUSION: Our patients were mainly older males with sole neurological involvement. Non-specific headache was the most common manifestation, and serum IgG4 levels were not useful for diagnosis. Typical radiology and tentorial thickening should suggest IgG4-RD and prompt an early biopsy. Moreover, accompanying hypophysitis could also be a clue. With steroids+ rituximab treatment, no relapse related to meningeal involvement was seen in long-term follow-up.

Drug retention rate and predictive factors of drug survival for secukinumab in radiographic axial spondyloarthritis.

The drug retention rate has been an important indicator for evaluating the treatment tolerance. Unfortunately, our knowledge of the secukinumab retention rate in radiographic axial spondyloarthritis (r-AxSpA) is limited. The objective of this study was to assess the retention rate of secukinumab and evaluate predictive factors of drug survival based on data from a real-life cohort. We retrospectively assessed 147 r-AxSpA patients between May 2018 and January 2020 from the HUR-BIO database. Secukinumab retention rates were analyzed using the Kaplan-Meier method and Cox proportional hazard model was used for predictors factors. The global retention rate of secukinumab was 55% at 12 months. r-AxSpA patients with obesity had a lower frequency of secukinumab discontinuation (29% vs. 50%, p = 0.013) in comparison r-AxSpA patients without obesity. In multivariate analysis, multiple TNFi usage had a higher risk of secukinumab discontinuation [HR 1.99 (1.09-3.62), p = 0.024]; on the other hand, obesity had a lower risk [HR 0.45 (0.27-0.90), p = 0.008]. Except for not using multiple TNFi, this real-life analysis showed for the first time that obesity is not an adverse risk factor for secukinumab drug retention in r-AxSpA. Secukinumab, which is an interleukin-17A inhibitor, could act via a different pathway than tumor necrosis factor inhibitors (TNFi). The identification of predictive factors such as obesity that may affect the individual drug selection may provide more appropriate biologic treatment strategies for r-AxSpA.

Pleuroparenchymal fibroelastosis in systemic sclerosis-associated interstitial lung disease.

BACKGROUND: To explore the frequency and clinical associations of radiologic pleuroparenchymal fibroelastosis (PPFE) in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). METHODS: In this single-center retrospective study, high resolution computed tomography (HRCT) images of 105 patients with SSc-ILD were examined for the presence of PPFE. Demographic, clinical, laboratory, and pulmonary function test (PFT) data of patients with and without PPFE were compared. RESULTS: PPFE was detected in 19 (18.1%) patients ('definite PPFE' in 13 and 'consistent with PPFE' in 6 patients). Patients with PPFE had higher age and longer disease duration than PPFE (-) patients (p < 0.05 for both). Radiologic usual interstitial pneumoniae (UIP) pattern was more frequent (26.3% vs. 4.7%, p = 0.01) and median force vital capacity (FVC) was lower in patients with PPFE (64% vs. 82%, p = 0.005). Spontaneous pneumothorax developed in one patient with PPFE. More deaths occured in PPFE (+) group during follow-up (31% vs. 11%, p = 0.04).

Anxiety levels before biologic initiation and changes with treatment in patients with psoriatic arthritis: HUR-BIO biologic registry results.

OBJECTIVES: Psoriatic arthritis (PsA) is an inflammatory musculoskeletal disease related to several comorbidities. Anxiety is an important comorbidity in PsA and the data is scarce. We aimed to understand the rates before biologic agents and change in anxiety with the treatment. METHODS: PsA patients from the Hacettepe University biologic database (HUR-BIO) were assessed for the high anxiety level (score ≥ 4) using the patient self-reported measure of anxiety on a 0-10 numerical scale, included in the Psoriatic Arthritis Impact of Disease questionnaire (PSAID-12). The rate and scores of anxiety were determined before starting biologic agents, at the first visit within 6 months. Changes in anxiety scores were assessed according to favorable treatment responses, and the correlation was evaluated by Spearman correlation analysis. RESULTS: From 520 patients registered, 147 [mean (SD) age 43.3 (12.4) years, 70.7% female] had anxiety score both at baseline and first visit within 6 months. Both the frequency of high anxiety level and mean (SD) scores decreased at the first visit [63.9% vs. 41.4%, 4.8 (3.4) vs. 3.2 (3.1) respectively, p < 0.001 for both] after a mean (SD) follow-up of 105.7 (22.2) days. There was also a positive correlation between the change in anxiety scores and all parameters tested for treatment response: pain, PGA, BASDAI, HAQ-DI, DAS-28, and also PsAID-12. CONCLUSION: Anxiety is a more frequent problem at biologic initiation than rates observed in the general PsA population. The rates show a decreasing trend and correlates with treatment response but is still high within 6 months under treatment. KEY POINTS: • As high as 65% of patients had a high anxiety levels before the initiation of bDMARDs. • The disease activity control is essential in reducing anxiety; however, rates are still high within 6 months. • Decreased anxiety scores and rates of the high anxiety level are linked to better outcomes.

Isolated spinal cord granulomatous angiitis: a case report and review of the literature.

INTRODUCTION: Isolated spinal cord angiitis (ISCA) is very rare disease. But, it is frequently encountered in the differential diagnosis of atypical spinal cord syndromes. CASE PRESENTATION AND REVIEW OF THE LITERATURE: We present a 31-year-old male who presented with progressive paraparesis, and diagnosed with pathologically confirmed ISCA. Longitudinal cystic transverse myelitis was documented in spinal MRI. He responded well to cyclophosphamide and steroid combination, and no relapse was noted during the 4-year follow-up. A standard systematic analysis of the germane literature disclosed 15 more ISCA cases. In total 16 cases (mean age: 46.5, 10 males), ISCA was diagnosed with pathological evaluation in all (Biopsy in 11, Autopsy in 5). MRI lesion is characterized by usually multisegmental longitudinal and sometimes cystic expansile lesions. In seven cases, it was described as "(pseudo)tumoral" by the authors. Albeit absence of elevation of CSF protein/WBC or "compatible" spinal MRI lesion may aid to exclude ISCA to some extent, pathological confirmation is currently necessary for the diagnosis. In 11 cases, ISCA was treated similar to primary supratentorial vasculitis. Mortality rate is 31%. DISCUSSION: ISCA diagnosis, a typical example of which we have presented here, can only be established by tissue examination. However, noninvasive diagnostic criteria are critically needed. Our data suggest that this can only be possible with multinational multicenter prospective registry.

The clinical features and treatment of eosinophilic granulomatosis with polyangiitis (EGPA) in Turkey: one or two distinct diseases?

Eosinophilic granulomatosis with polyangiitis (EGPA) is defined the disease as having two subgroups, ANCA (+) and ANCA (-). We aimed to compare EGPA subgroups in terms of clinical features, outcomes, and treatments. A multidisciplinary team was established under our vasculitis centre since October 2014. Totally 50 EGPA patients were enrolled. Clinical features, treatments, and outcomes (FFS, VDI, relapse) were reviewed. For relapse-free survival analysis, time to first relapse was compared according to ANCA phenotype by Kaplan-Meier survival analysis and log-rank test. 17 (34%) patients were in ANCA (+), 33 (66%) patients were in ANCA (-) group. ANCA (-) patients were significantly younger at the diagnosis time (37.9 ± 14.3 vs 53.8 ± 16.3; p = 0.001) and had more nasal polyposis (45.5% vs 11.8%; p = 0.017). ANCA (+) patients had higher BVAS (17[13] vs 9[4]; p = 0.002), renal involvement and peripheral neuropathy were more common in this group, while cardiac involvement was seen only in ANCA (-) group (n = 3). Biological agents (mepolizumab or rituximab) were prescribed to nine patients in ANCA (-) and two patients in ANCA (+) group. The median duration of follow-up was 47 (IQR 69.9) months. ~ 40% of patients had at least one relapse, but relapse-free survival rate was similar between the groups. However, the predictor of first relapse was elevated Ig E level [OR (95% CI): 6.5 (1.09-38.63) p = 0.04]. Consequently, both clinical features, disease activity, and treatments appear to be significantly different between EGPA subgroups. The relapse risk was similar although clinical features and treatment strategies were different. Also, elevated Ig E levels may be a precursor for the relapse.

A case report of intracranial hypertension and aseptic meningitis: anti-tumor necrosis factor associated or juvenile idiopathic arthritis related.

BACKGROUND: The adverse effects of tumor necrosis factor alpha inhibitors (TNFi) are well characterized but rare adverse events are increasing day by day. CASE: We presented an 18-year-old girl with rheumatoid factor positive polyarticular juvenile idiopathic arthritis (JIA) who developed fever, headache, and nausea after the second dose of adalimumab. In addition to her suspicious complaints for meningitis, she had bilateral papilledema and partial abducens nerve palsy. Leptomeningeal contrast enhancement was noted in magnetic resonance imaging (MRI) of the brain. Brain MRI venography was normal. The cerebrospinal fluid (CSF) opening pressure was high but CSF analysis was normal. She was diagnosed with non-infectious subacute meningitis. Since brain biopsy was not performed, no definite distinction could be made between TNFi related aseptic meningitis or cerebral involvement of JIA. Due to the onset of neurological complaints after initiation of adalimumab treatment and rare cerebral involvement in JIA, the drug-associated aseptic meningitis was likely to be responsible in our patient. Adalimumab was discontinued and methylprednisolone followed by methotrexate treatment were initiated. Her symptoms resolved and control brain MRI was normal. CONCLUSION: Pediatric rheumatologists should be aware of this potentially severe side effect of anti-TNF treatment.

Cancer incidence in Behçet's disease.

BACKGROUND: Previous studies demonstrated an increased cancer risk in autoimmune diseases. Behçet's disease (BD) was also reported to be associated with an increased risk of cancer, although the data is limited. AIMS: In this study, we aimed to assess cancer incidence in a large cohort of BD patients and to compare with the data of the same age and gender groups. METHODS: The study cohort consisted of BD patients of > 18 years of age who were prospectively recorded in the Hacettepe University Vasculitis Center. Data on any cancer was collected from the patient files. Cancer incidence was compared with age- and gender-specific cancer incidence rates of the normal population retrieved from the 2014 Turkish National Cancer Registry (TNCR) data using standardized incidence rates (SIR). RESULTS: Totally, 451 adult cases with BD were included. The median age of the cohort was 43 (20-75), and 52.5% of the patients were males. Eleven cancer cases were observed during a median of 124 months follow-up. Behçet's disease was associated with an increase in cancer risk compared with expected counts in the corresponding age and sex group (SIR 2.84, 95% CI 1.50-4.94, p < 0.001). Patients with papulopustular lesions had a trend toward a decreased risk of cancer (p = 0.060), and patients using azathioprine had a significantly decreased cancer risk (p = 0.031). CONCLUSION: This study revealed BD patients had approximately three times increased cancer risk compared with corresponding age and sex groups. Besides the routine care, increased attention for cancer surveillance is required in the follow-up of BD patients.

Management of Behcet's syndrome.

Behcet's syndrome (BS) is a variable vessel vasculitis with heterogeneous clinical features. Skin, mucosa and joint involvement can cause impairment of quality of life but do not cause permanent damage whereas untreated eye, vascular, nervous system and gastrointestinal system involvement can cause serious damage and even death. Management of BS as a multidisciplinary team enables a faster and more accurate diagnosis and well-integrated treatment strategies. Corticosteroids are the mainstay of therapy. Colchicine, AZA, ciclosporin-A, cyclophosphamide, IFN alpha, and tumour necrosis factor alpha inhibitors are other agents used as induction and/or maintenance therapy. Although biologic agents have been increasingly used, there are still unmet needs. Head-to-head comparison studies of some therapeutic options (e.g. TNF inhibitors vs IFN alpha in uveitis) are required. Novel therapeutic agents in the pipeline could change the standard of care for BS in the future.

Spinal and cerebral hematoma in systemic lupus erythematosus and antiphospholipid syndrome: is drug interaction the culprit?

OBJECTIVES: Thrombotic events are common in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Warfarin is the most commonly used anticoagulant drug for thrombosis treatment, but it is can interact with many drugs, foods, or medicinal herbs. Herein, we presented a case with SLE and APS who was complicated by spinal and cerebral hematoma as a result of warfarin interaction. CASE PRESENTATION: Spinal subdural hematoma and frontal intraparenchymal hematoma were occurred in our patient, who was in remission for 2 years with rituximab, hydroxychloroquine and warfarin. We learned that she had been using some herbal products (shepherd's purse and horsetail) and phenyramidol for a few days. Spinal and cerebral hematomas caused by the interaction of phenyramidol and warfarin were treated with fresh frozen plasma and vitamin K without the need for surgery. CONCLUSIONS: The drug interactions with warfarin can cause fatal hemorrhagic or thrombotic events. Especially, the patients with SLE and/or APS using warfarin should be warned not to use different medications or herbal agents.

Do ANCA-associated vasculitides and IgG4-related disease really overlap or not?

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and immunoglobulin G4-related disease (IgG4-RD) have some common features. The co-occurrence/concurrence of AAV and IgG4-RD was recently published by the collaborative European Vasculitis Study Group. First, we aimed to investigate ANCA positivity of our IgG4-RD cohort. Second, a literature review of co-occurrence/concurrence of AAV and IgG4-RD was done. METHODS: Data of 62 patients with IgG4-RD in Hacettepe Vasculitis Center Database were used. Patient dataset was designed to include demographic data, clinical characteristics, imaging and IgG4-RD, AAV and ANCA test results. At the next step, we performed a systematic literature review in PUBMED database covering the time period from 1976 until April 2018. Relevant publications were searched using these MeSH terms ''IgG4-related disease and Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis'', "IgG4-related disease and Eosinophilic Granulomatosis with Polyangiitis", "IgG4-related disease and Microscopic Polyangiitis" and "IgG4-related disease and Granulomatosis with Polyangiitis". RESULTS: Three (10.3%) of 29 patients had low titer ANCA positivity. These three patients didn't have any findings of vasculitis and no granuloma was seen in biopsy. In the literature review, we found 17 cases had features of both IgG4-RD and AAV. These cases were re-evaluated according to the Comprehensive Diagnostic Criteria for IgG4-RD. ANCA were positive in 15 of 17 patients (88%). CONCLUSION: None of our IgG4-RD patients overlapped with AAV. Only two patients in the literature review seemed to be fully compatible with both diseases. Even though AAV and IgG4-RD share similar clinical features, we think this might be a co-occurrence instead of a histopathological link.

Rare occupational cause of nasal septum perforation: Nickel exposure.

Many etiologies are held accountable for nasal septum perforations. Topical nasal drug usage, previous surgeries, trauma, nose picking, squamous cell carcinoma, some rheumatological disorders such as granulomatosis with polyangiitis (Wegener granulomatosis), some infectious diseases such as syphilis and leprosy are among the causes of the perforations. Occupational heavy metal exposures by inhalation rarely may also cause nasal septum perforation. Here, we present a 29-year-old patient without any known diseases, who is a worker at a metallic coating and nickel-plating factory, referred for investigation of his nasal cartilage septum perforation from an otorhinolaryngology clinic. The patient questioning, physical examination and laboratory assessment about rheumatic and infectious diseases were negative. There was a metallic smell in the breath during the physical examination. The analysis showed serum nickel level at 31 µg/l and urine nickel at 18 µg/l (84.11 µg/g creatinine). Other possible serum and urine heavy metal levels were within normal ranges. Nickel exposure is usually together with other heavy metals (chromium or cadmium), it is rarely alone. Nickel ingested by inhalation usually leads to respiratory problems such as reduced olfactory acuity, ulcers, septum perforation or tumors of the nasal sinuses. This case demonstrates the importance of occupational anamnesis and awareness of diagnosis. Int J Occup Med Environ Health 2017;30(6):963-967.