Airway Biopsy Results From Patients With Suspected Granulomatosis With Polyangiitis (2005-2015): Clinicopathological Correlation and Proposal of an Algorithm to Improve Diagnosis.

OBJECTIVES: The aim of this study was to review the histologic diagnostic yield of airway biopsies with a suspected granulomatosis with polyangiitis (GPA) diagnosis at a single center devoted to respiratory diseases using previously published criteria. A secondary aim was to apply the algorithm proposed by the European Medicines Agency to determine whether more biopsies were confidently identified as having GPA diagnoses. METHODS: From a total of 132 airway biopsies (2005-2015), 50 were randomly selected for second review by an expert pathologist, and previously published criteria were applied. Thereafter, antineutrophil cytoplasm autoantibody testing results and the European Medicines Agency algorithm were applied. RESULTS: Repeat review and application of the published criteria resulted in an increase from 16 to 25 diagnoses of GPA. This increased to 35 of 50 when antineutrophil cytoplasm autoantibody results and the European Medicines Agency algorithm were applied. Interobserver correlation was 57.5% among pathologists (κ = 0.19), which was likely due to missing clinical information and inadequate tissue samples. Patients with generalized disease were 2.6 times more likely to obtain diagnostic GPA airway biopsy results than those with limited disease (airway only). CONCLUSIONS: An increase in the diagnostic yield of this malady could be attained by following an algorithm that incorporates carefully retrieved clinical, endoscopic, and serologic data, coupled with systematic histopathologic sample review.

Frequency, treatment, evolution, and factors associated with the presence of tracheobronchial stenoses in granulomatosis with polyangiitis. Retrospective analysis of a case series from a single respiratory referral center.

OBJECTIVES: Granulomatosis with polyangiitis-a primary systemic vasculitis-most frequent manifestations are respiratory. Airway disease can present with stenosis, and although subglottic stenosis (SGS) is well described, narrowing distal to the glottis has been more recently the focus of reporting. Our objectives, therefore, are to describe the frequency, characteristics, and treatment of tracheobronchial stenoses (TBS) in granulomatosis with polyangiitis (GPA) at our institution, a national referral center for respiratory diseases. Also, to identify factors associated with TBS development in GPA. METHODS: We undertook a retrospective study of all identified TBS cases (n-29) in whom their demographics, clinical and paraclinical features, and treatment were analyzed with descriptive statistics. Comparisons between those who developed and did not develop TBS (n-79) were established with the χ2 test with Yates correction or two-tailed exact Fisher test for comparisons among groups with or without this complication. RESULTS: Females were predominantly affected by TBS (76%). Most patients had limited GPA (n-20, 69%). TBS appeared at a mean of 29 months after diagnosis of GPA. Main symptoms were dysphonia, stridor, and dyspnea. All TBS patients had tracheal involvement and 12 (41%) additional bronchial stenoses. Other accompanying manifestations by organ/system were rhinosinusal (n-26, 87%), musculoskeletal (n-16, 55%), ocular (n-13, 45%), pulmonary (n-12, 41%), renal (n-8, 27%), mucocutaneous (n-5, 17%), neurological (n-4, 13%). At TBS diagnosis, 17 patients were PR3-ANCA and/or C-ANCA positive, while 9 were MPO-ANCA and/or P-ANCA positive; results on the remaining were either negative or ANCA were not performed at that time. Seventeen patients had simultaneous medical (8 with glucocorticoid therapy, 9 with immunosuppressants) and surgical therapy, while the rest only the latter at the time of TBS diagnosis. Relapses were frequent (one in 18 patients; two in 11, three in 9 and 2 individuals had ≥4 relapses). Factors positively associated with TBS were the presence of general and musculoskeletal symptoms and rhinosinusal disease, while those negatively associated were prednisone oral daily dose >10mgqd and azathioprine intake. The extent of disease, either generalized or limited was not associated with TBS development, nor were ANCA levels. CONCLUSIONS: TBS are serious complications of GPA which can arise at any stage of the disease. Timely diagnosis plus optimal treatment and follow-up remain unmet needs.

Pulmonary Involvement in Systemic Vasculitis.

PURPOSE OF REVIEW: The purpose of this study is to describe the most relevant advances concerning lung involvement in the ANCA-associated vasculitides (excluding eosinophilic granulomatosis with polyangiitis which may have different disease mechanisms). Focus is on pathophysiology, recent important imagenological procedures, treatment, and outcome. RECENT FINDINGS: Emerging information exists on potential newly investigated diagnostic procedures (v.g. transbronchial cryobiopsies), detailed tomographic abnormalities, the potential favorable role of rituximab and the still uncertain one of plasma exchange in the treatment, and the increasing description of interstitial lung disease. Survival is reduced in case of both, diffuse alveolar hemorrhage and diffuse parenchymal disease. There is the need to expand the knowledge concerning better long-term treatment options with specific regimes, and to incorporate other measures regarding integral treatment in patients afflicted with lung involvement these maladies, as the outcome seems adverse in this scenario.

Pachymeningitis in granulomatosis with polyangiitis: case series with earlier onset in younger patients and literature review.

The objective of this study is to describe the characteristics of patients with pachymeningitis (PM) in granulomatosis with polyangiitis (GPA) from Latin America, including three young patients. This is a retrospective case series. Patients were classified according to the ACR criteria, the 2012 Chapel Hill Consensus Conference Nomenclature and the EMA algorithm. Demographic, clinical, serological, and neuroimaging characteristics are described. Thirteen patients (nine females, four males) were identified. Mean age ± SD of PM diagnosis was 35.5 ± 20.4 years (median 48, range 8-71 years). Mean time ± SD between GPA first symptom and PM diagnosis was 59.8 ± 70.1 months (median 48, range 2-252 months). An important difference between children and adults was the median time elapsed between first GPA symptoms and PM diagnosis (range 2-4 months vs 5-252 months, respectively). Chronic headache was present in all, followed by intracranial hypertension (n = 5), single cranial nerve palsy and orbital mass (n = 4), seizures (n = 3), cavernous sinus syndrome and multiple cranial nerve palsies (n = 2), and meningism and cerebellar syndrome (n = 1 each). At time of PM diagnosis, mean BVAS/WG (Birmingham Vasculitis Activity Score for Wegener's granulomatosis) was 4 ± 2.4 and mean VDI of 2 ± 1.6, mostly due to ENT damage. Gadolinium-enhanced brain MRI showed dural thickening in 12 patients and leptomeningeal enhancement in one. All received a combination of glucocorticoids plus immunosuppressants, rituximab being used favourably in one refractory case. Improvement was observed in 12 patients. Chronic headache should lead to suspect PM. PM predominates in localised GPA. Children may present it earlier in the disease course than adults. Treatment is non-standardised and remains difficult.

Nocturnal heart rate variability parameters as potential fibromyalgia biomarker: correlation with symptoms severity.

INTRODUCTION: At present, there is neither a laboratory test nor an imaging technique able to differentiate people with fibromyalgia (FM) from healthy controls. This lack of an objective biomarker has hampered FM recognition and research. Heart rate variability (HRV) analyses provide a quantitative marker of autonomic nervous system activity. Nighttime is a stable period in which most people are resting. Sleep is modulated by autonomic activity. Sleeping problems are prominent in FM. The objectives of this study are: 1) to explore different nocturnal HRV parameters as potential FM biomarkers and 2) to seek correlation between such HRV parameters and diverse FM symptoms. METHODS: We studied 22 women suffering from FM and 22 age-matched controls. All participants filled out several questionnaires related to FM symptoms. All participants used a Holter monitor over 24 hours while undertaking their routine activities during the day and while sleeping at their homes at night. Time-domain HRV parameters analyzed from 0000 to 0600 hours included, among others: mean normal-normal interbeat intervals (mean NN), standard deviation of the NN intervals (SDNN), and standard deviation of the successive NN differences (SDSD). RESULTS: Nocturnal SDNN of less than 114 ms had the greatest predictive value to set apart patients from controls with an odds ratio of 13.6 (95% confidence interval: 3.9 to 47.8). In patients, decreased nighttime HRV markers indicative of sympathetic predominance had significant correlations with several FM symptoms: SDSD was associated with pain intensity (r = -0.65, P = 0.001). SDNN correlated with constipation (r = -0.53, P = 0.001), and mean NN with depression (r = -0.53, P = 0.001). Controls displayed an opposite behavior. For them, increased nighttime SDNN correlated with Fibromyalgia Impact Questionnaire scores (r = 0.69, P = 0.001) and with other FM symptoms. CONCLUSIONS: Nocturnal HRV indices indicative of sympathetic predominance are significantly different in FM women when compared to healthy individuals. In FM patients, these HRV parameters correlated with several symptoms including pain severity. Opposite associations were seen in controls. FM may not be just one end of a continuous spectrum of common symptoms. Nocturnal HRV analyses are potential FM biomarkers.