IntroductionAt 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.MethodsWe 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).ResultsNocturnal 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.ConclusionsNocturnal 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.

We read with interest the article by Fernández-Casares et al. [1]. Pulmonary fibrosis (PF) seems to be a growing complication arising during the long-term evolution of microscopic polyangiitis (MPA). It seems, though, as when compared to idiopathic pulmonary fibrosis, it holds still a better prognosis than the latter [2].We want to share our observations regarding survival and differences in patients with MPA who developed PF or not. As in the case of the above-cited report, our patients attend a respiratory centre. Since November 2013 and until December 2014, 40 patients (mean age 54.2 years) have been diagnosed with MPA (according to the 2012 Chapel Hill Nomenclature Consensus) [3] at our institution. Ninety percent were MPO-ANCA, 5 % PR3-ANCA and 2.5 % double positive by indirect immunofluorescence. At the time of last follow-up since first symptoms of disease (median 43 months, range 11-213), 17 (42.5 %, nine males and eight females) have developed PF (two were histologically proven, and the rest was clinically and tomographically compatible with usual interstitial pneumonia [4]), with 14 developing PF prior to other MPA manifestations. Main clinical differences were as follows: gender (18 females without PF and 8 with PF; p=0.04), a higher frequency of myalgias (9 vs 3; p=0.008), nasal crusting and peripheral neuropathy (3 vs 0 for both findings; p=0.02), a lower frequency of diffuse alveolar haemorrhage (6 vs 15; p= 0.04), acute respiratory failure (1 vs 8; p=0.02), haematuria (6 vs 13; p=0.003) and lymphopaenia (0 vs 5; p=0.01) in those with PF. The latter also had higher Hb at presentation (mean 12.1 vs 10.6 g/dL; p=0.047), lower ESR (mean 18.8 vs 30.8; p=0.02) and higher damage as measured by the Vasculitis Damage Index [5] (mean 4.6 vs 2.6; p=0.008). At diagnosis, activity (BVAS score) [6] did not differ.By means of Kaplan-Meier analysis, we found that survival is decreased in those who develop PF by almost half. As shown in the figure, considering either the time of first MPA symptom (Fig. 1a) or the time from diagnostic confirmation (Fig. 1b), those with PF have shorter life expectancy than those without. Median survival of the whole group was 98 months, 104 for those with PF and 212 for those without. There were nine deaths, seven with PF and two without PF.These observations are in accordance with previous reports from different parts of the world, including the recent one from Latin America [1,7,8], in which it has also been observed that an important percentage of patients may present with PF before other disease characteristics appear [7]. The influence of ethnics on such outcome seems minimal, although a larger number of patients and longer follow-up is needed to conclusively state this. It is interesting that those without PF were predominantly females. Gender was independent from others not found to be distinct (laboural, tobaccoism) which may predispose males to develop PF more frequently. In trying to establish factors leading to MPA development in PF patients, eosinophils in BAL and low att...

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.

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