European guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology - Part I.

This guideline on mucous membrane pemphigoid (MMP) has been elaborated by the Task Force for Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology (EADV) with a contribution of physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline encompassing a systematic review of the literature until June 2019 in the MEDLINE and EMBASE databases. This first part covers methodology, the clinical definition of MMP, epidemiology, MMP subtypes, immunopathological characteristics, disease assessment and outcome scores. MMP describes a group of autoimmune skin and mucous membrane blistering diseases, characterized by a chronic course and by predominant involvement of the mucous membranes, such as the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal and oesophageal mucosa. MMP patients may present with mono- or multisite involvement. Patients' autoantibodies have been shown to be predominantly directed against BP180 (also called BPAG2, type XVII collagen), BP230, laminin 332 and type VII collagen, components of junctional adhesion complexes promoting epithelial stromal attachment in stratified epithelia. Various disease assessment scores are available, including the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), the Autoimmune Bullous Skin disorder Intensity Score (ABSIS), the 'Cicatrising Conjunctivitis Assessment Tool' and the Oral Disease Severity Score (ODSS). Patient-reported outcome measurements (PROMs), including DLQI, ABQOL and TABQOL, can be used for assessment of quality of life to evaluate the effectiveness of therapeutic interventions and monitor disease course.

European Guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology - Part II.

This guideline has been initiated by the task force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology, including physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline that systematically reviewed the literature on mucous membrane pemphigoid (MMP) in the MEDLINE and EMBASE databases until June 2019, with no limitations on language. While the first part of this guideline addressed methodology, as well as epidemiology, terminology, aetiology, clinical presentation and outcome measures in MMP, the second part presents the diagnostics and management of MMP. MMP should be suspected in cases with predominant mucosal lesions. Direct immunofluorescence microscopy to detect tissue-bound IgG, IgA and/or complement C3, combined with serological testing for circulating autoantibodies are recommended. In most patients, serum autoantibodies are present only in low levels and in variable proportions, depending on the clinical sites involved. Circulating autoantibodies are determined by indirect IF assays using tissue substrates, or ELISA using different recombinant forms of the target antigens or immunoblotting using different substrates. The major target antigen in MMP is type XVII collagen (BP180), although in 10-25% of patients laminin 332 is recognized. In 25-30% of MMP patients with anti-laminin 332 reactivity, malignancies have been associated. As first-line treatment of mild/moderate MMP, dapsone, methotrexate or tetracyclines and/or topical corticosteroids are recommended. For severe MMP, dapsone and oral or intravenous cyclophosphamide and/or oral corticosteroids are recommended as first-line regimens. Additional recommendations are given, tailored to treatment of single-site MMP such as oral, ocular, laryngeal, oesophageal and genital MMP, as well as the diagnosis of ocular MMP. Treatment recommendations are limited by the complete lack of high-quality randomized controlled trials.

Patient-reported outcomes in primary Sjogren's syndrome: comparison of the long and short versions of the Profile of Fatigue and Discomfort--Sicca Symptoms Inventory.

OBJECTIVES: The long-form 64-item Profile of Fatigue and Discomfort--Sicca Symptoms Inventory (PROFAD-SSI) questionnaire was developed as a patient-reported assessment tool for use in primary SS (PSS) and other rheumatic disorders. In this study, we assess whether the (shorter and more practical) 19-item PROFAD-SSI-SF (short form) gives similar results and whether a still briefer version using visual analogue scales (VASs) is feasible. METHODS: Questionnaire surveys comprising the long and short versions of the PROFAD-SSI were mailed to 43 patients with PSS and 50 patients with RA, who were asked to complete these contemporaneously as well as repeating the process 1 month later. PSS patients also completed a series of VASs comprising fatigue and sicca domains of the SSI. RESULTS: Surveys were returned from 35 PSS patients and 35 RA patients. All domains of the long- and short-form PROFAD-SSI showed strong correlations (Spearman rho between 0.779 and 0.996, P < 0.01). Factor analysis generally confirmed the previously validated domain structure with Cronbach's alpha = 0.99. The PROFAD-SF somatic fatigue domain correlated more strongly with a fatigue VAS than did the mental fatigue domain. The SSI-SF domain scores correlated with equivalent VAS scores. CONCLUSION: The long- and short-form PROFAD-SSI questionnaires correlate closely suggesting that the PROFAD-SF is valid as an outcome tool. Preliminary data also suggest that an even briefer form with compression of the domains into single VAS is also feasible.

The Sjögren's Syndrome Damage Index--a damage index for use in clinical trials and observational studies in primary Sjögren's syndrome.

OBJECTIVE: To validate a tool for assessment of accumulated damage in patients with Primary SS (PSS). METHODS: Of the total 114 patients fulfilling American-European Consensus Group (AECG) criteria for PSS 104 were included in the study and assessed by rheumatologists at T (time) = 0 months and T = 12 months. On each occasion, damage and activity data, and autoantibody status were collected. SF-36 and Profile of Fatigue and Discomfort-Sicca Symptoms Inventory (PROFAD-SSI) questionnaires were completed. Cross-sectional analysis of this data was subject to a process of expert validation by 11 ophthalmologists, 14 oral medicine specialists and 8 rheumatologists. Items were removed from the index if >or= 50% of respondents recommended exclusion. Statistical validation was performed on remaining items. Spearman's rank analysis was used to investigate associations between damage scores and other disease status measures and Wilcoxon matched-pair analysis to assess sensitivity to change in the damage score. RESULTS: Based on the expert validation, a 29-item damage score was agreed incorporating ocular, oral and systemic domains. Total damage score correlated with disease duration at study entry (r = 0.436; P < 0.001), physical function as measured by SF-36 (r = 0.250, T = 0 months; r = 0.261 T = 12 months) and activity as measured by the Sjögren's Systemic Clinical Activity Index (r = 0.213, T = 0 months; r = 0.215, T =12 months). Ocular damage score correlated with the 'eye dry' domain of PROFAD-SSI (r = 0.228, T = 0 months; r = 0.365, T = 12 months). Other associations not present on both assessments were considered clinically insignificant. On Wilcoxon analysis, the index was sensitive to change over 12 months (z = -3.262; P < 0.01). CONCLUSION: This study begins validation of a tool for collection of longitudinal damage data in PSS. We recommend further trial in both the experimental and clinical environment.

ERP components associated with an indirect emotional stop signal task in healthy and depressed participants.

Recent research has provided evidence to suggest that emotional stimuli may interfere with response inhibition, due to automatic capture of attention. Whilst previous studies have provided data regarding changes to event-related potentials (ERPs) in emotional Go/NoGo tasks, few studies to-date have utilized an emotional stop signal task (SST). Thirty-five participants were included in the study; 21 healthy controls and 14 depressed. An indirect emotional SST was employed, which consisted of the presentation of neutral, negative or positive visual images. The primary two-choice reaction time task required responding to frame colour (blue or green), whilst in 33% of trials an auditory stop signal was presented, with stop signal delay adjusted according to an adaptive tracking procedure. ERPs associated with both the primary visual task and the auditory SST were analysed using temporal principle components analysis (tPCA). In the primary task, reaction times were found to be slower for negative compared to neutral images. Stop signal reaction time (SSRT) was not found to be affected by image category or depression status. However, the NoGo-N2 component was found to be reduced for positive images, whilst the NoGo-P3 component was reduced for both positive and negative images in comparison to neutral images in the stop signal task. This effect was found to be enhanced for the depressed participants, indicating that inhibitory processing in the presence of positive stimuli may be inhibited to a greater extent in depressed individuals than in healthy controls. These findings provide further evidence for the ability of emotional valence and major depressive disorder to influence inhibitory processing.

Unregistered visual impairment: is registration a failing system?

BACKGROUND/AIMS: To assess the current level of under-registration of blindness and partial sight among patients attending a large teaching hospital, and to determine any risk factors for under-registration. METHODS: Medical records of all patients attending general ophthalmology outpatient clinics over a 3 month period were included in a retrospective analysis of registration rates; questionnaire survey assessing the level of knowledge of registration practices among 35 ophthalmologists working in the West Midlands. RESULTS: 146/2161 (7%) patients were eligible for blind or partial sight registration, or were in possession of a completed BD8 form. Of these 146 patients, 65 (45%) were unregistered with 18 fulfilling the criteria for blind and 47 for partially sight. In addition, 32/81 (40%) registered patients appeared to have been inappropriately registered. Partially sighted patients were more likely to be unregistered than blind patients (OR 2.31, 95% CI 1.15 to 4.63, p = 0187), and patients from ethnic minorities were more than three times more likely to be unregistered than white patients (OR 3.23, 95% CI 1.56 to 6.65, p = 0.0015). A patient with a treatable condition was more likely to be unregistered than a patient with an untreatable condition (OR 4.87, 95% CI 2.10 to 11.33, p = 0.0002). The overall level of knowledge of registration practices among doctors was found to be low and there was no indication of increasing knowledge with increasing experience. CONCLUSIONS: There has been little improvement in registration rates of visually impaired patients over the past decade. Ophthalmologists lack the necessary knowledge to cater for visually impaired patients' needs.

Age-related changes in quantitative EEG in attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) in children and adolescents is characterized by excessive restlessness and an extremely poor concentration span, resulting in impulsive and disruptive behavior. Clinical observation of ADHD in adults suggests that the hyperactivity component is diminished although the impulsive type behaviors remain apparent. EEG studies of children and adolescents with ADHD have reported significantly higher levels of low frequency activity (predominantly theta) and lower levels of beta activity than normal controls. METHODS: We examined the relationship between the age-related changes reported in clinical observation and changes in EEG activity occurring in a group of ADHD patients ranging in age from 6 to 42 years. Quantitative EEGs were obtained from the midline sites of 25 children, 25 adolescents and 25 adults diagnosed with ADHD, and compared with those of age matched normal controls. RESULTS: Theta activity was elevated in the ADHD groups across all age groups compared with the normal controls. The extent of the reduction in relative beta activity in the ADHD groups compared to normal controls decreased with increasing age. CONCLUSIONS: Given that the hyperactivity component in ADHD reduces with age while the impulsivity component remains, these data, in ADHD, suggest that decreased beta activity may be linked to hyperactivity and increased theta activity to impulsivity.

Eye movements reflect impaired face processing in patients with schizophrenia.

BACKGROUND: Impaired processing of faces in patients with schizophrenia may underlie aspects of disturbance in their social interaction. This study examined patterns of eye fixation in subjects with schizophrenia and non-psychiatric controls, while processing a high resolution picture of a neutral face and a nonbiological complex geometric stimulus. METHODS: Ten-second sequences of eye movement were recorded video-oculographically (50 samples/sec) while subjects were "free-viewing" the stimuli. An essential element of the study was customized software that ensured stimulus presentation on a video display only after subjects were fixated upon a centre-screen cue, so that all subjects began stimulus processing from the same point. RESULTS: Compared with the control group, subjects with schizophrenia exhibited reduced scanpath lengths and a tendency toward fewer fixations for the face stimulus. They also showed an initial relative right spatial hemineglect (for the first voluntary fixation) when viewing the Rey figure, but not when viewing the face stimulus. Overall, there were no significant differences between the schizophrenia and control groups in the lateral distribution of subsequent fixations for either stimulus. CONCLUSIONS: Disturbed spatial and temporal patterns of eye movement in some people with schizophrenia may reflect sub-optimal processing of face stimuli, that may predispose these individuals to dysfunctional interpretation of facial communication cues.

Nasal bilevel positive airway pressure therapy in children with a sleep-related breathing disorder and attention-deficit hyperactivity disorder: effects on electrophysiological measures of brain function.

OBJECTIVE: To examine the effect of nasal bilevel positive airway pressure (BiPAP) treatment for concurrent sleep-related breathing disorders (SRBDs) and attention-deficit hyperactivity disorder (ADHD) on electrophysiological measures of spontaneous brain activity and auditory stimulus processing. METHODS: Nineteen children diagnosed with both SRBD and ADHD participated. Electroencephalogram (EEG) activity was recorded during a resting period and an auditory oddball task before beginning BiPAP treatment, after 6 months on treatment, and after a subsequent 1 week non-treatment period. Treatment effects on EEG and event-related potentials (ERPs) to target stimuli were examined via topographic analysis. RESULTS: Thirteen of the initial 19 children completed 6 months of BiPAP therapy, with six lost mainly due to compliance problems. Children on BiPAP therapy showed a significant decrease in slow-wave (delta and theta) and an increase in fast wave (beta) EEG activity. The P3 component of the ERP showed treatment effects in amplitude and latency. CONCLUSIONS: The electrophysiological data suggest that SRBDs may contribute to ADHD symptomatology. Treatment of SRBD with BiPAP therapy in children with concurrent ADHD can lead to significant changes, in the direction of normalization, of the typical electrophysiological features of ADHD.

A review of psychophysiology in early onset psychosis.

Research on psychophysiological functioning in early onset psychosis is reviewed within the context of etiological formulations stressing perceptual and selective attention abnormalities. Electroencephalographic (EEG) measures, including resting EEG level, alpha blocking, average evoked response, and contingent negative variation, have received most attention in the literature; cardiovascular and electrodermal indices have not been so extensively explored in this group of children. While the nature of differential reactivity in early onset psychosis has not been thoroughly investigated, limited evidence suggests that the central behavioral anomalies associated with the condition may result from abnormal neurophysiological reactivity to sensory stimulation. Further studies of the psychophysiological functioning of these children should yield data useful in the clarification of etiology.

EOG correction: comparing different calibration methods, and determining the number of epochs required in a calibration average.

OBJECTIVE: A form of EOG correction called the 'aligned-artifact average' (AAA) method has been advanced by the authors. In contrast to many previous methods, this used a correction coefficient (B), based on an average of eye movements rather than raw data, to remove eye movement related contamination from the EEG. The first part of this study was aimed at determining whether a variation of this procedure that is more easily implemented would produce a similar correction. The second part was designed to determine the number of epochs needed in an average to correct adequately. METHODS: Subjects performed a series of eye movement tasks whilst EEG and EOG data were recorded. Data were manipulated according to either the AAA or an alternate new ERP method (NERP) and the resultant Bs were compared in part A. In part B, averages were created from varying numbers of epochs, and the resultant r(2)-values were compared. RESULTS: The AAA and NERP methods produced the same Bs, and averages with at least 40 epochs were required for adequate B estimation for both VEOG and HEOG. CONCLUSION: There is no difference between the AAA and NERP methods and thus it is acceptable to use the more easily implemented NERP method for EOG correction. It is recommended that when applying this procedure, at least 40 epochs should be used to make up the averages from which to calculate correction coefficients.

EOG correction of blinks with saccade coefficients: a test and revision of the aligned-artefact average solution.

OBJECTIVE: The 'aligned-artefact average' (AAA) procedure was advanced by the authors as a technique suitable for removing eye movement-related artefacts from the EEG. It was proposed that this method would correct both blink and non-blink artefact from the EEG, using the same set of correction coefficients (Bs). However, recent evidence suggests that this simplification is not always accurate. Thus, we test here a revision of the AAA, including an appropriate allowance for the radial EOG (REOG) component, that does allow the use of the same Bs for the correction of blink and non-blink artefact. METHODS: Blink (and saccade) ERP data from 15 subjects were corrected using the AAA method, with Bs calculated from the same blink (and saccade) data set (referent waveforms), or a different set of blink (and saccade) data, or using the new revised AAA procedure (RAAA). RESULTS: AAA Bs calculated from saccades corrected blinks poorly (and vice versa). However, the RAAA Bs corrected blink ERPs better than blink-derived Bs, and saccade ERPs better than saccade-derived Bs. It was also found that irrespective of correction type, inclusion of REOG improved correction. CONCLUSION: EOG correction is more accurate when the radial channel is included, but inclusion of REOG (and/or HEOG) is not sufficient to resolve the discrepancy between blink and saccade correction. Using the RAAA procedure, both blink and non-blink data can be corrected using the same set of Bs.

EEG-defined subtypes of children with attention-deficit/hyperactivity disorder.

OBJECTIVES: This study investigated the presence of EEG clusters within a sample of children with the combined type of attention-deficit/hyperactivity disorder (ADHD). METHODS: Subjects consisted of 184 boys with ADHD and 40 age-matched controls. EEG was recorded from 21 sites during an eyes-closed resting condition and Fourier transformed to provide estimates for total power, and relative power in the delta, theta, alpha and beta bands, and for the theta/beta ratio. Factor analysis was used to group sites into 3 regions, covering frontal, central and posterior regions. These data were subjected to cluster analysis. RESULTS: Three distinct EEG clusters of children with ADHD were found. These were characterized by (a) increased slow wave activity and deficiencies of fast wave, (b) increased high amplitude theta with deficiencies of beta activity, and (c) an excess beta group. CONCLUSIONS: These results indicate that children with ADHD do not constitute a homogenous group in EEG profile terms. This has important implications for studies of the utility of EEG in the diagnosis of ADHD. Efforts aimed at using EEG as a tool to discriminate ADHD children from normals must recognize the variability within the ADHD population if such a tool is to be valid and reliable in clinical practice.

Age and sex effects in the EEG: development of the normal child.

OBJECTIVES: This study investigated age-related changes and sex differences in the EEGs of normal children. METHODS: Forty boys and 40 girls, between the ages of 8 and 12 years, participated in this study. The EEG was recorded during an eyes-closed resting condition and Fourier transformed to provide estimates for total power, absolute and relative power in the delta, theta, alpha and beta bands, and for theta/alpha and theta/beta ratios. RESULTS: Absolute delta activity decreased with age. Relative delta and theta decreased and alpha and beta increased with increasing age. The theta/alpha and theta/beta ratios decreased with increasing age. All of these indicated a developmental reduction in slow wave activity. Maturational differences were found in the rates of change between the midline and the two hemispheres. In the absolute delta and the theta/beta ratio, the midline and the two hemispheres became more equipotential with age. In the beta band, power increased at a greater rate than in the two hemispheres. Sex differences were found, with males having less theta and more alpha than females. CONCLUSIONS: These results indicated that maturation occurs earlier at the midline than in the two hemispheres. Females were also found to have a developmental lag in the EEG compared with males.

Age and sex effects in the EEG: differences in two subtypes of attention-deficit/hyperactivity disorder.

OBJECTIVES: This study investigated age-related changes and sex differences in the EEGs of two groups of children with attention-deficit/hyperactivity disorder (ADHD) combined type and ADHD predominantly inattentive type, in comparison with a control group of normal children. METHODS: Forty boys and forty girls were included in each group. The EEG was recorded during an eyes-closed resting condition and Fourier transformed to provide estimates for total power, absolute and relative power in the delta, theta, alpha and beta bands, and for theta/alpha and theta/beta ratios. RESULTS: Total power, relative alpha, and the theta/alpha and theta/beta ratios were differentiated between all 3 groups. Sex differences between the ADHD subjects and the control group were greater in males than females and matured faster in males. With increasing age, the EEG of the ADHD inattentive group was found to change at a similar rate to the changes found in the normal group, with the differences in power levels remaining constant. In the ADHD combined group, the power was found to change at a greater rate than in the ADHD inattentive group, with power levels of the two ADHD groups becoming similar with age. CONCLUSIONS: These results are supportive of a two-component model of ADHD, with the hyperactive/impulsive component maturing with age and the inattentive component remaining more stable.

Graphical and statistical techniques for cardiac cycle time (phase) dependent changes in interbeat interval: problems with the Jennings et al. (1991) proposals.

Two apparently new effects in human cardiac responding, "primary bradycardia" and "vagal inhibition", were first described by the Laceys. These effects have been considered by some researchers to reflect differential cardiac innervation, analogous to similar effects observed in animal preparations with direct vagal stimulation. However, it has been argued that such effects arise merely from the data-analytic techniques introduced by the Laceys, and hence are not genuine cardiac cycle effects. Jennings, van der Molen, Somsen and Ridderinkhoff (Psychophysiology, 28 (1991) 596-606) recently proposed a plotting technique and statistical procedure in an attempt to resolve this issue. The present paper demonstrates that the plotting technique fails to achieve their stated aim, since it identifies data from identical cardiac responses as showing cardiac-cycle effects. In addition, the statistical procedure is shown to be reducible to a trivial test of response occurrence. The implication of these demonstrations, in the context of other work, is that this area of investigation has reached a dead end.

Correction for sinus arrhythmia in the evoked cardiac response: a timebase problem.

The detection and description of the evoked cardiac response (ECR) has received much attention in recent literature, with an increasing concentration upon the 'noise' problem of sinus arrhythmia (SA). A departure from extrapolated pre-stimulus activity, obtained by employing procedures of various complexities, has been proposed as an SA-free measure of the ECR. The use of such procedures without consideration of respiratory changes appears questionable. Simulation of HR protocols across a change in respiratory period indicates that spurious ECRs, similar in form to those in the published literature, may be produced by such techniques. A simple method of correcting the problem is outlined.

A factor-analytic examination of the unitary OR concept.

Recent studies have generated a four-system structure proposed as a replacement for Sokolov's unitary OR concept. This conceptualisation developed from a logical consideration of stimulus--response relationships based upon mean response magnitudes over subjects, and paid no attention to individual response types. It is conceivable that no individual subject exhibited responses compatible with such a formulation. This paper addressed that problem by using factor analysis as a means of descriptively summarising the data of each subject, and examining its compatibility with both unitary and four-system structures. Of 72 subjects, none exhibited a factor structure compatible with Sokolov's unitary concept, while 70 exhibited structures compatible with the four-system structure. These results support the validity of the structure proposed to replace the unitary OR.

Electrodermal responses to emotive and non-emotive words as a function of personality differences in affect level.

This study examined the use of the P scale of the Eysenck Personality Questionnaire as a pencil and paper estimate of level of affect lability. Groups of subjects differing on the P scale were presented with emotive and non-emotive words. High P (low affect) subjects appeared inhibited in their emotional rating of all words, and displayed a restricted range in their reporting of this rating. Further, the electrodermal activity elicited by these words differed between the groups, with high P subjects again appearing relatively inhibited. These results support the validity of the P scale as a measure of affect lability and have implications for a recent hypothesis of impaired functioning of the reticular activating system in early-onset psychosis. The results may also be interpreted to support the role of significance in elicitation of the orienting response.

Habituation of electrodermal and respiratory responses to visual stimuli as a function of personality differences in affect level.

The relationship between personality level of affect and habituation of electrodermal and respiratory measures was examined in two groups of normal subjects designated Low P (LP) and High P (HP) according to the P scale of the Eysenck Personality Questionnaire. Experiment 1 examined changes as a function of repeated presentation of simple visual stimuli. Group HP displayed reduced habituation rates for both respiratory pause and skin resistance response (SSR), although initial reactivity levels were similar for both groups. This effect was confirmed more strongly in Experiment 2, which utilized a simple counting task and groups separated more widely on P. The implications of these group differences were discussed in relation to the psychophysiological functioning of autistic children.