Developing classification criteria for skin-predominant dermatomyositis: the Delphi process.

BACKGROUND: The European League Against Rheumatism/American College of Rheumatology classification criteria for inflammatory myopathies are able to classify patients with skin-predominant dermatomyositis (DM). However, approximately 25% of patients with skin-predominant DM do not meet two of the three hallmark skin signs and fail to meet the criteria. OBJECTIVES: To develop a set of skin-focused classification criteria that will distinguish cutaneous DM from mimickers and allow a more inclusive definition of skin-predominant disease. METHODS: An extensive literature review was done to generate items for the Delphi process. Items were grouped into categories of distribution, morphology, symptoms, antibodies, histology and contextual factors. Using REDCap™, participants rated these items in terms of appropriateness and distinguishing ability from mimickers. The relevance score ranged from 1 to 100, and the median score determined a rank-ordered list. A prespecified median score cut-off was decided by the steering committee and the participants. There was a pre-Delphi and two rounds of actual Delphi. RESULTS: There were 50 participating dermatologists and rheumatologists from North America, South America, Europe and Asia. After a cut-off score of 70 during the first round, 37 of the initial 54 items were retained and carried over to the next round. The cut-off was raised to 80 during round two and a list of 25 items was generated. CONCLUSIONS: This project is a key step in the development of prospectively validated classification criteria that will create a more inclusive population of patients with DM for clinical research. What's already known about this topic? Proper classification of patients with skin-predominant dermatomyositis (DM) is indispensable in the appropriate conduct of clinical/translational research in the field. The only validated European League Against Rheumatism/American College of Rheumatology criteria for idiopathic inflammatory myopathies are able to classify skin-predominant DM. However, a quarter of amyopathic patients still fail the criteria and does not meet the disease classification. What does this study add? A list of 25 potential criteria divided into categories of distribution, morphology, symptomatology, pathology and contextual factors has been generated after several rounds of consensus exercise among experts in the field of DM. This Delphi project is a prerequisite to the development of a validated classification criteria set for skin-predominant DM.

Fatigue in systemic lupus erythematosus and other autoimmune skin diseases.

BACKGROUND: Fatigue is a well-established symptom in systemic lupus erythematosus (SLE), but has not been well characterized in other skin-limited autoimmune diseases such as cutaneous lupus erythematosus (CLE), amyopathic dermatomyositis (ADM) or autoimmune blistering diseases (AIBD). OBJECTIVES: In this retrospective study, we compared fatigue in controls (n = 84) with that in patients enrolled in prospective longitudinal databases with SLE (n = 165), CLE (n = 226), ADM (n = 136) and AIBD (n = 79). METHODS: We used the 36-Item Short Form Survey (SF-36) vitality scale to analyse median scores and the percentages of patients with clinically significant fatigue (defined as a score ≤ 35) between experimental groups and controls. RESULTS: Median and interquartile range (IQR) vitality scores demonstrated greater fatigue in the experimental groups (SLE 35, IQR 20-55; CLE 50, IQR 30-70; ADM 50, IQR 30-65; AIBD 55, IQR 35-70) than in controls (73, IQR 65-85) (P < 0·05 for each experimental group vs. control). The SLE group had worse fatigue than all of the other groups (P < 0·05 SLE vs. each group), but there was no difference between the CLE, ADM or AIBD groups (all P > 0·05). In addition, the experimental groups had more clinically significant fatigue (score ≤ 35) (SLE 44·2%, CLE 25·2%, ADM 31·6%, AIBD 24·1%) than controls (2%) (P < 0·01 for each experimental group vs. control). The SLE group had more clinically significant fatigue than the CLE group (P < 0·01); however, there was no difference in clinically significant fatigue between SLE and either ADM (P = 0·17) or AIBD (P = 0·055). CONCLUSIONS: These findings demonstrate that patients with skin-limited autoimmune disease experience more fatigue than controls. Fatigue is an important symptom that negatively affects quality of life for patients. It should be addressed by clinicians and measured in future clinical trials.

The diagnosis and classification of amyopathic dermatomyositis: a historical review and assessment of existing criteria.

BACKGROUND: Diagnostic criteria are used to identify a patient having a disease in a clinical setting, whereas classification criteria create a well-defined population for research purposes. The diagnosis and classification of amyopathic dermatomyositis (ADM) have not been recognized by most existing criteria for idiopathic inflammatory myopathies (IIMs). To address this, several criteria were proposed to define ADM either as a distinct disease entity or as a subset of the spectrum of IIMs. OBJECTIVES: To discuss the diagnosis and classification of ADM and to assesses the available criteria in identifying cases of ADM and/or distinguishing it from dermatological mimickers such as lupus erythematosus. METHODS: We conducted an extensive literature search using the PubMed database from June 2016 to August 2018, using the search terms 'amyopathic dermatomyositis', 'diagnosis' and 'classification'. RESULTS: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria, which are the only validated classification criteria for adult and juvenile IIM and their major subgroups, include three cutaneous items (Göttron sign, Göttron papules, heliotrope rash) to be able to classify ADM. This international and multispecialty effort is a huge step forward in the classification of skin-predominant disease in dermatomyositis. However, about 25% of the population with ADM do not meet two out of the three skin features and are misdiagnosed or classified as having a different disease entity, most commonly lupus erythematosus. CONCLUSIONS: These gaps rationalize the continuous assessment and improvement of existing criteria and/or the development of validated, separate and skin-focused criteria for DM.

Evaluation of the reliability and validity of the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) in paediatric cutaneous lupus among paediatric dermatologists and rheumatologists.

BACKGROUND: The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a reliable outcome measure for cutaneous lupus erythematosus (CLE) in adults used in clinical trials. However, it has not been validated in children, limiting clinical trials for paediatric CLE. OBJECTIVES: This study aimed to validate the CLASI in paediatrics. METHODS: Eleven paediatric patients with CLE, six dermatologists and six rheumatologists participated. The physicians were trained to use the CLASI and Physician's Global Assessment (PGA), and individually rated all patients using both tools. Each physician reassessed two randomly selected patients. Within each physician group, the intraclass correlation coefficient (ICC) was calculated to assess the reliability of each measure. RESULTS: CLASI activity scores demonstrated excellent inter- and intrarater reliability (ICC > 0·90), while the PGA activity scores had good inter-rater reliability (ICC 0·73-0·77) among both specialties. PGA activity scores showed excellent (ICC 0·89) and good intrarater reliability (ICC 0·76) for dermatologists and rheumatologists, respectively. Limitations of this study include the small sample size of patients and potential recall bias during the physician rerating session. CONCLUSIONS: CLASI activity measurement showed excellent inter- and intrarater reliability in paediatric CLE and superiority over the PGA. These results demonstrate that the CLASI is a reliable and valid outcome instrument for paediatric CLE.

Factors influencing elevated serum apolipoprotein B48 in diabetic and control participants.

Factors influencing the concentration of apolipoprotein B48 (apo B48) at fasting and post-prandial time frames are still being elucidated. This study assesses some possible contributing factors including the presence of type 2 diabetes and gender using an established enzyme-linked immunosorbent assay (ELISA) method. Apo B48 and triglyceride (TG) levels were measured before and for two, four and six hours post-prandially in 49 poorly controlled participants with type 2 diabetes and in 60 apparently healthy participants (controls). Apo B48 levels in the control participants increased post-prandially, peaking at four hours (14.81 ± 7.72 µg/mL) with similar responses demonstrated in TG concentrations. Post-prandial apo B48 levels were significantly higher in male control participants as demonstrated by apo B48 area under the curve (AUC); similar responses were also confirmed in triglyceride AUC. Post-prandial apo B48 concentrations in control participants correlated with HOMA-IR (P < 0.05). Apo B48 continued to increase throughout the six hours in participants with type 2 diabetes (17.73 ± 13.46 µg/mL), when levels were significantly greater than in the control participants (13.04 ± 7.67 µg/mL) (P < 0.05) despite a decrease in accompanying TG levels in participants with type 2 diabetes. Using an ELISA method, this study demonstrated that gender, insulin resistance (as evidenced by HOMA-IR) and diabetes status influence serum apo B48 levels. These effects were only apparent post-prandially.

Zenker's diverticulitis: a bitter pill to swallow.

Acute oesophageal obstruction from food bolus impaction is often triggered by underlying oesophageal pathology, both benign and malignant. These can be readily detected with standard investigations such as oesophagoscopy or computed tomography. Zenker's diverticulum (ZD) is a benign condition frequently presenting with chronic dysphagia or may be asymptomatic. We report the case of an 81-year-old man with a previously undiagnosed 1-cm ZD causing complete oesophageal obstruction secondary to localized oedema from an impacted ibuprofen tablet. Although initial clinical, endoscopic and radiological findings were equivocal and suspicious for upper oesophageal malignancy, symptoms rapidly settled in response to systemic corticosteroids. The diagnosis was later confirmed on barium swallow with no other clinical, radiological or histopathological abnormalities identified. In conclusion, ZD is an uncommon cause of acute oesophageal obstruction which may occur in diverticula of all sizes. Surgery should be performed in patients with recurrent symptoms or large diverticula.

Day of surgery admission--is this safe practise?

Day of surgery admission (DOSA) describes the process whereby patients are admitted to hospital and have surgery, on the same day. This is the current admission policy in our institution, for most elective Otolaryngology Head and Neck Surgery patients. We audited 75 consecutive patients admitted on the same day as surgery within our department between May 2006 and January 2007. Significant comorbidity was seen in 28 patients (37.3%). Preoperative investigations prior to surgery were conducted in 64 patients (85.3%). About 21 patients (28%) were delayed going to theatre and the average length of delay was 51 mins. Our cancellation rate was 5.3%. Hospital management have embraced the concept of DOSA in our institution without evaluating the risk to patients. If the DOSA policy is to continue it is imperative that an adequate preoperative assessment clinic is established to prevent negative outcomes for our patients.

Identification and characterization of the Egr-1 gene product, a DNA-binding zinc finger protein induced by differentiation and growth signals.

Egr-1 is an immediate-early response gene induced by diverse signals that initiate growth and differentiation. Its cDNA sequence predicts a protein with zinc fingers. We have generated an antiserum to the Egr-1 gene product and identified it as an 80-kilodalton short-lived protein in serum-stimulated mouse fibroblasts. The rat Egr-1 product has also been identified in nerve growth factor-induced PC12 cells. In addition, we show by cell fractionation and immunocytochemistry that the Egr-1 protein is located in the nucleus. We also demonstrate that it is phosphorylated. In vitro-generated Egr-1 protein binds with high affinity to the sequence CGCCCCCGC in a zinc-dependent manner.

Segmental colonic transit after oral 67Ga-citrate in healthy subjects and those with chronic idiopathic constipation.

UNLABELLED: Measurement of segmental colonic transit is important in the assessment of patients with severe constipation. 111In-diethylenetriamine pentaacetic acid (DTPA) has been established as the tracer of choice for these studies, but it is expensive and not readily available. 67Ga-citrate is an inexpensive tracer and when given orally is not absorbed from the bowel. It was compared with 111In-DTPA in colonic transit studies in nonconstipated control subjects and then in patients with idiopathic constipation. METHODS: Studies were performed after oral administration of 3 MBq (81 microCi) 67Ga-citrate or 4 MBq (108 microCi) 111In-DTPA in solution. Serial abdominal images were performed up to 96 h postinjection, and computer data were generated from geometric mean images of segmental retention of tracer, mean activity profiles and a colonic tracer half-clearance time. RESULTS: There were no differences in segmental retention of either tracer or in mean activity profiles between control subjects and constipated patients. Results in constipated subjects were significantly different from those in controls. The mean half-clearance times of tracer for control subjects were 28.8 h for 67Ga-citrate and 29.9 h for 111In-DTPA in control subjects and 75.0 h for 67Ga-citrate and 70.8 h for 111In-DTPA in constipated patients. CONCLUSION: Oral 67Ga-citrate can be used as a safe alternative to 111In-DTPA for accurate measurement of segmental colonic transit.

Vertical saccadic velocity determination in superior oblique palsy.

Vertical saccadic velocities were measured in various horizontal gaze positions in patients with known superior oblique weakness and compared to similar measurements in a normal control group. Marked slowing of the down saccade in the adducted position occurred in the patients with superior oblique weakness and not in the controls. This suggests that it is possible to differentiate oblique and rectus function by saccadic velocity analysis.

Effects of AY-22,241 (Actodigin) on electrical and mechanical activity of cardiac tissues.

AY-22,241 (Actodigin) is a new rapid-acting semisynthetic cardiotonic steroid. In experiments on contractility of cat papillary muscle, Actodigin (2 times 10(-7) to 4 times 10(-6) M) produced a dose-dependent positive inotropic effect, a marked increase in the maximum rate of force development, and no change in resting tension. Electrophysiologic studies performed with microelectrode techniques on isolated Purkinje fibers superfused with Tyrode solution, revealed dose-dependent decreases in resting membrane potential, action potential amplitude and duration, and the maximum rate of rise of phase 0 (Vmax). Purkinje fibers superfused with extracorporeally circulated blood from a donor dog receiving 0.075 mg/kg/min Actodigin showed small decreases in resting membrane potential preceding the onset of donor premature ventricular contractions. Progressive decreases in resting membrane potential, action potential amplitude and duration, and Vmax accompanied donor ventricular tachycardia. All effects were rapidly reversible, and compared to ouabain, equi-inotropic concentrations of Actodigin caused significantly less electrophysiologic toxicity.

Differences in tonsil core bacteriology in adults and children: a prospective study of 262 patients.

The tonsillar microflora of 262 patients with recurrent acute tonsillitis studied in 1989-1990 is presented. The patient population was divided into three age groups to determine any age-related features. One-hundred and forty-nine patients (57%) were in the 2-7-year-old group, 72 (28%) the 8-14-year-old age group, and the remaining 41 (15%) were over 15 years of age. H. influenzae was the single most common bacterium isolated from the centre of the tonsil (referred to as 'tonsil core'), and this was more prevalent in the 2-7-year-old age group. Staph aureus was the next most commonly isolated bacterium and was most frequently seen in the 8-14-year-old age group (29%). Anaerobic bacteriology was performed in 120 patients. Strict anaerobic species were isolated in significant numbers from the tonsil core in 5% but were present in the superficial culture in all. Anaerobes were present in moderate to heavy numbers in 32% of superficial swabs overall and this was more frequently seen in the older age groups. Mixed pathogens were found throughout all age groups and were most prevalent in the 8-14-year-old age group at 46%. The commonest mixture was H. influenzae and Staph aureus. Normal flora only was commonly found in the superficial swab and rarely in the tonsil core. The number of specimens containing a beta-lactamase producer was assessed for each group; this was similar in all of the groups ranging from 43% in the 2-7-year-old group and 53% in the 8-14-year-old group to 39% in the greater than 15-year-old group.

Bacteriology of tonsil and adenoid and sampling techniques of adenoidal bacteriology.

The value of pernasal swabs and direct adenoid swabs in chronic adenoid and adenotonsillar disease was assessed in 175 patients. Prior to adenoidectomy (53 patients) or adenotonsillectomy (122 patients), pernasal and direct adenoid swabs were taken. Adenoid currettings and tonsil tissue were cultured. Haemophilus influenzae was the bacterium most frequently isolated from adenoid currettings and from the centre (core) of the resected tonsil. There was a close relationship between the bacteriology of the pernasal swab and the adenoid tissue and tonsil core in 72 and 71% of patients, respectively. There was an identical profile of pathogens in 52 and 49%, respectively. We suggest that in children with adenoiditis or adenotonsillitis and hypertrophy of the adenoid, a pernasal swab should be used in preference to a throat swab in selecting appropriate antimicrobial therapy. Penicillin and ampicillin are not appropriate blind therapy in chronic adenoid and adenotonsillar infections because of the prevalence of beta-lactamase-producing aerobes (40%) in adenoid and tonsil core in these conditions.

A comparison of four methods of estimating the body composition of male endurance athletes.

Comparisons were effected of the following four methods of estimating the percent body fat (%BF) of 12 highly trained male endurance athletes (mean +/- SD = 2.20 +/- 4.9 years, 176.8 +/- 5.9 cm 64.2 +/- 6.4 kg): underwater weighing (UWW), total body water (TBW), total body potassium (TBK) and dual-energy X-ray absorptiometry (DEXA). The DEXA mean of 6.8% BF was significantly less (P < 0.05) than those estimated via UWW: 9.7% BF; TBW: 10.6% BF (fat-free mass of FFM = 72.0% H2O); and TBK: 9.7% BF (FFM = 66.6 mmol K.kg-1). Nevertheless, the DEXA % BF correlated 0.746 and 0.737 (both P < 0.01) with those from UWW and TBW, respectively; these were the only correlation coefficients to attain statistical significance (P < or = 0.05). Despite the similar means for UWW, TBW and TBK, 12 of the 36 individual differences between these three methods ranged from 3.2 to 10.4% BF. A critical assumption of UWW, which is regarded by many as the criterion method for the estimation of % BF, is that the FFM has a density of 1.100 g.cm-3. Use of in vivo-measured TBW and bone mineral (via DEXA) for the computation of FFM densities for our subjects, while assuming that the two other components of the FFM (protein and non-bone mineral) remained constant, resulted in scores ranging from 1.09541 to 1.10246 g.cm-3 (mean +/- SD = 1.09881 +/- 0.00254 g.cm-3). FFM and % BF differences between use of a constant FFM density of 1.100 g.cm-3 and the individual values ranged from -1.02 to 0.57 kg (mean +/- SD = -0.28 +/- 0.60 kg) and from -0.9 to 1.7% BF (mean +/- SD = 0.5 +/- 0.9% BF), respectively. It may be concluded that with young male athletes: (1) use of constants based on normal male cadavers yielded similar group means for % BF determined by UWW, TBW and TBK but the DEXA % BF correlated significantly with those from UWW and TBW; and (2) in vivo measurements of individual differences in TBW and bone mineral support the use of conventional UWW for the estimation of % BF.

Is human labour triggered by an increase in the rate of synthesis of prostaglandin G/H synthase?

The increase in the synthesis of prostaglandins by intrauterine tissues which occurs at the time of parturition may be the consequence of periparturient changes in several regulatory pathways. The aim of this study was to determine whether changes in the rate of synthesis of prostaglandin G/H synthase (PGHS) contribute to the labour-associated increase in prostaglandin synthesis by human chorioamnion and placenta. The rate of recovery of prostaglandin E2 (PGE2) synthesis following inhibition of PGHS by aspirin was used as an estimation of PGHS resynthesis. In tissues obtained following spontaneous delivery, the half-time recovery of PGE2 synthesis was 3.5 to 6.0-fold less (P less than 0.001; n = 5) than the half-time recovery observed in tissues obtained before the onset of labour. These data suggest that a periparturient increase in the rate of synthesis of PGHS contributes to enhanced prostaglandin synthesis at term.

Detection of splenosis: 99Tcm tin colloid scanning and computed transmission tomography compared.

Ten patients who had been splenectomized for trauma between 1 and 11 years previously were studied by computed tomography (CT) and radionuclide scanning with 99Tcm tin colloid on the same day. Computed tomography detected splenic tissue in three patients. Radionuclide scanning detected splenic tissue in eight patients, including two cases of typical splenosis not identified by CT. Radionuclide scanning was found to be more sensitive in the detection of residual splenic tissue than CT.

Laser aryepiglottoplasty for the treatment of neurasthenic laryngomalacia in cerebral palsy.

Patients with cerebral palsy usually suffer from lack of coordination in the neuromuscular mechanism in their upper airway and digestive tract. Difficulty in swallowing and aspiration are common problems in these patients, and stridorous breathing sometimes develops as a secondary symptom. Laryngoscopic examination revealed that redundant tissue in the aryepiglottic fold area was the cause of stridor and upper airway obstruction in four patients with cerebral palsy. We report on these four patients in whom laser reduction of the redundant mucosa led to dramatic improvements in stridor. Secondary benefits to family members and others were equally impressive.