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Importance First-line systemic therapy for morphea includes methotrexate with or without systemic corticosteroids. When this regimen is ineffective, not tolerated, or contraindicated, a trial of mycophenolate mofetil (MMF) or mycophenolic acid (MPA)—referred to herein asmycophenolate—is recommended; however, evidence to support this recommendation remains weak. Objective To evaluate the effectiveness and tolerability of mycophenolate for the treatment of morphea. Design, Setting, and Participants A retrospective cohort study was conducted from January 1, 1999, to December 31, 2018, among 77 patients with morphea from 8 institutions who were treated with mycophenolate. Main Outcomes and Measures The primary outcome was morphea disease activity, severity, and response at 0, 3 to 6, and 9 to 12 months of mycophenolate treatment. A secondary outcome was whether mycophenolate was a well-tolerated treatment of morphea. Results There were 61 female patients (79%) and 16 male patients (21%) in the study, with a median age at disease onset of 36 years (interquartile range, 16-53 years) and median diagnostic delay of 8 months (interquartile range, 4-14 months). Generalized morphea (37 [48%]), pansclerotic morphea (12 [16%]), and linear morphea of the trunk and/or extremities (9 [12%]) were the most common subtypes of morphea identified. Forty-one patients (53%) had an associated functional impairment, and 49 patients (64%) had severe disease. Twelve patients received initial treatment with mycophenolate as monotherapy or combination therapy and 65 patients received mycophenolate after prior treatment was ineffective (50 of 65 [77%]) or poorly tolerated (21 of 65 [32%]). Treatments prior to mycophenolate included methotrexate (48 of 65 [74%]), systemic corticosteroids (42 of 65 [65%]), hydroxychloroquine (20 of 65 [31%]), and/or phototherapy (14 of 65 [22%]). After 3 to 6 months of mycophenolate treatment, 66 of 73 patients had stable (n = 22) or improved (n = 44) disease. After 9 to 12 months of treatment, 47 of 54 patients had stable (n = 14) or improved (n = 33) disease. Twenty-seven patients (35%) achieved disease remission at completion of the study. Treatments received in conjunction with mycophenolate were frequent. Mycophenolate was well tolerated. Gastrointestinal adverse effects were the most common (24 [31%]); cytopenia (3 [4%]) and infection (2 [3%]) occurred less frequently. Conclusions and Relevance This study suggests that mycophenolate is a well-tolerated and beneficial treatment of recalcitrant, severe morphea.

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.

Background Autoimmune skin disease patients are standardly screened for tuberculosis via interferon-gamma release assays (IGRAs) prior to starting new immunosuppressive drugs or enrolling in clinical trials. Two commercial IGRAs, T-SPOT.TB and QuantiFERON-Tb Gold (QFT-G), are reported as either determinate (positive or negative) or indeterminate. Both tests utilize similar immunoenzymatic reactions for interferon-gamma detection, but differ in its quantification. Though the QFT-G is more widely used, studies have demonstrated that the T-SPOT.TB has lower rates of indeterminate results in immunosuppressed patients, and thus may prevent a delay in the initiation of necessary therapies or enrollment in clinical trials. The newest generation of QFT-G, the QuantiFERON-TB Gold Plus (QFT-Plus), has not been compared to the T-SPOT.TB in this patient population. We aim to investigate the performance of both the T-SPOT.TB and QFT-Plus, as indeterminate results represent a major barrier to receiving appropriate treatment in autoimmune skin disease patients. Methods This ongoing prospective study included 48 patients seen at the Hospital of the University of Pennsylvania. Venous blood samples were collected from patients and underwent tuberculosis screening with QFT-Plus and T-SPOT.TB IGRAs. The proportions of indeterminate and determinate (positive and/or negative) results among the two tests were compared. Results In the study population of 48 patients, 29% had a primary diagnosis of cutaneous lupus (n=14). There were 2 indeterminate results with the QFT-Plus and no indeterminate results with T-SPOT.TB. There was also one positive result that was seen with both the QFT-Plus and T-SPOT.TB. All patients with a primary diagnosis of cutaneous lupus had negative results for both QFT-Plus and T-SPOT.TB. Using a one-tailed Fischer test, there was no statistical significance when comparing QFT-Plus and T-SPOT.TB in autoimmune skin disease patients (p=0.25). Conclusions In this prospective study, the T-SPOT.TB had fewer indeterminate results compared to the QFT-Plus. Though this finding was not statistically significant, it is clinically important as indeterminate results preclude autoimmune skin disease patients from receiving necessary treatment. Compared to previous studies on the older generation of the QFT-G test, the QFT-Plus showed improvement in reducing the amount of indeterminate results. Despite this, we suggest using the T-SPOT.TB in tuberculosis screening for autoimmune skin disease patients who have an indeterminant QFT-G or QFT-Plus, as this test did not display any indeterminate results. The results of this study are limited by the small sample size. Funding Source(s): This project was supported by Oxford Immunotec, Inc.

Autoimmune skin disease patients are standardly screened for tuberculosis (TB) via interferon-gamma release assays (IGRAs) prior to starting immunosuppressive drugs or enrolling in clinical trials. Two commercial IGRAs, T-SPOT.TB (T-SPOT) and QuantiFERON-Tb Gold (QFT-G), are reported as either determinate (positive or negative) or indeterminate. Both tests utilize similar immunoenzymatic reactions for interferon-gamma detection, but differ in quantification. Though QFT-G is more widely used, studies have demonstrated that T-SPOT has lower rates of indeterminate results in immunosuppressed patients. The newest generation of QFT-G, QuantiFERON-TB Gold Plus (QFT-Plus), has not been compared to T-SPOT in this patient population. We aim to investigate the performance of T-SPOT and QFT-Plus in autoimmune skin disease patients. This prospective study included 48 patients. Venous blood samples were collected and underwent TB screening with QFT-Plus and T-SPOT IGRAs. The proportions of indeterminate and determinate results among the two tests were compared. There were 2 indeterminate results with QFT-Plus and no indeterminate results with T-SPOT. There was one positive result for QFT-Plus and T-SPOT. Using a one-tailed Fischer test, there was no statistical significance when comparing QFT-Plus and T-SPOT in autoimmune skin disease patients (P=0.25). Although not statistically significant, it is clinically important as indeterminate results preclude these patients from receiving necessary treatment. Compared to previous studies on QFT-G, QFT-Plus showed improvement in reducing the amount of indeterminate results. We suggest using T-SPOT in TB screening for autoimmune skin disease patients who have an indeterminate QFT-G or QFT-Plus, as this test did not display any indeterminate results.

OBJECTIVE: The objectives were to investigate the function of central auditory pathways and of the medial efferent olivocochlear system (MOCS). DESIGN: Event-related potentials (ERP) were recorded following the delivery of the stimulus /da/ in quiet and in ipsilateral, contralateral, and binaural noise conditions and correlated to the results of the auditory processing disorders (APD) diagnostic test battery. MOCS function was investigated by adding ipsilateral, contralateral, and binaural noise to transient evoked otoacoustic emission recordings. Auditory brainstem responses and pure tone audiogram were also evaluated. STUDY SAMPLE: Nineteen children (7 to 12 years old) with APD compared with 24 age-matched controls. RESULTS: Otoacoustic emissions and ABR characteristics did not differ between groups, whereas ERP latencies were significantly longer and of higher amplitudes in APD children than in controls, in both quiet and noise conditions. The MOCS suppression was higher in APD children. CONCLUSIONS: Findings indicate that children with APD present with neural deficiencies in both challenging and non-challenging environments with an increase in the timing of several central auditory processes correlated to their behavioral performances. Meanwhile, their modulation of the auditory periphery under noisy conditions differs from control children with higher suppression.

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 (Gottron sign, Gottron 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.

Objective Systemic lupus erythematosus (SLE) is a disorder that is heterogeneous and can be difficult to diagnose. One hallmark of the disease is the presence of antinuclear antibodies (ANAs), a feature that has been incorporated into multiple classification criteria over the years. In this study, we used a database of patients with cutaneous lupus erythematosus (CLE) to determine how many had a negative ANA and met criteria for SLE using the American College of Rheumatology (ACR) and/or Systemic Lupus International Collaborating Clinics (SLICC) criteria. Methods We used a database of 301 biopsy-proven CLE patients that contained information including ANA status and the presence of features of SLE. The database was searched for patients who had a negative ANA result and whether or not they met SLE criteria using the ACR and/or SLICC criteria. Results Of the 301 patients with biopsy-proven CLE and a known ANA, 111 had a negative ANA test (36.9%) and 27 had an ANA test that fluctuated (33.3%). In all, 20 ANA-negative patients met SLE criteria (18.0%), and 12 patients with a fluctuating ANA test met SLE criteria (44.4%). Of all patients who had either a negative or fluctuating ANA result and who met criteria for SLE (n = 32), 27 patients had involvement of ≥1 organ system other than skin (84.4%), and 13 patients had involvement of ≥2 organ systems other than skin (40.6%). Conclusion Our results show that an ANA is not always present in patients with systemic disease. This fact should be taken into consideration when devising SLE classification criteria to be used for clinical trials.

BACKGROUND: Cutaneous lupus erythematosus (CLE) refers to skin manifestations of the autoimmune disease lupus erythematosus (LE). While CLE has been extensively researched in the adult population, few studies exist in the pediatric population. The CLASI is a reliable outcome measure for CLE in the adult population, where it is commonly used in clinical trials for SLE. However, no study has validated this assessment tool in children, potentially limiting the conduct of clinical trials in pediatric SLE. METHODS: The study took place at the autoimmune disease clinic of the University of Pennsylvania, on March 3rd, 2018. Physician participants included 5 pediatric rheumatologists and 1 pediatric rheumatology fellow and 4 pediatric dermatologists and 2 dermatology fellows. Eleven pediatric patients with active CLE participated in this study. All physicians were given a 45-minute training session on the assessment of cutaneous lupus using two measurement tools: the CLASI and the Physician Global Assessment (PGA), which allow grading of skin activity and skin damage. Physicians then individually rated each patient using both tools. Following a 45-minute break, all physicians reassessed 2 patients using the same tools. Inter- and intra-rater reliability within each physician group was determined by intraclass correlation coefficient (ICC), type ICC and its confidence interval. RESULTS: The CLASI activity scores demonstrated excellent inter- and intra-rater reliability (ICC >0.90) among both dermatologists and rheumatologists. The PGA activity score had a good inter-rater reliability (ICC between 0.77–0.73) for both specialties. It had excellent intra-rater reliability for dermatologists (ICC =0.89), and good intra-rater reliability for rheumatologists. The CLASI damage score had good inter-rater reliability among dermatologists (ICC =0.76) and poor inter-rater reliability among rheumatologists (ICC =0.43). It had excellent intra-rater reliability among dermatologists (ICC =0.87) and good intra-rater reliability among rheumatologists (ICC =0.76). The PGA damage scores ranged from good to moderate ICC inter- and intra-rater reliability among both specialties (ICC between 0.76–0.50). CONCLUSIONS: These results demonstrate that the CLASI is a reliable and valid instrument tool to measure skin disease, especially activity, in pediatric CLE patients. The CLASI can be used in future clinical trials as well as in clinical practice for pediatric CLE to help standardize the evaluation of treatment effects on this disease.

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). In this retrospective study, we compared fatigue in controls (n=84) to patients enrolled in prospective longitudinal databases with SLE (n=165), CLE (n=226), ADM (n=136), and AIBD (n=79). We used the Short-Form 36 (SF-36) vitality scale to analyze median scores and percentage of patients with clinically significant fatigue (defined as a score ≤a5) between experimental groups and controls. Median vitality scores demonstrated greater fatigue in experimental groups (SLE =35, IQR =20–55; CLE =50, IQR =30–70; ADM =50, IQR =30–65; AIBD =55, IQR =35–70) than controls (73, IQR =65–85) (P0.05), ADM (P>0.05), or AIBD (P>0.05). In addition, 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

Spontaneous otoacoustic emissions (SOAEs) are found in most healthy ears, and can be used to measure the health of the cochlear structures and feedback mechanism. According to existing literature, right ears tend to exhibit greater numbers of SOAEs than left ears (Bilger et al., 1990) and females tend to show higher incidence of SOAEs than males (Moulin et al., 1993). The SOAE prevalence has not been extensively studied in children with Auditory Processing Disorder (APD), a disorder with unknown etiology that reduces one's ability to process auditory information. This study examined the prevalence and ear advantage of SOAEs between genders in children diagnosed with APD. SOAEs were investigated in 19 children (7 girls and 12 boys) with APD and 2 4 typically developing children (14 girls and 10 boys) aged 7-12. Right ear advantage was more prevalent in control (71%) than APD subjects (42 %). However, over 30% more females exhibited a right ear advantage than males in each group. Although the results are not significant, our findings indicate that the lack of right ear advantage for SOAE is more prevalent in children with APD, particularly in males, suggesting that cochlear mechanisms or their control might be somehow affected in APD.

The current study examined the baseline neurophysiological responses between children with auditory processing disorder (APD) and the control group. Auditory event related potentials were recorded in 23 children with APD (ages 7–12 years, mean age = 8.9 years) and 25 age-matched control children in response to a /da/ presented to each ear separately (right and left ear conditions). A no-sound condition was recorded as well. Baseline neurophysiological activity was measured as the root mean square amplitude of the 100 ms pre-stimulus period. Preliminary analysis of data from 19 children with APD and 13 controls indicated that the APD group showed significantly greater pre-stimulus amplitude than the control group in the left ear condition, F(1, 30) = 4.415, p = 0.044, but we did not find significant group differences in the no-sound and right ear conditions, F(1, 30) = 2.237, p = 0.15 and F(1, 30) = 0.088, p = 0.77, respectively. The results suggest that children with APD may need a longer time period to return to a resting state than control children when the left ear is stimulated. Hence, these results may indicate asymmetrical neural activities of the auditory pathways in APD.