A difficult diagnosis of eosinophilic fasciitis: A case report.

Eosinophilic fasciitis can be a debilitating diagnosis and is often delayed given its similarities to other sclerotic conditions including morphea, such as bound-down indurated skin and inflammation and sclerotic thickening of tissue layers on histopathology. Delaying treatment can lead to joint contracture and residual hardness in skin which has both cosmetic and functional implications. Therefore, finding the definitive diagnosis and differentiating from other sclerotic diseases is important early in the disease course. We present a case of a 77-year-old female with a generalized rash on her back and extremities, and progressive symptoms of pain, joint contractures, and limited movement, which highlights the challenges in diagnosis and management given clinical and histological parallels between eosinophilic fasciitis and morphea.

Automated airway quantification associates with mortality in idiopathic pulmonary fibrosis.

OBJECTIVES: The study examined whether quantified airway metrics associate with mortality in idiopathic pulmonary fibrosis (IPF). METHODS: In an observational cohort study (n = 90) of IPF patients from Ege University Hospital, an airway analysis tool AirQuant calculated median airway intersegmental tapering and segmental tortuosity across the 2nd to 6th airway generations. Intersegmental tapering measures the difference in median diameter between adjacent airway segments. Tortuosity evaluates the ratio of measured segmental length against direct end-to-end segmental length. Univariable linear regression analyses examined relationships between AirQuant variables, clinical variables, and lung function tests. Univariable and multivariable Cox proportional hazards models estimated mortality risk with the latter adjusted for patient age, gender, smoking status, antifibrotic use, CT usual interstitial pneumonia (UIP) pattern, and either forced vital capacity (FVC) or diffusion capacity of carbon monoxide (DLco) if obtained within 3 months of the CT. RESULTS: No significant collinearity existed between AirQuant variables and clinical or functional variables. On univariable Cox analyses, male gender, smoking history, no antifibrotic use, reduced DLco, reduced intersegmental tapering, and increased segmental tortuosity associated with increased risk of death. On multivariable Cox analyses (adjusted using FVC), intersegmental tapering (hazard ratio (HR) = 0.75, 95% CI = 0.66-0.85, p < 0.001) and segmental tortuosity (HR = 1.74, 95% CI = 1.22-2.47, p = 0.002) independently associated with mortality. Results were maintained with adjustment using DLco. CONCLUSIONS: AirQuant generated measures of intersegmental tapering and segmental tortuosity independently associate with mortality in IPF patients. Abnormalities in proximal airway generations, which are not typically considered to be abnormal in IPF, have prognostic value. CLINICAL RELEVANCE STATEMENT: Quantitative measurements of intersegmental tapering and segmental tortuosity, in proximal (second to sixth) generation airway segments, independently associate with mortality in IPF. Automated airway analysis can estimate disease severity, which in IPF is not restricted to the distal airway tree. KEY POINTS: • AirQuant generates measures of intersegmental tapering and segmental tortuosity. • Automated airway quantification associates with mortality in IPF independent of established measures of disease severity. • Automated airway analysis could be used to refine patient selection for therapeutic trials in IPF.

Placebo response rates and potential modifiers in double-blind randomized controlled trials of second and newer generation antidepressants for major depressive disorder in children and adolescents: a systematic review and meta-regression analysis.

Children and adolescents with major depressive disorder (MDD) appear to be more responsive to placebo than adults in randomized placebo-controlled trials (RCTs) of second and newer generation antidepressants (SNG-AD). Previous meta-analyses obtained conflicting results regarding modifiers. We aimed to conduct a meta-analytical evaluation of placebo response rates based on both clinician-rating and self-rating scales. Based on the most recent and comprehensive study on adult data, we tested whether the placebo response rates in children and adolescents with MDD also increase with study duration and number of study sites. We searched systematically for published RCTs of SNG-AD in children and/or adolescents (last update: September 2017) in public domain electronic databases and additionally for documented studies in clinical trial databases. The log-transformed odds of placebo response were meta-analytically analyzed. The primary and secondary outcomes were placebo response rates at the end of treatment based on clinician-rating and self-rating scales, respectively. To examine the impact of study duration and number of study sites on placebo response rates, we performed simple meta-regression analyses. We selected other potential modifiers of placebo response based on significance in at least one previous pediatric meta-analysis and on theoretical considerations to perform explorative analyses. We applied sensitivity analyses with placebo response rates closest to week 8 to compare our data with those reported for adults. We identified 24 placebo-controlled trials (2229 patients in the placebo arms). The clinician-rated placebo response rates ranged from 22 to 62% with a pooled response rate of 45% (95% CI 41-50%). The number of study sites was a significant modifier in the simple meta-regression analysis [odds ratio (OR) 1.01, 95% CI 1.01-1.02, p = 0.0003, k = 24) with more study sites linked to a higher placebo response. Study duration was not significantly associated with the placebo response rate. The explorative simple analyses revealed that publication year may be an additional modifier. However, in the explorative multivariable analysis including the number of study sites and the publication year only the number of study sites reached a p value ≤ 0.05. The self-rated placebo response rates ranged from 1 to 68% with a pooled response rate of 26% (95% CI 10-54%) (k = 6; n = 396). This meta-analysis confirms a high pooled placebo response rate in children and adolescents based on clinician ratings, which exceeds that observed in the most recent meta-analysis of placebo effects in adults (36%; 95% CI 35-37%) published in 2016. However, and similar to findings in adults, the pooled response rates based on self-ratings were substantially lower. In accordance with previous meta-analyses, we corroborated the number of study sites as significant modifier. In comparison to the recent adult meta-analysis, the substantially lower number of pediatric studies entails a reduced power to detect modifiers. Future studies should provide more precise and homogenous information to support discovery of potential modifiers and consider no-treatment-if ethically permissible-to allow differentiation between placebo and spontaneous remission rates. If these differ, practicing clinicians should facilitate placebo effects as an addition to the verum effect to maximize benefits. Further research is required to explain the discrepant response rates between clinician and self-ratings.

Right Forearm Eruption Associated With Playing Minecraft: A Case of Contact Dermatitis Related to Computer Gaming.

This submission highlights the importance of careful history taking along with a strong index of suspicion for an exogenous cause of dermatitis. In particular, it highlights the importance of being aware of the latest trends and exposure risks for contact dermatitis.

Hidradenitis Suppurativa and the Association With Hematological Malignancies.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease affecting skin sites with a high density of apocrine glands. HS commonly presents after puberty, with most patients diagnosed in the second decade of their life. Several studies have investigated smoking, obesity, hypertension, diabetes, and dyslipidemia as possible underlying risk factors for HS. However, we encountered 2 patients with a long-standing history of untreated leukemia who developed late-onset HS. OBJECTIVE: To investigate the presence of malignancy as an underlying risk factor for development of HS. METHOD: The PubMed and Scopus databases were searched for keywords such as hidradenitis suppurativa, malignancy, cancer, and epidemiology. OBSERVATION: Only 1 retrospective Swedish study with 2119 patients investigated the prevalence of cancer, including 6 hematopoietic malignancies, in HS patients. However, the study did not assess the timeline of developing HS in relation to the cancer diagnosis. We report 2 patients with a long-standing history of hematopoietic cancers who received no continuous treatments for their malignancies and developed late-onset HS: a 60-year-old male patient with hairy cell leukemia and a 68-year-old male patient with chronic lymphocytic leukemia who developed HS later in life. CONCLUSION: Multiple epidemiologic studies found the average age of HS diagnosis to be well prior to the fourth decade of life. The latency of the HS diagnosis as well as the presence of long-standing leukemia in both of our patients raises the necessity for assessing the possibility of malignancy, especially hematopoietic cancer, as a risk factor for HS. LIMITATION: This is a small retrospective analysis including only 2 patients. Larger studies would better assess the role of malignancy, leukemia in particular, as a possible risk factor for development of HS.

Schnitzler Syndrome Without a Monoclonal Gammopathy: A Case Report.

BACKGROUND: Schnitzler syndrome (SS) is a rare autoinflammatory disorder characterized by a recurrent urticarial rash and a monoclonal immunoglobulin M gammopathy, as well as 2 of the following minor criteria: recurrent fever (>38°C), objective signs of abnormal bone remodeling, elevated C-reactive protein level or leukocytosis, and a neutrophilic infiltrate on skin biopsy. Alternatively, a monoclonal immunoglobulin G gammopathy may be present along with 3 minor criteria for diagnosis. OBJECTIVE: To report a rare case of SS without monoclonal gammopathy and inform physicians of this possible clinical presentation so that treatment is not delayed. METHODS: We report a case of a 62-year-old white man with a clinical diagnosis of SS without monoclonal gammopathy. He presented with chronic urticaria unresponsive to conventional therapy. RESULTS AND CONCLUSIONS: To our knowledge, there have only been 3 case reports of SS in the absence of monoclonal gammopathy documented in the literature. SS should be considered based on clinical presentation, even in the absence of monoclonal gammopathy, to facilitate appropriate management.

Trends in Non-Melanoma Skin Cancer (Basal Cell Carcinoma and Squamous Cell Carcinoma) in Canada: A Descriptive Analysis of Available Data.

BACKGROUND: Despite its increased incidence and status as the most prevalent cancer in Canada, there is a paucity of epidemiological data on non-melanoma skin cancer (NMSC). OBJECTIVE: To assess trends of keratinocyte carcinomas (KC) in Canada over 5 decades. METHODS: Articles published from 1960 to 2015 on NMSC in Canada were identified through MEDLINE. Six articles met our search criteria. RESULTS: Overall, KC has increased. However, the rate of increase in the past decade has slowed down and decreased in younger age cohorts. Men had higher incidences of KC. In both sexes, the basal cell carcinoma and squamous cell carcinoma ratio was ≥2.5:1. Keratinocyte carcinomas were most commonly located on the head and neck, and increasing rates are occurring on the trunk. LIMITATIONS: The methods of registering skin cancer cases vary among different provinces. CONCLUSION: Keratinocyte carcinomas incidence is overall increasing; however, there may be evidence that the incidence is leveling off and decreasing in younger age cohorts.

Decreasing Rates of Neomycin Sensitization in Western Canada.

BACKGROUND: Neomycin contact sensitization rates in North America range from 7% to 13%, whereas in Europe they average approximately 1.9%. OBJECTIVES: Given that topical neomycin products are no longer readily available in Canada, the aim of this study was to examine what influence this may have had on neomycin sensitization rates in the 3 western provinces. METHODS: On the basis of an observation originally communicated by L. M. Parsons and C. Zhang of the University of Calgary, which suggested significantly reduced rates of neomycin sensitization in Calgary, Alberta, Canada, a multicenter study of patch test results from 5690 patient charts was undertaken. Data from 3 other western Canadian Universities (the University of Saskatchewan, the University of Alberta, and the University of British Colombia) were analyzed. Data were available from 2001 to 2013 for the University of Saskatchewan (except 2006), whereas the University of Alberta and the University of British Columbia had data from 2009 to 2013. Descriptive statistics, trend analysis, and risk estimates were determined using SPSS version 20. RESULTS: Sensitization rates for neomycin have decreased in western Canada and are now similar to those of Europe. CONCLUSIONS: This trend is likely influenced by the reduced availability of over-the-counter and prescription neomycin products in Canada.

PCQoL: A Quality of Life Assessment Measure for Pachyonychia Congenita.

BACKGROUND: Pachyonychia congenita (PC) is a rare but often debilitating, dominantly inherited disorder. New treatments require more accurate instruments for evaluating changes in the quality of life in these patients. OBJECTIVES: This study was undertaken to develop and validate a quality of life questionnaire for PC patients (PCQoL). METHODS: Relevant factors influencing quality of life in PC patients were identified and incorporated into the well-recognized, general questionnaire, the Dermatology Life Quality Index (DLQI), to establish a disease-specific measure, the PCQoL. Classical test theory (CTT) and Rasch analysis (RA) were used to analyze and validate the PCQoL. RESULTS: CTT analysis established test-retest reliability and internal consistency for the PCQoL. Concurrent and construct validity for the DLQI and the PCQoL were also validated. Chi-square-based infit and outfit statistics indicated that the Rasch model fits the observed responses very well. RA reconfirmed reliability, internal consistency, reasonable homogeneity, construct validity, and the presence of three RA-based domains. CONCLUSION: The PCQoL questionnaire is a measure validated by both CTT and RA. It appears to be a valuable tool in measuring quality of life modifications in PC individuals with keratoderma.

Pustular psoriasis complicated with acute generalized exanthematous pustulosis.

BACKGROUND: Pustular psoriasis of the digits (acrodermatitis continua of Hallopeau) may be localized to one or more digits for over an extended period of time. Characteristic presentation is that of tender, diffusely eroded, and fissured pustular plaques on one or more digits. Transition to other forms of psoriasis and to generalized pustular psoriasis is known to occur. These patients have an increased risk of acute generalized exanthematous pustulosis (AGEP) compared to the general population. Pustular psoriasis is often therapy resistant. MAIN OBSERVATIONS: We report the case of a 54-year-old Caucasian woman who presented with a pustular psoriasis flare complicated by AGEP. Treatment course included hospital admission, cyclosporine, acitretin, and discontinuation of cephalexin. CONCLUSION: The precipitating factor in the course of treatment is thought to be cephalexin. When treating patients with pustular psoriasis the occurrence of druginduced complications should be carefully examined. Our case suggests that avoidance of ß-lactam antibiotics in these patients is warranted unless absolutely indicated.

Flow cytometric analysis of regulatory T cells during hyposensitization of acquired allergic contact dermatitis.

BACKGROUND: We previously demonstrated that repeated intradermal steroid injections administered at weekly intervals into positive patch-test sites induce hyposensitization and desensitization. OBJECTIVE: To examine changes in CD4CD25CD127lo/ regulatory T cells during the attenuation of the patch-test response. METHODS: Ten patients with known allergic contact dermatitis were patch tested weekly for 10 weeks. The patch-test site was injected intradermally with 2 mg triamcinolone. At weeks 1 and 7, a biopsy was performed on the patch-test site in 6 patients, and flow cytometry was performed assessing CD4CD25CD127lo/ regulatory T cells. Secondary outcomes were clinical score, reaction size, erythema, and temperature. Statistical analysis included regression, correlation, and repeated-measures analysis of variance. RESULTS: The percentage of CD4CD25CD127lo/ regulatory T cells, measured by flow cytometry, increased from week 1 to week 7 by an average of 19.2%. The average grade of patch-test reaction decreased from +++ (vesicular reaction) to ++ (palpable erythema). The mean drop in temperature following treatment was 0.28°C per week. The mean area decreased 8.6 mm/wk over 10 weeks. CONCLUSIONS: Intradermal steroid injections of weekly patch-test reactions resulted in hyposensitization of the allergic contact dermatitis reaction. CD4CD25CD127lo/ regulatory T cells showed a tendency to increase; however, further studies are needed to determine if this is significant.

Impact of wait times on spinal cord stimulation therapy outcomes.

OBJECTIVE: Presently, the long-term success rate of spinal cord stimulation (SCS) ranges from 47% to 74%. SCS efficacy is inversely proportional to the passage of time between development of chronic pain syndrome and time of implantation. To improve outcomes, implantation should be performed early. This study identifies sources of delay and offers suggestions for improvement. METHODS: A retrospective analysis of 437 SCS patients examines delays to accessing SCS at various points in the referral stream, from initial diagnosis, family physician, and various specialist treatments, to implantation. Analysis of variance evaluated the effect of age, sex, treating specialty, and their interactions on implantation delay. A multiple linear regression model was developed to assess factors contributing to implantation delay. RESULTS: From time of onset of chronic pain to implantation, patients endured a delay of 65.4 ± 2.04 months. Initial physician contact occurred at a mean of 3.4 ± 0.12 months after development of pain syndrome. Family physicians managed cases for 11.9 ± 0.45 months and various specialists for an additional 39.8 ± 1.22 months. Neurosurgeons were quickest to refer to an implant physician (average wait-time 32.28 ± 2.64 months), while orthopedic surgeons and nonimplanting anesthesiologists took the longest, contributing to wait times of 51.60 ± 5.04 months and 58.08 ± 5.76 months, respectively. Once the decision for implantation was made, the implanting physician required 3.31 ± 0.09 months to organize the procedure. A gradual decline in wait times was observed from 1980 to present. CONCLUSION: To improve SCS success rates, physicians involved in the treatment for chronic pain should refer these cases early to an implant physician once failure of medical management becomes apparent.

Hyposensitization and desensitization in allergic contact dermatitis.

BACKGROUND: Acquired allergic contact dermatitis (ACD) causes significant morbidity. Certain occupations predispose workers to ACD, especially those that may damage the skin barrier. Allergic contact dermatitis has significant socioeconomic effects. Allergic contact dermatitis is difficult to treat, particularly if exposure is unavoidable. OBJECTIVE: The objective of this study was to establish the efficacy of intradermal steroid injections in inducing specific antigen hyposensitization when administered weekly into shifted patch-test sites. METHODS: Prospective, open-label trial included 10 patients with ACD. Each week for up to 8 weeks, patients were patch-tested to their known allergen, and the patch-test site was injected with triamcinolone. Primary outcomes were clinical score, reaction size, erythema, and thermal characteristics. Statistical analysis included regression, correlation, repeated measures, and analysis of variance with contrast variables. RESULTS: Overall results suggest significant decreases in patch-testing reactions as evidenced by improved clinical scores, reaction sizes, and reduced heat production. In 3 patients, the patch test became negative. This desensitized state persisted for 2 months in 1 patient and for 4 months in the other 2 patients. CONCLUSIONS: Repetitive treatments of weekly, shifted, positive patch test sites with intradermal steroid injections show a tendency toward allergen-specific hyposensitivity and in some cases to nonreactivity at repeat patch testing. This finding may influence future management of ACD.

The use of spinal cord stimulation in pain management.

SUMMARY Pain is a complex behavior process, the anatomy and physiology of which is not completely understood, and is subject to continuous exploration and research. Following on the heels of Melzack and Wall's gate control theory of pain (1965), Shealey et al., in 1967, were the first to implant stimulation electrodes over the dorsal columns in an attempt to provide relief for patients with chronic, intractable pain. Since then, significant strides in both the technological and therapeutic sides have facilitated the evolution of spinal cord stimulation (SCS) in the management of a variety of pain pathologies. High-quality evidence attests to the efficacy and cost-effectiveness of this modality. In contrast to conventional medical management, SCS offers long-lasting symptom relief, improved quality of life and functional capability, often achieving these goals at a reduced cost. This article illustrates the present status, challenges and future of SCS.

Quantifying the importance of galactofuranose in Aspergillus nidulans hyphal wall surface organization by atomic force microscopy.

The fungal wall mediates cell-environment interactions. Galactofuranose (Galf), the five-member ring form of galactose, has a relatively low abundance in Aspergillus walls yet is important for fungal growth and fitness. Aspergillus nidulans strains deleted for Galf biosynthesis enzymes UgeA (UDP-glucose-4-epimerase) and UgmA (UDP-galactopyranose mutase) lacked immunolocalizable Galf, had growth and sporulation defects, and had abnormal wall architecture. We used atomic force microscopy and force spectroscopy to image and quantify cell wall viscoelasticity and surface adhesion of ugeAΔ and ugmAΔ strains. We compared the results for ugeAΔ and ugmAΔ strains with the results for a wild-type strain (AAE1) and the ugeB deletion strain, which has wild-type growth and sporulation. Our results suggest that UgeA and UgmA are important for cell wall surface subunit organization and wall viscoelasticity. The ugeAΔ and ugmAΔ strains had significantly larger surface subunits and lower cell wall viscoelastic moduli than those of AAE1 or ugeBΔ hyphae. Double deletion strains (ugeAΔ ugeBΔ and ugeAΔ ugmAΔ) had more-disorganized surface subunits than single deletion strains. Changes in wall surface structure correlated with changes in its viscoelastic modulus for both fixed and living hyphae. Wild-type walls had the largest viscoelastic modulus, while the walls of the double deletion strains had the smallest. The ugmAΔ strain and particularly the ugeAΔ ugmAΔ double deletion strain were more adhesive to hydrophilic surfaces than the wild type, consistent with changes in wall viscoelasticity and surface organization. We propose that Galf is necessary for full maturation of A. nidulans walls during hyphal extension.