Reactive granulomatous dermatitis as a clinically relevant and unifying term: a retrospective review of clinical features, associated systemic diseases, histopathology and treatment for a series of 65 patients at Mayo Clinic.

BACKGROUND: Reactive granulomatous dermatitis (RGD) is an umbrella term used to describe interstitial granulomatous dermatitis (IGD), palisaded neutrophilic and granulomatous dermatitis (PNGD), and interstitial granulomatous drug eruption (IGDR). OBJECTIVE: The aim of this study was to describe systemic associations of RGD, explore possible associations between histopathologic findings and systemic RGD associations and determine clinical relevance of RGD subtypes. METHODS: We retrospectively studied clinical and histopathologic characteristics of patients with RGD from 1990 through 2020. RESULTS: Of 65 patients with RGD (41 women, 24 men; median age at diagnosis, 62 years), 37 had IGD, 26 had PNGD, and 2 had IGDR. Fifty patients (76.9%) had an associated systemic condition; rheumatologic conditions were identified for 34 (52.3%) patients. The associated systemic condition occurred before RGD in approximately 75% of patients. Statistical analyses did not show significant associations between specific subtypes of RGD and systemic diseases or treatment response, and specific histopathologic findings were not predictive of an associated systemic disease. CONCLUSIONS: Although most patients with RGD had an associated systemic condition, subtypes of RGD did not correlate with systemic associations, lending support to the use of the umbrella term RGD.

In Vivo reflectance confocal microscopy of cutaneous acute graft-versus-host disease: concordance with histopathology and interobserver reproducibility of a glossary with representative images.

BACKGROUND: The reliability to non-invasively identify features of inflammatory dermatoses by reflectance confocal microscopy (RCM) remains unknown. Lack of formal training among RCM readers can result in inconsistent assessments, limiting clinical utility. Specific consensus terminology with representative images is necessary to ensure consistent feature-level interpretation among RCM readers. OBJECTIVES: (1) Develop a glossary with representative images of RCM features of cutaneous acute graft-versus-host disease (aGVHD) for consistent interpretation among observers, (2) assess the interobserver reproducibility among RCM readers using the glossary, and (3) determine the concordance between RCM and histopathology for aGVHD features. METHODS: Through an iterative process of refinement and discussion among five international RCM experts, we developed a glossary with representative images of RCM features of aGVHD. From April to November 2018, patients suspected of aGVHD were imaged with RCM and subsequently biopsied. 17 lesions from 12 patients had clinically and pathologically confirmed cutaneous aGVHD. For each of these lesions, four dermatopathologists and four RCM readers independently evaluated the presence of aGVHD features in scanned histopathology slides and 1.5 × 1.5 mm RCM submosaics at 4 depths (blockstacks) respectively. RCM cases were adjudicated by a fifth RCM expert. Interobserver reproducibility was calculated by mean pairwise difference (U statistic). Concordance between modalities was determined by fraction of assignments with agreement. RESULTS: We present a glossary with representative images of 18 aGVHD features by RCM. The average interobserver reproducibility among RCM readers (75%, confidence interval, CI: 71-79%) did not differ significantly from dermatopathologists (80%, 76-85%). The concordance between RCM and histopathology was 59%. CONCLUSIONS: By using the glossary, the interobserver reproducibility among RCM readers was similar to the interobserver reproducibility among dermatopathologists. There was reasonable concordance between RCM and histopathology to visualize aGVHD features. The implementation of RCM can now be advanced in a variety of inflammatory conditions with a validated glossary and representative image set.

Generalized Electrical Substitution Methods and Detectors for Absolute Optical Power Measurements.

We have developed generalized methods for electrical substitution optical measurements, as well as cryogenic detectors which can be used to implement them. The new methods detailed here enable measurement of arbitrary periodic waveforms by an electrical substitution radiometer (ESR), which means that spectral and dynamic optical power can be absolutely calibrated directly by a primary standard detector. Cryogenic ESRs are not often used directly by researchers for optical calibrations due to their slow response times and cumbersome operation. We describe two types of ESRs with fast response times, including newly developed cryogenic bolometers with carbon nanotube absorbers, which are manufacturable by standard microfabrication techniques. These detectors have response times near 10 ms, spectral coverage from the ultraviolet to far-infrared, and are ideal for use with generalized electrical substitution. In our first tests of the generalized electrical substitution method with FTS, we have achieved uncertainty in detector response of 0.13 % (k=1) and total measurement uncertainty of 1.1 % (k=1) in the mid-infrared for spectral detector responsivity calibrations. The generalized method and fast detectors greatly expand the range of optical power calibrations which can be made using a wideband primary standard detector, which can shorten calibration chains and improve uncertainties.

Clinical and histopathological features of adult patients with dermatomyositis and melanoma differentiation associated-5 autoantibody seropositivity status, as determined by commercially available testing: a retrospective, single-institution comparative cohort study.

BACKGROUND: Although melanoma differentiation associated (MDA)-5 autoantibodies have been widely explored in dermatomyositis (DM), most studies have relied on MDA-5 autoantibody testing performed in research settings, rather than the now-available commercial laboratory tests. AIM: To characterize the clinical and histopathological data in patients with DM and circulating MDA-5 autoantibodies, as defined by commercially available testing. METHODS: This was a retrospective review of patients with DM who underwent MDA-5 antibody testing. All available skin biopsy slides were reviewed. RESULTS: Cutaneous features more prevalent in MDA-5-positive DM included Raynaud phenomenon (RP) (P < 0.001), cutaneous ulcerations (P = 0.01), mechanic hands (P < 0.02), palmar papules (P < 0.01), oral ulcers (P = 0.024) and alopecia (P = 0.03). Joint and pulmonary involvement were more common in patients with MDA-5-positive DM (both P < 0.001) as was dysphagia (P < 0.01). Myopathy (P = 0.4) and malignancy (P = 0.34) were not statistically different between the cohorts. Vasculopathy was more common in MDA-5-positive DM (P < 0.01), while spongiosis was less common (P < 0.02). CONCLUSION: This study not only confirms some known associations between disease manifestations and MDA-5 autoantibody status, as determined by commercially available tests, but also identifies new associations, including RP and dysphagia.

Room temperature laser power standard using a microfabricated, electrical substitution bolometer.

The design and performance of a room temperature electrical substitution radiometer for use as an absolute standard for measuring continuous-wave laser power over a wide range of wavelengths, beam diameters, and powers are described. The standard achieves an accuracy of 0.46% (k = 2) for powers from 10 mW to 100 mW and 0.83% (k = 2) for powers from 1 mW to 10 mW and can accommodate laser beam diameters (1/e2) up to 11 mm and wavelengths from 300 nm to 2 µm. At low power levels, the uncertainty is dominated by sensitivity to fluctuations in the thermal environment. The core of the instrument is a planar, silicon microfabricated bolometer with vertically aligned carbon nanotube absorbers, commercial surface mount thermistors, and an integrated heater. Where possible, commercial electronics and components were used. The performance was validated by comparing it to a National Institute of Standards and Technology primary standard through a transfer standard silicon trap detector and by comparing it to the legacy "C-series" standards in operation at the U.S. Air Force Metrology and Calibration Division (AFMETCAL).

Syncope in a 14yo female with ventricular tachycardia; an atypical etiology.

Wide complex tachycardias are rare in the pediatric population and may be due to ventricular tachycardia, aberrant conduction or antidromic tachycardia each with multiple underlying etiologies. We present a 14 yo female in extremis with syncope at rest witnessed by her mother, found in ventricular tachycardia by EMS who challenged with IVF hydration and amiodarone. Consecutive adequate fluid challenges and antiarrhythmics in the emergency department failed requiring synchronized cardioversion for stabilization. Subsequent viral panels, imaging, genetic testing and cardiac biopsy confirmed a diagnosis of arrhythmogenic right (and left) ventricular dysplasia.

Nature of fiber-coupled detector responsivity measurements at 0.1% using a primary standard.

We demonstrate the capability to measure the absolute power responsivity of optical fiber-coupled detectors at an expanded uncertainty of 0.1%, by direct comparison with a cryogenic primary standard. To facilitate synchronous power measurements, commercial all-fiber beam-splitters direct laser diode light simultaneously to the device under test and the primary standard. We investigate the use of single-mode, polarisation maintaining, and photonic crystal fibers to access the cryogenic standard, and report a reduction in the temperature dependent effective refractive index of these fibers of 0.1%, 0.15% and 0.3% respectively in going from room temperature to 5 K. We also evaluate the polarisation dependent loss of the beam-splitters, the stability of the beam-splitter ratio between the cryogenic detector and the device under test and the temporal and modal stability of the Fabry-Pérot laser diode sources. It is shown that the stability of the optical fiber beam-splitters limits the overall performance of the measurement system to an expanded uncertainty of 0.1%.

Differential expression of interferon-induced genes and other tissue-based biomarkers in acute graft-versus-host disease vs. lupus erythematosus in skin.

BACKGROUND: In both acute graft-versus-host disease (GVHD) and lupus erythematosus (LE), the patient's own tissues are subjected to immunological assault via complex mechanisms influenced by interferon (IFN) and other cytokines. Although not typically confused clinically, these entities have overlapping histopathological findings in the skin. AIM: To assess whether GVHD can be differentiated from LE using molecular methods on skin specimens. METHODS: We developed a quantitative reverse transcription PCR assay based on previously identified tissue-based biomarkers of cutaneous GVHD, and compared gene expression in GVHD with that in LE. RESULTS: Both entities showed robust expression of IFN-induced genes and of genes encoding proteins involved in antigen presentation, cell signalling and tissue repair. Levels of gene expression differed significantly in GVHD compared with LE, particularly those of IFN-induced genes such as MX1, OAS3, TAP1 and STAT3 (P < 0.01). Three logistic regression models could differentiate the two entities with a high degree of certainty (receiver operating characteristic area under the curve of 1.0). CONCLUSION: The study demonstrates the feasibility of distinguishing between microscopically similar inflammatory dermatoses using tissue-based molecular techniques.

International Bullous Diseases Group: consensus on diagnostic criteria for epidermolysis bullosa acquisita.

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a complex autoimmune bullous disease disease with variable clinical presentations and multiple possible diagnostic tests, making an international consensus on the diagnosis of EBA essential. OBJECTIVES: To obtain an international consensus on the clinical and diagnostic criteria for EBA. METHODS: The International Bullous Diseases Group (IBDG) met three times to discuss the clinical and diagnostic criteria for EBA. For the final voting exercise, 22 experts from 14 different countries voted on 50 different items. When > 30% disagreed with a proposal, a discussion was held and re-voting carried out. RESULTS: In total, 48 of 50 proposals achieved consensus after discussion. This included nine diagnostic criteria, which are summarized in a flow chart. The IBDG was unable to determine one procedure that would be applicable worldwide. A limitation of the study is that differential diagnosis of bullous systemic lupus erythematosus has not been addressed. CONCLUSIONS: This first international consensus conference established generally agreed-upon clinical and laboratory criteria defining the clinical classification of and diagnostic testing for EBA. Holding these voting exercises in person with the possibility of discussion prior to voting has advantages in reaching consensus over Delphi exercises with remote voting.

Verification of calibration methods for determining photon-counting detection efficiency using superconducting nano-wire single photon detectors.

In recent years several ways to radiometrically calibrate optical fiber-coupled detectors have been developed. However, fiber-coupled calibration methods for single photon detectors have not been compared by national metrology institutes in order to validate their equivalence or traceability to the international systems of units yet.. Here, we present the comparison of radiometric calibration methods traceable to a NIST cryogenic radiometer at the 'few-photon' level. The calibration methods are based on metrology grade optical power meters. The expanded (k = 2) relative standard uncertainties of the calibration methods for the detection efficiency are of the order of 0.5%. However, the results changed relatively by 10% with a different set of optical fibers and mating connectors. These results stress the importance of fiber-core dimensions and fiber-connector repeatability.

Underreported use of palliative care and patient-reported outcome measures to address reduced quality of life in patients with calciphylaxis: a systematic review.

Calciphylaxis is associated with significant morbidity and mortality. Palliative care (PC) is a subspecialty that treats the pain and stress of serious illness. To assess whether the role of quality of life (QoL) indices, patient-reported outcome measures and PC have been studied in patients with calciphylaxis, we performed a systematic literature review. Several databases were searched from inception to October 2016 according to modified Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. We searched for papers on calciphylaxis that mentioned the symptoms and supportive needs of patients, QoL or outcome measures to report symptom severity, and the involvement of PC. Twelve papers met the inclusion criteria. Reported patient symptoms included pain, skin lesion resolution and pruritus, with the first being the most frequently reported. Four papers measured pain using a previously verified patient-reported outcome measure, including the Visual Analogue Scale. One paper used a verified QoL measure, the Dermatology Quality of Life Index. No tool was used consistently. Eight papers reported the use of hospice care or PC in the treatment of calciphylaxis. No outcome measure was used to prompt PC involvement. Overall, QoL indices, patient-reported outcome measures and PC are underreported in the treatment of calciphylaxis. PC may be a resource to assist in symptom management and adaptive coping strategies for patients from the onset of disease.

Leukocytoclastic vasculitis in children: clinical characteristics, subtypes, causes and direct immunofluorescence findings of 56 biopsy-confirmed cases.

BACKGROUND: Leukocytoclastic vasculitis (LCV) in children is a complex group of conditions. OBJECTIVES: This study presents the demographics, clinical features, direct immunofluorescence (DIF) results and suspected aetiologies of 56 biopsy-confirmed cases of leukocytoclastic vasculitis in children. METHODS: Retrospective review of 56 children seen at Mayo Clinic in Rochester, Minnesota, from 1993 to 2013 with clinical features and cutaneous biopsy consistent with LCV. RESULTS: Twenty-seven (48%) cases were found to be due to IgA vasculitis (Henoch-Schonlein purpura). The remaining cases were found to be due to cutaneous small-vessel vasculitis (n = 19, 34%), urticarial vasculitis (n = 5, 9%), ANCA-associated vasculitis (n = 4, 7%) and acute haemorrhagic oedema of infancy (n = 1, 2%). IgA vasculitis was found to be associated with abdominal pain (P = 0.008), whereas the non-IgA vasculitis group was associated with headache (P = 0.052). Children with IgA vasculitis had palpable purpura (P = <0.001), petechia (P = 0.057), vesicles (P = 0.009) and involvement of the buttock (P = 0.004) more frequently than the non-IgA vasculitis group. On DIF, perivascular IgA was positive in IgA vasculitis compared to non-IgA vasculitis cases (P = <0.001), the other conjugates were similar between the two groups. CONCLUSION: The most common subtype of biopsy-confirmed LCV in children is IgA vasculitis. Clinical features, exam characteristics and DIF results can be helpful in determining the subtype of cutaneous vasculitis in children.

Henoch-Schönlein purpura and systemic disease in children: retrospective study of clinical findings, histopathology and direct immunofluorescence in 34 paediatric patients.

BACKGROUND: Henoch-Schönlein purpura (HSP), an IgA-mediated small vessel vasculitis, is the most common form of vasculitis in children. HSP is commonly associated with systemic involvement of the gastrointestinal tract, joints and kidneys. Renal involvement is the main cause of morbidity and mortality in HSP. OBJECTIVES: To characterize the clinical, histopathological and direct immunofluorescence (DIF) findings, and to correlate the findings with systemic disease in 34 children with HSP seen at our institution. METHODS: This was a retrospective review of paediatric patients with HSP and with available biopsy specimens seen at our institution between 1993 and 2013. RESULTS: Thirty-four paediatric patients were identified (mean age 10·7 years). Renal involvement was found in 17 (50%) patients, gastrointestinal tract involvement in 22 (65%) and joint involvement in 23 (68%). Renal involvement was significantly associated with papillary dermal oedema on histopathology (P < 0·01) and the presence of perivascular C3 on DIF (P = 0·01). The presence of lesions above the waist was significantly associated with gastrointestinal involvement (P = 0·03), as was the presence of clinically apparent oedema (P = 0·01). CONCLUSIONS: This study suggests that in children with HSP, microscopic dermal oedema and C3 on DIF may be predictive of renal involvement. Patients with clinically apparent oedema and lesions above the waist are more likely to have gastrointestinal involvement.

Evidence-based guidelines for laboratory screening for infectious diseases before initiation of systemic immunosuppressive agents in patients with autoimmune bullous dermatoses.

Autoimmune bullous dermatoses (ABD) compromise the skin's innate barrier function for preventing infection. Treating patients with ABD frequently requires systemic immunosuppressive therapy, often with multiple agents. Currently, no pretreatment infection testing guidelines are available for clinicians caring for patients with ABD. We performed a systematic literature review in other medical disciplines that use similar iatrogenic immunosuppressive medications to treat various diseases and conditions and developed infection-testing recommendations for patients with ABD before initiating immunosuppressive therapy. Assessing individual patient risk factors for latent infection and preventable communicable diseases can direct testing for select infections before starting immunosuppressive therapy. Testing patients for hepatitis B virus, hepatitis C virus, and Mycobacterium tuberculosis infection is recommended before initiating rituximab treatment.

Evaluating the thermal damage resistance of graphene/carbon nanotube hybrid composite coatings.

We study laser irradiation behavior of multiwalled carbon nanotubes (MWCNT) and chemically modified graphene (rGO)-composite spray coatings for use as a thermal absorber material for high-power laser calorimeters. Spray coatings on aluminum test coupon were exposed to increasing laser irradiance for extended exposure times to quantify their damage threshold and optical absorbance. The coatings, prepared at varying mass % of MWCNTs in rGO, demonstrated significantly higher damage threshold values at 2.5 kW laser power at 10.6 µm wavelength than carbon paint or MWCNTs alone. Electron microscopy and Raman spectroscopy of irradiated specimens show that the coating prepared at 50% CNT loading endure at least 2 kW x cm(-2) for 10 seconds without significant damage. The improved damage resistance is attributed to the unique structure of the composite in which the MWCNTs act as an efficient absorber of laser light while the much larger rGO sheets surrounding them, dissipate the heat over a wider area.

Prevalence and public health implications of state laws that criminalize potential HIV exposure in the United States.

For the past three decades, legislative approaches to prevent HIV transmission have been used at the national, state, and local levels. One punitive legislative approach has been enactment of laws that criminalize behaviors associated with HIV exposure (HIV-specific criminal laws). In the USA, HIV-specific criminal laws have largely been shaped by state laws. These laws impose criminal penalties on persons who know they have HIV and subsequently engage in certain behaviors, most commonly sexual activity without prior disclosure of HIV-positive serostatus. These laws have been subject to intense public debate. Using public health law research methods, data from the legal database WestlawNext© were analyzed to describe the prevalence and characteristics of laws that criminalize potential HIV exposure in the 50 states (plus the District of Columbia) and to examine the implications of these laws for public health practice. The first state laws were enacted in 1986; as of 2011 a total of 67 laws had been enacted in 33 states. By 1995, nearly two-thirds of all laws had been enacted; by 2000, 85 % of laws had been enacted; and since 2000, an additional 10 laws have been enacted. Twenty-four states require persons who are aware that they have HIV to disclose their status to sexual partners and 14 states require disclosure to needle-sharing partners. Twenty-five states criminalize one or more behaviors that pose a low or negligible risk for HIV transmission. Nearly two-thirds of states in the USA have legislation that criminalizes potential HIV exposure. Many of these laws criminalize behaviors that pose low or negligible risk for HIV transmission. The majority of laws were passed before studies showed that antiretroviral therapy (ART) reduces HIV transmission risk and most laws do not account for HIV prevention measures that reduce transmission risk, such as condom use, ART, or pre-exposure prophylaxis. States with HIV-specific criminal laws are encouraged to use the findings of this paper to re-examine those laws, assess the laws' alignment with current evidence regarding HIV transmission risk, and consider whether the laws are the best vehicle to achieve their intended purposes.

Atomic clock with 1×10(-18) room-temperature blackbody Stark uncertainty.

The Stark shift due to blackbody radiation (BBR) is the key factor limiting the performance of many atomic frequency standards, with the BBR environment inside the clock apparatus being difficult to characterize at a high level of precision. Here we demonstrate an in-vacuum radiation shield that furnishes a uniform, well-characterized BBR environment for the atoms in an ytterbium optical lattice clock. Operated at room temperature, this shield enables specification of the BBR environment to a corresponding fractional clock uncertainty contribution of 5.5×10(-19). Combined with uncertainty in the atomic response, the total uncertainty of the BBR Stark shift is now 1×10(-18). Further operation of the shield at elevated temperatures enables a direct measure of the BBR shift temperature dependence and demonstrates consistency between our evaluated BBR environment and the expected atomic response.