Experience of a Single Academic Center Using IL-1 Inhibition for Rare Dermatologic Conditions.

Evidence-based literature regarding management of rare and severe dermatologic disease is limited. Canakinumab and anakinra, two therapeutics used for inhibiting IL-1 pathways, have seen increased utilization for treatment of refractory dermatoses. We sought to better characterize the breadth of dermatologic conditions for which these medications could be utilized.

Anti-beta 2 glycoprotein I IgA in the SLICC classification criteria dataset.

OBJECTIVE: Anti-beta 2 glycoprotein I IgA is a common isotype of anti-beta 2 glycoprotein I in SLE. Anti-beta 2 glycoprotein I was not included in the American College of Rheumatology (ACR) SLE classification criteria, but was included in the Systemic Lupus International Collaborating Clinics (SLICC) criteria. We aimed to evaluate the prevalence of anti-beta 2-glycoprotein I IgA in SLE versus other rheumatic diseases. In addition, we examined the association between anti-beta 2 glycoprotein I IgA and disease manifestations in SLE. METHODS: The dataset consisted of 1384 patients, 657 with a consensus physician diagnosis of SLE and 727 controls with other rheumatic diseases. Anti-beta 2 glycoprotein I isotypes were measured by ELISA. Patients with a consensus diagnosis of SLE were compared to controls with respect to presence of anti-beta 2 glycoprotein I. Among patients with SLE, we assessed the association between anti-beta 2 glycoprotein I IgA and clinical manifestations. RESULTS: The prevalence of anti-beta 2 glycoprotein I IgA was 14% in SLE patients and 7% in rheumatic disease controls (odds ratio, OR 2.3, 95% CI: 1.6, 3.3). It was more common in SLE patients who were younger patients and of African descent (p = 0.019). Eleven percent of SLE patients had anti-beta 2 glycoprotein I IgA alone (no anti-beta 2 glycoprotein I IgG or IgM). There was a significant association between anti-beta 2 glycoprotein I IgA and anti-dsDNA (p = 0.001) and the other antiphospholipid antibodies (p = 0.0004). There was no significant correlation of anti-beta 2 glycoprotein I IgA with any of the other ACR or SLICC clinical criteria for SLE. Those with anti-beta 2 glycoprotein I IgA tended to have a history of thrombosis (12% vs 6%, p = 0.071), but the difference was not statistically significant. CONCLUSION: We found the anti-beta 2 glycoprotein I IgA isotype to be more common in patients with SLE and in particular, with African descent. It could occur alone without other isotypes.

Coping with COVID-19: An Examination of the Role of (Non)Religiousness/(Non)Spirituality.

Psychological distress and coping strategies employed during collective trauma events may vary for theists and atheists, as well as others along the (non)religious spectrum. The present study explored these differences via data collected from a US-based sample during the COVID-19 pandemic. Statistical models suggested relationships between maladaptive coping and distress for all participants and potential differences in coping and, in turn, distress between participants high and low in institutional religiousness and individual spirituality. Additionally, all participants, though especially nonreligious participants, appeared less able to engage in adaptive emotion-focused coping strategies. Implications for future research are provided.

Protean Neurologic Manifestations of Two Rare Dermatologic Disorders: Sweet Disease and Localized Craniofacial Scleroderma.

PURPOSE OF REVIEW: To describe diverse neurologic and neuroradiologic presentations of two rare, immunologically mediated skin conditions: Sweet disease and localized scleroderma (morphea). RECENT FINDINGS: Core syndromes of neuro-Sweet disease (NSD) are steroid responsiveness, recurrent meningitis, and encephalitis. Focal neurologic, neuro-vascular, and neuro-ophthalmologic syndromes have been reported recently in NSD. A variety of steroid-sparing treatments and biologics have been used for relapsing NSD. Localized craniofacial scleroderma is associated with seizures, headaches, and, less commonly, focal deficits and cognitive decline. Immunosuppressive therapy may be required in patients with disease progression; some refractory cases have responded to IL-6 inhibition. Our review provides an up-to-date reference for neurologists faced with a patient with a history or skin findings consistent with Sweet disease or localized scleroderma. We hope that it will stimulate collaborative studies aimed at unraveling the pathogenesis of these disorders, better characterization of their neurologic manifestations, and discovery of optimal therapeutic solutions.

A systematic review and meta-analysis of the effects of topical nitrates in the treatment of primary and secondary Raynaud's phenomenon.

BACKGROUND: Multiple placebo-controlled trials have assessed locally applied topical nitrate preparations in treating Raynaud's phenomenon (RP). OBJECTIVES: The objective of this meta-analysis was to assess the effects of local topical nitrates in primary and secondary RP with respect to a combined end point integrating parameters of digital blood flow and clinical severity. METHODS: A systematic review was performed using MEDLINE, Embase, and the Cochrane library. Only trials comparing locally applied topical nitrates with placebo comparators were included. Studies were appraised for bias by 2 independent reviewers. RESULTS: A total of 7 placebo-controlled trials including 346 patients were used in the meta-analysis; 4 trials used nitroglycerin ointments, 2 used the nitroglycerin gel vehicle MQX-503, and 1 used compounded nitrite. The meta-analysis results supported a moderate-to-large treatment effect in RP (standardized mean difference [SMD] = 0.70; 95% CI, 0.35-1.05; P < .0001). Subgroup analyses showed a large treatment effect in secondary RP (SMD = 0.95; 95% CI, 0.25-1.65; P = .008) and moderate effect in primary RP (SMD = 0.45; 95% CI, 0.05-0.85; P = .03). LIMITATIONS: Limitations include the inclusion of multiple topical nitrate preparations and integration of different outcomes assessments. CONCLUSION: Local topical nitrates have significant efficacy in the treatment of both primary and secondary RP.

Knowingly but naively: The overpowering influence of innocence on interrogation rights decision-making.

Most suspects waive the guaranteed protections that interrogation rights afford them against police intimidation. One factor thought to motivate suspects' inclination to waive their rights stems from the acquiescence bias whereby suspects mindlessly comply with interrogators' requests. However, research bearing on the phenomenology of innocence has demonstrated the power of innocents' mindset, which could motivate some innocent suspects to waive their rights knowingly (instead of mindlessly complying). To test these ideas, participants (N = 178) were (a) rightfully (guilty) or wrongfully (innocent) accused of wrongdoing during an experimental session, (b) administered 1 of 2 forms that by signing either waived or invoked their rights to a student advocate, and (c) given questions to assess their degree of knowing during the decision-making process (i.e., extent to which individuals were cognizant of their decisions). Results demonstrated that unknowing innocent and guilty individuals tended to passively comply, engaging in a pre-interrogation acquiescence bias by signing waive and invoke forms at similar rates. But, as participants became more cognizant of their decisions, they acquiesced at lower rates and their change from acquiescence differed depending on their status. As innocents became more cognizant, they signed the waiver form at higher rates than the invoke form, thereby demonstrating that innocence can motivate some suspects to knowingly forgo their rights. Conversely, as guilty individuals became more cognizant, they signed the invoke form at higher rates than the waiver form. These findings have implications for reforming pre-interrogation protocols, protecting suspects' civil liberties, and preventing innocents from offering false self-incriminating evidence. (PsycINFO Database Record

Botulinum toxin for treatment of Raynaud phenomenon in CREST syndrome.

Calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome is a form of a rare, clinical subtype of systemic sclerosis, known as limited systemic sclerosis. Limited systemic sclerosis, including CREST syndrome, manifests as fibrotic skin changes restricted to the hands and face, with vascular, musculoskeletal, and visceral involvement. We present a case of a 75-year-old woman with a longstanding history of CREST syndrome complicated by a digital ulceration and persistent pain associated with recalcitrant Raynaud phenomenon. After failing a number of first-line pharmacologic therapies such as diltiazem, sildenafil, and topical nitropaste, the patient was started on a trial of botulinum toxin for the left second digit, with 10 unit injections into both webspaces for a total of 20 units. Following injection, the patient reported no further baseline pain in the affected finger and an over fifty-percent improvement in discomfort with manipulation of the digit at a follow-up time of one week. The ulceration started healing within the following three weeks. This result was maintained at a follow-up time of six weeks.

Metal-binding hydrazone photoswitches for visible light reactivity and variable relaxation kinetics.

The range of applications for photoswitching moieties is diverse, and the ability to design switches with variable photochemical and physical properties is consequently important for realizing their potential. Previously we reported on the photochromism of (E)-N'-(1-(2-hydroxyphenyl)ethylidene)isonicotinohydrazide (HAPI), an aroylhydrazone compound first developed as a transition metal chelator. Herein we report the synthesis of structurally related aroylhydrazone chelators and explore the effect of these modifications on their UVA, UVC and blue light photoreactivity, photostationary state composition, photoisomer thermal stability, and relative iron(iii) binding affinity. These findings will inform the next generation of aroylhydrazone photoswitches for metal-gated photoswitching applications.

Papular mucinosis, or localized lichen myxedematosis (LM) (discrete papular type).

Lichen myxedematosus is condition characterized by localized areas of dermal deposition of mucin, presenting with firm papules localized to few areas of the body. The condition needs to be excluded from scleromyxedema, which, in addition to the firm papular eruption, has areas of induration and is usually associated with a monoclonal gammopathyand systemic symptoms. We present a 62-year-old woman with a several-year history of asymptomatic, firm papules over the face and arms with no evidence of thyroid disease or a monoclonal gammopathy,which is consistent with a diagnosis of localized lichen myxedematosus, the discrete papular variant. The patient is being treated with a topical calcineurininhibitor.

Primary anetoderma with undifferentiated connective tissue disease.

Anetoderma is a rare benign elastolytic disorder that is characterized by focal loss of elastin fibers on histopathology and is often recalcitrant to treatment. We present a case of a patient with a 20-year history of pruritic and painful hyperpigmented atrophic papules clustered on the neck, axillae, inframammary folds, and right medial thigh. Although the histopathologyof her axillary lesions was consistent with anetoderma, her clinical presentation is unusual given the extent of involvement, reported pain and pruritus, and sharp demarcation of the distribution. The diagnosticuncertainty of this case led to added difficulty in management of a disease that is already notoriously difficult to treat and may significantly impact patient's quality of life.

Overcoming Innocents' Naiveté: Pre-interrogation Decision-making Among Innocent Suspects.

Suspects, especially innocent ones, are highly susceptible to waiving their interrogation rights. This research tested the ability of two strategies to overcome innocent suspects' willingness to waive their rights. One strategy was based on the social influence of scarcity (i.e., not constraining the pre-interrogation time limit). The other strategy focused on disrupting individuals' cognitive fluency during the decision-making process (i.e., violating their induced expectation of offering a waiver). Disrupting innocent individuals' cognitive fluency increased their willingness to invoke their rights and, notably, was not qualified by interactions with any other factors. However, scarcity did not influence individuals' pre-interrogation decision-making. Results also further established the association between innocent individuals' naïve mindset and their willingness to waive their rights - specifically, innocents' willingness to waive their rights increased with the strength of their just world beliefs. The theoretical and applied implications of these findings are discussed. The importance and benefit of reforming pre-interrogation protocols using fair and feasible strategies that would disrupt suspects' cognitive fluency are emphasized. Copyright © 2016 John Wiley & Sons, Ltd.

Lichen planus pigmentosus.

Lichen planus pigmentosus (LPP) is a type oflichenoid dermatitis with superficial dermalmelanophages that presents as symmetrical,hyperpigmented macules and patches that aredistributed over the forehead, temples, cheeks, andneck. The condition most often occurs in darkerskinned individuals and is frequently resistant totreatment. Here we present a patient of Egyptiandecent with a lacy reticulated LPP eruption on theface.

Dermatomyositis, clinically presenting with cutaneous ulcers, with histopathologic evidence of perforating collagenosis.

Dermatomyositis is a systemic, autoimmune diseasewith a variety of clinical features that often includemyositis and characteristic cutaneous findings. Asubset of patients with dermatomyositis developcutaneous ulcers, often in the setting of vasculitis orvasculopathy. We present a case of dermatomyositiswith cutaneous ulcers that show perforatingcollagenosis on histopathologic examination.Acquired reactive perforating collagenosistypically occurs in the setting of diabetes mellitus,chronic renal failure, and other pruritic conditions,and this case represents a rare association withdermatomyositis, which may ultimately be helpful inelucidating the pathophysiology of this perforatingdisorder.

A multifunctional, light-activated prochelator inhibits UVA-induced oxidative stress.

UVA radiation can damage cells and tissues by direct photodamage of biomolecules as well as by initiating metal-catalyzed oxidative stress. In order to alleviate both concerns simultaneously, we synthesized a multifunctional prochelator PC-HAPI (2-((E)-1-(2-isonicotinoylhydrazono)ethyl)phenyl (trans)-3-(2,4-dihydroxyphenyl)acrylate) that contains a trans-(o-hydroxy)cinnamate ester photocleavable protecting group that is cleaved upon UVA exposure to release a coumarin, umbelliferone, and an aroylhydrazone metal chelator, HAPI (N'-[1-(2-hydroxyphenyl)ethyliden]isonicotinoylhydrazide). While the prochelator PC-HAPI exhibits negligible affinity for iron, it responds rapidly to UVA irradiation and converts to an iron-binding chelator that inhibits iron-catalyzed formation of reactive oxygen species and protects cells from UVA damage.

The world is not fair: an examination of innocent and guilty suspects' waiver decisions.

Suspects' decisions to waive or invoke their interrogation rights can have a considerable impact on their eventual legal fate. Although innocent and guilty suspects show differences in waiver rates, research has yet to examine whether innocent and guilty individuals' waiver decisions are differentially influenced by dispositional and situational factors. The current research examined the relationship among a dispositional factor (just world beliefs), a situational factor (social proof pressures-i.e., influencing others to believe that certain behaviors are normative) and innocent and guilty individuals' waiver decisions. Social proof pressures influenced the preinterrogation decisions of guilty individuals holding strong just world beliefs but not guilty individuals holding weak just world beliefs. However, social proof pressures influenced the preinterrogation decisions of innocent individuals holding weak just world beliefs but not innocent individuals holding strong just world beliefs. Results also indicated that strong just world beliefs are associated with attenuated stress responses to an accusation among innocent individuals but exacerbated stress responses among guilty individuals, thereby helping to explain why guilty and innocent individuals are differentially influenced by situational and dispositional factors. The theoretical and applied implications of these effects are discussed with an emphasis on the consequences of suspects' mindset during the preinterrogation decision-making process.

Sarcoidosis.

We present a 28-year-old man with a one-year history of cutaneous lesions in old scars and tattoos with concomitant subcutaneous nodules and myopathy. A skin biopsy specimen showed cutaneous sarcoidosis. We discuss the multiple aspects of this case, which represent unique presentations of this systemic disease as well as review isomorphic and isotopic responses.

Extracellular generation of adenosine by the ectonucleotidases CD39 and CD73 promotes dermal fibrosis.

Adenosine has an important role in inflammation and tissue remodeling and promotes dermal fibrosis by adenosine receptor (A2AR) activation. Adenosine may be formed intracellularly from adenine nucleotides or extracellularly through sequential phosphohydrolysis of released ATP by nucleoside triphosphate diphosphohydrolase (CD39) and ecto-5'-nucleotidase (CD73). Because the role of these ecto-enzymes in fibrosis appears to be tissue specific, we determined whether these ectonucleotidases were directly involved in diffuse dermal fibrosis. Wild-type and mice globally deficient in CD39 knockout (CD39KO), CD73 (CD73KO), or both (CD39/CD73DKO) were challenged with bleomycin. Extracellular adenosine levels and dermal fibrosis were quantitated. Adenosine release from skin cultured ex vivo was increased in wild-type mice after bleomycin treatment but remained low in skin from CD39KO, CD73KO, or CD39/CD73DKO bleomycin-treated mice. Deletion of CD39 and/or CD73 decreased the collagen content, and prevented skin thickening and tensile strength increase after bleomycin challenge. Decreased dermal fibrotic features were associated with reduced expression of the profibrotic mediators, transforming growth factor-ß1 and connective tissue growth factor, and diminished myofibroblast population in CD39- and/or CD73-deficient mice. Our work supports the hypothesis that extracellular adenosine, generated in tandem by ecto-enzymes CD39 and CD73, promotes dermal fibrogenesis. We suggest that biochemical or biological inhibitors of CD39 and/or CD73 may hold promise in the treatment of dermal fibrosis in diseases such as scleroderma.

Characterization of a photoswitching chelator with light-modulated geometric, electronic, and metal-binding properties.

Photoswitching molecules are utilized for a variety of applications where the rapid manipulation of the molecules' chemical properties and spatial orientations allows for new spatiotemporal control over molecular-scale interactions and processes. Here, we present a hydrazone-containing transition metal chelator, HAPI ((E)-N'-[1-(2-hydroxyphenyl)ethyliden]isonicotinoylhydrazide), that displays dual-wavelength photoswitching behavior. Several of its metal complexes, however, are inert to photoreaction and thereby add another layer of control over the photoswitch system. The light-induced twist in HAPI structure is accompanied by a dramatic change in electronic properties as well as chelator strength. This work introduces HAPI as the prototype for a class of molecules with properties that may be optimized for a variety of experimental applications that take advantage of phototriggered molecular changes.

White fibrous papulosis of the neck.

We present a 76-year old woman with a five-year history of asymptomatic, white papules that were grouped on the lateral and posterior aspects of the neck, inferior axillae, and central mid-back. The histopathologic findings showed thickened collagen bundles. A diagnosis of white fibrous papulosis of the neck was made, which is believed to be a manifestation of intrinsic aging. There are no treatments for white fibrous papulosis of the neck. One hypothesized approach is the application of a topical anti-oxidant to reduce free-radical induced aging.