Congenital Langerhans cell histiocytosis presenting in a 27-week-gestation neonate

Abstract

Langerhans cell histiocytosis is exceedingly rare in premature infants, and the few cases reported suggest a poor prognosis with systemic involvement. We present a case of Langerhans cell histiocytosis limited to a single cutaneous lesion, presenting in a 27-week-gestation infant, which is the youngest gestational age of reported Langerhans cell histiocytosis cases. The lesion showed spontaneous resolution by 41 weeks corrected gestational age, and systemic involvement was absent, demonstrating a mild course of skin-only Langerhans cell histiocytosis in a premature infant.

Geographic tonguelike presentation in a child with pityriasis rosea: Case report and review of oral manifestations of pityriasis rosea

Abstract

Oral lesions are rarely reported in patients with pityriasis rosea. We report a case of a 3-year-old boy with clinical evidence of generalized pityriasis rosea who developed asymptomatic oral lesions similar in appearance to geographic tongue. The generalized eruption and tongue lesions resolved simultaneously within 4 weeks. We also review the literature on the oral manifestations of Pityriasis rosea.

Bascule syndrome associated with syncopal episodes

Abstract

Bascule syndrome is a recently described benign vasomotor dermatosis characterized by Bier anemic spots, cyanosis, and urticaria-like eruption. We report a case of a 13-year-old girl with cutaneous lesions consistent with Bascule syndrome who had had three exercise-related syncopal episodes. It would be recommended to exclude orthostatic intolerance or postural orthostatic tachycardia syndrome when evaluating patients with Bascule syndrome.

Subacute cutaneous lupus erythematosus presenting in twins

Abstract

Subacute cutaneous lupus erythematosus is a clinically distinct form of cutaneous lupus erythematosus, with age of onset typically in the second to fifth decades. Eleven cases have been reported in childhood, and we present the first known case of subacute cutaneous lupus erythematosus in identical twins. Although flares are typically photo-induced, we present an annular eruption typical of subacute cutaneous lupus erythematosus with concurrent pinworm infestation, with recurrence of disease with cutaneous larva migrans. The patient's identical twin had a similar eruption with pinworm infection. This case highlights the possibility of parasitic infestation as a trigger for subacute cutaneous lupus erythematosus in genetically susceptible individuals.

Parental use of sun protection for their children—does skin color matter?

Abstract

Background/Objectives

Excessive sun exposure during childhood is a risk factor for skin cancer. This study aimed to compare the frequency of ideal sun protection use between parents with lighter- and darker-skinned children and explore their attitudes and beliefs on sun safety and their choice of sun protection.

Methods

Parents of children aged 6 months to 6 years completed self-administered questionnaires about sun protection practices for their children. Parents assessed their child's Fitzpatrick phototype and were divided into lighter- (Fitzpatrick phototype I-III) and darker-skinned (Fitzpatrick phototype IV-VI) groups. Sun safety guidelines from the Canadian Dermatology Association were used to qualify ideal sun protection.

Results

A total of 183 parents were included. Overall, 31 parents (17%) used ideal sun protection for their children. As their children grew older, parents were less likely to use ideal sun protection (odds ratio = 0.69, 95% confidence interval = 0.53-0.90). Parents in the lighter-skinned group were more likely to use ideal sun protection for their children (odds ratio = 7.4, 95% confidence interval = 2.7-20.1), believe that sun exposure was harmful (odds ratio = 17.2, 95% confidence interval = 4.0-74.9), and perceive value in sun protection (odds ratio = 11.4, 95% confidence interval = 3.3-39.0); the darker-skinned group believed that darker skin tones provided more sun protection (odds ratio = 12.4, 95% confidence interval = 6.1-25.4).

Conclusion

Ideal parental sun protection efforts are overall low, particularly in parents of darker-skinned children. The identified attitudes toward and beliefs about sun safety may aid in delivery of future sun protection interventions, especially in multiracial populations.

Treatment outcomes of vitiligo in Asian children

Abstract

This retrospective study aimed to identify factors that predict treatment response in a cohort of Asian children with vitiligo. Shorter duration of vitiligo was associated with better repigmentation. Patients with focal vitiligo of short duration have a good chance of achieving repigmentation with topical agents alone.

Skin lesions serve as clues to relapse of pediatric blastic plasmacytoid dendritic cell neoplasm

Abstract

A 10-year-old girl with a history of blastic plasmacytoid dendritic cell neoplasm, a rare malignancy in children, presented with recurrent skin eruptions beginning while on maintenance chemotherapy, including mildly pruritic skin-colored plaques, tender indurated nodules, and violaceous bound-down plaques. This case highlights an unusual presentation of relapsed blastic plasmacytoid dendritic cell neoplasm on chemotherapy, with skin lesions providing important clues to the progression of systemic disease.

Time-resolved fluorescence spectroscopy for the diagnosis of oral lichen planus

Summary

Background

Lichen planus (LP) is a T-cell mediated autoimmune disorder of unknown aetiology that affects the skin, nails, oral and genital mucous membranes. Conventionally, oral LP (OLP) is diagnosed through clinical assessment and histopathological confirmation by oral biopsy.

Aim

To explore the use of time-resolved fluorescence spectroscopy (TRFS) to detect fluorescence lifetime changes between lesional OLP and perilesional normal mucosa.

Methods

In this pilot study, measurements of lesional and perilesional buccal and mouth floor mucosa were conducted in vivo with a TRFS system. Histopathological findings were consistent with OLP in 8 out of 10 patients biopsied. Two patients with histopathological diagnoses of frictional hyperkeratosis and oral candidiasis, respectively, were excluded from the study.

Results

Our preliminary data show that lifetime values in the 360–560 nm spectral range indicate a significant differentiation between normal and diseased tissue. In contrast to the standard oral biopsy procedure, this technique is noninvasive, painless, time-efficient and safe.

Conclusions

Future studies are needed to better elucidate the diagnostic capability of TRFS and to further explore the sources of fluorescence contrast. This pilot study suggests that, based on fluorescence lifetime parameters, TRFS is a very promising technology for the development of a novel OLP diagnostic technique.

Development and validation of a reproducible model for studying post-inflammatory hyperpigmentation

Abstract

Post-inflammatory hyperpigmentation (PIH) has been reported to be the second most important dermatological diagnosis in the African American population with up to 20% of diagnoses linked to PIH (Alexis et al., 2007). The prevalence of PIH is also high in Hispanic populations ranging from 6 to 7.5% (Sanchez, 2003). Although more frequent in dark-skinned individuals (Davis and Callender, 2010), PIH is not uncommon in fair skin types representing 5.7% of dermatological problems in a population of European ancestry with skin types I to III (Taylor et al., 2008).

This article is protected by copyright. All rights reserved.

Answers to CME examination

CME examination

CME examination

Journal Based CME Instructions and Information

To fee or not to fee? The ethical issues of concierge medicine/dermatology

Concierge medicine is an emerging practice model that involves direct contracting with patients for medical services, often charging a flat monthly or yearly fee. There is considerable variation among concierge practices, but most include administrative service fees with an upfront annual payment to remain on a smaller patient panel.1

An open-label exploratory study evaluating the efficacy and safety of ingenol mebutate gel 0.05% for the treatment of verruca vulgaris

To the Editor: Current therapies for common warts (verruca vulgaris) often require months of treatment and focus on destruction, removal of callus, or stimulation of a local immune response.1-3 Topical use of ingenol mebutate gel, 0.05%, indicated for the treatment of actinic keratosis, induces necrosis and an inflammatory reaction.4 A recent case study series provided evidence for the efficacy of ingenol mebutate against anogenital warts.5

Frontal fibrosing alopecia and cutaneous comorbidities: A potential relationship with rosacea

To the Editor: Frontal fibrosing alopecia (FFA) is an increasingly prevalent lymphocytic, cicatricial alopecia with a yet unknown etiopathogenesis. Some cutaneous diseases have been associated with FFA, but the existing literature is limited to retrospective studies and case reports.1-3 The objective of our study was to analyze the frequency of associated cutaneous conditions in a large cohort of FFA patients.

A cross-sectional study of YouTube videos about atopic dermatitis

To the Editor: Patients are increasingly looking to online platforms for health information.1 One popular online platform is YouTube, which is a free video-streaming service. The loose content regulations of YouTube allow users to broadcast false information as easily as accurate information. One study found that most of the YouTube videos about tanning beds portrayed them in a positive light and another found that half of YouTube videos on immunizations did not explicitly support them.2,3 We conducted a cross-sectional study on the information on YouTube about atopic dermatitis (AD) by performing 5 searches on YouTube using the search terms "atopic dermatitis," "eczema," "eczema tips," "eczema cure," and "eczema treatment." We screened the first 2 pages of results for inclusion.

Iotaderma #289

Reply to: “The microbial flora of taxane therapy–associated nail disease in cancer patients”

See related letter on page 607

Response to: “Maintenance of Certification: A grandfatherly ethical analysis”

See related article on page 627

Crown vessels and follicular white dot: New dermoscopic findings in a case of solitary reticulohistiocytoma

A 17-year-old girl presented with 2-month history of solitary progressively enlarging asymptomatic 6- × 6-mm light pink-yellow nontender dome-shaped nodule over her left cheek with surface scaling, a solitary violaceous area, and peripheral telangiectasia (Fig 1).

Referral patterns to an osteoporosis clinic for dermatology patients undergoing prolonged corticosteroid therapy

To the Editor: Glucocorticoids are frequently used in dermatology. Glucocorticoid-induced osteoporosis (GIOP) is a well-recognized side effect with substantial morbidity. GIOP prevention measures are essential for bone health. Studies have shown dermatologists are underutilizers of bisphosphonates, first-line agents for osteoporosis prevention.1 A high-risk osteoporosis clinic (HIROC) developed by the rheumatology department was established at the Geisinger Medical Center. This retrospective cohort study reviewed dermatology patients taking oral glucocorticoids for more than 30 consecutive days to determine referral patterns to the HIROC, completion rate of referrals, and follow-up interventions.

Reply to: “Psychiatric adverse events during treatment with brodalumab: Analysis of psoriasis clinical trials”

I want to thank Dr Rieder1 for drawing attention to the challenges faced by brodalumab. I agree with nearly all the points made, although I hope Dr Rieder's prediction that the Risk Evaluation and Mitigation Strategies (REMS) program will doom this drug prove to be untrue.

Dermatology Calendar

Answers to CME examination

In response to Lebwohl et al, “Psychiatric adverse events during treatment with brodalumab: Analysis of psoriasis clinical trials”

To the Editor: I would like to commend Lebwohl et al for their thorough and transparent analysis of the psychiatric adverse events associated with the brodalumab trials.1 One of the first systemic agents for psoriasis to be examined in a study enrolling a population with no specific psychiatrically related exclusion criteria, brodalumab in some ways fell victim to its own noble aims. In retrospect, it should not have been unexpected that a trial enrolling a large cohort of middle-aged white men with moderate-to-severe psoriasis, some of whom had additional suicide risk factors, resulted in several episodes of suicidal ideation and behavior (SIB).

Editorial Board

The microbial flora of taxane therapy–associated nail disease in cancer patients

See related letter on page e71

Table of Contents

The U.K. approach to putting patient safety first when receiving non-surgical cosmetic therapies: The cosmetic practice standards authority

The 2013 Keogh Review of Cosmetic Regulation stated: In fact, a person having a non-surgical cosmetic intervention has no more protection and redress than someone buying a ballpoint pen or a toothbrush. This Department of Health Review of the regulation of Cosmetic Interventions presented the stark reality that non-surgical treatments are not regulated, patients are not protected and there needs to be significant change.1

The role of the OVOL1–OVOL2 axis in normal and diseased human skin

OVOLs (OVO-like proteins) are transcribed from ubiquitously conserved genes encoding a C2H2 zinc finger transcription factor in mammals [1,2]. Functional studies on Ovol1 and Ovol2 using knockout mice have suggested that these genes play a pivotal role in the development of epithelial tissues arising from germ cells [2–4]. However, the role of the OVOL1–OVOL2 axis in normal and diseased tissues remains unclear.

Improving the efficacy of PET-CT imaging in head and neck cancer management and surveillance through the multidisciplinary team: a multi-centre, retrospective cohort analysis of 51 patients

Abstract

• There has been a recent move towards image-guided surveillance of N2/N3 disease in HNSCC and neck dissection only in selected cases
• PET-CT demand is rising and alters management in a third of HNSCC patients
• PET-CT is expensive and can lead to unnecessary and harmful investigations, delaying treatment
• The MDT is significantly less likely to request an inappropriate PET-CT than the individual clinician
• Collaboration among specialists may minimise the ordering of inappropriate PET-CTs, reducing costs and improving patient safety and management

Effects of treatment for psoriasis on circulating levels of leptin, adiponectin and resistin: a systematic review and meta-analysis

Abstract

Background

Metabolic syndrome, a risk factor of cardiovascular disease, is more common in psoriatic patients compared to general population. Circulating adipokine concentrations are altered in psoriatic patients and are suggested to represent the pathophysiologic link between psoriatic lesions and metabolic alterations.

Objectives

To systematically review the literature for studies that investigated possible differences in the circulating levels of leptin, adiponectin or resistin in psoriatic patients before and after any treatment intervention and meta-analyze the best evidence available.

Methods

Search was conducted in three databases (PubMed, Central, EMBASE). Eligible for the review were studies that have assessed leptin, adiponectin or resistin concentrations in patients with psoriasis before and after any topical or systemic treatment.

Result

After treatment, blood concentrations of leptin were similar to the relevant ones before treatment (SMD: 0.06, 95% CI: -0.09 to 0.20), with no heterogeneity among studies (I²: 0%, p = 0.875). After treatment, blood concentrations of adiponectin were similar to the relevant ones before treatment (SMD: -0.14, 95% CI: -0.34 to 0.05), with significant heterogeneity among studies (I²: 36.8%, p = 0.032). After treatment, blood concentrations of resistin were significantly lower as compared to the relevant ones before treatment (SMD: 0.50, 95% CI: 0.20 to 0.79), with significant heterogeneity among studies (I²: 61.4%, p < 0.001).

Conclusions

There is no evidence that treatment for psoriasis modifies leptin and adiponectin concentrations. In the opposite way, treatment intervention reduces resistin concentrations, a finding that is expected to be of clinical importance.

This article is protected by copyright. All rights reserved.

A randomized, multi-national, non-inferiority, phase III trial to evaluate the safety and efficacy of BF-200 ALA gel versus MAL cream in the treatment of non-aggressive basal cell carcinoma with photodynamic therapy (PDT)

Abstract

Background

Basal cell carcinoma (BCC) represents the most common non-melanoma skin cancer worldwide affecting mainly adult, fair-skinned individuals. The WHO distinguishes aggressive and non-aggressive forms of which prototypical variants of the latter are primary nodular and superficial BCC.

Objectives

To demonstrate non-inferiority of BF-200 ALA (a nanoemulsion gel containing 5-aminolaevulinic acid) compared to MAL (a cream containing methyl-aminolevulinate) in the treatment of non-aggressive BCC with photodynamic therapy (PDT). Non-inferiority of the primary efficacy variable (overall patient complete response 12 weeks after last PDT) would be declared if the mean response for BF-200 ALA was no worse than that for MAL, within a statistical margin of Δ = -15%.

Patients/Methods

The study was a randomized, phase III trial performed in Germany and the UK with ongoing 5-year follow-up. Of 281 randomized patients, 138 were treated with BF-200 ALA, 143 with MAL. Patients received two PDT sessions one week apart. Remaining lesions 12 weeks after the second PDT were retreated. Illumination was performed with a red light source (635 nm, 37 J/cm²). Results shown include clinical endpoints as well as patients' reassessment 12 months after the last PDT.

Results

Of the BF-200 ALA-treated patients, 93.4% were complete responders compared to 91.8% in the MAL group. The difference of means was 1.6 with a one-sided 97.5% CI of -6.5, establishing non-inferiority (p<0.0001). Results for secondary efficacy parameters were in line with the primary outcome. Recurrence rates 12 months after the last treatment were ≤ 10%.

Conclusions

Treatment of non-aggressive BCC with BF-200 ALA-PDT is highly effective and well tolerated with proven non-inferiority to MAL-PDT and demonstrates low recurrence rates after 1-year follow-up.

This article is protected by copyright. All rights reserved.

Pilocarpine and Artificial Saliva for the Treatment of Xerostomia and Xerophthalmia of Sjögren's Syndrome: A double blind control trial

Abstract

Background

Sjögren's Syndrome (SS) is associated with xerostomia and xerophthalmia. Pilocarpine stimulates the secretion of saliva.

Objectives

Investigate and compare the efficacy of pilocarpine and artificial saliva as symptomatic treatments for xerostomia and xerophthalmia in patients with SS.

Patients and Methods

A double-blind, randomized, controlled study was performed. 72 patients with SS were assigned randomly to receive ten drops of pilocarpine (5 mg) or 10 drops of artificial saliva, orally, t.i.d.for 12 weeks. Patients were evaluated at baseline and periodically throughout the study by whole saliva and tear flow for global assessment of their dryness as well as for any adverse effects.

Results

Patients receiving pilocarpine had a statistically significant improvement in their salivary flow (p< 0.0001), lachrymal flow (p< 0.0001), and their subjective global assessment (p< 0.0001), compared with patients on artificial saliva. The most common side effects were sialorrhea and nausea.

Limitations

As the pilocarpine was in solution (drops), it was possible for the dosage to become inaccurate.

Conclusions

Pilocarpine is more effective than artificial saliva for enhancing salivary and lachrymal secretion in patients with SS. This is the first study comparing the efficacy of pilocarpine and artificial saliva as treatments for xerostomia and xerophthalmia in SS.

This article is protected by copyright. All rights reserved.

The synergistic activities of the combination of TNF-α, IL-17A, and IFN-γ in epidermal keratinocytes

Abstract

Psoriasis vulgaris is a common chronic inflammatory skin disease characterized by abnormal epidermal hyperplasia and the infiltration of cells including neutrophils and T cells.¹ Th1 and Th17 cells particularly infiltrate psoriatic lesions, and they are thought to play critical roles in the pathogenesis. Psoriatic keratinocytes are morphologically abnormal, and they are also involved in the cell infiltration.

Antibody agents that block key cytokines have been successfully used clinically for psoriasis.

This article is protected by copyright. All rights reserved.

A Review of Clinical Trial Registry Use in Dermatology Systematic Reviews

Abstract

An inherent qualification of systematic reviews is that they attempt to collate all relevant empirical evidence. While properly conducted systematic reviews are considered the gold standard for determining health care policy and clinical decision making, they are vulnerable to publication bias¹. Publication bias occurs when statistically nonsignificant data from unpublished literature are omitted from systematic reviews and meta-analyses².

This article is protected by copyright. All rights reserved.

Eccrine sweat glands associate with the human hair follicle within a defined compartment of dermal white adipose tissue

Summary

Background

Eccrine sweat glands (ESGs) are critical for thermoregulation and involved in wound healing. ESGs have traditionally been considered as separate skin appendages without connection to the pilosebaceous unit (PSU). However, recent preliminary evidence has encouraged the hypothesis that PSU and ESG are more interconnected than previously thought.

Objective

To reevaluate the morphology of human skin adnexa with an integrated 3D perspective in order to explore the possible interconnections that the PSU and the ESG may form.

Methods

A systematic 3D reconstruction method of skin sections, direct visualization of human scalp follicular unit transplant grafts and a scalp strip ex vivo were used to validate and further explore the hypothesis.

Results

We demonstrate that the coiled portion of most ESGs is morphologically integrated into the PSU of human scalp skin and forms a structural unit that is embedded into a specific, HF-associated region of dermal white adipose tissue (dWAT). This newly recognized unit is easily accessible and experimentally tractable by organ culture of follicular units and can be intravitally visualized.

Conclusions

We propose a model of functional human skin anatomy in which ESGs are closely associated with the PSU and the dWAT to form a common homeostatic tissue environment, which may best be encapsulated in the term adnexal skin unit (aSU). The challenge now is to dissect how each component of this superstructure of human skin functionally cooperates with and influences the other under physiological conditions, during regeneration/repair and in selected skin diseases.

This article is protected by copyright. All rights reserved.

Correction of T cell deficiency in ZAP-70 knockout mice by simple intraperitoneal adoptive transfer of thymocytes

Summary

The tyrosine kinase ZAP-70 (zeta-chain associated protein of 70 kDa) plays a key role in T cell development and signaling. In the absence of ZAP-70, T cell development is arrested in the CD4⁺CD8⁺ double positive stage, thus ZAP-70 homozygous knockout (ZAP-70^-/-) mice have no mature T cells in their peripheral lymphoid organs and blood, causing severe immunodeficiency.

We investigated the early kinetics and long-term effects of wild-type thymocyte transfer on T cell repopulation in ZAP-70^-/- mice. We used a single intraperitoneal (ip.) injection to deliver donor thymocytes to the recipients.

Here, we show that after ip. injection donor thymocytes leave the peritoneum through milky spots in the omentum and home to the thymus, where most probably donor-originated CD4^-CD8^- double negative thymocytes restore T cell development and the disrupted thymic architecture. Subsequently, newly developed, donor-originated, single-positive αβ T cells appear in peripheral lymphoid organs, where they form organized T cell zones. The established chimerism was found to be stable, as donor-originated cells were present in transferred ZAP-70^-/- mice as late as 8 months after ip. injection.

We demonstrate that a simple, ip. injection of ZAP-70^+/+ thymocytes is a feasible method for the long-term reconstitution of T cell development in ZAP-70 deficient mice. This article is protected by copyright. All rights reserved.

Immunoassay methods used in clinical studies for the detection of anti-drug antibodies to adalimumab and infliximab

Summary

Objective: To examine the assay formats used to detect anti-drug antibodies (ADA) in clinical studies of the anti-TNF monoclonal antibodies adalimumab and infliximab in chronic inflammatory disease and their potential impact on pharmacokinetic and clinical outcomes.

Methods: Using findings of a recent systematic literature review of the immunogenicity of 11 biologic/biosimilar agents, we conducted an ancillary qualitative review of a subset of randomized controlled trials and observational studies of the monoclonal antibodies against anti-tumor necrosis factor adalimumab and infliximab.

Results: Among studies of adalimumab and infliximab, the immunoassay method used to detect antibodies was reported in 91/111 (82%) and 154/206 (75%) adalimumab and infliximab studies, respectively. In most adalimumab and infliximab studies, an enzyme-linked immunosorbent assay or radioimmunoassay was used [85/91 (93%) and 134/154 (87%), respectively]. ADA incidence varied widely across assays and inflammatory diseases (adalimumab, 0–87%; infliximab, 0–79%). Pharmacokinetic and clinical outcomes were only reported for ADA-positive patients in 38/91 (42%) and 61/154 (40%) of adalimumab and infliximab studies, respectively. Regardless of assay format or biologic used, ADA formation was associated with lower serum concentrations, reduced efficacy, and elevated rates of infusion-related reactions.

Conclusion: Consistent with previous recommendations to improve interpretation of immunogenicity data for biologics, greater consistency in reporting of assay methods and clinical consequences of ADA formation may prove useful. Additional standardization in immunogenicity testing and reporting, application of modern, robust assays that satisfy current regulatory expectations, and implementation of international standards for marketed products may help improve our understanding of the impact of immunogenicity to biologics. This article is protected by copyright. All rights reserved.

A quarter of patients with type 1 diabetes have co-existing non-islet autoimmunity; the findings of a UK population-based family study

Summary

Individuals with type 1 diabetes (T1D) are at increased risk of coeliac disease (CD), autoimmune thyroiditis and autoimmune gastritis, but the absolute risks are unclear. The aim of this study was to investigate the prevalence of autoantibodies to tissue transglutaminase (TGA), thyroid peroxidase (TPOA), and gastric H⁺/K⁺-ATPase (ATPA) and their genetic associations in a well-characterised population-based cohort of individuals with T1D from the Bart's-Oxford family study for whom islet autoantibody prevalence data were already available. Autoantibodies in sera from 1072 patients (males/females 604/468; median age 11.8 years, median T1D duration 2.7 months) were measured by radioimmunoassays; HLA class II risk genotype was analysed in 973 (91%) using PCR-SSP. The prevalence of TGA (and/or history of CD), TPOA and ATPA in patients was 9.0%, 9.6%, and 8.2%, respectively; 3.2% had two or more autoantibodies. Females were at higher risk of multiple autoimmunity; TGA/CD were associated with younger age, and TPOA with older age. ATPA were uncommon in patients under 5 years, and more common in older patients. Anti-glutamate decarboxylase autoantibodies were highly predictive of co-existing TPOA/ATPA. TGA/CD were associated with HLA DR3-DQ2, with the DR3-DQ2/DR3-DQ2 genotype conferring the highest risk, followed by DR4-DQ8/DR4-DQ8. ATPA were associated with DR3-DQ2, DRB1*0404 (in males) and the DR3-DQ2/DR4-DQ8 genotype (in females). TPOA were associated with the DR3-DQ2/DR3-DQ2 genotype. Almost one quarter of patients diagnosed with T1D under 21 years have at least one other organ specific autoantibody. HLA class II genetic profiling may be useful in identifying those at risk of multiple autoimmunity. This article is protected by copyright. All rights reserved.

Separation of plasma-derived exosomes into CD3(+) and CD3(-) fractions allows for association of immune cell and tumor cell markers with disease activity in HNSCC patients

Summary

Head and neck squamous cell carcinoma (HNSCC) is a highly immunosuppressive malignancy. Exosomes in HNSCC patients' plasma are enriched in inhibitory cargo and mediate immunosuppression. As these exosomes are products of various cells, the cellular origin of immunoregulatory proteins they carry is unknown. To test whether tumor- or T cell-derived exosomes in patient's plasma are immunosuppressive and impact on disease activity, we separated CD3(-) from CD3(+) exosomes by immunocapture using anti-CD3 Abs. The exosome protein cargo was evaluated for immunoregulatory proteins using on-bead flow cytometry. Tumor protein-enriched CD3 (-) exosomes were CD44v3(+). Surprisingly, mean levels of PD-L1, CTLA-4 and COX-2 were similar in CD3(+) and CD3(-) exosomes, although the latter induced higher (p<0.0025) ex vivo apoptosis of CD8(+) T cells and greater (p<0.005) conversion of CD4+ T cells to CD4(+)CD39(+) Treg. CD3(+) and CD3(-) exosomes carrying high levels of immunosuppressive proteins were highly effective in mediating these functions. Exosomes of patients with UICC stage III/IV disease had higher levels of PD-L1 and COX-2 than stage I/II patients (p<0.005). Patients with nodal involvement had exosomes with the higher inhibitory protein content than N0 patients (p<0.03). CD3(+) and CD3(-) exosomes of HNSCC patients had higher PD-L1, COX-2 and CD15s levels than healthy donors' exosomes (p<0.009), although levels of immunostimulatory OX40 or OX40L were not different. By isolating CD3(-)/CD44v3-enriched and CD3(+) exosomes from plasma, the cellular origins of immunoregulatory proteins they carry were identified. Association of exosome molecular profiles with disease progression supports the exosome potential as future cancer biomarkers. This article is protected by copyright. All rights reserved.

Sunscreen use in schools: a content analysis of U.S. state laws

A technique for teaching and photo-documentation of direct endoscopic rigid oesophagoscopy

Abstract

Direct oesophagoscopy is largely a diagnostic procedure performed for a variety of symptoms (e.g. unilateral otalgia or odonophagia) or as part of a panendoscopy to exclude a synchronous primary; therefore good visualisation of abnormal mucosa is essential. The current standard oesophagoscopy technique involves direct visualisation from approximately 25cm down a narrow, illuminated oesophagoscope limiting visualisation of abnormal mucosa. Usually performed by a single operator, the technique is difficult to teach, as the trainee is unable to visualise what the trainer is seeing endoluminally and visa versa.

This article is protected by copyright. All rights reserved.

Lipomatoses

Summary

Lipomatoses are benign proliferations of adipose tissue, often with typical distribution patterns, which usually occur without clear causes. In contrast to circumscribed lipomas, they develop diffusely and symmetrically and are not surrounded by a fibrous pseudocapsule.

The most common form is benign symmetric lipomatosis (BSL; Launois-Bensaude syndrome), of which four types are distinguished based on the distribution pattern of hyperplastic adipose tissue. The etiology and pathogenesis of the disease are still largely unknown, although some forms appear to have a hereditary basis or to be associated with increased alcohol consumption. In some cases, mitochondrial dysfunctions have been detected. Lipomatoses may be solitary, but may also be associated with other symptoms or illnesses (comorbidity). Effective drug therapies are not known, but surgical procedures can alleviate the symptoms.

Lipomatosis dolorosa, which can be distinguished from BSL, occurs predominantly in middle-aged women and is characterized by proliferation of adipose tissue and severe pain in the affected areas. Various differential diagnoses and concomitant illnesses need to be considered, in particular depression. There are no evidence-based recommendations for therapy. Repetitive lidocaine infusions can achieve temporary improvement. Recurrence after surgical intervention is not uncommon, but long-term success is also possible.

Dermatologic surgery in children: an update on indication, anesthesia, analgesia and potential perioperative complications

Summary

Background

Children undergoing dermatosurgical procedures require, unlike adults, particular attention; the administration of various analgesics, anesthetics or sedatives requires a thorough knowledge of drug pharmacokinetics and pharmacodynamics. Furthermore, there are concerns that drugs used for sedation/general anesthesia may result in anesthetic/analgesic complications in children undergoing surgery, with a risk of impaired mental development.

Objectives

Based on our clinical experience and a literature review, we illustrate the most commonly used analgesic, anesthetic and sedative drugs in pediatric dermatosurgery, and identify risk factors and complications following dermatosurgical procedures.

Results

Topical anesthetics can be used in children for superficial dermatologic procedures or prior to infiltration anesthesia. Maximum recommended doses based on body weight should be calculated in order to avoid overdosage of local anesthetics. General anesthesia in dermatosurgery is considered safe and has a low rate of side effects. However, caution is advised in children under the age of one due to potential long-term neurological side-effects. NSAIDs and opioids play a significant role in analgesia for children.

Conclusions

This article reviews currently available data on analgesia, anesthesia and complications that may arise in pediatric dermatosurgery. These data may be useful in optimizing the safety and quality of care and in improving parent counseling.

Long-distance alteration of lymphatic drainage in a melanoma patient after axillary lymph node dissection

Huge pedunculated tumor of the thigh

Is manual acne therapy medically necessary?

Asymptomatic yellowish papules on the upper arms

Issue Information

GATA-3 staining in primary cutaneous apocrine cribriform carcinoma: usefulness To differentiate it from breast cancer metastasis

ABSTRACT

BACKGROUND

Primary cutaneous apocrine cribriform carcinoma (PCACC) is a rare tumor, clinically appearing as a solitary nodule, mostly involving extremities of females and this lesion usually raise a differential diagnosis with metastatic cribriform carcinomas, especially breast cancer.

DESIGN

To study GATA3 expression in a series of 14 primary cutaneous cribriform carcinomas and to test this immunostaining usefulness to differentiate this tumor from metastatic breast cancer.

RESULTS

No primary cutaneous apocrine cribriform carcinoma express GATA3. Breast cancer metastasis express GATA3 in 100% of our studied cases.

CONCLUSION

Even when GATA3 expression has been reported in many benign and malignant adnexal tumors, mostly the sebaceous, follicular and apocrine ones, as well as in many other neoplasms, GATA3 staining to differentiate PCACC from skin breast cancer metastasis has a high negative predictive value. A positive GATA3 staining in this context should led to rule out PCACC with a high level of confidence.

Potential efficacy of a RNAi-based topical treatment for psoriasis

History of Morgellons disease: from delusion to definition

Influence of land use on the health of a detritivorous fish ( Ancistrus mullerae ) endemic to the Iguassu ecoregion: relationship between agricultural land use and severe histopathological alterations

Abstract

This study aimed to evaluate the histopathological biomarkers of the gills and liver of endemic catfish to test the hypothesis that, in environments under intense land use by agricultural activities, histopathological alterations occur more severely. Samples were collected by electrofishing in seven streams in the Lower Iguaçu basin quarterly from August 2015 to February 2016. The gills and livers were processed according to routine histological methods and examined by light microscopy. The histopathological alterations observed in fish from the streams with a higher percentage of natural vegetation cover were considered modest and indicated normal functioning of the organ (such as edema, hyperplasia, and leukocyte infiltration). As predicted, fish collected in streams with higher agricultural influence presented moderate to severe damage (aneurysm, vacuolization and cytoplasmic degeneration, and pyknotic nucleus). The abundance of chloride cells was significantly increased in the gills of Ancistrus mullerae collected in rural streams. In addition, in most streams, mucous cells were more abundant during the rainy period. Significant differences were observed in the histopathological index (HI) of the gills and livers, where severe histopathological alterations occurred in fish from streams with a higher agricultural influence. The observed alterations were more severe in the liver than in the gills, which are indeed related to the liver's key role in the detoxification of xenobiotics. We conclude that more severe histological alterations occurred in fish from streams with the highest land use by agricultural activities. Thus, our work provides important insight into the conservation and management of natural resources.

Exposure to hexavalent chromium in welders: Results of the WELDOX II field study

Abstract

Objectives

Exposure to hexavalent chromium (Cr(VI)) has been primarily studied in chromate production. Here, we measured personal exposure to respirable Cr(VI) together with airborne and urinary Cr and Ni in welders to explore levels and associations between various measures of exposure.

Methods:

Shift concentrations of Cr(VI), Cr, and Ni were measured in respirable welding fumes in 50 men who used either gas metal arc welding (GMAW) (n = 24) or tungsten inert gas welding (TIG) (n = 19) as their major technique. Cr and Ni were determined in pre- and post-shift urine samples. Concentrations below the limit of quantification (LOQ) were multiply imputed. Spearman correlation coefficients (r_s) were calculated with 95% confidence intervals (CIs) to explore associations between the exposure variables, and regression models were applied to estimate the effect of the parent metal on the urinary concentration.

Results:

Regarding the respirable Cr(VI), 62% of the measurements were below the LOQ, the 75^th percentile was 0.50 µg m⁻³_, and 8 out of 50 (16%) welders exceeded 1 µg m⁻³. The highest shift concentration that occurred as a result of shielded metal arc welding (SMAW) was 180 µg m⁻³. The Cr(VI) content in total Cr ranged from 4 to 82% (median 20%), although the concentration correlated with total Cr (r_s 0.55, 95% CI 0.46; 0.64). The correlation between Cr(VI) and Ni was weaker (r_s 0.42, 95% CI 0.34; 0.51) than that between total Cr and Ni in welding fumes (r_s 0.83, 95% CI 0.74; 0.92). Both Cr(VI) and total Cr influenced the urinary Cr concentrations in post-shift samples (P = 0.0008 and P ≤ 0.0001, respectively). The airborne shift exposure was a weaker determinant than the Cr content in pre-shift urine samples, which strongly correlated with post-shift urinary Cr (r_s 0.78, 95% CI 0.69; 0.87).

Conclusions:

The Cr(VI) content in total Cr varied considerably in welding fumes. The majority of welders using GMAW or TIG presented with shift concentrations of respirable Cr(VI) below 1 µg m⁻³. However, very high Cr(VI) concentrations may occur, for example in SMAW. The urinary concentration of total Cr, cannot be used to precisely determine the shift concentration of respirable Cr(VI) in welders.

Renal fungus ball in a patient with retroperitoneal fibrosis: Unique complication in a rare disease

Summary

Candida fungus ball is a rare presentation of urinary tract infections among adult patients and is associated with considerable morbidity. Because clinical signs are not specific, diagnosis is often delayed. Furthermore, treatment is occasionally difficult, and the approach to such cases varies widely among different centers. In this report, we describe a patient with retroperitoneal fibrosis who developed a renal fungus ball. Management of this challenging case is discussed, and review of the literature is presented.

Response of soil microbial communities to red mud-based stabilizer remediation of cadmium-contaminated farmland

Abstract

In this work, a field test was conducted to investigate the effects of heavy metal stabilizer addition on brown rice and microbial variables in a cadmium (Cd)-contaminated farmland from April to October in 2016. Compared with the control, red mud-based stabilizer (RMDL) effectively reduced the concentration of Cd in brown rice (with the removal rate of 48.14% in early rice, 20.24 and 47.62% in late rice). The results showed that adding 0.3 kg m⁻² RDML in early rice soil or soil for both early and late rice increased the microbial biomass carbon (MBC), the number of culturable heterotrophic bacteria and fungi, and the catalase activity in soil at different stages of paddy rice growth. Furthermore, there was no notable difference in the diversity of the bacterial species, community composition, and relative abundance at phylum (or class) or operational taxonomic unit (OTU) levels between the control and treatment (RMDL addition) groups. In a word, RMDL could be highly recommended as an effective remediation stabilizer for Cd-contaminated farmland, since its continuous application in paddy soil cultivating two seasons rice soil could effectively decrease the Cd content in brown rice and had no negative impact on soil microorganisms.

Efficacy of MAS063DP lotion vs 0.02% triamcinolone acetonide lotion in improving post-ablative fractional CO2 laser resurfacing wound healing: a split-face, triple-blinded, randomized, controlled trial

Abstract

Proven as effective acne scar treatment, ablative fractional carbon dioxide (AFCO₂) laser requires post-laser wound healing care. MAS063DP is a multicomponent nonsteroidal anti-inflammatory moisturizer for effective post-laser treatment. This study compares the efficacy of MAS063DP and 0.02% triamcinolone acetonide (TA) lotion for post-laser wound healing and complications. A split-face, triple-blinded, clinical study was performed in 16 patients, aged 20–50 years, receiving AFCO₂ on both sides of the face, with MAS063DP on one side and 0.02% TA on the other side for 7 days twice daily. Digital photography, hemoglobin, and melanin index at baseline were obtained immediately after laser treatment and then at days 3, 5, 7, and 30. Erythema, edema, crusting, adverse effects, and post-inflammatory hyperpigmentation (PIH) were followed every visit. Sixteen patients, mean age 38.6 (8.4) years, with moderate–severe atrophic scar and skin phototype III–IV completed the study. Clinical improvement of edema, erythema, crusting, and hyperpigmentation was observed from day 3 to day 30 (P < 0.001), with no statistically significant difference in both groups. There was also no statistical difference of hemoglobin, melanin index, and texture at days 3, 5, 7, and 30. Melanin index at day 30 was significantly less than baseline in both MAS063DP and 0.02% TA. With PIH in 50% of cases, both treatments demonstrated good safety profiles and no serious adverse reactions. MAS063DP could be an effective treatment for post-laser wound healing and complications, compatible to 0.02% TA.

The in-hospital burden of hidradenitis suppurativa in patients with inflammatory bowel disease: a decade nationwide analysis from 2004 to 2014

Abstract

Background

Hidradenitis suppurativa (HS) is a chronic inflammatory disease that significantly affects the patient's quality of life. Multiple studies have shown a strong association between HS and inflammatory bowel disease (IBD). Our primary goal was to explore the in-hospital burden of HS on patients with IBD. Our secondary goal was to establish unique baseline characteristics and comorbidities of IBD patients with HS.

Methods

This was a retrospective cohort study using the National Inpatient Sample (NIS) database for the years 2004 through 2014. All patients with ICD-9 CM codes for any diagnosis of IBD and HS were included. The primary outcome was the medical and financial burden of HS on patients with IBD. Medical burden was measured by in-hospital morbidity and mortality, and financial burden was measured by resource utilization.

Results

A total of 3,079,332 admissions with IBD were recorded, of which 4369 had a concomitant diagnosis of HS. IBD-HS patients were significantly younger and mostly African-American females; they were more likely to be smokers, obese, and have diabetes mellitus, depression, and anemia. There was no mortality difference between the IBD-HS and IBD-only groups; nevertheless, there was a higher likelihood of developing sepsis in the IBD-HS cohort (4.9% vs. 2.6%; P < 0.001). Patients with IBD-HS had an increased hospital length of stay (5 vs. 4 days; P < 0.001) and higher total hospitalization costs ($13,272 vs. $12,237; P = 0.013).

Conclusions

This large-scale study strengthens the evidence that these two inflammatory conditions are truly associated and establishes their joint effect on overall morbidity, mortality, and resource utilization.

Recent advances and development in epidermal and dermal drug deposition enhancement technology

Abstract

Skin is the largest and easily accessible organ of the body. Increases in incidences of dermatological disorders, demand for drug targeting, and patient compliance have increased the popularity of topical drug delivery amongst the people. However, drug delivery across the skin is still a challenge for researchers because permeation of maximum drugs is hindered by the upper layer of the epidermis (stratum corneum). Several approaches like use of chemical permeation enhancers and physical methods such as sonophoresis, iontophoresis, electroporation, microneedles, etc., have been used to deliver the drugs topically. These methods of topical drug delivery have some limitations and drawbacks. Therefore new techniques based on nano drug delivery system such as ultradeformable liposomes, nanostructured lipid carriers, nanoemulsions, solid lipid nanoparticles, lipospheres, nanoparticles, and ethosomes have been exploited for enhancing epidermal and dermal drug deposition. Development of these nanosytems requires a good understanding of mechanism of drug permeation, physicochemical properties of drug and carriers, and technological advancements in methodology. Therefore, this article covers recent advances in epidermal and dermal drug deposition enhancement approaches, biopharmaceutical challenges with dermal drug delivery, issues in formulation development, and regulatory aspects of nanosystem. This review article also discusses the concern of topical drug delivery in immunization, gene delivery, and cosmeceuticals.

Cutaneous Refractile Foreign Body Microemboli with Intravascular Injection of Oral Medication

Abstract

Injection drug abuse (IDA) is known to cause a spectrum of systemic and cutaneous complications. Despite the increasing incidence of IDA around the world, there is a paucity of literature discussing cutaneous complications from a dermatopathologic perspective. We present a case of a 35-year-old male with a complex medical history of Von Willebrand disease, Behcet's disease and diverticular disease. Following a sigmoidectomy/colostomy for diverticular perforation, he presented with fever and an indurated right arm displaying livedoid purpura. The right distal fingertips showed purpura with focal ulceration. A punch biopsy of the right wrist did not show evidence of inflammatory vasculitis or pyogenic infection, but instead demonstrated a focus of polarizing, refractile material occluding a dilated arterial lumen within the mid-dermis. The patient admitted to injecting a suspension of crushed ondansetron (Zofran) tablets into the antecubital area to control post-operative nausea. It is known that direct intravascular injection of foreign material can cause distal ischemia and necrosis, either by local vasoconstriction, thrombosis, or formation of microemboli, as in this patient. Our objective is to bring awareness to this rarely reported phenomenon, and to raise clinical suspicion for IDA when confronted with such a unique vasculopathic pattern.