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Background: ATTR (ATTRv) amyloidosis neuropathy is characterized by progressive sensorimotor and autonomic nerve degeneration secondary to amyloid deposition caused by a misfolded transthyretin protein (TTR). Small nerve fiber neuropathy is an early clinical manifestation of this disease resulting from the dysfunction of the Aδ and C small nerve fibers. Tafamidis, a selective TTR stabilizer, has proven its efficacy in the earlier stages of hATTR. Objectives: To evaluate the clinical course and utility of cutaneous pathological biomarkers in patients with ATTR amyloidosis treated with tafamidis compared to control patients. Methods: Forty patients diagnosed with early stages of ATTRv amyloidosis (polyneuropathy disability [PND] scores 0‐II) underwent small and large nerve fiber neurological evaluations, and annual skin biopsies for intraepidermal nerve fiber density (IENFD) and amyloid deposition index (ADI) estimation. Thirty patients were allocated to receive tafamidis, and 10 patients served as controls. Tafamidis pharmacokinetics analysis was performed in patients who received the treatment. Results: At baseline, 12% of patients in stage PND 0 and 28% in PND I displayed small nerve fiber denervation in the distal thigh, whereas 23% and 38%, respectively, in the distal leg. Similarly, 72% and 84% had amyloid deposition in the distal thigh and 56% and 69% in the distal leg. Following 1 year of treatment, the tafamidis group showed significant clinical improvement compared to the control group, revealed by the following mean differences (1) −9.3 versus −4 points (p = <.00) in the patient's neuropathy total symptom score 6 (NTSS‐6) questionnaire, (2) −2.5 versus +2.8 points (p = <.00) in the Utah Early Neuropathy Score (UENS), and (3) +1.2°C versus −0.6 (p =.01) in cold detection thresholds. Among the patients who received tafamidis, 65% had stable or increased IENFD in their distal thigh and 27% in the distal leg. In contrast, all patients in the control group underwent denervation. The ADI either decreased or remained constant in 31% of the biopsies in the distal thigh and in 24% of the biopsies in the distal leg of the tafamidis‐treated patients, whereas it rose across all the biopsies in the control group. At the 4‐year follow‐up, the tafamidis group continued to display less denervation in the distal thigh (mean difference [MD] of −3.0 vs. −9.3 fibers/mm) and the distal leg (mean difference [MD] −4.9 vs. −8.6 fibers/mm). ADI in tafamidis‐treated patients was also lower in the distal thigh (10 vs. 30 amyloid/mm2) and the distal leg (23 vs. 40 amyloid/mm2) compared to control patients. Plasma tafamidis concentrations were higher in patients with IENFD improvement and in patients with reduced amyloid deposition. Patients without amyloid deposition in the distal leg at baseline displayed delayed disease progression at 4 years. Conclusions: Cutaneous IENFD and amyloid deposition assessments in the skin of the distal thigh and distal leg are valuable biomarkers for early diagnosis of ATTR amyloidosis and for measuring the progression of small nerve fiber neuropathy. Early treatment with tafamidis slows the clinical progression of the disease, skin denervation, and amyloid deposition in the skin. Higher plasma concentrations of tafamidis are associated with better disease outcomes, suggesting that increasing the drug dose could achieve better plasma concentrations and response rates. This study describes the longest small nerve fiber neuropathy therapeutic trial with tafamidis and is the first to report small fiber symptoms, function, and structural assessments as outcomes. [ABSTRACT FROM AUTHOR]

Over recent decades, peripheral sensory abnormalities, including the evidence of cutaneous denervation, have been reported among the non-motor manifestations in amyotrophic lateral sclerosis (ALS). However, a correlation between cutaneous innervation and clinical features has not been found. The aims of this study were to assess sensory involvement by applying a morpho-functional approach to a large population of ALS patients stratified according to King's stages and correlate these findings with the severity and prognosis of the disease. We recruited 149 ALS patients and 41 healthy controls. Patients undertook clinical questionnaires for small fibre neuropathy symptoms (Small Fiber Neuropathy Symptoms Inventory Questionnaire) and underwent nerve conductions studies (NCS) and 3-mm punch skin biopsies from leg, thigh and fingertip. We assessed intraepidermal nerve fibre (IENF) and Meissner corpuscle (MC) density by applying an indirect immunofluorescence technique. Moreover, a subset of 65 ALS patients underwent a longitudinal study with repeat biopsies from the thigh at 6- and 12-month follow-ups. Serum NfL levels were measured in 40 patients. Sensory symptoms and sensory NCS abnormalities were present in 32.2% and 24% of patients, respectively, and increased across clinical stages. Analogously, we observed a progressive reduction in amplitude of the sensory and motor ulnar nerve potential from stage 1 to stage 4. Skin biopsy showed a significant loss of IENFs and MCs in ALS compared with healthy controls (all P < 0.001). Across the clinical stages, we found a progressive reduction in MCs (P = 0.004) and an increase in IENFs (all P < 0.027). The increase in IENFs was confirmed by the longitudinal study. Interestingly, the MC density inversely correlated with NfL level (r = −0.424, P = 0.012), and survival analysis revealed that low MC density, higher NfL levels and increasing IENF density over time were associated with a poorer prognosis (all P < 0.024). To summarize, in patients with ALS, peripheral sensory involvement worsens in parallel with motor disability. Furthermore, the correlation between skin innervation and disease activity may suggest the use of skin innervation as a putative prognostic biomarker. [ABSTRACT FROM AUTHOR]

Background: Bovine besnoitiosis (elephant skin disease) caused by Besnoitia besnoiti is a costly endemic disease in the Middle East, Asia, and tropical and subtropical Africa and is also emerging as a significant problem in Europe. This study is aimed at determining the prevalence of B. besnoiti in blood and skin biopsies of cattle as well as evaluating the risk factors associated with the infection among cattle in Mosul, Iraq. Methods and results: To achieve this aim, four hundred and sixty apparently healthy cattle of different breeds, ages, and sexes were sampled from seven different locations in Mosul, Iraq. Blood and skin biopsies were carefully collected from each cattle, and these samples were subjected to molecular analysis. The detection of B. besnoiti was molecularly confirmed by the presence of 231 bp of ITS-1 in the rDNA gene of the protozoan. Besnoitia besnoiti DNA was present in 74 (16.09%; 95% CI = 13.01–19.72) and 49 (10.65%; 95% CI = 8.15–13.80) of the blood and skin biopsies, respectively, that were analyzed. Age, breed, and sex were significantly (p < 0.05) associated with the occurrence of B. besnoiti among cattle in the study area. Conclusions: Findings from this study will serve as baseline data in the epidemiology, prevention, and control of the protozoan among cattle in Iraq. [ABSTRACT FROM AUTHOR]

Objectives Adult T-cell leukemia/lymphoma (ATLL) is a rare aggressive T-cell leukemia/lymphoma associated with human T lymphotropic virus type 1 infection. The patients might present with skin rash before, at, or after the diagnosis. The dermatopathologic finding might be diagnostically very challenging. Methods We retrospectively identified 110 patients with ATLL at a single institution in a 19-year period, with 19 patients having skin biopsies. Clinical, dermatopathologic, immunophenotypic, and molecular findings were studied. Results The cohort included 13 skin-first (5 acute, 5 lymphomatous, 2 chronic, 1 smoldering), 6 skin-second (4 acute, 1 lymphomatous, 1 smoldering), and 91 patients without skin biopsy. Some nonphotoprotected areas of body such as the forearm and lower lip were also seen. Skin manifestations included papular (5), erythroderma (1), nodulotumoral (3), plaques (1), patches (1), and a combination of skin rashes (2). Histopathologic findings included large pleomorphic cells, angiocentrism, epidermal infiltration with large Pautrier-like microabscesses, and folliculotropism. Fifteen (78.9%) cases showed CD4+/CD7–/CD25+. Next-generation sequencing study was conducted on 5 patients using either blood or bone marrow samples, revealing multiple genetic mutations across multiple signaling pathways. Conclusions Pleomorphic large, atypical cells with CD4+/CD25+/CD7– immunophenotype from a non–"bathing trunk" location, especially in a patient from endemic regions, raise suspicion for ATLL. T-cell receptor gene rearrangement is almost always positive, and the neoplasm usually demonstrates multiple mutations by next-generation sequencing study. [ABSTRACT FROM AUTHOR]

The whale shark (Rhincodon typus) is a filter-feeding organism that can be considered a sentinel species, and Bahía de los Ángeles (BLA) in the Gulf of California is an important sighting site for these elasmobranchs. This filter-feeding organism can be considered a pollutant sampler from the marine environment. Persistent organic pollutants are toxic compounds with high mobility and environmental persistence, bioaccumulation and trophic transfer. Among these are polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs). The present work aimed to determine concentrations of PAHs and OCPs in whale shark skin biopsies, collected in 2021 at BLA. Mean detected levels of PAHs and OCPs were 279.4 ng/g dw (dry weight) and 1478.1 ng/g dw, respectively. Analysis of similarities between the ordered sizes (4.2–7.6 m) and the concentrations of PAHs and OCPs indicated no significant differences. Individual PAHs detected indicate pyrogenic and petrogenic sources; the presence of pesticides at levels higher than those of hydrocarbons may be related to agricultural activity in the areas surrounding the Baja California peninsula. This study is the first report of PAH levels in R. typus for the Gulf of California and Mexico. [ABSTRACT FROM AUTHOR]

BACKGROUND: Leprosy, Hansen's disease, is a chronic granulomatous infectious disease caused by Mycobacterium leprae. It is a slowly progressive, chronic infectious disease which mainly affects peripheral nerve and skin. AIMS AND OBJECTIVES: This article aims to study the various histological types of leprosy in a tertiary care hospital. MATERIALS AND METHODS: It was a retrospective study carried out from January 2021 to September 2023. A series of 109 clinically suspected skin lesions of leprosy were examined histopathologically. RESULTS: In our study, out of the 109 cases the most common histopathological type of leprosy was borderline tuberculoid i.e. 43 cases (39.4%). 2nd most common type in our study was tuberculoid type which included 16 cases (14.6%). Borderline borderline type had 11 cases (10.0%), lepromatous type 14 cases (12.8%), indeterminate 14 cases (12.8%) and histoid type 2 cases (1.8%). CONCLUSION: The spectrum of leprosy presentation is very wide. The findings in our study were more common in males and present mostly in the 21 to 40 years of life. Most common histopathological finding was borderline tuberculoid type. [ABSTRACT FROM AUTHOR]

Epigenetic approaches for estimating the age of living organisms are revolutionizing studies of long‐lived species. Molecular biomarkers that allow age estimates from small tissue biopsies promise to enhance studies of long‐lived whales, addressing a fundamental and challenging parameter in wildlife management. DNA methylation (DNAm) can affect gene expression, and strong correlations between DNAm patterns and age have been documented in humans and nonhuman vertebrates and used to construct "epigenetic clocks". We present several epigenetic clocks for skin samples from two of the longest‐lived cetaceans, killer whales and bowhead whales. Applying the mammalian methylation array to genomic DNA from skin samples we validate four different clocks with median errors of 2.3–3.7 years. These epigenetic clocks demonstrate the validity of using cytosine methylation data to estimate the age of long‐lived cetaceans and have broad applications supporting the conservation and management of long‐lived cetaceans using genomic DNA from remote tissue biopsies. [ABSTRACT FROM AUTHOR]

Background: Histopathology protocols for processing dermatopathology specimens vary among laboratories. Objective: To determine an optimal histopathology protocol to minimize cost and turnaround time (TAT) for biopsy specimens in a dermatopathology laboratory. Methods: A prospective, 4‐month study compared the mean cost and TAT of producing one versus two initial H&E slides, and zero versus three unstained slides that could be used for frequently used special or immunohistochemical (IHC) stains. Results: For all cases, cost was lower for one versus two initial H&E slides, with an insignificant increase in TAT. Producing three vs zero unstained slides incurred higher cost, with no reduction in TAT. In a subset of cases in which frequently used special or IHC stains were performed, cost and TAT were optimized by producing one initial H&E and three unstained slides. Conclusion: A protocol of one initial H&E slide and zero unstained slides optimizes cost and TAT in our dermatopathology laboratory. Pigmented lesions and inflammatory dermatoses may benefit from the addition of unstained slides. Further study is needed to quantify this benefit and evaluate for other cases for which an alternative protocol is advantageous. [ABSTRACT FROM AUTHOR]

Background: Generally, in practical dermatology, the term artifacts is used to describe what is called pathomimia which means self-inflicted lesions or that lesions induced accidentally on oral mucosa and skin. Regarding dermatopathology, the word, 'artefact' comes from the Latin term, 'Ars' = art and 'factum' = made. This study evaluates types of artifacts, frequencies, and their impact on final diagnosis. Patients and method: This observational, cross-sectional study. The study worked on 590 dermatological slides, that stained with hematoxylin and eosin stain. Slides evaluated from archive and that collected during time of study which occur from June 2022 to November 2022, in Al-Yarmouk Teaching Hospital, Baghdad, Iraq, analyzed for artifacts under light microscope. Results: Totally 590 slides were evaluated, only 69 (11.695%) show no artifacts. Slides with artifact(s) counting 521(88.305%). Histopathological artifacts were accounted for 931 because more 45% of total examined slides show two or more artifacts. Folding artifacts were the most common type, while artefacts related to fixation were the least 307(32.975%), 6(0.644%) respectively. Conclusion: Histopathological evaluation of skin biopsies had long, and multiple stages done by the dermatologist, assistant pathologists, and lab technicians. That led to increased incidence of errors and artifacts. Artifacts invariably occur in the majority of dermatopathological slides and may interfere with the interpretation of histopathological diagnosis. These artefacts should be recognized and do all effort to avoid or at least, minimized them, which yet defied even with soft tissue handle and wrong techniques avoidance. [ABSTRACT FROM AUTHOR]

Background: Vesiculobullous disorders (VBDs) are extant with diverse clinical manifestations. Vesicles and bullae are fluid-filled cavities present within or beneath the epidermis. They are autoimmune blistering disorders in which autoantibodies are directed against target antigens present in the epidermis and dermo-epidermal junction. Objective: Evaluation of the various clinicodemographic profile of patients with a pattern of distribution (subtypes) of VBDs of the skin and assess the association between clinical aspects and histological changes in vesiculobullous lesions of the skin. Materials and Methods: The study material constituted 93 cases of VBDs out of 936 skin biopsies reported over two and a half years (January 2016 to June 2018) from the tertiary care center. A detailed history of the patients was taken, and a complete physical and dermatological examination with findings including clinical diagnosis was recorded. Histopathological examination (incisional/excisional/punch biopsy) was done in each case. The clinico-demographic evaluation was done and the results were correlated with histopathological findings. Results: Vesiculobullous lesions constituted 10.06% of all skin biopsies. The majority of cases were of pemphigus vulgaris (PV) 30 (32.25%) followed by 16 (17.2%) of bullous pemphigoid. In 83 cases (89.24%) histopathology findings were consistent with clinical diagnosis. Out of 34 cases that were diagnosed clinically as PV , the histopathological study proved 30 cases (88.23%) as PV. Conclusion: Vesiculobullous lesions of the skin are a heterogeneous group of disorders. It is essential to differentiate each pattern of subtype based on clinical examination and histopathological findings. Histopathological diagnosis with clinical correlation plays a major role in arriving at the diagnosis.

Mieke Hulens,1 Frans Bruyninckx,2 Dietmar Rudolf Thal,3,4 Ricky Rasschaert,5 Chris Bervoets,6– 8 Wim Dankaerts1 1Department of Rehabilitation Sciences, Musculoskeletal Rehabilitation Research Unit, Faculty of Kinesiology and Rehabilitation Sciences, KU Leuven, Leuven, Belgium; 2Department of Physical Medicine & Rehabilitation, EMG-Laboratory, University Hospitals of Leuven, Leuven, Belgium; 3Department of Imaging and Pathology, Laboratory of Neuropathology, and Leuven Brain Institute, KU Leuven, Leuven, Belgium; 4Department of Pathology, University Hospitals of Leuven, Leuven, Belgium; 5Department of Neurosurgery, AZ Rivierenland, Bornem, Belgium; 6Department of Neurosciences, Adult Psychiatry, KU Leuven, Leuven, Belgium; 7Department of Ophthalmology, University Hospitals of Leuven, Leuven, Belgium; 8Department Adult Psychiatry, University Psychiatric Center of KU Leuven, Leuven, BelgiumCorrespondence: Mieke HulensDepartment of Rehabilitation Sciences, Musculoskeletal Rehabilitation Research Unit, Faculty of Kinesiology and Rehabilitation Sciences, University of Leuven, Tervuursevest 101, Leuven, Belgium, Tel +32 478 338003, Fax +32 16 32 91 97, Email miekehulens@gmail.comPurpose: Tarlov cysts (TCs) are dilated nerve root sheaths originating from increased cerebrospinal pressure. Patients with TCs often complain of neuropathic pain and paresthesia. The aim of this study was to retrospectively review intraepidermal nerve fiber density (IENFD) and electrodiagnostic (EDX) data from TC patients.Patients and Methods: Lower leg skin biopsy results and EDX data from the L2–S4 myotomes of patients with lumbar or sacral TCs ≥ 8 mm were retrieved from a database of a physical medicine clinic. Patients with compressive pathology, diabetes mellitus and chemotherapy were excluded.Results: IENFD data from 17 patients and EDX data from 24 patients with TCs ≥ 8 mm were available. The mean age was 47 ± 10y, and 83% were women. In 82% of patients, the IENFD was below the 5th percentile by age and sex. EDX showed increased Hoffmann reflex latencies in 25%, increased anal reflex latencies in 95%, and a patchy distribution of neurogenic motor unit potentials in 100%. More than 50% of needle EMG abnormalities appeared in myotomes unrelated to the location of the TCs.Conclusion: Small- and/or large-fiber neuropathy was documented in a significant proportion of patients with TCs. The novel findings may add to the understanding of the mechanisms involved in symptomatic TCs. We propose that pathologically elevated cerebrospinal fluid pressure not only dilates some of the nerve root sheaths to form TCs but also potentially damages axons in nondilated nerve root sheaths and neurons in the dorsal root ganglia.Keywords: perineural cysts, skin biopsies, radicular pain, anal reflex, nerve conduction studies, fibromyalgia

Background: Obtaining high quality RNA from skin biopsies is complex due the physical composition and high content of nucleases of this tissue. This becomes particularly challenging when using compromised skin samples with necrotic, inflammed or damaged areas, such as those from patients suffering skin conditions, which affect more than 900 million people annually. We evaluated the impact of the biopsy size and tissue preservation method on the quality and quantity of RNA extracts. Methods: Skin lesion biopsies were obtained from patients with cutaneous leishmaniasis (CL). Biopsy specimens of 2 mm (n = 10) and 3 mm (n = 59) were preserved in Allprotect® reagent, and 4 mm biopsies in OCT (n = 54). Quality parameters were evaluated using Nanodrop and Bioanalyzer. The informativeness of the extracted samples for downstream analyses was evaluated using RT-qPCR and RNA-Seq. Results: The success rate, based on quality parameters of RNA extraction from tissue biopsies stored in OCT and 2 mm biopsies stored in Allprotect®, was 56% (30/54) and 30% (3/10), respectively. For 3 mm skin biopsies stored in Allprotect® was 93% (55/59). RNA preparations from 3 mm-Allprotect® biopsies had an average RIN of 7.2 ± 0.7, and their integrity was not impacted by sample storage time (up to 200 days at -20°C). RNA products were appropriate for qRT-PCR and RNA-seq. Based on these results, we propose a standardized method for RNA extraction from disrupted skin samples. This protocol was validated with lesion biopsies from CL patients (n = 30), having a success rate of 100%. Conclusions: Our results indicate that a biopsy size of 3 mm in diameter and preservation in Allprotect® for up to 200 days at -20°C, are best to obtain high quality RNA preparations from ulcerated skin lesion biopsy samples.

River dolphins from the genus Inia are widely distributed in the Amazon, Orinoco and Tocantins River basins. Current knowledge on the dietary habits of these species is poor and based on stomach contents from stranded animals. We used carbon and nitrogen stable isotopes to evaluate the diet preferences and trophic niche of the boto (Inia geoffrensis geoffrensis) and the bufeo (I. g. boliviensis) in three rivers from the Amazon and Tocantins basins. Samples were obtained from skin biopsies taken from social animals near fish markets during a tagging program or from dart biopsies of wild individuals. Prey isotopic data were obtained from fish collected during the surveys, catches by local fishermen or published data. Contribution of prey to consumer diet was calculated through isotope mixing models and trophic niches were represented by the isotopic niche area. Piscivore prey was the main item in the diet of bufeos and botos from Tapajós and Tocantins River wild group, whereas botos from Tocantins market group showed differences in diet and a lower trophic position probably mediated by human feeding near markets. Isotopic niche area was greater for Tapajós botos than for Tocantins market group botos and bufeos, which can be an effect of the homogenization of the human-mediated diet and low samples sizes, in the case of the market group and bufeos, respectively. Results presented here, represent a first attempt toward a better understanding of the trophic ecology of this endemic and threatened species through stable isotope analysis. [ABSTRACT FROM AUTHOR]

Quantitative grading of testing has research and clinical relevance. QASAT (quantitative scale for grading of cardiovascular reflex tests, transcranial Doppler, sudomotor testing, and small fiber densities from skin biopsies) is an objective instrument for grading dysautonomia, related small fiber neuropathy and cerebral blood flow. QASAT uses established autonomic tests (deep breathing, Valsalva maneuver, tilt test, sudomotor test) and skin biopsies for assessment of small fibers. Calculations of scores are complex. This paper presents a qpack—an open source software package that implements QASAT in a Python programming language. The qpack automatically generates reproducible scores of each test and reduces calculation errors. Datasets for verifying the correct qpack implementation are provided. The goal of qpack is to facilitate availability, reproducibility, and quality of autonomic studies and skin biopsies for assessment of small fibers. Qpack is easy to use with standard Python distributions, can be incorporated into routine clinical or research autonomic testing and it is freely available. [ABSTRACT FROM AUTHOR]

Leishmania infantum is a protozoan causing human zoonotic visceral leishmaniasis (ZVL) and visceral–cutaneous canine leishmaniosis (CanL) in the Mediterranean Basin. L. infantum is able to infect a large number of wild and domestic species, including cats, dogs, and horses. Since the 1990s, clinical cases of equine leishmaniasis (EL), typically characterized by cutaneous forms, have been increasingly diagnosed worldwide. The aim of the present study was to evaluate the presence of clinical forms of EL in CanL-endemic areas in Italy, where exposure of equine populations was ascertained from recent serological surveys. For this purpose, formalin-fixed and paraffin-embedded skin biopsies of 47 horses presenting chronic dermatitis compatible with EL were retrospectively selected for the study and subjected to conventional and q-PCR. A singular positivity for L. infantum was found; BLAST analysis of sequence amplicons revealed a 99–100% homology with L. infantum sequences. The histological examination revealed a nodular lymphoplasmacytic and histiocytic infiltrate; immunohistochemistry showed rare macrophages containing numerous positive amastigotes. The present retrospective study reports, for the first time, a case of a cutaneous lesion by L. infantum occurring in an Italian horse. Pathological and healthy skin samples should be investigated on a larger scale to provide information on the potential clinical impact of EL in the practice, and to define the role of horses in epidemiological ZVL and CanL scenarios. [ABSTRACT FROM AUTHOR]

Non-inflammatory alopecia is a frequent skin problem in dogs, causing damaged coat integrity and compromised appearance of affected individuals. In this study, we examined the Cesky Fousek breed, which displays atypical recurrent flank alopecia (aRFA) at a high frequency. This type of alopecia can be quite severe and is characterized by seasonal episodes of well demarcated alopecic areas without hyperpigmentation. The genetic component responsible for aRFA remains unknown. Thus, here we aimed to identify variants involved in aRFA using a combination of histological, genomic, and transcriptomic data. We showed that aRFA is histologically similar to recurrent flank alopecia, characterized by a lack of anagen hair follicles and the presence of severely shortened telogen or kenogen hair follicles. We performed a genome-wide association study (GWAS) using 216 dogs phenotyped for aRFA and identified associations on chromosomes 19, 8, 30, 36, and 21, highlighting 144 candidate genes, which suggests a polygenic basis for aRFA. By comparing the skin cell transcription pattern of six aRFA and five control dogs, we identified 236 strongly differentially expressed genes (DEGs). We showed that the GWAS genes associated with aRFA are often predicted to interact with DEGs, suggesting their joint contribution to the development of the disease. Together, these genes affect four major metabolic pathways connected to aRFA: collagen formation, muscle structure/contraction, lipid metabolism, and the immune system. [ABSTRACT FROM AUTHOR]

Background/Aim: Chloride intracellular channel protein 1 (CLIC1) activates inflammasomes in rheumatoid (RA) and psoriatic (PsA) arthritis. We studied CLIC1 expression in RA and PsA patients’ skin with vasculitis and its variability depending on the therapy used. Materials and Methods: CLIC1 immunoexpression was evaluated in the vascular (CLIC1-V) and stromal (CLIC1-S) compartments of the RA and PsA skin biopsies of patients treated with methotrexate (MTX), leflunomid (LFN), corticotherapy (CT), or biological therapies. Results: MTX significantly reduced CLIC1-S expression (p=0.016), whereas LFN decreased CLIC1-V (p<0.001). LFN therapy duration also correlated with CLIC1-V (p<0.001). CT decreased CLIC1-S expression (p=0.006). CLIC1-S expression persisted in skin biopsies despite of erythrocyte sedimentation rate (ESR, p=0.018) and C reactive protein (CRP, p=0.0026) normalisation. For PsA, CLIC1-S expression significantly related to MTX (p<0.022). Both CLIC1-S (p<0.001) and CLIC1-V (p=0.007) decreased by biological therapies in RA. Conclusion: CLIC1 expression is strongly influenced by the therapy used. Our data strongly support the extensive evaluation of CLIC1 in RA as a potential marker of inflammation and tool to predict therapy response. [ABSTRACT FROM AUTHOR]

Leishmania infantum is a protozoan causing human zoonotic visceral leishmaniasis (ZVL) and visceral–cutaneous canine leishmaniosis (CanL) in the Mediterranean Basin. L. infantum is able to infect a large number of wild and domestic species, including cats, dogs, and horses. Since the 1990s, clinical cases of equine leishmaniasis (EL), typically characterized by cutaneous forms, have been increasingly diagnosed worldwide. The aim of the present study was to evaluate the presence of clinical forms of EL in CanL-endemic areas in Italy, where exposure of equine populations was ascertained from recent serological surveys. For this purpose, formalin-fixed and paraffin-embedded skin biopsies of 47 horses presenting chronic dermatitis compatible with EL were retrospectively selected for the study and subjected to conventional and q-PCR. A singular positivity for L. infantum was found; BLAST analysis of sequence amplicons revealed a 99–100% homology with L. infantum sequences. The histological examination revealed a nodular lymphoplasmacytic and histiocytic infiltrate; immunohistochemistry showed rare macrophages containing numerous positive amastigotes. The present retrospective study reports, for the first time, a case of a cutaneous lesion by L. infantum occurring in an Italian horse. Pathological and healthy skin samples should be investigated on a larger scale to provide information on the potential clinical impact of EL in the practice, and to define the role of horses in epidemiological ZVL and CanL scenarios.

ABSTRACT Human skin microbiota has been described as a “microbial fingerprint” due to observed differences between individuals. Current understanding of the cutaneous microbiota is based on sampling the outermost layers of the epidermis, while the microbiota in the remaining skin layers has not yet been fully characterized. Environmental conditions can vary drastically between the cutaneous compartments and give rise to unique communities. We demonstrate that the dermal microbiota is surprisingly similar among individuals and contains a specific subset of the epidermal microbiota. Variability in bacterial community composition decreased significantly from the epidermal to the dermal compartment but was similar among anatomic locations (hip and knee). The composition of the epidermal microbiota was more strongly affected by environmental factors than that of the dermal community. These results indicate a well-conserved dermal community that is functionally distinct from the epidermal community, challenging the current dogma. Future studies in cutaneous disorders and chronic infections may benefit by focusing on the dermal microbiota as a persistent microbial community. IMPORTANCE Human skin microbiota is thought to be unique according to the individual's lifestyle and genetic predisposition. This is true for the epidermal microbiota, while our findings demonstrate that the dermal microbiota is universal between healthy individuals. The preserved dermal microbial community is compositionally unique and functionally distinct to the specific environment in the depth of human skin. It is expected to have direct contact with the immune response of the human host, and research in the communication between host and microbiota should be targeted to this cutaneous compartment. This novel insight into specific microbial adaptation can be used advantageously in the research of chronic disorders and infections of the skin. It can enlighten the alteration between health and disease to the benefit of patients suffering from long-lasting socioeconomic illnesses.

Background: Although treatment guidelines exist for melanoma in situ and invasive melanoma, guidelines for other melanocytic skin lesions do not exist.Objective: To examine pathologists' treatment suggestions for a broad spectrum of melanocytic skin lesions and compare them with existing guidelines.Methods: Pathologists (N = 187) completed a survey and then provided diagnoses and treatment suggestions for 240 melanocytic skin lesions. Physician characteristics associated with treatment suggestions were evaluated with multivariable modeling.Results: Treatment suggestions were concordant with National Comprehensive Cancer Network guidelines for the majority of cases interpreted as melanoma in situ (73%) and invasive melanoma (86%). Greater variability of treatment suggestions was seen for other lesion types without existing treatment guidelines. Characteristics associated with provision of treatment suggestions discordant with National Comprehensive Cancer Network guidelines were low caseloads (invasive melanoma), lack of fellowship training or board certification (melanoma in situ), and more than 10 years of experience (invasive melanoma and melanoma in situ).Limitations: Pathologists could not perform immunohistochemical staining or other diagnostic tests; only 1 glass side was provided per biopsy case.Conclusions: Pathologists' treatment suggestions vary significantly for melanocytic lesions, with lower variability for lesion types with national guidelines. Results suggest the need for standardization of treatment guidelines for all melanocytic lesion types. [ABSTRACT FROM AUTHOR]

Wild birds are frequently exposed to the zoonotic tick-borne bacteria Borrelia burgdorferi sensu lato (s.l.), and some bird species act as reservoirs for some Borrelia genospecies. Studying the tropism of Borrelia in the host, how it is sequestered in different organs, and whether it is maintained in circulation and/or in the host's skin is important to understand pathogenicity, infectivity to vector ticks and reservoir competency. We evaluated tissue dissemination of Borrelia in blackbirds (Turdus merula) and great tits (Parus major), naturally and experimentally infected with Borrelia genospecies from enzootic foci. We collected both minimally invasive biological samples (feathers, skin biopsies and blood) and skin, joint, brain and visceral tissues from necropsied birds. Infectiousness of the host was evaluated through xenodiagnoses and infection rates in fed and moulted ticks. Skin biopsies were the most reliable method for assessing avian hosts' Borrelia infectiousness, which was supported by the agreement of infection status results obtained from the analysis of chin and lore skin samples from necropsied birds and of their xenodiagnostic ticks, including a significant correlation between the estimated concentration of Borrelia genome copies in the skin and the Borrelia infection rate in the xenodiagnostic ticks. This confirms a dermatropism of Borrelia garinii, B. valaisiana and B. turdi in its avian hosts. However, time elapsed from exposure to Borrelia and interaction between host species and Borrelia genospecies may affect the reliability of skin biopsies. The blood was not useful to assess infectiousness of birds, even during the period of expected maximum spirochetaemia. From the tissues sampled (foot joint, liver, spleen, heart, kidney, gut and brain), Borrelia was detected only in the gut, which could be related with infection mode, genospecies competition, genospecies-specific seasonality and/or excretion processes. [ABSTRACT FROM AUTHOR]

This case report describes the clinical course of a child who developed staphylococcal scalded skin syndrome (SSSS) after a burn injury. The intent is to aid other units in recognizing the presentation of SSSS after a pediatric burn and to optimize subsequent management. The main clinical finding was of rapid, progressive, superficial epidermal loss at sites separate from the original burn, involving 55% of the total body surface area, 13 days after a 6% scald burn to the face, neck, and chest. Diagnosis was confirmed by multidisciplinary team clinical assessment and histopathology of an intraoperative skin biopsy. This confirmed epidermal cleavage at the granular cell layer. These findings were later supported by Staphylococcus aureus cultured from the burn wound, and a positive epidermolytic toxin A assay. Management was with general medical supportive care, clindamycin and flucloxacillin intravenous antibiotic therapy, and cleansing and dressing of the areas of epidermal loss. Key learning points from this case were that SSSS presented after a burn injury and that 13 days elapsed between the burn and SSSS. Factors differentiating it from toxic epidermal necrolysis are described, including the value of histopathology in confirming the diagnosis. The prompt use of antibiotics and attentive wound care are advocated as an effective management strategy. [ABSTRACT FROM AUTHOR]

Lumpy skin disease (LSD) diagnosis is primarily based on clinical surveillance complemented by PCR of lesion crusts or nodule biopsies. Since LSD can be subclinical, the sensitivity of clinical surveillance could be lower than expected. Furthermore, real-time PCR for the detection of LSD viral DNA in blood samples from subclinical animals is only intermittently positive. Therefore, this study aimed to investigate an acceptable, easily applicable and more sensitive testing method for the detection of clinical and subclinical LSD. An animal experiment was conducted to investigate ear notches and biopsies from unaffected skin taken from the neck and dorsal back as alternatives to blood samples. It was concluded that for early LSD confirmation, normal skin biopsies and ear notches are less fit for purpose, as LSDV DNA is only detectable in these samples several days after it is detectable in blood samples. On the other hand, blood samples are less advisable for the detection of subclinical animals, while ear notches and biopsies were positive for LSD viral DNA in all subclinically infected animals by 16 days post infection. In conclusion, ear notches could be used for surveillance to detect subclinical animals after removing the clinical animals from a herd, to regain trade by substantiating the freedom of disease or to support research on LSDV transmission from subclinical animals.

Introduction: Leprosy also known as Hansen’s disease is one of the oldest disease known to mankind. It is a chronic infectious disease caused by Mycobacterium leprae. It still remains as a major public health problem facing India. Nearly, 60% of all world leprosy cases are reported from India. The spectrum of presentation of leprosy is very wide. Histopathology is an important tool in making a definitive diagnosis. The objective of the study is to describe the histopathological profile of leprosy in the state of Bihar. Aim: To study the histopathological spectrum of leprosy at a tertiary care centre of Bihar. Materials and Methods: A retrospective hospital-based study of clinically diagnosed leprosy cases was conducted over a period of 28 months (January 2015 to April 2017). Lesional skin biopsies obtained were fixed, processed and stained with Haematoxylin and Eosin (H&E) followed by Ziehl-Neelsen (ZN) staining. The lesions were classified on microscopy as per Ridley-Jopling classification. Results: A total of 200 cases were studied. Highest incidence was in the 11 to 30 years age group for both males and females. Males were more affected (M:F=2.4:1). Most common clinical feature was loss of sensation. The commonest reported histopathological type was borderline lepromatous (43%) followed by borderline (17%). Overall ZN staining was positive in 56 (28%) cases. Conclusion: The spectrum of presentation of leprosy is very wide and there is clinical overlap between different types of leprosy. Histopathology still remains the gold standard for early diagnosis and classification of the disease. Accurate diagnosis forms the backbone for appropriate treatment and preventing deformities and drug resistance.

Screening for systemic amyloidosis is typically carried out with abdominal fat aspirates with varying reported sensitivities. Fat aspirates are preferred for use in primary screening instead of organ biopsies as they are less invasive and thereby minimize the potential risk of complications. At Odense Amyloidosis Center, we performed a prospective study on whether the combined use of fat aspirate and tru-cut skin biopsy could increase the diagnostic sensitivity. Both fat aspirates and skin biopsies were screened with Congo Red staining, and positive biopsies were subsequently subtyped using immunoelectron microscopy and mass spectrometry. Seventy-six patients were included. In total, 24 patients had systemic amyloidosis (11 AL, 12 wtATTR, 1 AA), and 6 patients had localized amyloidosis. Combined fat aspirate and skin biopsy were Congo Red-positive in 15 patients (overall sensitivity (OS) 62.5%). Fat aspirates were positive in 14 patients (OS 58.3%), and the skin biopsy was positive in 5 patients (OS 20.8%). In only one patient did the skin biopsy add extra diagnostic information. The sensitivity differed between AL and ATTR amyloidosis—81.8% and 41.7%, respectively. Using skin biopsy as the only screening method is not recommended.

Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of systemic lupus erythematosus (SLE). However, little is known about the implication of NETs in cutaneous lupus. In this case series of 30 patients, we compared the amounts of neutrophils producing NETs in cutaneous lesions of different subtypes of lupus (5 with discoid lupus or DLE, 5 with subacute cutaneous lupus or SCLE, 11 with acute cutaneous SLE, 7 with lupus panniculitis and 2 with chilblains). Immunofluorescence was performed on formalin‐fixed paraffin‐embedded skin biopsies using antibodies against neutrophilic granules (elastase, myeloperoxidase, PR‐3 proteins and citrullinated histone 3). Dihydroethidium staining was performed to detect reactive oxygen species (ROS), known inducers of NETs. NETs were detected in the different subtypes of cutaneous lupus as well as in cutaneous lesions of SLE. The amounts of neutrophils producing NETs were significantly higher in lupus panniculitis (49%), acute cutaneous SLE (41%) and DLE (32%), in comparison with SCLE (5%) and chilblains (0%). This suggests that NETs might be associated with more tissue damage and scarring. ROS were observed in the different cutaneous subtypes of lupus independent of NETs. [ABSTRACT FROM AUTHOR]

Background: Hyperalgesia, defined as hypersensitivity to pain, refers to sensitization of nociceptors to normal levels of pain.Objectives: We aimed to determine whether hyperalgesia occurs due to the development of sensitization following repeated applications of platelet-rich plasma (PRP), and to ascertain the mechanism responsible for inducing hyperalgesia.Methods: This study, performed between 2016 and 2017, involved 32 rats. A 2 cm × 2 cm area was shaved on the back of 10 experimental and 10 sham control animals. In the experimental animals this area was divided into 4 equal squares of 1 cm × 1 cm, and these squares were numbered 1 (no treatment; only the needle was inserted), 2 (0.2 mL, saline), 3 (0.2 mL, nonactivated PRP), and 4 (0.2 mL, activated PRP). The response of the animals to painful stimuli in these areas was investigated with Von Frey filaments, immediately before application and 4 weeks after the last application. Skin biopsies were taken, and growth factors were evaluated pathologically and biochemically.Results: Hyperalgesia developed in all 4 areas of each experimental rat but not in the sham group. However, areas 3 and 4 had smaller Von Frey g values than areas 1 and 2. When growth hormones were assessed histopathologically and biochemically, nerve growth factor (NGF) levels were found to be higher in areas 3 and 4 than in areas 1 and 2 and the sham group.Conclusions: Both nonactivated and activated PRP resulted in greater hypersensitivity than saline and sham treatment. Development of hyperalgesia may be associated with an increase in NGF as well as increased inflammatory mediators. [ABSTRACT FROM AUTHOR]

Although chronic pain after amputation is frequent, the underlying mechanisms are still not well understood. It is widely accepted that the pathogenesis of postamputation pain is multifactorial, with both peripheral and central mechanisms playing an essential role. However, recent studies suggest that the immune system plays an important role in different neuropathic pain conditions, including postamputation pain. Eleven amputees were included in this clinical study. Information on the type and intensity of spontaneous postamputation pain was obtained and evoked pain responses for brush, cold, and warm allodynia and pinprick hyperalgesia were determined. In addition, skin biopsies were taken from the amputated site and a contralateral control site and analysed for possible markers of pain: IbA1 (macrophages), calcitonin gene-related peptide (CGRP), and substance P (SP). Irrespectively of the type and intensity of postamputation pain, no differences were found in IbA1, CGRP, and SP levels between the amputated site and the control site. Although no differences between the sites were seen in this study, this new method seems promising for our understanding of skin changes in amputees. In future studies, staining for other cytokines and inflammatory mediators in skin biopsies could provide new insight into the mechanisms of postamputation pain. [ABSTRACT FROM AUTHOR]

Background Histoid leprosy is a subtype of leprosy with distinct clinical presentation and histologic features. It accounts for <4% of leprosy cases. The exact location of histoid leprosy along the immune spectrum and its relation to other subtypes is unclear. Aim To evaluate the local immune phenomenon which define histoid leprosy. Design Parallel skin biopsies from histoid lesions and from unremarkable skin in patients with histoid leprosy were evaluated and the histologic findings compared. Methods Formalin fixed, paraffin embedded tissue sections from lesional and non-lesional biopsies were assessed for changes in epidermis and dermis; type and extent of infiltrate, presence or absence of pseudocapsule and associated reactions. Bacillary index was evaluated using Wade Fite stain for lepra bacilli. Results Amongst 208 leprosy cases, six cases of histoid leprosy were identified (2.88%). The cases showed presence of nodules, patches and plaques overlying clinically unremarkable skin. Fourteen skin biopsies were evaluated of which the lesional biopsies showed equal proportion of fusocellular, fusocellular epithelioid and fusocellular-vacuolated histology. A greater circumscription was noted in lesional biopsies; however the cellular content of the infiltrate was similar in lesional and non-lesional biopsies. A case of erythema nodosum leprosum in histoid leprosy was also seen. Conclusions Ours is the first study comparing normal and lesional skin in histoid leprosy. Though the histoid lesions appear to have a derivation from lepromatous leprosy, the local histologic and clinical alterations may be a result of heightened local immunity or reactive local modifying factors. [ABSTRACT FROM AUTHOR]

Introduction: Leprosy also known as Hansen's disease is one of the oldest disease known to mankind. It is a chronic infectious disease caused by Mycobacterium leprae. It still remains as a major public health problem facing India. Nearly, 60% of all world leprosy cases are reported from India. The spectrum of presentation of leprosy is very wide. Histopathology is an important tool in making a definitive diagnosis. The objective of the study is to describe the histopathological profile of leprosy in the state of Bihar. Aim: To study the histopathological spectrum of leprosy at a tertiary care centre of Bihar. Materials and Methods: A retrospective hospital-based study of clinically diagnosed leprosy cases was conducted over a period of 28 months (January 2015 to April 2017). Lesional skin biopsies obtained were fixed, processed and stained with Haematoxylin and Eosin (H&E) followed by Ziehl-Neelsen (ZN) staining. The lesions were classified on microscopy as per Ridley-Jopling classification. Results: A total of 200 cases were studied. Highest incidence was in the 11 to 30 years age group for both males and females. Males were more affected (M:F=2.4:1). Most common clinical feature was loss of sensation. The commonest reported histopathological type was borderline lepromatous (43%) followed by borderline (17%). Overall ZN staining was positive in 56 (28%) cases. Conclusion: The spectrum of presentation of leprosy is very wide and there is clinical overlap between different types of leprosy. Histopathology still remains the gold standard for early diagnosis and classification of the disease. Accurate diagnosis forms the backbone for appropriate treatment and preventing deformities and drug resistance. [ABSTRACT FROM AUTHOR]

Haematobia irritans exigua, commonly known as buffalo fly (BF), causes economic losses of about AUD $100 million per annum to the Australian cattle industry in terms of decreased production and costs of control. Lesions associated with BF infestation range from raised, dry, alopecic, hyperkeratotic or scab encrusted to severe hemorrhagic areas of ulceration which represent a major animal welfare concern. BF transmits a filarial nematode, Stephanofilaria sp., which has been speculatively associated with BF lesion development. The existing literature indicates that the sensitivity of currently used diagnostic techniques to detect Stephanofilaria in skin lesions is low and that there is currently no sequence for Stephanofilaria available on GenBank. Our objective is to develop a PCR method to detect Stephanofilaria in BF lesions. Skin biopsies were collected from 10 freshly slaughtered cattle hides having obvious BF eye lesions. Samples were collected from the center and the edge of the BF lesion as well as from adjacent normal tissue. Each skin punch was cut into 5-6 slices and immersed in normal saline before incubation overnight at 22°C. Eight nematodes were recovered from the saline by microscopic examination and preserved in ethanol. Nematode DNA will be extracted using conventional extraction methods. Specific primers will be used to amplify the ITS regions of rDNA and coxI region of the mtDNA and the amplified DNA will be sequenced. Primers will be designed from these regions to detect the presence of Stephanofilaria and used in PCR studies to clarify the etiology and epidemiology of BF lesions.

Little is known about the spectrum of pediatric skin disorders requiring biopsy/excision, their indication, impact on further management, and the accuracy of clinical diagnosis. We aimed to address these questions in the patient population seen at our Swiss University referral center for Pediatric Dermatology and Plastic Surgery. All skin biopsies/excisions performed in patients aged ≤ 16 years over a period of 2 years were retrospectively analyzed. A total of 506 samples were included. The majority of biopsies/excisions (n = 413, 82%) was performed for tumors, cysts, and hamartomas and 18% for other skin conditions. Malignant tumors were found in 12 samples (2%) from four patients. In 121 (24%) patients, the histopathology had an important impact on patient management. In 80 (16%) cases, the pathology did not match with the clinical diagnosis. In 382 (75%) cases, excision was the treatment of choice. Of these, the indication for surgery was based on patient's request in 181 (47%) cases.Conclusion: Surgical interventions for pediatric skin disorders are performed for diagnostic and therapeutic reasons. In this cohort, histopathology was essential for treatment in one quarter of cases. Skin tumors, cysts, and hamartomas often require excision during childhood, with families' request and esthetic considerations playing an important role. What is Known: • The spectrum of pediatric skin conditions has been studied in outpatient, inpatient, and emergency settings. • In contrast, no data exist on the spectrum of pediatric skin disorders undergoing biopsy/excision specifically. What is New: • We analyze biopsies/excisions in children, focusing on diagnosis, indication, and impact on patient management. • Surgical interventions for skin disorders in children are often performed for tumors and hamartomas with esthetic considerations playing a relevant role. If used for diagnostic purposes, they are often performed to confirm or rule out severe skin disease. [ABSTRACT FROM AUTHOR]

Background Propionibacterium acnes is frequently cultured in patients undergoing both primary and revision shoulder surgery. The purpose of this study was to evaluate the efficacy and safety of preoperative oral administration of doxycycline in decreasing the colonization of skin around the shoulder by P. acnes . Methods This was a single-institution, prospective, randomized controlled trial of male patients undergoing shoulder arthroscopy. Patients were randomized to receive oral doxycycline (100 mg twice a day) for 7 days or to the standard of care (no drug). Before skin incision, 2 separate 3-mm punch biopsy specimens were obtained from the sites of the anterior and posterior arthroscopic portals and were sent for culture in anaerobic and aerobic medium held for 13 days. Results There were 22 of 37 (59.5%) patients in the no-drug group and 16 of 37 (43.2%) patients in the doxycycline group who had at least 1 dermal culture positive for P. acnes ( P  = .245). In the no-drug group, 10 patients (45.5%) had 1 positive culture and 12 (54.5%) had 2 positive cultures (34 total positive cultures [45.9%]). In the doxycycline group, 6 (37.5%) patients had 1 positive culture and 10 (62.5%) had 2 positive cultures (26 total positive cultures [35.1%]; P  = .774). Discussion Administration of oral doxycycline for 7 days before surgery did not reduce colonization of P. acnes significantly. Given the potential risk for emergence of bacterial resistance and the adverse effects associated with administration of antibiotics, we do not recommend routine use of oral doxycycline for preoperative decolonization of the shoulder. [ABSTRACT FROM AUTHOR]

Skin biopsies are a valuable technique in the diagnosis of cutaneous inflammatory and neoplastic conditions. We were interested to test the minimal size or equivalent volume by dilution of proteolytically disassociated skin tissue required to allow the isolation and propagation of cutaneous cells, for freezing, storage and biochemical analysis. It was possible to propagate with 100% efficiency fibroblast and melanocytic cells from a 0.1 to 0.5 mm equivalent neonatal foreskin sample using a combination of DispaseII and CollagenaseIV. The smallest tissue dilution that allowed melanocytic cell culture was 0.01 mm, which equated to approximately 16 cells based on the average skin density of melanocytes. However, passaging of cells to create frozen stocks was achieved routinely only from 1 mm skin, equating to 1560 cells. Tissue-specific antigen expression of these cultures was tested by western blot of total protein extracts. There was no pigmentation antigen expression in fibroblast cultures; however, smooth muscle actin protein expression was high in fibroblast but absent from melanocytic cell strains. Melanocytic cells expressed pigmentation antigens and E-cadherin, but these were not detected in fibroblasts. Moreover, maturation of these melanocytic cells resulted in a decrease of Dopachrome Tautomerase antigen expression and induction of Tyrosinase protein consistent with the differentiation potential seen in cell cultures derived routinely from large sections of skin tissue. [ABSTRACT FROM AUTHOR]

Background Palmoplantar pustular psoriasis (PPPP) is a variant of psoriasis, which has significant negative impact on quality of life. The cellular and molecular inflammatory pathways involved in PPPP have not been well studied. Objective Study the expression of cytokines and chemokines involved in the IL-17/IL-23 axis in palmoplantar pustular psoriasis and other difficult to treat psoriasis areas (palms, scalp, elbows and lower legs). Methods Skin biopsies were performed on a total of 80 patients with PPPP, non-pustular palmoplantar psoriasis (NPPPP), or psoriasis located on elbows, knees and scalp as well as 10 healthy subjects. RT-PCR, immunohistochemistry and flow cytometry on cells extracted from skin biopsies were used to compare PPPP to other forms of psoriasis. Results There was a significant (p < 0.05) increase in the expression of IL-1β, IL-6, LL-37, IL-19, IL-17A, CXCL1 and CXCL2 in PPPP as compared to NPPPP. However, there was no significant difference in expression of IL-23 in PPPP as compared to NPPPP and other forms of psoriasis. The proportion of IL-22 + but not IL-17A + mast cells was higher in PPPP as compared to NPPPP (p < 0.05). Conclusion These results suggest that the IL-17A pathway may play a more important role in PPPP than in NPPPP. [ABSTRACT FROM AUTHOR]

A determination of how the color of animal integument is produced is a starting point for investigations into the function and evolution of coloration. The mechanisms that give rise to the color of bare skin of New World vultures are largely unexplored. Here, we investigate the source of color production in the bare skin of Turkey Vultures (Cathartes aura) and Black Vultures (Coragyps atratus). Using UV–vis reflectance spectroscopy, we found evidence that hemoglobin is the primary pigment responsible for the red coloration of the bare skin on the heads of Turkey Vultures, and that eumelanin is responsible for the black coloration of the bare skin on the heads of Black Vultures. Light microscopy of incisional skin samples further supported these mechanisms of color production by revealing the presence of numerous blood vessels near the surface of the Turkey Vulture skin, and a high concentration of melanosomes in the skin of Black Vultures. Using high performance liquid chromatography (HPLC), we detected carotenoids within the skin of both species with significantly higher total concentrations of carotenoids in the skin of Turkey Vultures compared to the skin of Black Vultures. The carotenoids detected were dietary carotenoids that typically produce yellow coloration when accumulated in integument and were present in low concentrations. We hypothesize that the dietary carotenoids present do not contribute to the color of the skin, but rather help to compensate for the lack of melanosomes found in Turkey Vulture skin. The presence of additional carotenoids may act as an antioxidant to minimize UV damage when the bare Turkey Vulture head skin is exposed to direct sunlight for prolonged periods of time when soaring and scavenging for food. [ABSTRACT FROM AUTHOR]

Background: Skin diseases are common in childhood and they are common reasons for pediatric visits to the hospital. In spite of this high occurrence, there are very few prospective studies addressing this issue. Aims: The present study was directed at determining the spectrum of dermato-pathological lesions encountered in a large general tertiary care hospital, over a two-year period. Materials and Methods: 107 cases formed the total sample studied, in a part prospective and part retrospective study. A detailed clinical history was recorded on a proforma prepared for the purpose and gross photographs were taken wherever possible. Results: Skin biopsies accounted for 7.29% of the total surgical pathology load, 55.44% of the total pediatric biopsies and 10.82% of the total number of skin biopsies. The age and sex distribution pattern revealed that the maximum number of biopsies (62.61%) were of older children, with a male preponderance (57.94%). The anatomic distribution pattern indicated predominant involvement of the limbs (59.82%). The maximum numbers of cases were of infectious nature (24.29%); the most frequently encountered being borderline tuberculoid Hansen′s disease (8.4%). A positive correlation with the clinical diagnosis was obtained in 56.07% cases. Conclusions: Histopathology contributed to the diagnosis in a significant number of (82.23%) cases, indicating its importance and utility.

The definitive diagnosis of spotted fever group (SFG) rickettsioses in humans is challenging due to the retrospective nature and cross reactivity of the serological methods and the absence of reliable and consistent samples for molecular diagnostics. Existing data indicate the transient character of bacteremia in experimentally infected animals. The ability of arthropod vectors to acquire rickettsial infection from the laboratory animals in the absence of systemic infection and known tropism of rickettsial agents to endothelial cells of peripheral blood vessels underline the importance of local infection and consequently the diagnostic potential of skin samples. In order to evaluate the diagnostic sensitivity of rickettsial DNA detection in blood and skin samples, we compared results of PCR testing in parallel samples collected from model laboratory animals infected with Rickettsia rickettsii , Rickettsia parkeri and Rickettsia slovaca -like agent at different time points after infection. Skin samples were collected from ears – away from the site of tick placement and without eschars. Overall, testing of skin samples resulted in a higher proportion of positive results than testing of blood samples. Presented data from model animals demonstrates that testing of skin samples from sites of rickettsial proliferation can provide definitive molecular diagnosis of up to 60–70% of tick-borne SFG rickettsial infections during the acute stage of illness. Detection of pathogen DNA in cutaneous samples is a valuable alternative to blood-PCR at least in model animals. [ABSTRACT FROM AUTHOR]

Background: Leprosy remains an important health problem mainly in the African and South-East Asia regions. Type 1 reaction is an immune-mediated phenomenon known to complicate at least 30% of patients of leprosy. Diagnosing type 1 reaction correctly is important for timely institution of therapy to prevent and treat neuropathy-associated disability and morbidity. There is paucity of literature on definitive criteria for histologic diagnosis of type 1 reaction. This study was conducted to determine the key histologic variables for diagnosing type 1 reaction. Methods: This was a prospective study recruiting 104 patients with borderline leprosy. Three pathologists blinded to the clinical diagnosis independently assessed the cases. The agreement between each histological variable and clinical diagnosis was then calculated by using Cohen's kappa (κ) coefficient. Results: Histological diagnosis of type 1 reaction was given to 27 (67.5%) of 40 clinically diagnosed cases of type 1reaction cases. Histological variables chosen as key variables for histological diagnosis of type 1 reaction were presence of giant cells, dermal edema, intragranuloma edema, granuloma fraction 31- 50%, and presence of medium to large giant cells. Conclusion: This study has shown that T1R are still underdiagnosed histologically in comparison with clinical assessments. The key variables for diagnosing type 1 reaction were proposed. [ABSTRACT FROM AUTHOR]

Multiplex real-time polymerase chain reaction (PCR) demonstrates greater sensitivity than nested PCR in formalin-fixed, paraffin-embedded tissues and provides an effective method to specifically identify cases of Rocky Mountain spotted fever, rickettsialpox, and Rickettsia parkeri rickettsiosis by using skin biopsy specimens.Background. Rickettsia rickettsii, Rickettsia parkeri, and Rickettsia akari are the most common causes of spotted fever group rickettsioses indigenous to the United States. Infected patients characteristically present with a maculopapular rash, often accompanied by an inoculation eschar. Skin biopsy specimens are often obtained from these lesions for diagnostic evaluation. However, a species-specific diagnosis is achieved infrequently from pathologic specimens because immunohistochemical stains do not differentiate among the causative agents of spotted fever group rickettsiae, and existing polymerase chain reaction (PCR) assays generally target large gene segments that may be difficult or impossible to obtain from formalin-fixed tissues.Methods. This work describes the development and evaluation of a multiplex real-time PCR assay for the detection of these 3 Rickettsia species from formalin-fixed, paraffin-embedded (FFPE) skin biopsy specimens.Results. The multiplex PCR assay was specific at discriminating each species from FFPE controls of unrelated bacterial, viral, protozoan, and fungal pathogens that cause skin lesions, as well as other closely related spotted fever group Rickettsia species.Conclusions. This multiplex real-time PCR demonstrates greater sensitivity than nested PCR assays in FFPE tissues and provides an effective method to specifically identify cases of Rocky Mountain spotted fever, rickettsialpox, and R. parkeri rickettsiosis by using skin biopsy specimens. [ABSTRACT FROM AUTHOR]

Abstract: Chronic-inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated disease with no known biomarkers for diagnosing the disease or assessing its prognosis. We performed transcriptional profiling microarray analysis on skin punch biopsies from 20 CIDP patients and 17 healthy controls to identify disease-associated gene expression changes. We demonstrate changes in expression of genes involved in immune and chemokine regulation, growth and repair. We also found a combination of two upregulated genes that can be proposed as a novel biomarker of the disorder. [Copyright &y& Elsevier]

Background Axonal damage in large myelinated nerve fibres occurs in about 70% of patients with severe sepsis, known as critical illness polyneuropathy and contributes significantly to an increased short- and long-term morbidity and mortality in this population. Among other pathophysiological mechanisms, autonomic dysregulation, characterized by high concentrations of circulating catecholamines in the presence of impaired sympathetic modulation of heart and vessels have been discussed. We hypothesize that autonomic small fibre neuropathy play an important role in autonomic failure. Methods Single center, non-randomized, controlled, observational study. Skin biopsies of patients with severe sepsis and/or septic shock are compared with those of age-matched controls. In order to assess impairment of small nerve fibres, skin biopsies are taken at onset of severe sepsis, and two and 16 weeks later. Intraepidermal nerve fibre densities are histologically analyzed using anti protein gene product (PGP) 9.5 immunostaining. In addition, standardized clinical examinations, as Medical Research Council (MRC) scores of muscle strength, Rankin scores, and standardized nerve conduction studies of the right median nerve, the right tibial nerve, the left fibular nerve, and both sural nerves are performed, to identify critical illness polyneuropathy and to neurophysiologically quantify the damage of large nerve fibres. Discussion The study will allow to describe the frequency of small fibre neuropathy in patients with severe sepsis up to four months after onset of severe sepsis and to evaluate its relationship to critical illness polyneuropathy. [ABSTRACT FROM AUTHOR]

Pemphigus foliaceus is one of the most frequently occuring auto-immune skin conditions in the dog and cat. It is characterised by a pustular, crusting dermatosis and affects mainly middle-aged-to-older dogs. In this article, veterinary dermatologist Mark Craig presents key 'disease facts' for the practicing veterinarian on the most common condition of the pemphigus complex in the dog and cat. Clinical features, diagnostic steps, treatment options and prognosis will be discussed. [ABSTRACT FROM AUTHOR]

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Microorganisms have been implicated in the pathogenesis of psoriasis. Previous studies of psoriasis and normal skin have used swabs from the surface rather than skin biopsies. In this study, biopsies were taken from 10 patients with psoriasis and 12 control subjects from unmatched sites. Samples were analysed with massive parallel pyrosequencing on the 454 platform targeting the 16S rRNA gene and the variable regions V3-V4. The samples grouped into 19 phyla, 265 taxon and 652 operational units (OTUs) at 97% identity. A cut-off abundance level was set at 1%. The three most common phyla in both normal and psoriasis skin were Firmicutes (39% psoriasis, 43% normal skin), Proteobacteria (38% psoriasis, 27% normal skin) and Actinobacteria (5% psoriasis, 16% normal skin, p = 0.034). In trunk skin, Proteobacteria were present at significantly higher levels in psoriasis compared to controls (52 vs. 32%, p = 0.0113). The commonest genera were Streptococci in both psoriasis (32%) and normal skin (26%). Staphylococci were less common in psoriasis (5%) than in controls (16%), as were Propionibacteria (psoriasis 0.0001669%, controls 0.0254%). Both Staphylococci and Propionibacteria were significantly lower in psoriasis versus control limb skin ( p = 0.051, 0.046, respectively). This study has shown some differences in microbiota between psoriasis and normal skin. Whether these are of primary aetiological significance, or secondary to the altered skin of psoriasis remains to be determined. [ABSTRACT FROM AUTHOR]

Presently, there is no information about the functionality of the immune system in the franciscana dolphin (Pontoporia blainvillei), a small dolphin from southern Brazil. As in the case of the franciscana, the population of southern right whale (Eubalaena australis) which inhabits Brazilian waters has not yet been surveyed in what concerns MHC expression. For the first time it was possible to observe the DQB gene expression in skin of these two species of cetacean using RT-PCR. Skin pieces of the animals were collected to RNA extraction. The fragment corresponding to DQB exon 2 was amplified, cloned and sequenced. A total of five alleles were found, one to franciscana and four to southern right whale. The observed dN/dS ratio of 2.77 (P = 0.03) suggests that this gene is under balancing selection pressure (positive Darwinian selection). The sequences indicate that, in both species analysed, the DQB gene is functional. [ABSTRACT FROM PUBLISHER]