Skin Punch Biopsies Research Articles

Punch biopsies in tattooed skin: Complications and patient‐reported outcomes

AbstractBackgroundDespite the popularity and usage of tattoos in modern society, various complications can occur such as allergic tattoo reactions, infections, tattoo removal complications and chronic granulomatous inflammatory tattoo reactions such as sarcoidosis. Histopathology of skin biopsies in tattoos is crucial in the diagnostic process of complications. As tattoos are frequently obtained for cosmetic reasons, cosmetic consequences of a skin biopsy in a tattoo are important. Remarkably, no studies have been performed regarding the consequences and expected outcome of taking a punch biopsy of tattooed skin.ObjectivesThe objective of this study is to report on the possible complications and patient‐reported cosmetic outcomes after punch biopsies in tattooed skin. Specifically, this study aims to assess the impact on appearance, symptoms and psychosocial burden of biopsies in tattooed skin, using the SCAR‐Q.MethodsPatients who underwent a punch biopsy of tattooed skin at the Tattoo Clinic in the Alrijne Hospital between 2021 and 2023 were included. To evaluate patient satisfaction of the biopsy scar the SCAR‐Q and a questionnaire regarding the recovery of the punch biopsy was used.ResultsThe final cohort consisted of 50 patients. Across all scales, the median scores on the SCAR‐Q questionnaire were consistent with the maximum score. Patients scored significantly better on the appearance scale when the biopsy was taken longer than 8 months ago. Two‐third of the patients reported no postbiopsy symptoms, with the remainder experiencing itch, pain or redness, which typically resolved within 10 days (88%). Remarkably, 42% of the patients reported the biopsy scar was not visible on the skin anymore. Scars on the lower extremities and trunk were significantly more frequently visible, as well as scars among patients aged 40 and above.ConclusionsThis study demonstrates that the cosmetic and psychological impact of punch biopsies in tattooed skin is minimal and the recovery is fast with minimal symptoms. For this reason, biopsies of tattooed skin should not be avoided in the diagnostic process.

Immune response profiles from humans experimentally exposed to Phlebotomus duboscqi bites.

Cutaneous leishmaniasis is a neglected vector-borne parasitic disease prevalent in 92 countries with approximately one million new infections annually. Interactions between vector saliva and the human host alter the response to infection and outcome of disease. To characterize the human immunological responses developed against saliva of Phlebotomus duboscqi, a Leishmania major (L. major) vector, we repeatedly exposed the arms of 14 healthy U.S volunteers to uninfected P. duboscqi bites. Blood was collected a week after each exposure and used to assess total IgG antibodies against the proteins of P. duboscqi salivary gland homogenate (SGH) and the levels of IFN-gamma and IL-10 from peripheral blood mononuclear cells (PBMCs) stimulated with SGH or recombinant sand fly proteins. We analyzed skin punch biopsies of the human volunteer arms from the insect bite site and control skin site after multiple P. duboscqi exposures (four volunteers) using immunohistochemical staining. A variety of immediate insect bite skin reactions were observed. Late skin reactions to insect bites were characterized by macular hyperpigmentation and/or erythematous papules. Hematoxylin and eosin staining showed moderate mononuclear skin infiltrate with eosinophils in those challenged recently (within 2 months), eosinophils were not seen in biopsies with recall challenge (6 month post bites). An increase in plasma antigen-specific IgG responses to SGH was observed over time. Western Blot results showed strong plasma reactivity to five P. duboscqi salivary proteins. Importantly, volunteers developed a cellular immunity characterized by the secretion of IFN-gamma upon PBMC stimulation with P. duboscqi SGH and recombinant antigens. Our results demonstrate that humans mounted a local and systemic immune response against P. duboscqi salivary proteins. Specifically, PduM02/SP15-like and PduM73/adenosine deaminase recombinant salivary proteins triggered a Th1 type immune response that might be considered in future development of a potential Leishmania vaccine.

Smart Use of Skin Biopsy Punch in Treating Keloids: A Single-Center Retrospective Study.

Treatment of scarring has long been a problem due to high incidence and recurrence. Despite many existing treatment therapies, the efficacy remains unstable. To determine the efficacy and safety of skin biopsy punch in combination with corticosteroid injection (BPCI) in treating keloids. This was a retrospective study. In total, 16 patients with keloids received BPCI. Changes in scar appearance, accompanied symptoms, and Vancouver Scar Scale (VSS) were analyzed. Patient satisfaction, VAS scores, and adverse effects were also evaluated. Scar appearance, accompanied symptoms, and VSS scores improved significantly after the treatment. The total effective rate was 93.75% at an 18-month follow-up on average. The mean reduction rate of VSS score was 58.44% (p < 0.0001), especially in height and pliability (84.44% and 78.19%, p < 0.0001). The recurrence rate in this study was 12.5% (n = 2) at an 18-month follow-up on average. Mild adverse effects of pain, pruritus, hypopigmentation, and telangiectasia were recorded. This study demonstrated BPCI might be an effective and safe therapy in keloids with a low long-time recurrence rate and well tolerance for patients. This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

CD112 Supports Lymphatic Migration of Human Dermal Dendritic Cells.

Dendritic cell (DC) migration from peripheral tissues via afferent lymphatic vessels to draining lymph nodes (dLNs) is important for the organism's immune regulation and immune protection. Several lymphatic endothelial cell (LEC)-expressed adhesion molecules have thus far been found to support transmigration and movement within the lymphatic vasculature. In this study, we investigated the contribution of CD112, an adhesion molecule that we recently found to be highly expressed in murine LECs, to this process. Performing in vitro assays in the murine system, we found that transmigration of bone marrow-derived dendritic cells (BM-DCs) across or adhesion to murine LEC monolayers was reduced when CD112 was absent on LECs, DCs, or both cell types, suggesting the involvement of homophilic CD112-CD112 interactions. While CD112 was highly expressed in murine dermal LECs, CD112 levels were low in endogenous murine dermal DCs and BM-DCs. This might explain why we observed no defect in the in vivo lymphatic migration of adoptively transferred BM-DCs or endogenous DCs from the skin to dLNs. Compared to murine DCs, human monocyte-derived DCs expressed higher CD112 levels, and their migration across human CD112-expressing LECs was significantly reduced upon CD112 blockade. CD112 expression was also readily detected in endogenous human dermal DCs and LECs by flow cytometry and immunofluorescence. Upon incubating human skin punch biopsies in the presence of CD112-blocking antibodies, DC emigration from the tissue into the culture medium was significantly reduced, indicating impaired lymphatic migration. Overall, our data reveal a contribution of CD112 to human DC migration.

Folliculin gene-negative Birt-Hogg-Dube syndrome: a case report

Introduction and importance: Birt-Hogg-Dube (BHD) is a rare genetic disorder that results from a mutation in the folliculin (FLCN) gene. Manifestations include pulmonary cysts, fibrofolliculomas, renal tumors, and pneumothoraces. Genetic testing can be used to confirm the diagnosis when suspected. BHD syndrome is diagnosed in patients with negative FLCN gene results using diagnostic criteria. Case presentation: A male in his 20s presented with recurrent pneumothoraces. A physical examination revealed bumps on his face and upper body. A chest computed tomography scan revealed cystic lesions. Blood tests, ESR, and CRP levels were unremarkable. Punch skin biopsy revealed fibrofolliculomas. Genetic testing for the FLCN mutation returned negative. His history, physical exam, imaging, and histopathology suggested BHD syndrome despite having a negative family history and genetic analysis. Eventually, the patient was diagnosed with FLCN gene-negative BHD syndrome. Clinical discussion: More than a hundred families have been identified to have BHD worldwide. There are a few cases in the literature describing patients phenotypically presenting with BHD despite having a negative genetic analysis. One study in Japan found 16 out of 157 individuals having a clinical presentation of BHD with no mutations. Also, decreased expression of the FLCN mRNA may lead to BHD. Conclusion: BHD syndrome can present with a negative FLCN gene mutation; however, patients must meet the known diagnostic criteria such as criteria made by Menko et al., Gupta et al., and Schmidt et al. in order to have a diagnosis of BHD syndrome. Also, a qualitative decrease of FLCN with the absence of mutations may also lead to BHD.

Transient immune activation without loss of intraepidermal innervation and associated Schwann cells in patients with complex regional pain syndrome

BackgroundComplex regional pain syndrome (CRPS) develops after injury and is characterized by disproportionate pain, oedema, and functional loss. CRPS has clinical signs of neuropathy as well as neurogenic inflammation. Here, we asked whether skin biopsies could be used to differentiate the contribution of these two systems to ultimately guide therapy. To this end, the cutaneous sensory system including nerve fibres and the recently described nociceptive Schwann cells as well as the cutaneous immune system were analysed.MethodsWe systematically deep-phenotyped CRPS patients and immunolabelled glabrous skin biopsies from the affected ipsilateral and non-affected contralateral finger of 19 acute (< 12 months) and 6 chronic (> 12 months after trauma) CRPS patients as well as 25 sex- and age-matched healthy controls (HC). Murine foot pads harvested one week after sham or chronic constriction injury were immunolabelled to assess intraepidermal Schwann cells.ResultsIntraepidermal Schwann cells were detected in human skin of the finger—but their density was much lower compared to mice. Acute and chronic CRPS patients suffered from moderate to severe CRPS symptoms and corresponding pain. Most patients had CRPS type I in the warm category. Their cutaneous neuroglial complex was completely unaffected despite sensory plus signs, e.g. allodynia and hyperalgesia. Cutaneous innate sentinel immune cells, e.g. mast cells and Langerhans cells, infiltrated or proliferated ipsilaterally independently of each other—but only in acute CRPS. No additional adaptive immune cells, e.g. T cells and plasma cells, infiltrated the skin.ConclusionsDiagnostic skin punch biopsies could be used to diagnose individual pathophysiology in a very heterogenous disease like acute CRPS to guide tailored treatment in the future. Since numbers of inflammatory cells and pain did not necessarily correlate, more in-depth analysis of individual patients is necessary.

A triple combination of latanoprost, fractional CO2 laser, and platelet-rich plasma in localized vitiligo: A clinical and histopathologic study.

Several treatment modalities are available for the treatment of vitiligo due to the lack of a uniformly effective therapy. Topical latanoprost 0.005% is an effective topical treatment. Fractional CO2 laser alone or combined with platelet-rich plasma (PRP) has been proposed as effective adjunctive therapies. We aimed to compare the efficacy of topical latanoprost 0.005% (Ioprost®, Orchidia, Egypt) combined with either add-on fractional CO2 laser or fractional CO2 -PRP versus topical latanoprost monotherapy in the treatment of localized stable vitiligo. The study included 60 patients randomly assigned into three equal groups. Group A patients received topical latanoprost drops only. Group B patients received topical latanoprost drops and fractional CO2 laser sessions at 2-week interval for 3 months. Group C patients received topical latanoprost drops and fractional CO2 laser sessions combined with PRP at a 2-week interval for 3 months. The mean improvement score by the physician was calculated 4 months after the start of the study. Punch skin biopsies were obtained before treatment and 4 months from the beginning of the study and stained with H&E and HMB-45 antibody for evaluation of pigmentation. Significant clinical improvement of vitiligo lesions with significant increase of re-pigmentation were reported in the three treated groups. Latanoprost in combination with fractional CO2 and PRP was associated with more significant therapeutic outcomes than either combined latanoprost and fractional CO2 or latanoprost alone. Fractional CO2 laser-PRP enhances the therapeutic efficacy of latanoprost 0.005% in the treatment of localized stable vitiligo.

Clinical, histopathological and immunohistochemical evaluation of ultraviolet A1 treatment in early-stage mycosis fungoides.

Mycosis fungoides (MF) is the most common variant of cutaneous T-cell lymphomas primarily involving the skin. Early-stage MF is characterised by non-specific skin lesions and non-diagnostic biopsies. While skin-focused treatments, such as PUVA and narrowband UVB (nbUVB), are the most frequently recommended treatments, the UVA1 efficacy has been researched in recent years. The purpose of this study was to evaluate the clinical, histopathological and immunohistochemical aspects of UVA1 treatment in patients with early-stage MF. The modified severity weighted assessment scale (mSWAT) was used for total skin body scoring before and after treatment. Skin punch biopsies were taken from the patients before and after treatment. UVA1 therapy was performed five times each week. This study included 26 patients with early-stage MF. The total number of UVA1 sessions varied between 15 and 34. Complete response was observed in 8 (30.8%) of 26 patients (30.8%). The median mSWAT score decreased statistically significantly from 7.1 to 2.0 after treatment (p < .001). Histopathological complete response was observed in 2 (9.5%) of 21 patients. A statistically significant decrease in dermal interstitial infiltrate was observed on histopathological examination after treatment (p = .039). Epidermal CD4/CD8 levels decreased statistically significantly higher from a median of 2.5-1.2 in the complete clinical response group after treatment (p = .043). According to our results, UVA1 treatment has an effect on early-stage MF in terms of clinical, histopathological and immunohistochemistry.

Malignancy smells in the air: widespread eroded, hemorrhagic, and lichenified plaques in an older man

Paraneoplastic pemphigus (PNP) is a rare autoimmune mucocutaneous disease associated with underlying neoplasia. It is typically characterized by painful mucosal erosions and dark, patchy skin eruptions. A 66-year-old male was admitted to the internal medicine outpatient clinic with complaints of suddenly started rashes, loss of appetite, dyspepsia, weakness, and unexplained gross weight loss. The patient was cachectic and physical examination revealed widespread eroded, erythematous, thick-middle, yellow-pitted, lichenified plaques on bilateral arms and legs and the hands and feet dorsum. Scattered seborrheic keratosis lesions on the trunk were also detected. He had microcytic anemia with elevated CA 19-9 measures. Abdomen computed tomography showed a malignant mass in the antrum. Endoscopic biopsy of the gastric mass revealed poorly differentiated adenocarcinoma composed of discohesive signet ring cells and skin punch biopsy was compitable with paraneoplastic pemphigus.&#x0D; In patients with rapidly developing skin lesions with constitutional symptoms, underlying malignancies should be kept in mind.

α-synuclein antibody 5G4 identifies idiopathic REM-sleep behavior disorder in abdominal skin biopsies

IntroductionIdiopathic REM-sleep behavior disorder (iRBD) is considered the most specific prodromal marker of Parkinson's disease (PD). With the need to improve early detection of prodromal α-synucleinopathies, several methods to identify peripheral α-synuclein (α-syn) pathology have been exploited in manifest and prodromal PD with varying diagnostic accuracy. Recently, a disease specific 5G4 antibody has been evaluated in skin biopsies of manifest PD patients. The aim of our study was to analyze the 5G4 α-syn immunoreactivity in skin biopsies of deeply phenotyped subjects with iRBD and controls. MethodsThe study cohort consisted of 28 patients with PD, 24 subjects with iRBD and 27 healthy controls, recruited from the CEGEMOD, PDBIOM and PARCAS cohorts. All subjects were deeply phenotyped and assessed for prodromal PD (pPD) probability based on MDS research criteria. Abdominal skin punch biopsies were processed and stained using a conformation specific 5G4 α-syn antibody as well as axonal markers SMI-31 and S100. Results5G4-positivity was identified in 23/28 PD patients, 20/24 iRBD subjects and 8/27 healthy controls. Compared to healthy controls, sensitivity and specificity reached 83.33 % and 70.37 % for iRBD; and 82.14 % and 70.37 % for PD, respectively. 5G4-positivity rate in our study was irrespective of the calculated pPD probability of iRBD subjects. ConclusionsThis work establishes the diagnostic yield of conformation specific 5G4 α-syn antibody testing in skin biopsies of subjects with pPD, specifically iRBD. The diagnostic accuracy for this method seems to be similar for both manifest and prodromal PD and is not dependent on the pPD probability ratios.

Prospective incidence epidemiology study protocol: conducting active surveillance to assess the burden of Lyme disease (BOLD) in primary care practices in endemic areas of six European countries

IntroductionLyme disease (LD) is the most frequent tick-borne disease in the moderate climates of Europe. This study will inform the phase III efficacy study for Pfizer and Valneva’s investigational Lyme...

CD8+ aggressive T-cell lymphoma (T-NHL) involving the liver and skin: a case study

Abstract Introduction/Objective Aggressive T-NHL involving cutaneous and visceral organs is rare. We report a case with a complex presentation that was found to have hepatic and skin lesions simultaneously. We emphasize the importance of the clinicopathological correlation and diagnostic work-up for such a rare case Methods/Case Report A 60-year-old male with alcoholic cirrhosis presented with abdominal pain, fever, and night sweats for over two weeks. Detailed physical evaluation revealed a tender, indurated, erythematous papule on the left upper back. Lab results showed leukopenia, anemia, and increased LDH. PET-CT showed multiple hypermetabolic lesions in the liver, skin, and deep soft tissue above and below the diaphragm. A liver biopsy revealed a diffuse sheath of large atypical lymphoid cells with small lymphocytes in the background. Atypical lymphoid cells stained positive for CD45, CD2, CD3, CD8, TIA-1, CD5 (partial), granzyme B (partial), βF1 (partial); and negative for ALK, BCL-2, CD4, CD7, CD10, CD30, CD56, and TCRδ. Ki-67 was 70%. The skin punch biopsy revealed epidermotropic infiltration of lymphocytes with a similar immunophenotype as the liver lesion. Bone marrow biopsy showed no involvement. The differential diagnosis includes primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-NHL with visceral dissemination, peripheral CD8+ T-NHL, lymphomatoid papulosis, CD8-positive mycosis fungoides, and hepatosplenic T-NHL. The visceral involvement excludes lymphomatoid papulosis and CD8-positive mycosis fungoides. The absence of bone marrow involvement excludes hepatosplenic T-NHL. The prominent liver involvement favors the diagnosis of peripheral CD8+ T-NHL. However CD8+ aggressive epidermotropic cytotoxic T-NHL still cannot be entirely excluded due to the epidermotropic CD8 positive T-cell infiltration of the dermis and subcutaneous adipose tissue. Further evaluation for JAK2 mutation and TBX21 amplification can help distinguish it from Peripheral CD8- positive T-NHL. Results (if a Case Study enter NA) NA Conclusion The subclassification of CD8+ T-NHL into distinct entities with overlapping clinical and histological characteristics is challenging without molecular tests. However, clinicopathological correlation with appropriate work-up can help narrow the differential diagnoses.

Gene expression changes of angiogenesis factors during basal skin cancer laser treatment

Background: Basal cell carcinoma is the most widespread malignant skin neoplasm. Angiogenesis is critical for the growth and metastasis of malignant tumors.&#x0D; Aims: To study the levels of representation of transcripts in the foci of basal cell skin cancer before and after the therapy of genes for angiogenesis proteins and their receptors.&#x0D; Materials and methods: The study included 31 patients with confirmed basal cell skin cancer who received treatment, using a pulsed dye laser and long-pulsed neodymium laser. The patients provided skin punch biopsies from BCC lesions and after therapy from the same localization. The gene expression was analyzed with real-time reverse transcription PCR using endogeneous control, and the gene expression ration changes during the therapy were calculated according to Livaks double delta formulae.&#x0D; Results:&#x0D; An increased expression of the matrix metalloproteinase MMP9 and the tachykinin precursor TAC1 genes were revealed in skin biopsy samples of the superficial and nodular form of basal cell skin cancer during laser pulsed therapy. The expression of tumor necrosis factor TNF, epidermal growth factor receptor EGFR, fibroblast growth factor FGF2 genes increases to a lesser extent.&#x0D; It was shown that the expression of the calcitonin-related polypeptide alpha CALCA gene in the skin of patients is at basal level, which makes it possible to exclude the influence of the neuropeptide on the basal cell skin cancer pathogenesis.&#x0D; Conclusions:&#x0D; Among the factors of neoangiogenesis potentially influencing the development of basal cell skin cancer, the leading role of expression of the MMP9 matrix metalloproteinase and TAC1 precursor protein of tachykinin has been shown. Simultaneous changes in the level of these proteins may be due to neuroimmune interactions in the epidermis, which is probably realized by mast cells as the microenvironment of the basal cell carcinoma.

PSX-30 Scratching the Surface: Investigating the Nature and Potential Causes of Pruritic Cattle

Abstract Depending on the year, during the winter months, cattle begin to rub bare patches on their skin due to pruritus which leads to concern from cattle producers, especially the purebred breeders. Upon further investigation by veterinarians, the cause is not always caused by lice, as many may think. This study aimed to provide insight into the cause and potential prevention/treatment of pruritic beef cattle in western Canada by examining herds that met the study’s criteria of having more than 30% of the herd exhibiting pruritus. Seven herds were examined in the winter of 2023: one from Manitoba, two from Saskatchewan, and four from Alberta. Producers from each herd completed a detailed survey on treatments, nutrition, and environmental conditions and provided feed, water, and bedding samples. Within each herd, five cattle considered non-pruritic, and ten cattle considered pruritic by visual appraisal were enrolled for standard data collection consisting of documentation and photos of skin lesions localized to pruritic areas, general health clinical exam, lice exam/collection, mite exam/collection of hairs, skin hydration (corneometer), blood chemistry and vitamin/minerals, and kidney/liver enzymes for mycotoxins. A subset of the group (1 non-pruritic and 4 pruritic) was selected for advanced data collection, including dermal hypersensitivity (grass, alfalfa, grain, weeds, and molds) measured by swelling score and infrared camera temperature measurement compared with positive and negative controls, skin punch biopsies for eosinophils (IgE) and liver biopsies for copper levels. Only 21/101 cattle had lice (18 animals &amp;lt; 10 lice per 6.5 cm2). No significant correlation was observed between cattle with lice and being pruritic (P &amp;gt; 0.05). Dermal hypersensitivity was very low across both pruritic and non-pruritic cattle and was not different (P &amp;gt; 0.05). Skin hydration readings within animals comparing pruritic and non-pruritic areas on their body showed only one herd having significantly (P &amp;lt; 0.05) drier skin on pruritic locations compared with normal locations. Vitamin A, E, and copper blood analysis showed no significant difference between pruritic and non-pruritic cattle. However, liver biopsy copper levels were (P = 0.01) less in pruritic than non-pruritic cattle. Results suggest that the cause of pruritic cattle is not necessarily a result of intense lice infestations but rather multifactorial in nature, and a decision tree for producers and veterinarians should be developed to aid in determining the correct course of action to alleviate pruritic cattle in the field.

Cutaneous Metastasis as a Diagnostic Prelude in a 48-year-old Female

Abstract Cutaneous metastasis (CM) describes the spread of a distant primary tumor into the skin. The overall incidence of CM ranges from 5% to 10% with breast cancer having the highest rate in women. CM of breast carcinoma origin may manifest as erysipelas-like erythema on the chest, having distinct raised borders and edema due to lymphatic obstruction termed as carcinoma erysipeloides. In most cases, CM is recognized after the initial diagnosis of primary internal malignancy. However, in 0.6–1% of cases, CM served as the first presenting sign of malignancy. A 48-year-old female presented with multiple, erythematous patches, and plaques with clear-cut raised margins, some topped with violaceous pinpoint papules and nodules on the chest, abdomen, and back. No palpable breast mass was appreciated. There was noted nipple retraction and axillary lymphadenopathy. A 4-mm skin punch biopsy revealed nests of large pleomorphic cells on the papillary dermis admixed with mitotic figures and attempts of ductal formation. CK7 and CEA were positive. Results of ultrasonography and mammogram were highly suspicious of malignancy. Core needle biopsy of the breast mass revealed an invasive ductal carcinoma. In the context of an eczematous presentation on the chest area without palpable nodules or mass on breast examination, a diagnostic challenge is expected. Interestingly, our patient represents a small group of CM having cutaneous lesions as their primary manifestation. A high index of suspicion supplemented with proper clinicopathologic and radiologic correlation is crucial for the diagnosis of CM. A multidisciplinary referral is required for adequate management and overall survival rate.

Refractory drug-induced systemic small-vessel vasculitis with two varied extracutaneous manifestations: a case report and review of the literature

BackgroundClopidogrel and ticagrelor are rarely reported to cause vasculitis via drug hypersensitivity reaction, largely mediated by T cells and immunoglobulin E (IgE). Despite therapeutic advances, the etiology of refractory vasculitides remains incompletely understood. Recently, (non)immunological mechanisms bypassing T cells and IgE have been proposed to explain resistance to standard immunosuppressants. Herein, we report a case of refractory drug-induced systemic small-vessel vasculitis with varied extracutaneous manifestations and incorporate multiple sources of data to provide detailed accounts of complex (non)immunological phenomena involved in this case. Study objectives are to provide an insight about rare presentations of commonly used drugs, upgrade the pathophysiological concepts of drug-induced vasculitis, raise need for further investigation to define causes and risk factors for refractory vasculitis, and discuss most of the current knowledge suggesting novel therapeutic approaches to treat this vasculitis. To our knowledge, this is the first case of the two flares of systemic small-vessel vasculitis in a single patient in response to clopidogrel and ticagrelor exposure, respectively. However, this report is limited by attribution/observer bias.Case presentationWe herein report a 24-year-old Caucasian male student with a medical history of mild seasonal allergic rhinoconjunctivitis, tension-type headaches, posttraumatic arterial stenosis, and previous exposure to ibuprofen, acetylsalicylic acid, and mRNA coronavirus disease 2019 (COVID-19) vaccine who suffered largely from acute urticaria and dyspnea after 20 days of acetylsalicylic acid and clopidogrel introduction. A skin punch biopsy confirmed leukocytoclastic vasculitis. Serologic antibody testing, complement analysis, microbiologic testing, and cancer biomarkers revealed no abnormalities. Regarding the patient’s medical history, both acetylsalicylic acid and clopidogrel were exchanged for ticagrelor. Furthermore, the addition of naproxen, cyclosporine, bilastine, prednisolone, and montelukast resulted in complete recovery. After 7 days, diarrhea and hematuria occurred. Urinalysis and computed tomography showed reversible proteinuria with gross hematuria and hypodense changes in kidney medulla, respectively, associated with discontinuation of ticagrelor and naproxen. In addition, the patient recovered completely without any immunosuppression up-titration.ConclusionsThis case highlights the role of clopidogrel and ticagrelor as possible triggering agents for systemic small-vessel vasculitis and offers an insight into novel therapeutic strategies for refractory vasculitides. Further research is needed to build on the findings of a current report.

Evaluation of modulation of immunity by lymph node transfer: A preliminary histological evidence in lymphedema patients.

The exact knowledge of the local biological and immunological effects of vascularized lymph node transfer (VLNT) continues to be an emerging science but a positive control positive control over infectious and immune-mediated processes is often advocated. Knowing the characterization of the inflammatory infiltrate associated with lymphedema, the aim of this paper is to verify the hypothesis that VLNT is able to modulate the inflammatory and immune microenvironment of lymphedematous tissue by evaluating any modification of the local inflammatory cell infiltrate. A prospectively database of patients who received VLN transfer for lower extremity lymphedema between January 2018 and December 2020 was reviewed. Nine patients diagnosed with extremities' stage II secondary lymphedema were included, with a mean age of 55.3 (range 39-66 years) years. Gastroepiploic lymph node transfer was performed in all patients and transferred heterotopically. Full thickness 6-mm skin punch biopsies were obtained from all voluntary lymph node transfer patients at identical sites of the lymphedematous limb during the surgical procedure of VLNT (T0) and 1 year later (T1). Immunohistochemistry was performed using antibodies against the following markers: anti-CD3; anti-CD4; anti-CD8; anti-CD68. Data at T0 were compared to those at T1. Post-operative course was uneventful in all cases experiencing a significant reduction (almost a third) in terms of cellulitis episodes: The median duration of follow-up for patients was 28.3 months (range 12-40). The analysis of the density of the inflammatory cells as a whole revealed a significant reduction at T1 compared to T0. Specifically, CD3 expression levels turned from 16.36 ± 3.421 (cells/mm2 ) pre-operatively to 7.6 ± 1.511 (cells/mm2 ) post-operatively (p < .0001). CD4+ cells turned from 7.270 ± 3.421 (cells/mm2 ) at T0 to 4.815 ± 1.511 cells/mm2 at T1 (p = .0173). CD8 expression values decreased from 4.360 ± 3.421 (cells/mm2 ) to 2.753 ± 1.451 (cell/mm2 ) at T1 (p = .0003). Monocyte/macrophage marker CD68 varied from 8.208 ± 2.314 (cells/mm2 ) at T0 to 7.600 ± 1876 (cells/mm2 ) at T1 (p = .0003). VLNT decreases skin and subcutaneous tissues' infiltration of inflammatory cells, providing one explanation for the positive control of lymph node transfer procedure over infectious and immune-mediated processes.

Expanding the spectrum of neonatal-onset AIFM1-associated disorders.

Pathogenic variants in AIFM1 have been associated with a wide spectrum of disorders, spanning from CMT4X to mitochondrial encephalopathy. Here we present a novel phenotype and review the existing literature on AIFM1-related disorders. We performed EEG recordings, brain MRI and MR Spectroscopy, metabolic screening, echocardiogram, clinical exome sequencing (CES) and family study. Effects of the variant were established on cultured fibroblasts from skin punch biopsy. The patient presented with drug-resistant, electro-clinical, multifocal seizures 6 h after birth. Brain MRI revealed prominent brain swelling of both hemispheres and widespread signal alteration in large part of the cortex and of the thalami, with sparing of the basal nuclei. CES analysis revealed the likely pathogenic variant c.5T>C; p.(Phe2Ser) in the AIFM1 gene. The affected amino acid residue is located in the mitochondrial targeting sequence. Functional studies on cultured fibroblast showed a clear reduction in AIFM1 protein amount and defective activities of respiratory chain complexes I, III and IV. No evidence of protein mislocalization or accumulation of precursor protein was observed. Riboflavin, Coenzyme Q10 and thiamine supplementation was therefore given. At 6 months of age, the patient exhibited microcephaly but did not experience any further deterioration. He is still fed orally and there is no evidence of muscle weakness or atrophy. This is the first AIFM1 case associated with neonatal seizures and diffuse white matter involvement with relative sparing of basal ganglia, in the absence of clinical signs suggestive of myopathy or motor neuron disease.

Case report on localized bullous pemphigoid in two young females

Bullous pemphigoid (BP) is a chronic autoimmune bullous eruption that is characterized by pruritic, tense sub-epidermal bullae. It commonly affects those aged 60 years and above. It has no gender predilection. It can be generalized or localized. This is a case report of 2 female patients with localized BP presenting as recurrent skin rash of more than 1 year duration which were later referred to the dermatology clinic. The patients were both females less than 40 years of age who have been having recurrent skin rash that have been associated with intense itching localized to a unilateral lower limb. The first patient had obvious bullae and ulcers while the second didn’t have any obvious bullae. Initial clinical diagnoses did not consider BP. Punch skin biopsy was done in both cases that revealed histologic features confirming BP. Clinicians should have high index of suspicion of BP even in cases of localized chronic wound or recurrent ulcers irrespective of the age of patient.

Skin Extracellular Matrix Breakdown Following Paclitaxel Therapy in Patients with Chemotherapy-Induced Peripheral Neuropathy.

The chemotherapeutic agent paclitaxel causes peripheral neuropathy, a dose-limiting side effect, in up to 68% of cancer patients. In this study, we investigated the impact of paclitaxel therapy on the skin of breast cancer patients with chemotherapy-induced peripheral neuropathy (CIPN), building upon previous findings in zebrafish and rodents. Comprehensive assessments, including neurological examinations and quality of life questionnaires, were conducted, followed by intraepidermal nerve fiber (IENF) density evaluations using skin punch biopsies. Additionally, RNA sequencing, immunostaining for Matrix-Metalloproteinase 13 (MMP-13), and transmission electron microscopy provided insights into molecular and ultrastructural changes in this skin. The results showed no significant difference in IENF density between the control and CIPN patients despite the presence of patient-reported CIPN symptoms. Nevertheless, the RNA sequencing and immunostaining on the skin revealed significantly upregulated MMP-13, which is known to play a key role in CIPN caused by paclitaxel therapy. Additionally, various genes involved in the regulation of the extracellular matrix, microtubules, cell cycle, and nervous system were significantly and differentially expressed. An ultrastructural examination of the skin showed changes in collagen and basement membrane structures. These findings highlight the presence of CIPN in the absence of IENF density changes and support the role of skin remodeling as a major contributor to CIPN.