Dermal Vessels Research Articles

Targeting miR-27a/VE-cadherin interactions rescues cerebral cavernous malformations in mice.

Cerebral cavernous malformations (CCMs) are vascular lesions predominantly developing in the central nervous system (CNS), with no effective treatments other than surgery. Loss-of-function mutation in CCM1/krev interaction trapped 1 (KRIT1), CCM2, or CCM3/programmed cell death 10 (PDCD10) causes lesions that are characterized by abnormal vascular integrity. Vascular endothelial cadherin (VE-cadherin), a major regulator of endothelial cell (EC) junctional integrity is strongly disorganized in ECs lining the CCM lesions. We report here that microRNA-27a (miR-27a), a negative regulator of VE-cadherin, is elevated in ECs isolated from mouse brains developing early CCM lesions and in cultured ECs with CCM1 or CCM2 depletion. Furthermore, we show miR-27a acts downstream of kruppel-like factor (KLF)2 and KLF4, two known key transcription factors involved in CCM lesion development. Using CD5-2 (a target site blocker [TSB]) to prevent the miR-27a/VE-cadherin mRNA interaction, we present a potential therapy to increase VE-cadherin expression and thus rescue the abnormal vascular integrity. In CCM1- or CCM2-depleted ECs, CD5-2 reduces monolayer permeability, and in Ccm1 heterozygous mice, it restores dermal vessel barrier function. In a neonatal mouse model of CCM disease, CD5-2 normalizes vasculature and reduces vascular leakage in the lesions, inhibits the development of large lesions, and significantly reduces the size of established lesions in the hindbrain. Furthermore, CD5-2 limits the accumulation of inflammatory cells in the lesion area. Our work has established that VE-cadherin is a potential therapeutic target for normalization of the vasculature and highlights that targeting miR-27a/VE-cadherin interaction by CD5-2 is a potential novel therapy for the devastating disease, CCM.

Cutaneous Vasculitis: Review on Diagnosis and Clinicopathologic Correlations.

Cutaneous vasculitis is an inflammatory disease affecting the dermal blood vessel walls. The skin is a privileged organ in the setting of vasculitis since it is easily accessible for physical examination and safe biopsy, allowing an accurate characterization of inflammatory lesions. The skin is often involved. Also, cutaneous vasculitis can reflect a cutaneous component of a systemic vasculitis, a skin-limited or skin-dominant expression or variant of a systemic vasculitis, or be a single-organ vasculitis per se. Vasculitis lesions are multiple and polymorphic. They may induce a wide spectrum of clinical manifestations depending on the location and the size of the vessels involved. The depth of affected vessels is correlated with the type of cutaneous lesions. Involvement of small superficial vessels results mostly in urticarial, but relatively persistent plaques, papules, and palpable purpura. Involvement of vessels in the dermohypodermic junction or hypodermis results in ulcers, nodules, or livedo. The type of inflammatory infiltrate is also a key finding for the diagnosis of cutaneous vasculitis. Leukocytoclastic vasculitis is not a disease per se but the result of a pathophysiological process common to different causes. A better knowledge of the vascular anatomy of the skin, elementary lesions, and histological characteristics of dermatologic manifestations would allow a more relevant and more efficient diagnostic approach. We also propose a list of additional exams to be performed in front of skin lesions suggestive of vasculitis. The aim of our article is to provide an overview of elementary skin lesions and clinicopathologic correlations in cutaneous and systemic vasculitis.

TGF-beta and TNF-alpha cooperatively induce mesenchymal transition of lymphatic endothelial cells via activation of Activin signals.

Lymphatic systems play important roles in the maintenance of fluid homeostasis and undergo anatomical and physiological changes during inflammation and aging. While lymphatic endothelial cells (LECs) undergo mesenchymal transition in response to transforming growth factor-β (TGF-β), the molecular mechanisms underlying endothelial-to-mesenchymal transition (EndMT) of LECs remain largely unknown. In this study, we examined the effect of TGF-β2 and tumor necrosis factor-α (TNF-α), an inflammatory cytokine, on EndMT using human skin-derived lymphatic endothelial cells (HDLECs). TGF-β2-treated HDLECs showed increased expression of SM22α, a mesenchymal cell marker accompanied by increased cell motility and vascular permeability, suggesting HDLECs to undergo EndMT. Our data also revealed that TNF-α could enhance TGF-β2-induced EndMT of HDLECs. Furthermore, both cytokines induced the production of Activin A while decreasing the expression of its inhibitory molecule Follistatin, and thus enhancing EndMT. Finally, we demonstrated that human dermal lymphatic vessels underwent EndMT during aging, characterized by double immunostaining for LYVE1 and SM22α. These results suggest that both TGF-β and TNF-α signals play a central role in EndMT of LECs and could be potential targets for senile edema.

Lumpy Skin Disease Is Characterized by Severe Multifocal Dermatitis With Necrotizing Fibrinoid Vasculitis Following Experimental Infection.

Lumpy skin disease is a high-consequence disease in cattle caused by infection with the poxvirus lumpy skin disease virus (LSDV). The virus is endemic in most countries in Africa and an emerging threat to cattle populations in Europe and Asia. As LSDV spreads into new regions, it is important that signs of disease are recognized promptly by animal caregivers. This study describes the gross, microscopic, and ultrastructural changes that occur over time in cattle experimentally challenged with LSDV. Four calves were inoculated with wildtype LSDV and monitored for 19 to 21 days. At 7 days after inoculation, 2 of the 4 cattle developed multifocal cutaneous nodules characteristic of LSD. Some lesions displayed a targetoid appearance. Histologically, intercellular and intracellular edema was present in the epidermis of some nodules. Occasional intracytoplasmic inclusion bodies were identified in keratinocytes. More severe and consistent changes were present in the dermis, with marked histiocytic inflammation and necrotizing fibrinoid vasculitis of dermal vessels, particularly the deep dermal plexus. Chronic lesions consisted of full-thickness necrosis of the dermis and epidermis. Lesions in other body organs were not a major feature of LSD in this study, highlighting the strong cutaneous tropism of this virus. Immunohistochemistry and electron microscopy identified LSDV-infected histiocytes and fibroblasts in the skin nodules of affected cattle. This study highlights the noteworthy lesions of LSDV and how they develop over time.

A case of Henoch-Sch\xf6nlein purpura associated with scrub typhus

BackgroundHenoch-Schönlein purpura (HSP) may be caused by several allergens. However, to date, HSP caused by Orientia tsutsugamushi has not been reported. Here, we report an unusual rash with features of HSP caused by Orientia tsutsugamushi.Case presentationA man visited a tertiary hospital with bilateral symmetrical purpura and fever. He presented with an eschar in the left popliteal fossa and proteinuria. He was diagnosed with tsutsugamushi disease by indirect fluorescent antibody and positive polymerase chain reaction tests. Purpura biopsy demonstrated a feature of leukocytoclastic vasculitis and IgA deposition in dermal vessels, indicative of HSP.ConclusionsWhen examining patients with unique rashes, such as in this case, we suggest investigating out-door activities and evidence of mite bites. Furthermore, differential diagnosis of tsutsugamushi disease should be considered when necessary.

The role of C-afferents in mediating neurogenic vasodilatation in plantar skin after acute sciatic nerve injury in rats

BackgroundVasomotor regulation of dermal blood vessels, which are critical in the function of the skin in thermoregulatory control, involves both neural and non-neural mechanisms. Whereas the role of sympathetic nerves in regulating vasomotor activities is comprehensively studied and well recognized, that of sensory nerves is underappreciated. Studies in rodents have shown that severance of the sciatic nerve leads to vasodilatation in the foot, but whether sympathetic or sensory nerve fibers or both are responsible for the neurogenic vasodilatation remains unknown.ResultsIn adult Sprague–Dawley rats, vasodilatation after transection of the sciatic nerve gradually diminished to normal within 3–4 days. The neurotmesis-induced neurogenic vasodilatation was not detectable when the sciatic nerve was chronically deafferentated by selective resection of the dorsal root ganglia (DRGs) that supply the nerve. Specific activation of C-afferents by intra-neural injection of capsaicin resulted in neurogenic vasodilatation to a magnitude comparable to that by neurotmesis, and transection of the sciatic nerve pre-injected with capsaicin did not induce further vasodilatation.ConclusionsOur results collectively indicate that vasodilatation after traumatic nerve injury in rats is predominantly mediated by C-fiber afferents.

P38 MAPK Isoforms as Modulators of Oncogenic Phenotypes in Inflammatory Breast Cancer

Inflammatory Breast Cancer (IBC) is a rare, aggressive, and highly metastatic subtype of breast cancer; accounting for approximately 1–6% of all breast cancer diagnoses in the United States and 7–10% of breast cancer‐associated deaths in Western countries. The aggressiveness of this disease is generally attributed to the formation of diffuse tumor cell clusters, known as tumor emboli, that block the dermal lymphatic vessels near the chest wall, a key hallmark of IBC. Clinically, it has been documented that most of IBC cases are either HER2 amplified or Triple Negative (TN‐IBC), the latter being the most difficult to treat. As a result, there is a dire need to understand the molecular profile of IBC to further develop more efficient targeted therapies. It has been reported that 17β‐Estradiol (E2) exerts non‐genomic signaling in ER‐negative IBC and non‐IBC cells using estrogen receptors GPR30 and estrogen receptor alpha variant 36 (ERα‐36), which activate the PI3K/AKT/ERK pathways involved in oncogenic phenotypes. p38 isoforms alpha, beta, gamma, and delta have been demonstrated to modulate proliferation, migration, apoptosis, and cell senescence via stress‐induced pathways or mitogen‐activated pathways. Also, it has been shown that these isoforms have context‐dependent functions depending on tissue type, expression and activation level, and the pathways involved. Nevertheless, the effects of these isoforms have yet to be elucidated in IBC. Preliminary data suggest that estrogen mediates p38 activation when IBC cells are treated with E2. For this reason, we hypothesize that estrogenmediated activation is involved in p38‐induced oncogenesis via non‐genomic signaling in an isoform‐dependent manner in IBC cell lines. A comparison of p38 isoforms expression was done on both IBC and non‐IBC cell lines via Western blot and qRT‐PCR, presenting differential expression profiles. This data was then used to design a knockdown model to study the effects of the most predominant isoforms on oncogenic phenotypes. Treatment using SB202190, a potent p38 inhibitor, caused a significant decrease in cell viability of several breast cancer cell lines when performing a dose response curve. Ongoing studies include assessing the effects of p38 inhibition and knockdown on proliferation, invasion, migration, and tumor emboli formation under basal and endocrine conditions. To recapitulate, understanding E2 responsiveness by ER‐negative cell lines may provide great insight into novel targeted therapies using the non‐genomic signaling pathway; in particular, p38 signaling appears to be a key effector of prooncogenesis in IBC.

Angiokeratoma of Fordyce: A diagnostic enigma

Angiokeratomas are rare, benign ectasias of scrotal dermal vessels with a male preponderance. They are usually asymptomatic, although rarely they may present as an acute bleed. We present a case report of a 27 year old male with multiple large papules over scrotum associated with intense pruritis. Excision of scrotal skin was performed. Patient was followed up for one year, without any recurrence.

A rare case of cutaneous vasculitis with diagnostic difficulty in coexistence of serum anti‐PR3 antibody and in vivo IgA deposits in the skin

Dear Editor, Granulomatosis with polyangiitis (GPA) represents a necrotizing granulomatous inflammation involving the upper and lower respiratory tract with necrotizing vasculitis at small- to medium-sized vessels.1 GPA is also characterized by the presence of serum antineutrophil cytoplasmic antibodies (ANCAs), consisting of ANCA-associated vasculitis (AAV). In contrast, IgA vasculitis is an immune complex disease affecting small vessels in various organs, involving the skin, gastrointestinal tract, kidneys, and arthritic joints.1 Both disease phenotypes sometimes overlap and are difficult to discriminate. Here, we report an exemplified case of cutaneous vasculitis with simultaneous positivity for in vivo IgA immunofluorescence in the dermal small vessels and serum antiproteinase 3 (PR3) ANCA. An otherwise healthy 40-year-old Japanese man presented with high-grade fever, arthralgia, and painful swelling with purpura in bilateral lower limbs 2 days ago. Examination showed multiple small-sized palpable purpura and violaceous, coalescent papules (Figure 1A,B). Histopathology of the lesional purpura showed leukocytoclastic vasculitis without granuloma formation throughout the dermis (Figure 1C,D). Direct immunofluorescence showed IgA deposits at blood vessel walls (Figure 1E). Abnormal laboratory data included an elevated serum PR3-ANCA (89.9 U/mL; ref. <3.5 U/mL). Serum cryoglobulins and renal function were within normal limits. Ophthalmologic examination revealed no abnormalities. Contrast-enhanced computed tomography (CT) detected no granulomas or organ involvements, except mild ethmoid sinusitis and pulmonary emphysema. He was initially diagnosed with IgA vasculitis with anti-PR3 ANCA and treated with oral prednisolone 40 mg/d (0.5 mg/kg/d). His fever and arthralgia were subsided, but the purpuric eruption rapidly spread to the trunk. Upon the ongoing oral steroid, a high-dose intravenous cyclophosphamide was added, and the skin lesions improved with concomitant decrease of serum PR3-ANCA titer. Thereafter, the daily dose of oral steroid was tapered to 5 mg/d during 1 year of follow-up, but his symptoms have never relapsed. Our case poses a diagnostic dilemma in the coexistence of in vivo IgA deposit at the dermal blood vessels and seropositive anti-PR3 ANCA. Moreover, the serum antibody titer was consistent with the clinical course, supporting the provisional diagnosis of GPA rather than IgA vasculitis, albeit no detectable granulomas in any organs. An alternative diagnosis arises the possibility of IgA vasculitis with positive PR3-ANCA. However, there has been a documented case who primarily diagnosed with IgA vasculitis but later developed pulmonary hemorrhage with granuloma and required immunosuppressive therapy2. A careful follow-up is hence mandatory for life-threatening complications abruptly activated in GPA. Antineutrophil cytoplasmic antibody-associated vasculitis has been considered as a pauci-immune condition that is unrelated to immune complex basis.3 However, an updated case series implicates the possible overlapping of AAV and immune complex vasculitis, as seen in ANCA-associated glomerulonephritis with complement and/or immunoglobulin deposition in kidney.4, 5 The concept is strengthened by observation that the complement depletion completely blocked anti-MPO ANCA-induced crescentic glomerulonephritis in mice.6 Alternative complement activation may, in part, coexist as the pathogenic modifier of AAV. Combining these with evidence that the tissue-bound complements and immunoglobulins are degraded by locally infiltrating leukocytes,7 the disease stage-/tissue-dependent activation of immune complex system may aid interpretation of the complex pauci-immunity in AAV. The authors declare no conflict of interest. Obtained. Approval of the research protocol: No human participants were included. Registry and the Registration No.: N/A. Animal Studies: N/A.

Abstract P3-01-08: Infiltrating immune cells in the tumor emboli of inflammatory breast cancer

Abstract INTRODUCTION: Inflammatory breast cancer (IBC) is a rare and aggressive type of locally advanced breast cancer. The hallmark of IBC is the presence of E-Cadherin positive tumor emboli within the dermal and parenchymal lymphatic vessels. These tumor emboli are thought to be responsible for the clinical presentation by the physical obstruction of draining lymph vessels. In addition, the intravascular growth of tumor emboli may account for the typical diffuse growth pattern and the fast local spread associated with IBC. Tumor emboli can result from encircling lymphovasculogenesis or lymphovascular invasion and little is known about the infiltrating immune cells in these emboli. This is the first study to investigate the immune infiltrate in the tumor emboli of patients with IBC. METHODOLOGY: To analyze the immune composition of the emboli, four slides of 24 IBC patients were stained according to a validated protocol and scored using the VISIOPHARM® software that makes virtual multiplexing possible after the alignment of different digital slides. We used four validated antibodies: CD79α (B-cell lineage), CD8 (cytotoxic T-cells), FOXP3 (Tregs) and CD163 (Tumor associated macrophages; TAMs), combined with a standard H&amp;E stained section to mark the tumor area and tumor emboli on pretreatment biopsy sections. RESULTS: Half of the IBC patients presented with a hormone receptor positive carcinoma (54.2% - n= 13/24) and 8 out of 21 patients with initially localized disease achieved complete pathological response (pCR) after neo-adjuvant chemotherapy (NACT). Our results are summarized in table 1. Table 1: For every staining we report the number of patients that have infiltrated emboli, the median density in the invasive carcinoma (IC), the median density in the emboli (E) and the ratio between the invasive tumor and emboli in table 1.# patientsDensity (IC) #/μm2Density (E) #/μm2Ratio Density E/ICP-valueCD812/24 (50 %)19.62.40.11&amp;lt; .001CD16319/23 (83 %)35.412.80.43.02CD79α11/24 (46 %)18.23.50.31.01FOXP34/23 (17 %)5.10.30.04.003 Patients with more immune cells in the invasive carcinoma (IC) also had more immune cells in the emboli (E). This correlation was significant for all stainings (Table 1). CD163+ macrophages are the most abundant immune cells in emboli, especially when compared to the invasive carcinoma, whereas CD8+ cells were uncommon in the emboli. The density of CD8+ cells in the invasive carcinoma or emboli did not predict pCR. Interestingly, patients with a higher IC/E CD8 density ratio achieved more often pCR (Kruskal-Wallis χ = 3.6, P = 0.05). Only 20.8% (n= 5/24) had invasive carcinoma directly surrounding the intravascular emboli, however, median overall survival in these patients was significantly shorter (P= 0.003). CONCLUSIONS: This is the first study looking at infiltrating immune cells in IBC. Although based on a small discovery cohort of only 24 patients, we showed that there is a strong correlation between the density of immune cells in the emboli and the density in the invasive carcinoma. Furthermore, we demonstrate that TAMs are the predominant immune cell type in IBC emboli. Cytotoxic T cells are less common and having more CD8+ cells in the invasive carcinoma compared to the emboli was associated with pCR. Patients with invasive carcinoma directly surrounding the emboli had a worse prognosis. Citation Format: Christophe Van Berckelaer, Charlotte Rypens, Peter Vermeulen, Steven Van Laere, Peter Van Dam, Cecile Colpaert. Infiltrating immune cells in the tumor emboli of inflammatory breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-01-08.

Inflammatory breast cancer cells are characterized by abrogated TGFβ1-dependent cell motility and SMAD3 activity.

Inflammatory breast cancer (IBC) is an aggressive form of breast cancer with elevated metastatic potential, characterized by tumor emboli in dermal and parenchymal lymph vessels. This study has investigated the hypothesis that TGFβ signaling is implicated in themolecular biology of IBC. TGFβ1-induced cell motility and gene expression patterns were investigated in three IBC and three non-IBC (nIBC) cell lines. Tissue samples from IBC and nIBC patients were investigated for the expression of nuclear SMAD2, SMAD3, and SMAD4. SMAD protein levels were related to gene expression data. TGFβ1-induced cell motility was strongly abrogated in IBC cells (P = 0.003). Genes differentially expressed between IBC and nIBC cells post TGFβ1 exposure revealed attenuated expression of SMAD3 transcriptional regulators, but overexpression of MYC target genes in IBC. IBC patient samples demonstrated a near absence of SMAD3 and -4 expression in the primary tumor compared to nIBC patient samples (P < 0.001) and a further reduction of staining intensity in tumor emboli. Integration of gene and protein expression data revealed that a substantial fraction of the IBC signature genes correlated with SMAD3 and these genes are indicative of attenuated SMAD3 signaling in IBC. We demonstrate attenuated SMAD3 transcriptional activity and SMAD protein expression in IBC, together with obliterated TGFβ1-induced IBC cell motility. The further reduction of nuclear SMAD expression levels in tumor emboli suggests that the activity of these transcription factors is involved in the metastatic dissemination of IBC cells, possibly by enabling collective invasion after partial EMT.

Characterization of Phthirus pubis With Ex Vivo Dermoscopy.

Pubic lice are smaller, less pigmented, and less mobile than head lice, and thus more difficult to observe with naked eye.1 In addition, the increasing habit of pubic hair removal has led to a falling incidence of pubic lice owing to the destruction of its natural habitat.2 This may be responsible for the atypical patterns of Phthirus pubis infestation in other parts of the body (eyebrows, axillae, trunk)2 and may be an underestimated cause of resistant pruritus and dermatitis. In vivo dermoscopy is useful for identifying nits and lice on the skin in these cases.1,3 However, a better characterization of the parasite can be made by collecting it from the skin surface with a transparent adhesive tape. This ex vivo dermoscopy is a simple and convenient method that allows for a more hygienic and detailed examination (Fig. 1), with no need of other devices, such as direct,3 confocal,4 or electron microscopy.5P. pubis has a short and broad body with 6 legs. The first pair of legs is slim; the second and third pairs are thicker and carry brown claws for grasping hair. The anterior portion has small mouthparts, used for probing the skin and withdrawing blood from dermal vessels. The ingested blood flows through the digestive tract, identified as brown-reddish structures in both sides and middle of the body (Video, Supplemental Digital Content 1, https://links.lww.com/OLQ/A453). External openings of the respiratory system, called spiracles, are seen as several brown dots at the periphery of the body. Air enters through them and is delivered to the organs by air tubes, depicted as a network of brown longitudinal and transverse lines.4,5Figure 1: Dermoscopic characterization of P. pubis (DermLite DL4W, contact, polarized light). Broad and triangular body with 2 anterior slim legs, and 4 posterior thick legs with dark brown claws (C). D indicates digestive system, brown-reddish colored due to ingested blood; M, mouthparts with antennae; S, spiracles, corresponding to the external openings of the respiratory system, which is conformed by arranged and branching air tubes (T).First-line treatment is topical 1% permethrin. Other pediculicide drugs include 0.2% phenothrin, 0.5% malathion, 1% lindane, and topical or oral ivermectin.6 In conclusion, ex vivo handheld dermoscopy is a useful technique for a quick bedside diagnosis of pediculosis and species identification.Video: Ex vivo dermoscopy showing an alive P. pubis removed from the skin (Supplemental Digital Content 1, https://links.lww.com/OLQ/A453). Note the peristaltic movements pumping the ingested blood through the digestive system (DermLite DL4W, contact, polarized light).

Livedo Racemosa: Clinical, Laboratory, and Histopathological Findings in 33 Patients.

Livedo racemosa is a cutaneous finding characterized by a persistent, erythematous, or violaceous discoloration of the skin, in a broken, branched, discontinuous, and irregular pattern. A retrospective review of 33 cases with clinical diagnosis of livedo racemosa over the past 6 years was evaluated in the dermatology department of a tertiary care hospital. We found predominance in Caucasian women (78.8%); age ranged from 8 to 81 years, with a mean age of 36 years. Livedo racemosa was described as generalized in 12 patients (36.4%), although the main localization was on lower limbs (42%). After laboratory testing and histopathological examinations, 12 patients (36.4%) were classified with idiopathic livedo racemosa; secondary diseases were diagnosis in 21 patients (63.6%), including Sneddon's syndrome, cutaneous polyarteritis nodosa, systemic lupus erythematosus, and others. Medical history of thrombotic events was described in 8 (24.2%) patients, and also 8 (24.2%) patients had abnormal results for 2 or more thrombophilia laboratory tests. Skin biopsy showed no histological abnormalities in 11 cases (33.3%), thrombosis of dermal blood vessels in 10 (30.3%), intimal/subintimal thickening in 7 (21.2%), and vasculitis in 5 (15.2%). In conclusion, livedo racemosa is a clinical feature that might be correlated to vascular disorders, such as thrombotic and/or hypercoagulable states, autoimmune diseases, and neoplastic diseases, or it can be secondary to specific medications. It is essential to establish a correct approach in cases of livedo racemosa, which includes anamnesis, physical examination, laboratory test, histological examination, and complementary examination according to clinical findings, in order to diagnosis underlying causes.

Clinical, Histopathological and Immunohistochemistry Evaluation of Reactive Cutaneous Histiocytosis in Canine in Western Amazonia

Background: Canine reactive cutaneous histiocytosis (RCH) is an immuneproliferative disease of skin histiocytes and is uncommon in occurrence. Its description in the literature is scarce and clinical studies are limited by the insufficient characterization of the patients' pathological findings. The objective of this report is to describe the clinical, histological and immunohistochemical findings of a case of canine reactive cutaneous histiocytosis in the state of Acre, Amazonia, Brazil.Case: It was attended at the Federal University of Acre, a 7-year-old male American pit bull terrier dog with nodular, allopecic and ulcerated lesions in the dorsal region of the ear, with purulent discharge and exacerbated painful tenderness. The animal was domiciled on the bank of the river Acre, municipality of Rio Branco, state of Acre, and suffered frequent parasitism by sandflies, especially in the head region. In the histopathological evaluation, hyperplastic cells were found, a large ulcerated area with the presence of fibrin and neutrophilic infiltrate in the epidermis. In the dermal layer, an inflammatory reaction pattern was identified, with the presence of fibrous connective tissue, dilated blood vessels and edema, however little defined. There was an intense presence of histiocytes with anisocytosis, in addition to neutrophils, plasma cells and lymphocytes in the perivascular and perianexal region. In immunohistochemistry, lysozyme and cell markers CD1a and Thy1 were detected, but negative result for E-cadherin and CD11d. The immunosuppressive therapy indicated with prednisolone, plus cephalexin for secondary infections and topical treatment, with clinical remission within two years. Discussion: Although the etiopathogenesis of RCH is poorly understood, it is believed that, in addition to the genetic factor, the disease is triggered by an antigenic trigger on the skin, such as dogs susceptible to ticks and sandflies. The accumulation of defense cells in the skin tissue, against the antigenic stimulus, generates primarily an inflammatory process too. Immune maladjustment of dendritic cells and leukocytes occurs in the walls of dermal vessels, as well as exacerbated recruitment of histiocytes, characteristics seen in cell morphology analyzes. In RCH, the proliferation of histiocytes between collagen fibers and the infiltration of round cells in the dermis are indicative of the disease, as evidenced in this report. The immunohistochemistry is the method of choice, which allows establishing the cellular origin that triggered the disease, although the characterization of a differentiation cluster is underused in veterinary medicine. In this context, we seek to identify histiocytes, which comprise the group of cells derived from CD34 +, macrophage precursors, dendritic and Langerhans cells of the epithelial tissue, which act as antigen presenters. It can be concluded that canine RCH is an uncommon disease resulting from an inflammatory process of the dermis with difficult to identify immune dysregulation. Differential diagnosis with systemic histiocytosis, cutaneous histiocytoma, histiocytic sarcoma, as well as leishmaniasis and mycobacteriosis, are fundamental through histopathological, serological and immunohistochemical evaluations, to establish the definitive diagnosis of the disease, as well as the prognosis, and to better direct the therapeutic approach of the case.

Decreased CCN3 in Systemic Sclerosis Endothelial Cells Contributes to Impaired Angiogenesis

Systemic sclerosis (SSc) is a rare and severe connective tissue disease combining autoimmune and vasculopathy features, ultimately leading to organ fibrosis. Impaired angiogenesis is an often silent and life-threatening complication of the disease. We hypothesize that CCN3, a member of the CCN family of extracellular matrix proteins, which is an antagonist of the profibrotic protein CCN2 as well as a proangiogenic factor, is implicated in SSc pathophysiology. We performed skin biopsies on 26 patients with SSc, both in fibrotic and nonfibrotic areas for 17 patients, and collected 18 healthy control skin specimens for immunohistochemistry and cell culture. Histological analysis of nonfibrotic and fibrotic SSc skin shows a systemic decrease of papillary dermis surface as well as disappearance of capillaries. CCN3 expression is systematically decreased in the dermis of patients with SSc compared with healthy controls, particularly in dermal blood vessels. Moreover, CCN3 is decreased invitro in endothelial cells from patients with SSc. We show that CCN3 is essential for endothelial cell migration and angiogenesis invitro. In conclusion, CCN3 may represent a promising therapeutic target for patients with SSc presenting with vascular involvement.

Zosteriform lymphangioma circumscriptum and angiokeratoma: A rare co-occurrence

Lymphangioma circumscriptum (LC) is a rare benign hamartomatous malformation of lymph vessel manifesting at birth or during early childhood. Angiokeratomas (AK) are vascular ectasia of papillary dermal blood vessels with secondary epidermal changes. AK and/or LC are one of the common vascular malformations associated with Klippel–Trenaunay syndrome (KTS). The simultaneous appearance of LC and AK has been reported rarely, and the occurrence of LC, AK, and port-wine stain in a patient of KTS is even rarer. Thereby, we report a case of co-occurrence of LC and AK in the same patient without systemic involvement.

Hand Hygiene Practices and Risk and Prevention of Hand Eczema during the COVID-19 Pandemic.

Hand Hygiene Practices and Risk and Prevention of Hand Eczema during the COVID-19 Pandemic.

Tissue-remodelling M2 Macrophages Recruits Matrix Metallo-proteinase-9 for Cryotherapy-induced Fibrotic Resolution during Keloid Treatment.

Cryotherapy is used to treat keloid scars; however, the molecular and pathological mechanisms are not clearly understood. This study retrospectively evaluated the efficacy of combined treatment with cryotherapy and intralesional triamcinolone injection (Cryo+TA) or intralesional TA monotherapy (TA) in 40 Asian patients with keloid scars. Scar improvement was assessed using the Vancouver Scar Scale and Global Improvement Scale. Clinical improvement in scars, especially reduced vascularity and redness, was significantly greater in the Cryo+TA group than in the TA group. Cryotherapy-treated and untreated keloid tissue was collected from six patients for analysis. Histologically, collagen bundles from cryotherapy-treated keloid tissue were more fibrillar and abnormal thickness was reduced. Immunohistochemical staining showed a reduced number of dermal vessels after cryotherapy. Moreover, CD163+ M2 macrophages and matrix metalloproteinase-9 (MMP-9) were significantly increased in cryotherapy-treated tissue. Double immunofluorescence staining revealed co-expression of CD163 and MMP-9. These data indicate that cryotherapy recruits tissue-remodelling M2 macrophages with accompanying MMP-9, suggesting that cryotherapy-recruited M2 macrophages function in fibrotic resolution during keloid treatment.

Angiokeratoma circumscriptum of children: A case of postinjury with a lesion on the foot

Angiokeratoma circumscriptum vascular lesions are defined by ectasia of the papillary dermal vessels, and the etiology is unknown. We report a rare case of angiokeratoma circumscriptum following the excision of a lipoma, from the same area, on the right foot 3 years prior. Therefore, this case indicates that the injury could be involved in the development of angiokeratoma circumscriptum.

Dermoscopy of Pityriasis Lichenoides Chronica in an Indian Girl.

Background: A 16-year-old girl presented with multiple dusky red to brown-colored papules with centrally adherent scales scattered over the trunk and extremities (with sparing of the face), interspersed with multiple faint hypopigmented macules [Figure 1]. The lesions had started appearing three years back with gradual progression. The self-healing lesions had left the hypopigmented macules with no varioliform scars. Occasional itching was the only symptom. There was no history of eruption of crops of vesicular/hemorrhagic/crusted papules, fever, painful lymphadenopathy, or systemic symptoms.Figure 1: Clinical image of the anterior abdomen of a 16-year-old Indian girl showing scattered brown papules with adherent scales, interspersed with faint ill-defined hypopigmented areasPolarized dermoscopic examination (Escope videodermoscope, ×20) from the truncal lesions revealed yellowish-orange to light brown-colored structureless areas, with focal superficial scales, and multiple scattered dark brown-black colored granules, globules, and clods. Only a few scattered dotted and nondotted vessels could be appreciated. Focal areas of hypopigmentation were seen in the lesional periphery [Figure 2]. A clinicodermoscopic diagnosis of pityriasis lichenoides chronica (PLC) was confirmed on histopathology that revealed small mounds of parakeratosis and epidermal infiltration by lymphocytes and red blood cells (RBCs). The dermoepidermal junction showed occasional necrotic keratinocytes. Focal interface vacuolar change and sparse superficial perivascular lymphocytic infiltrate with extravasation of RBCs were seen in the papillary dermis [Figure 3]. Focal melanophages were also seen in the papillary and mid-dermis.Figure 2: Dermoscopic image from a lesion on the anterior abdomen revealing yellowish-orange to light brown-colored structureless area with focal scales, and focal areas of hypopigmentation in the lesional periphery (blue arrows). Note the paucity of vascular structures – only a few focal vessels can be appreciated. Additionally, note the multiple scattered dark brown-black granules, globules, and clods, possibly suggestive of postinflammatory hyperpigmentation, typical of darker skin types [Escope videodermoscope, polarized, ×20]Figure 3: Histopathology confirming the diagnosis of pityriasis lichenoides chronica (PLC) showing small mounds of parakeratosis and epidermal infiltration by lymphocytes and red blood cells (RBCs). The dermoepidermal junction shows occasional necrotic keratinocytes. Focal interface vacuolar change and sparse superficial perivascular lymphocytic infiltrate with extravasation of RBCs can be seen in the papillary dermis. Focal melanophages in the mid-to-upper dermis are also seen [hematoxylin and eosin, ×400]Pityriasis lichenoides (PL) constitutes a spectrum of skin disorders with acute (pityriasis lichenoides et varioliformis acuta [PLEVA]) and chronic (PLC) forms. Approximately 20% of cases occur in children.[1] The etiology of PL remains uncertain. Although inflammatory response triggered by an infection has been proposed by many, the possibility of PL representing a T-cell lymphoproliferative disorder has not been ruled out. PLEVA and PLC represent a continuous spectrum with overlap in presentation.[2] In contrast to the abrupt crops of vesicular to necrotic erythematous macules and papules accompanied with systemic symptoms are archetypical of PLEVA, lesions of PLC are milder, have a gradual onset, and heal with postinflammatory hypo- (PIHy) or hyperpigmentation (PIH). The varioliform scarring of PLEVA is, however, not seen in PLC. Dermoscopy of PLC has been detailed by Errichetti et al. in seven Caucasian patients, the most common finding being orange-yellowish structureless areas, followed by focally distributed nondotted and dotted vessels, and scattered hypopigmented areas.[3] In contrast with the dermoscopic findings of PLC seen in white skin, we observed an add-on brownish hue over the yellowish-orange areas, only a few vessels but multiple scattered dark-brown-black granules, globules, and clods. Although conjectural, we believe that these additional pigmented structures suggest post inflammatory hyperpigmention, a specific dermoscopic finding described commonly in inflammatory dermatoses in the darker skin types.[4] The difficulty in observing vascular structures may also be attributable to the predominant pigmented background. Errichetti et al. have histologically correlated the orange-yellowish structureless areas of PLC to the presence of hemosiderin degradation products stemming from extravasated RBCs, and the vascular components to dilatation of superficial dermal vessels.[3] The dermoscopic differentiation of PLC from some of its close differentials is given in Table 1.Table 1: Dermoscopic differentiation of pityriasis lichenoides chronica from important clinical differentialsDeclaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.