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Bullous systemic lupus erythematosus (BSLE) is a rare autoimmune subepidermal blistering disease with a female predominance characterized as an acute vesicobullous eruption in patients with systemic lupus erythematosus (SLE). Here we report a case of BSLE in a 16-year-old boy that does not adhere to the criteria originally established and suggest a new outlook on this condition.
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Vesícula/patologia , Lúpus Eritematoso Sistêmico/patologia , Administração Oral , Adulto , Vesícula/tratamento farmacológico , Glucocorticoides/administração & dosagem , Humanos , Infusões Intravenosas , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Metilprednisolona/administração & dosagem , Prednisolona/administração & dosagem , PulsoterapiaRESUMO
Trichodysplasia spinulosa (TS) is a unique, rare clinical and histological dermatologic entity described mainly in a setting of immunosuppression. It is caused by a novel human polymoavirus, TS-associated polyomavirus. Reduction of immunosuppression and/or anti-viral therapy is the main therapeutic strategies used to treat such cases. We report a biopsy-proven case of TS in a male renal transplant patient who presented to a dermatology outpatient clinic in Montreal, Canada, in 2015. He was managed with valgancyclovir with no obvious response. Subsequently, a trial of topical imiquimod was commenced. Awareness of TS can prompt early diagnosis and management to prevent possible complications.
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Dermatopatias , Humanos , Masculino , Biópsia , CanadáRESUMO
Cutaneous angiosarcomas are rare soft tissue tumours originating from hematogenous vasculature that are aggressive and carry a poor prognosis. We describe the case of a 73-year-old man with a low-grade well-differentiated angiosarcoma. Our case distinguishes itself from those previously reported in the slow progression and important delay to the presentation of 30 months and survival time of 5.5 years. Additionally, its severe clinical appearance (T2 stage) but milder pathological picture (T1 stage) is very uncommon. A repeat biopsy is warranted when results are inconclusive and there is a high clinical suspicion of angiosarcoma.
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Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, immune dysregulation, and multi-organ fibrosis. Interstitial lung disease (ILD) is a complication of SSc and a leading cause of SSc-death. The administration of hypochlorous acid (HOCl) intradermally in the mouse (HOCl-SSc) purportedly shows several features typical of SSc. We studied the model by injecting BALB/c mice daily intradermally with HOCl for 6-weeks, an exposure reported to induce lung fibrosis. On day 42, the skinfold thickness and the dermal thickness were two and three times larger respectively in the HOCl group compared to controls. HOCl treatment did not result in histological features of pulmonary fibrosis nor significant changes in lung compliance. Automated image analysis of HOCl mice lungs stained with picrosirius red did not show increased collagen deposition. HOCl injections did not increase pulmonary mRNA expression of pro-fibrotic genes nor induced the production of serum advanced oxidation protein products and anti-topoisomerase 1 antibodies. Immune cells in bronchoalveolar lavage fluid (BALF) and whole lung digests were not increased in HOCl-treated animals. Since lung fibrosis is proposed to be triggered by oxidative stress, we injected HOCl to Nrf2-/- mice, a mouse deficient in many antioxidant proteins. Lung compliance, histology, and BALF leukocyte numbers were comparable between Nrf2-/- mice and wild-type controls. We conclude that the HOCl-SSc model does not manifest SSc-lung disease.
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Doenças Pulmonares Intersticiais , Fibrose Pulmonar , Escleroderma Sistêmico , Animais , Camundongos , Fibrose Pulmonar/metabolismo , Ácido Hipocloroso/metabolismo , Bleomicina/efeitos adversos , Bleomicina/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Pele/metabolismo , Fibrose , Doenças Pulmonares Intersticiais/patologia , Escleroderma Sistêmico/patologia , Pulmão/patologia , Modelos Animais de DoençasRESUMO
Inadequate tissue blood supply as may be found in a wound or a poorly vascularised graft, can result in tissue ischemia and necrosis. As revascularization is a slow process relative to the proliferation of bacteria and the onset of tissue necrosis, extensive tissue damage and loss can occur before healing is underway. Necrosis can develop rapidly, and treatment options are limited such that loss of tissue following necrosis onset is considered unavoidable and irreversible. Oxygen delivery from biomaterials exploiting aqueous decomposition of peroxy-compounds has shown some potential in overcoming the supply limitations by creating oxygen concentration gradients higher than can be attained physiologically or by air saturated solutions. We sought to test whether subdermal oxygen delivery from a material composite that was buffered and contained a catalyst, to reduce hydrogen peroxide release, could ameliorate necrosis in a 9 × 2 cm flap in a rat model that reliably underwent 40 % necrosis if untreated. Blood flow in this flap reduced from near normal to essentially zero, along its 9 cm length and subdermal perforator vessel anastomosis was physically prevented by placement of a polymer sheet. In the middle, low blood flow region of the flap, treatment significantly reduced necrosis based on measurements from photographs and histological micrographs. No change was observed in blood vessel density but significant differences in HIF1-α, inducible nitric oxide synthase and liver arginase were observed with oxygen delivery.
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Pele , Retalhos Cirúrgicos , Ratos , Animais , Pele/irrigação sanguínea , Pele/patologia , Retalhos Cirúrgicos/irrigação sanguínea , Retalhos Cirúrgicos/patologia , Isquemia/patologia , Isquemia/prevenção & controle , Oxigênio/uso terapêutico , Necrose/patologiaRESUMO
Adenoid cystic carcinoma is predominantly a tumor of the parotid glands and can sometimes be found in other glands. In most cases, skin location is usually a metastatic presentation and rarely a primary tumor. We describe the case of a 59-year-old female patient presenting with a 5-mm skin-colored nodule on the abdomen histologically compatible with a primary cutaneous adenoid cystic carcinoma. Extensive workup revealed no other primary source, nor evidence of metastatic disease; therefore, wide local excision was the preferred treatment given the low potential of recurrence. As this adnexal carcinoma is rare and its morphology non-specific clinically, we wanted to raise awareness of this entity and its management.
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Melanoma is an immunogenic cancer with a high response rate to immune checkpoint inhibitors (ICIs). It harbors a high mutation burden compared with other cancers and, as a result, has abundant tumor-infiltrating lymphocytes (TILs) within its microenvironment. However, understanding the complex interplay between the stroma, tumor cells, and distinct TIL subsets remains a substantial challenge in immune oncology. To properly study this interplay, quantifying spatial relationships of multiple cell types within the tumor microenvironment is crucial. To address this, we used cytometry time-of-flight (CyTOF) imaging mass cytometry (IMC) to simultaneously quantify the expression of 35 protein markers, characterizing the microenvironment of 5 benign nevi and 67 melanomas. We profiled more than 220,000 individual cells to identify melanoma, lymphocyte subsets, macrophage/monocyte, and stromal cell populations, allowing for in-depth spatial quantification of the melanoma microenvironment. We found that within pretreatment melanomas, the abundance of proliferating antigen-experienced cytotoxic T cells (CD8+CD45RO+Ki67+) and the proximity of antigen-experienced cytotoxic T cells to melanoma cells were associated with positive response to ICIs. Our study highlights the potential of multiplexed single-cell technology to quantify spatial cell-cell interactions within the tumor microenvironment to understand immune therapy responses.
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Melanoma , Humanos , Citometria por Imagem , Linfócitos do Interstício Tumoral , Linfócitos T Citotóxicos , Microambiente TumoralRESUMO
Cutaneous xanthomas are the result of dermal deposition of lipid, mostly caused by disorders of lipid metabolism. Less commonly, they occur in the setting of cholestatic liver disease, leading to accumulation of lipoprotein X, a rare form of dyslipidemia that does not respond well to conventional treatments. We describe an atypical presentation of sudden diffuse xanthomas secondary to lipoprotein X dyslipidemia in the context of cholestatic fulminant hepatitis caused by trimethoprim-sulfamethoxazole hypersensitivity. Histopathology was also atypical and showed an unusual verrucous appearance consisting of overlying epidermal hyperplasia with hyperkeratosis. Our patient had significant improvement, after normalization of her lipid panel under cholestyramine and 13 sessions of apheresis, with topical corticosteroids offering some relief. This rare case shows the importance of recognizing atypical presentations of xanthomas, particularly when they do not respond to conventional dyslipidemia treatments.
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We present a rare case of a 61-year-old woman presenting with a widespread erosive eruption on her torso and extremities. Although the lesions were histologically compatible with toxic epidermal necrolysis, clinically the patient was hemodynamically stable, had no mucosal involvement and had no relevant medical history or potentially incriminating medications. Further investigations uncovered a new diagnosis of systemic lupus erythematosus, with this toxic epidermal necrolysis-like eruption being the first presentation of the disease. This case highlights the importance of broadening the differential diagnosis in patients presenting with acute widespread cleavage of the epidermis, using the spectrum of acute syndrome of apoptotic pan-epidermolysis as a reference.
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The high background tumor mutation burden in cutaneous melanoma limits the ability to identify significantly mutated genes (SMGs) that drive this cancer. To address this, we performed a mutation significance study of over 1,000 melanoma exomes, combined with a multi-omic analysis of 470 cases from The Cancer Genome Atlas. We discovered several SMGs with co-occurring loss-of-heterozygosity and loss-of-function mutations, including PBRM1, PLXNC1 and PRKAR1A, which encodes a protein kinase A holoenzyme subunit. Deconvolution of bulk tumor transcriptomes into cancer, immune and stromal components revealed a melanoma-intrinsic oxidative phosphorylation signature associated with protein kinase A pathway alterations. We also identified SMGs on the X chromosome, including the RNA helicase DDX3X, whose loss-of-function mutations were exclusively observed in males. Finally, we found that tumor mutation burden and immune infiltration contain complementary information on survival of patients with melanoma. In summary, our multi-omic analysis provides insights into melanoma etiology and supports contribution of specific mutations to the sex bias observed in this cancer.
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Melanoma , Neoplasias Cutâneas , Biomarcadores Tumorais/genética , Proteínas Quinases Dependentes de AMP Cíclico , RNA Helicases DEAD-box/genética , Feminino , Humanos , Masculino , Melanoma/genética , Neoplasias Cutâneas/genética , Melanoma Maligno CutâneoRESUMO
Discoid or chronic lupus erythematosus is an autoimmune disease that produces skin lesions on the face and scalp. Rarely do lesions present with linear configuration, but when they do, the lesions often follow the lines of embryologic migration. A 24-year-old man presented with a slowly progressing asymptomatic violaceous linear patch running from the root of his frontal scalp to the nasal tip. A Doppler ultrasound and skin biopsy were performed and the histological findings demonstrated characteristic findings of discoid lupus erythematosus. A full physical examination, review of systems and laboratory investigations showed no indication of systemic lupus. High potency topical steroids and calcineurin inhibitors were prescribed along with photoprotection. At 4-month follow-up, all his lesions had mostly cleared. We report here the first case, to our knowledge, of discoid lupus erythematosus with en coup de saber presentation mimicking morphea.
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This is a 40-year-old woman with sideroblastic anemia with B cell immunodeficiency, periodic fevers, and developmental delay syndrome, who has genital and extragenital lichen sclerosus on the abdomen and the upper back that have become erythematous and painful during febrile episodes. This report summarizes the published cases of sideroblastic anemia with B cell immunodeficiency, periodic fevers, and developmental delay and highlights associated mucocutaneous features.
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BACKGROUND: Familial hypercholesterolemia is a genetic lipoprotein disorder characterized by elevated plasma low-density lipoprotein cholesterol level, (tendinous xanthomas, xanthelasmas, and premature arcus corneus) and early onset atherosclerotic cardiovascular disease. Familial hypercholesterolemia is caused by mutations in the low-density lipoprotein receptor, apolipoprotein B or proprotein convertase subtilisin/kexin type 9 genes. Rare mutations in low-density lipoprotein receptor adapter protein 1, APOE p.Leu167del or lysosomal acid lipase genes can mimic FH. The prevalence of heterozygous familial hypercholesterolemia is estimated to be 1/250 worldwide, although some populations with founder effects show a higher prevalence. The rare homozygous form has an estimated prevalence of 0.000004 or 1/250,000 and is characterized by markedly elevated low-density lipoprotein cholesterol, skin manifestations (planar xanthomas, tendinous xanthomas) in childhood and extremely premature atherosclerotic cardiovascular disease. While tendinous xanthomas are considered pathognomonic for familial hypercholesterolemia, they can also be found in rare diseases, including sitosterolemia. Here, we report a case of severe tendinous xanthomatosis with heterozygous familial hypercholesterolemia due to the low-density lipoprotein receptor del >15 kb mutation. The phenotypic expression of the disease is out of proportion with the genetic diagnosis or biochemical measurements. CASE REPORT: We report the case of 51-year-old woman of French-Canadian origin diagnosed with heterozygous familial hypercholesterolemia since age 12. She presented with hypercholesterolemia with total cholesterol 7.6 mmol/L, with an imputed low-density lipoprotein cholesterol level of 6.5 mmol/L. She had extensive tendinous xanthomas of the Achilles tendons, knees, elbows and metacarpophalangeal joints. Because of cosmetic disfigurement, she had multiple excisions of Achilles, knee and elbow xanthomas, albeit with rapid recurrence. Our patient has a significant family history of lung cancer and other autoimmune diseases associated with familial hypercholesterolemia and xanthoma. Lipid-lowering therapy was started, at age 12; which included initially cholestyramine, then changed to statin and ezetimibe. Eventually, evolocumab was added. Despite trying different lipid-lowering therapy, there has been no noticeable decrease in the size of the xanthomas. CONCLUSION: Our patient has severe xanthomatosis out of proportion with the genetic diagnosis or biochemical measurements. Her xanthomatosis did not improve by pharmacological therapy consisting of statins and evolocumab despite a 50% reduction in low-density lipoprotein cholesterol. It is likely that the patient presented here has a second genetic disorder that leads to extensive xanthomatosis.
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Hiperlipoproteinemia Tipo II/diagnóstico , Receptores de LDL/genética , Xantomatose/patologia , Anticolesterolemiantes/uso terapêutico , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , LDL-Colesterol/sangue , Ezetimiba/uso terapêutico , Feminino , Homozigoto , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/genética , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Pessoa de Meia-Idade , Linhagem , Xantomatose/etiologiaRESUMO
Teaching awards are commonly regarded as an incentive to encourage pedagogic excellence. Inasmuch as their effectiveness depends on how they are perceived by faculty, the authors investigated the impact of a teaching award in the Faculty of Medicine (Faculty Honor List for Educational Excellence) on the attitudes of award recipients and departmental chairs. A questionnaire was designed to sample opinion on the extent to which the Honor List program was publicized, whether the award contributed to recognition and/or stature in the academic unit, and whether it was personally valued by recipients. The questionnaire was sent to all 23 departmental chairs and to all 43 faculty members who had received the award between 1998 and 2002; 78% of the chairs and 77% of the recipients responded. The results revealed marked discrepancies between the perceptions of chairs and recipients. Chairs, although uncertain of the effect on quality of teaching, largely regarded the award as prestigious and well publicized within their departments. A notably smaller percentage of award recipients shared these views. Nonetheless, 93% of recipients valued the award highly, and 45% of recipients indicated that the award inspired them to enhance the quality of their teaching.
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Distinções e Prêmios , Educação Médica/normas , Docentes de Medicina/normas , Ensino/normas , Humanos , Quebeque , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Pachyonychia congenita (PC) is a rare autosomal dominant disease whose main clinical features include hypertrophic onychodystrophy and palmoplantar keratoderma. The new classification is based on genetic variants with mutations in keratin KRT6A, KRT6B, KRT6C, KRT16, KRT17, and an unknown mutation. Here, we present a case of PC with unusual clinical and histological features and a favorable response to oral acitretin. CASE: A 49-year-old male presented with diffuse and striate palmoplantar keratoderma, thickened nails, knuckle pads, and pseudoainhum. Histology showed compact hyperkeratosis, prominent irregular acanthosis, and extensive epidermolytic hyperkeratosis, suggestive of Vörner's palmoplantar keratoderma. However, keratin 9 and 1 were not mutated, and full exome sequencing showed heterozygous missense mutation in type I keratin K16. CONCLUSION: To our knowledge, epidermolytic hyperkeratosis has not been previously described with PC. Our patient had an excellent response, maintained over the last 5 years, to a low dose of acitretin. We wish to emphasize the crucial role of whole exome sequencing in establishing the correct diagnosis.
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Derivação Arteriovenosa Cirúrgica , Hemangiossarcoma/secundário , Neoplasias Pulmonares/secundário , Neoplasias Cutâneas/patologia , Evolução Fatal , Hemangiossarcoma/diagnóstico , Humanos , Terapia de Imunossupressão , Transplante de Rim , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/diagnósticoRESUMO
BACKGROUND: The complement system is composed of bactericidal and hemolytic proteins that increase capillary leakage and inflammatory cell migration. The role of complement C3 to augment wound healing has not yet been studied. METHODS: We examined the effects of topical complement C3 formulation at two concentrations (10 and 100 nM) on the rat surgical skin incision model. Skin was examined for maximal breaking strength and sectioned for histological examination. Fibronectin and collagen I content were measured using western blot analysis. RESULTS: There was a statistically significant 74% increase in maximum wound strength with the topical application of 100 nM of C3 at day 3 (850 ± 138 g) when compared to the control rats (490 ± 57 g). Histological correlation was seen with an increased inflammatory cell and fibroblast infiltration in treated wounds as compared to control rats as early as 3 days post-wounding. Western blots revealed increased fibronectin and collagen I levels in C3 treated wounds. CONCLUSIONS: Topical application of complement C3 in collagen formulation to skin wounds significantly increases wound healing as early as 3 days after wounding. This is correlated with increased inflammatory cell recruitment and the subsequent early fibroblast migration and increased collagen deposition and organization in wounds.
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Colágeno Tipo I/administração & dosagem , Complemento C3/administração & dosagem , Portadores de Fármacos , Pele/lesões , Deiscência da Ferida Operatória/prevenção & controle , Cicatrização/efeitos dos fármacos , Administração Tópica , Animais , Western Blotting , Proteína C-Reativa/metabolismo , Movimento Celular , Complemento C3/metabolismo , Fibroblastos/fisiologia , Fibronectinas/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Deiscência da Ferida Operatória/metabolismoRESUMO
Background. Complements C3 and C5 have independently been shown to augment and increase wound healing and strength. Our goal was to investigate the combinatorial effect of complements C3 and C5 on wound healing. Methods. Each rat served as its own control where topical collagen was applied to one incision and 100 nM of C3 and C5 in collagen vehicle was applied to the other incision (n = 6). To compare between systemic effects, a sham group of rats (n = 6) was treated with collagen alone on one wound and saline on the other. At day 3, the tissue was examined for maximal breaking strength (MBS) and sectioned for histological examination. Results. There was a statistically significant 88% increase in MBS with the topical application of C3C5 when compared to sham wounds (n < 0.05). This was correlated with increased fibroblast and collagen deposition in the treated wounds. Furthermore, there appeared to be an additive hemostatic effect with the C3C5 combination. Conclusions. The combination of complements C3 and C5 as a topical application drug to skin wounds significantly increased wound healing maximum breaking strength as early as 3 days.