Case for diagnosis. Hyperpigmented and excoriated papules and nodules in a diabetic patient

Abstract Reactive perforating collagenosis is a rare perforating dermatosis clinically characterized by intensely pruritic hyperpigmented papules, plaques, and nodules with a central keratotic plug. Histopathology reveals transepidermal elimination of collagen fibers. Its pathophysiology is still under investigation, but the acquired form has been linked to systemic conditions such as diabetes mellitus and chronic kidney disease. However, it has also been described as a paraneoplastic syndrome. The authors present the case of a 65-year-old diabetic patient in which a myeloproliferative neoplasm was suspected.

Case for diagnosis. Hyperpigmented and excoriated papules and nodules in a diabetic patient.

Reactive perforating collagenosis is a rare perforating dermatosis clinically characterized by intensely pruritic hyperpigmented papules, plaques, and nodules with a central keratotic plug. Histopathology reveals transepidermal elimination of collagen fibers. Its pathophysiology is still under investigation, but the acquired form has been linked to systemic conditions such as diabetes mellitus and chronic kidney disease. However, it has also been described as a paraneoplastic syndrome. The authors present the case of a 65-year-old diabetic patient in which a myeloproliferative neoplasm was suspected.

Teledermatología asincrónica a través de WhatsApp®: experiencia en la Pontificia Universidad Católica de Chile

Background: In Chile, there is little access to Dermatology outpatient consultations in the public health care system, which has favored the development of tele dermatology (TD). Aim: To assess satisfaction levels of primary care providers with a TD channel via the social networking app WhatsApp® and the concordance between the diagnosis of general practitioners and dermatologists at Pontificia Universidad Católica de Chile. Material and Methods: An electronic survey was answered by the general practitioners who participate in the TD channel. In 417 cases, the diagnostic concordance between general practitioners and specialists was assessed. Results: The survey was answered by 84 practitioners. General satisfaction levels with the platform were over 95%. Satisfaction levels with the response speed and the management suggested by the specialist were over 90%. Over 80% of the practitioners read the consultation sent by dermatologists and considered that their dermatological knowledge improved. Diagnostic concordance between practitioners and specialists was 41%. Conclusions: TD via a WhatsApp® group linked to a university is a low cost and easy to implement intervention, generating high levels of satisfaction among general practitioners.

Early origins of allergy and asthma (ARIES): study protocol for a prospective prenatal birth cohort in Chile.

BACKGROUND: Growing evidence shows that atopic dermatitis (AD), food allergy (FA), allergic rhinitis, and asthma are largely determined during the first 1000 days (time elapsed from conception to the 2nd birthday). The ARIES birth cohort aims to determine prenatal and perinatal conditions, as well as genetic and epigenetic factors, that participate in the early setting of immune responses, and the role of these in the later determination of the risk of allergic diseases and asthma in the offspring. METHODS: We have designed a birth cohort of 250 families with prenatal recruitment (~ 14 weeks). We will genotype relevant allergy/asthma-associated variants in trios and will perform immunophenotyping and evaluation of allergy biomarkers in cord blood. At 1 and 2 years of age we will assess if infants have developed allergic sensitization, AD, FA, as well as biomarkers of asthma including the asthma predictive index. We will also evaluate how maternal conditions modify immune programming through epigenetic modifications and will then depict newborn epigenetic cues of allergy/asthma risk. Next, we will assess composition/diversity of maternal gut, placenta, breastmilk and infant gut microbiome and their association with immunophenotype and biomarkers at birth, and clinical outcomes at age 1 and 2. Finally, we plan to assess how environmental exposures (perinatal outdoor and indoor pollution, allergens and endotoxin) affect the incidence of allergic sensitization, AD, FA, and risk of asthma. DISCUSSION: The in-depth study of the ARIES birth cohort shall provide crucial information to understand the rising incidence of allergies and asthma in developing countries, and hopefully provide cues on how to prevent and treat these diseases. TRIAL REGISTRATION: clinicaltrials.gov NCT04186949, retrospectively registered on December 5, 2019.

[Assessment of an asyncronic tele dermatology system for primary care physicians via social networking app WhatsApp]. / Teledermatología asincrónica a través de WhatsApp®: experiencia en la Pontificia Universidad Católica de Chile.

BACKGROUND: In Chile, there is little access to Dermatology outpatient consultations in the public health care system, which has favored the development of tele dermatology (TD). AIM: To assess satisfaction levels of primary care providers with a TD channel via the social networking app WhatsApp® and the concordance between the diagnosis of general practitioners and dermatologists at Pontificia Universidad Católica de Chile. MATERIAL AND METHODS: An electronic survey was answered by the general practitioners who participate in the TD channel. In 417 cases, the diagnostic concordance between general practitioners and specialists was assessed. RESULTS: The survey was answered by 84 practitioners. General satisfaction levels with the platform were over 95%. Satisfaction levels with the response speed and the management suggested by the specialist were over 90%. Over 80% of the practitioners read the consultation sent by dermatologists and considered that their dermatological knowledge improved. Diagnostic concordance between practitioners and specialists was 41%. CONCLUSIONS: TD via a WhatsApp® group linked to a university is a low cost and easy to implement intervention, generating high levels of satisfaction among general practitioners.

Helicobacter pylori pediatric infection changes FcεRI expression in dendritic cells and Treg profile in vivo and in vitro.

H. pylori infection shows an inverse relationship with allergies. Dendritic cells regulate mucosal immune responses including the induction of T regulatory cells which are fundamental in Helicobacter pylori-induced dampening of allergies. In this respect expression of high-affinity IgE receptor (FcεRI) has been associated with a regulatory dendritic cell profile. Therefore we aimed to evaluate possible mechanisms by which H. pylori infection might modify atopy in pediatric patients. Here we show that H. pylori-infected children exhibited both increased expression of FcεRI on peripheral myeloid and plasmacytoid dendritic cells and higher levels of Foxp3 and Latency Associated Peptide on T regulatory cells. Moreover, exposure to H. pylori drove increased FcεRI expression and IL-10 secretion by both pediatric H. pylori-exposed monocyte derived dendritic cells and T cells. Finally, we show a positive correlation between expression of FcεRI in circulating myeloid DCs and total Treg cells, suggesting that in children, H. pylori infection may have a modulating role in atopy, mediated by both altered surface expression of FcεRI on children's DC and an increased T regulatory cell profile.

A novel treatment for idiopathic knuckle pads with cantharidin-podophylotoxin-salicylic acid.

Knuckle pads are benign subcutaneous nodules that appear most frequently on the small joints of the hands. In children, they are often idiopathic, and no universally effective treatment has been reported. We present the case of an adolescent successfully treated with a combination of topical cantharidin -podophylotoxin -salicylic acid.

Small Extracellular Vesicles in Rat Serum Contain Astrocyte-Derived Protein Biomarkers of Repetitive Stress.

BACKGROUND: Stress precipitates mood disorders, characterized by a range of symptoms present in different combinations, suggesting the existence of disease subtypes. Using an animal model, we previously described that repetitive stress via restraint or immobilization induced depressive-like behaviors in rats that were differentially reverted by a serotonin- or noradrenaline-based antidepressant drug, indicating that different neurobiological mechanisms may be involved. The forebrain astrocyte protein aldolase C, contained in small extracellular vesicles, was identified as a potential biomarker in the cerebrospinal fluid; however, its specific origin remains unknown. Here, we propose to investigate whether serum small extracellular vesicles contain a stress-specific protein cargo and whether serum aldolase C has a brain origin. METHODS: We isolated and characterized serum small extracellular vesicles from rats exposed to restraint, immobilization, or no stress, and their proteomes were identified by mass spectrometry. Data available via ProteomeXchange with identifier PXD009085 were validated, in part, by western blot. In utero electroporation was performed to study the direct transfer of recombinant aldolase C-GFP from brain cells to blood small extracellular vesicles. RESULTS: A differential proteome was identified among the experimental groups, including aldolase C, astrocytic glial fibrillary acidic protein, synaptophysin, and reelin. Additionally, we observed that, when expressed in the brain, aldolase C tagged with green fluorescent protein could be recovered in serum small extracellular vesicles. CONCLUSION: The protein cargo of serum small extracellular vesicles constitutes a valuable source of biomarkers of stress-induced diseases, including those characterized by depressive-like behaviors. Brain-to-periphery signaling mediated by a differential molecular cargo of small extracellular vesicles is a novel and challenging mechanism by which the brain might communicate health and disease states to the rest of the body.

Mastitis granulomatosa idiopática recurrente tratada con dapsona: reporte de un caso / Recurrent idiopathic granulomatous mastitis treated with dapsone: a case report

La mastitis granulomatosa idiopática (IGM, por sus siglas en inglés) es una afección inflamatoria crónica infrecuente y benigna de los senos. Puede simular tres trastornos mamarios muy frecuentes: carcinoma de mama, mastitis y absceso mamario. La IGM se presenta típicamente como una masa mamaria unilateral y dolorosa. La etiología de la IGM no está bien definida, pero se ha propuesto que podría ser una reacción inmune localizada del tejido mamario.El diagnostico de IGM recurrente es complejo porque los hallazgos clínicos y radiológicos no son específicos, por lo que el estudio histopatológico es crucial. El cáncer de mama, la inflamación gra-nulomatosa infecciosa y no infecciosa deben des-cartarse. El tratamiento de la IGM es controver-tido, e incluye vigilancia estrecha, medicamentos inmunosupresores, antibióticos si hay evidencia de infección y escisión quirúrgica. Presentamos un caso de IGM recurrente tratada con dapsona, con buena respuesta a tratamiento, demostrando que este fármaco podría ser una buena alternativa terapéutica debido a su efecto inmunomodulador, antiinflamatorio y ahorrador de esteroides.

Idiopathic granulomatous mastitis (IGM) is an uncommon, non-malignant, chronic inflamma-tory breast condition. It can mimic three very fre-quent breast disorders: breast carcinoma, mastitis and breast abscess. IGM typically presents as a unilateral and painful breast mass. The etiology of IGM is not well defined, but it has been pro-posed that it could be localized immune reaction to breast tissue. The diagnosis of recurrent IGM is complex be-cause clinical and radiological findings are nons-pecific, therefore histopathologic evaluation is crucial. Breast cancer and infectious and nonin-fectious granulomatous inflammation should be discarded. Treatment of IGM is controversial, including close monitoring, immunosuppressive drugs, antibiotics if there is infection evidence and surgical excision. This is a case report of recurrent IGM treated with Dapsone, with good response to treatment, showing that this drug could be a good therapeutic alternative due to its immunomodulatory and anti-inflammatory and steroid sparing.

Distribución nerviosa intradiscal en articulaciones temporomandibular humanas mediante técnica de tinción de Sihler: un enfoque cadavérico descriptivo / Nerve distribution in human temporomandibular articular disc using Sihler staining technique: a cadaveric descriptive approach

Introducción: La expresión variable en la sintomatología de los trastornos temporomandibulares (TTM) es un desafío para el clínico; así, el origen del dolor y la estructura comprometida no son fáciles de identificar. El disco articular está directamente vinculado a la función mandibular y, en condiciones patológicas, puede verse alterada su posición y consecuentemente su zona de carga. Si bien la presencia de terminaciones nerviosas y los troncos nerviosos potencialmente involucrados en su inervación han sido identificados, la forma en que los nervios se distribuyen al interior del disco no se ha precisado aún. El objetivo de este estudio fue describir la distribución nerviosa del disco articular de la articulación temporomandibular en cadáveres humanos. Material y método: Se realizó disección anatómica de ocho discos articulares de articulaciones temporomandibulares del lado derecho de cadáveres conservados. Los discos articulares fueron sometidos al método de tinción de Sihler y observados bajo lupa estereoscópica y transiluminación. Se realizó fotografía estandarizada y se dividió el disco en 5 zonas (medial, lateral, anterior, posterior, central) caracterizando la distribución nerviosa. Resultados: Se observó presencia de estructuras nerviosas en todas las zonas excepto en la zona central. Las estructuras nerviosas discurren como troncos simples o múltiples en dirección antero-posterior con un número variable de colaterales en las áreas lateral y medial del disco, comunicando la zona retrodiscal con la porción posterior del músculo pterigoideo lateral en todas las muestras. Conclusión: Existe un patrón de inervación común en los discos estudiados. El disco se encuentra inervado en su periferia por troncos nerviosos que presentan un trayecto anteroposterior. La comunicación entre distintas regiones anatómicas por continuidad nerviosa, así como el patrón de inervación del disco, podrían explicar situaciones de dolor local y referido en TTM

Introduction: Variable expression of symptomatology in temporomandibular disorders (TMD) is a challenge for clinician, because source of pain is not easy to identify. Articular disc is directly linked to the mandibular function and in pathological conditions can be altered its position and consequelty its zone of load. The aim of this study was to describe the intradiscal nerve distribution of temporomandibular joint disc in human cadavers. Although the presence of sensitive nerve terminals in the disc and the nerve trunks potentially involved have been identified, the way the nerves are distributed inside disc remains unprecised. Material and method: Anatomical dissection of 8 articular discs of the temporomandibular joints on the right side of preserved cadavers was performed. The articular discs were subjected to the Sihler staining method and then observed under a stereoscopic loupe and transillumination, A standardized photograph was perform by arbitrarily dividing the disk into 5 zones (medial, lateral, anterior, posterior, central) and characterized thebnerve distribution. Results: Presence of nerve structures was observed in all areas except the central zone. Nerve structures run as a single or multiple trunk in anterior-posterior direction with a variable number of collateral in lateral and medial areas of disc, comunicating retrodiscal zone and posterior zone of lateral pterigoid muscle in all samples. Conclusion: It can be identified a common inervation pattern in all discs. The disc is innervated in its periphery by nerve trunks that present an anterioriposterior path. The communication between different anatomical regions by nervous continuity, as well as the innervation pattern of the disc, could explain situations of local pain and referred in TMD

Complicaciones infecciosas severas del territorio maxilofacial: presentación de casos clínicos / Severe infectious complications of the maxillofacial territory: clinical cases presentation

RESUMEN: Las infecciones en el territorio maxilofacial, son cuadros frecuentes, de origen polimicrobiano, con manifestaciones clínicas muy variables y que están asociadas a múltiples vías de ingreso de los microorganismos al territorio. Un gran porcentaje de estas infecciones se origina en la cavidad oral, principalmente en lesiones bacterianas que sufren los dientes. La compleja anatomía de la cabeza y el cuello, permiten que muchas de estas infecciones se diseminen por espacios profundos, llegando a comprometer órganos o regiones anatómicas adyacentes, que pueden llevar a cuadros clínicos de alto riesgo vital. Los casos clínicos presentados en este artículo corresponden a pacientes tratados en el hospital San Juan de Dios a causa de procesos infecciosos del territorio maxilofacial, por equipos multidisciplinarios.

ABSTRACT: Infections in the maxillofacial territory are frequent cases of polymicrobial origin, with very variable clinical manifestations and are associated with multiple entering pathways of microorganisms in the territory. A large percentage of these infections originate in the oral cavity, mainly in bacterial lesions that undergo experienced by the teeth. The complex anatomy of the head and neck allows many of these infections to spread through deep spaces, leading to compromising adjacent organs or anatomical regions, which can lead to high-risk clinical conditions. The clinical cases presented in this article correspond to patients treated at the San Juan de Dios hospital because of infectious processes of the maxillofacial territory, by multidisciplinary teams.

Neuroplastin deletion in glutamatergic neurons impairs selective brain functions and calcium regulation: implication for cognitive deterioration.

The cell adhesion molecule neuroplastin (Np) is a novel candidate to influence human intelligence. Np-deficient mice display complex cognitive deficits and reduced levels of Plasma Membrane Ca2+ ATPases (PMCAs), an essential regulator of the intracellular Ca2+ concentration ([iCa2+]) and neuronal activity. We show abundant expression and conserved cellular and molecular features of Np in glutamatergic neurons in human hippocampal-cortical pathways as characterized for the rodent brain. In Nptn lox/loxEmx1Cre mice, glutamatergic neuron-selective Np ablation resulted in behavioral deficits indicating hippocampal, striatal, and sensorimotor dysfunction paralleled by highly altered activities in hippocampal CA1 area, sensorimotor cortex layers I-III/IV, and the striatal sensorimotor domain detected by single-photon emission computed tomography. Altered hippocampal and cortical activities correlated with reduction of distinct PMCA paralogs in Nptn lox/loxEmx1Cre mice and increased [iCa2+] in cultured mutant neurons. Human and rodent Np enhanced the post-transcriptional expression of and co-localized with PMCA paralogs in the plasma membrane of transfected cells. Our results indicate Np as essential for PMCA expression in glutamatergic neurons allowing proper [iCa2+] regulation and normal circuit activity. Neuron-type-specific Np ablation empowers the investigation of circuit-coded learning and memory and identification of causal mechanisms leading to cognitive deterioration.

Spironolactone inhibits the activity of the Na+/H+ exchanger in the aorta of mineralocorticoid-induced hypertensive rats.

INTRODUCTION: Aldosterone can induce changes in the expression or activity of Na(+)/H(+) exchanger isoform 1 (NHE-1) in vascular smooth muscle cells. We aimed to clarify whether chronic mineralocorticoid receptor activation exerts an effect on the activity of NHE-1 in the aorta of mineralocorticoid-induced hypertensive rats. METHODS: Uninephrectomized male Sprague-Dawley rats received subcutaneously 10 mg/week of desoxycorticosterone (DOCA) with or without 20 mg/kg of spironolactone, or vehicle alone (n = 20). After four weeks of treatment, the animals were sacrificed; the aorta was excised for subsequent studies, including histological analysis, RT-PCR, Western blot, measurement of NHE-1 activity and vascular contractility in the presence or absence of the selective NHE-1 inhibitor ethyl-isopropyl amiloride (EIPA). RESULTS: Chronic DOCA treatment increased the NHE-1 activity, systolic and diastolic blood pressure, and aortic wall thickness. All these effects were prevented by co-treatment with Spironolactone (p < 0.05). Phenylephrine-induced vascular contractility was significantly reduced in the DOCA group when EIPA was added in the media (p < 0.05). No significant differences in NHE-1 mRNA or protein levels were detected between groups. CONCLUSIONS: Chronic DOCA administration induced functional and morphological alterations in the rat aorta that are partially explained by enhanced NHE-1 activity and prevented by spironolactone. However, we did not observe changes in the NHE-1 transcript or protein levels, suggesting that the effect may be due to post-transcriptional modifications induced by mineralocorticoid receptor activation.

Extradigital Symplastic Glomus Tumor of the Hand: Report of 2 Cases and Literature Review.

Glomus tumor is a rather common tumor of the hand, which presents with a classic triad of symptoms of high temperature, sensitivity and pain, and localized tenderness. Most glomus tumors are located in the digits, especially in subungueal areas. However, extradigital tumors are less frequent, and little is known about their clinical and histopathological features. Two cases of extradigital symplastic glomus tumor are presented. An active clinical and pathological awareness to avoid misdiagnosis or delayed diagnosis of this uncommon lesion is highlighted.

Postirradiation Pseudosclerodermatous Panniculitis of the Leg: Report of a Case and Review of the Literature.

Postirradiation pseudosclerodermatous panniculitis presents as an erythematous indurated plaque, on a previously irradiated area. Histopathologically, thick and sclerotic septa and inflammatory infiltrate with foamy histiocytes and adiponecrosis are seen. To date, 12 cases have been reported worldwide. Hereby, we report the case of a 68-year-old woman who developed an indurated painful erythematous plaque on her right leg after radiotherapy for a soft tissue sarcoma, with a septal panniculitis and lobular adiponecrosis on histopathological examination. This is the 13th case reported and the second of extrathoracic location.

Scleromyxedema without paraproteinemia.

BACKGROUND: Scleromyxedema is a rare generalized form of lichen myxedematosus, a chronic cutaneous mucinosis of unknown etiology usually associated with a monoclonal gammopathy and underlying systemic disorders. It is characterized by the presence of lichenoid papules and diffuse indurations of the skin. Histologically, mucin deposits are observed in the dermis as variable degrees of fibrosis. Numerous treatment modalities have been reported as producing partial or inconsistent responses associated with significant adverse effects. METHODS: We report an unusual case of scleromyxedema not associated with monoclonal gammopathy in a young patient who was treated with thalidomide. RESULTS: Patient remained stable with maintenance of injuries despite treatment with thalidomide. CONCLUSIONS: Scleromyxedema is a rare presentation for which a defined therapeutic regimen remains to be established. Treatment with thalidomide has proved to be effective in the management of these patients. We suggest that these patients should be followed up with periodic protein electrophoresis with immunofixation for a monoclonal component in blood and urine. As the therapeutic approach to scleromyxedema remains challenging and treatment is based on symptomatic presentation, further clinical studies to substantiate an effective therapeutic regimen with a positive long-term safety and risk profile are required.

Basic fibroblast growth factor reduces functional and structural damage in chronic kidney disease.

Chronic kidney disease (CKD) is characterized by loss of renal function. The pathological processes involved in the progression of this condition are already known, but the molecular mechanisms have not been completely explained. Recent reports have shown the intrinsic capacity of the kidney to undergo repair after acute injury through the reexpression of repairing proteins (Villanueva S, Cespedes C, Vio CP. Am J Physiol Regul Integr Comp Physiol 290: R861-R870, 2006). Stimulation with basic fibroblast growth factor (bFGF) could accelerate this process. However, it is not known whether bFGF can induce this phenomenon in kidney cells affected by CKD. Our aim was to study the evolution of renal damage in animals with CKD treated with bFGF and to relate the amount of repairing proteins with renal damage progression. Male Sprague-Dawley rats were subjected to 5/6 nephrectomy (NPX) and treated with bFGF (30 µg/kg, NPX+bFGF); a control NPX group was treated with saline (NPX+S). Animals were euthanized 35 days after bFGF administration. Functional effects were assessed based on serum creatinine levels; morphological damage was assessed by the presence of macrophages (ED-1), interstitial α-smooth muscle actin (α-SMA), and interstitial collagen through Sirius red staining. The angiogenic factors VEGF and Tie-2 and the epithelial/tubular factors Ncam, bFGF, Pax-2, bone morphogenic protein-7, Noggin, Lim-1, Wnt-4, and Smads were analyzed. Renal stem cells were evaluated by Oct-4. We observed a significant reduction in serum creatinine levels, ED-1, α-SMA, and Sirius red as well as an important induction of Oct-4, angiogenic factors, and repairing proteins in NPX+bFGF animals compared with NPX+S animals. These results open new perspectives toward reducing damage progression in CKD.