Ligneous conjunctivitis: Fresh-frozen plasma and heparin use intra-and postoperatively, a report of two cases.

Ligneous conjunctivitis is a rare chronic form of recurrent membranous inflammation and plasminogen deficiency. Ocular manifestations may be associated with sites other than mucous membranes, such as the oral cavity, internal ear, respiratory, genitals, and kidney. Treatment is extremely difficult because of the lack of topic plasminogen drops, and a high volume is required for systemic supplementation. This report aimed to present two patients with ligneous conjunctivitis treated with membrane excision, topical fresh-frozen plasma, and heparin intra-, and postoperatively. No recurrence was found in the ligneous membrane in the 12-month follow-up. The use of topical fresh-frozen plasma and heparin after membrane excision could be effective to avoid recurrence.

X-linked genodermatoses from diagnosis to tailored therapy.

Background: Genodermatoses are rare heterogeneous genetic skin diseases with multiorgan involvement. They severely impair an individual's well-being and can also lead to early death. Methods: During the progress of this review, we have implemented a targeted research approach, diligently choosing the most relevant and exemplary articles within the subject matter. Our method entailed a systematic exploration of the scientific literature to ensure a compre-hensive and accurate compilation of the available sources. Results: Among genodermatoses, X-linked ones are of particular importance and should always be considered when pediatric males are affected. Regardless of other syndromic forms without prevalence of skin symptoms, X-linked genodermatoses can be classified in three main groups: keratinization defects, pigmentation defects, and inflammatory skin diseases. Typical examples are dyskeratosis congenita, keratosis follicularis spinulosa decalvans, hypohidrotic ectodermal dysplasia, chondrodysplasia punctata, hypohidrotic ectodermal dysplasia, incontinentia pigmenti, chronic granulomatous disease, CHILD syndrome and ichthyosis. In this field, genetic diagnosis of the specific disease is important, also considering that numerous clinical trials of orphan drugs and genetic therapies are being proposed for these rare genetic diseases. Conclusions: Thus, this chapter starts from clinical to molecular testing and ends with a review of all clinical trials on orphan drugs and gene therapy for genodermatoses.

Clinical and molecular diagnosis of genodermatoses: Review and perspectives.

Genodermatoses are a complex and heterogeneous group of genetic skin disorders characterized by variable expression and clinical and genetic heterogeneity, rendering their diagnosis challenging. DNA-based techniques, like whole-exome sequencing, can establish a diagnosis in 50% of cases. RNA-sequencing is emerging as an attractive tool that can obtain information regarding gene expression while integrating functional genomic data with regard to the interpretation of variants. This increases the diagnostic rate by an additional 10-15%. In the present review, we detail the clinical steps involved in the diagnosis of genodermatoses, as well as the current DNA-based technologies available to clinicians. Herein, the intention is to facilitate a better understanding of the possibilities and limitations of these diagnostic technologies. In addition, this review could guide dermatologists through new emerging techniques, such as RNA-sequencing and its applications to familiarizing them with future techniques. Currently, this multi-omics approach is likely the best strategy designed to promote the diagnosis of patients with genodermatoses and discover new skin disease genes that could result in novel targeted therapies.

Therapeutic options for perifolliculitis capitis abscedens et suffodens: A review.

Perifolliculitis capitis abscedens et suffodiens (PCAS) is a chronic skin inflammatory disease characterized by relapsing folliculitis and painful, fluctuant abscesses, sinus tracts, and scars. The treatment of PCAS is challenging and clinical practice varies a lot, and how to choose the best treatment for PCAS is a real problem for clinicians. We reviewed articles providing treatment options for patients with PCAS in different databases. Dermatologists may find this review helpful to meet the challenges of PCAS management, but there is still a lack of authoritative guidelines. In the future, more robust randomized control trials are needed to determine the best treatment for PCAS.

Primary Localized Cutaneous Amyloidosis: A Retrospective Study of an Uncommon Skin Disease in the Largest Tertiary Care Center in Switzerland.

BACKGROUND: Primary localized cutaneous amyloidosis (PLCA) is defined by the deposition of amyloid protein in the skin without systemic involvement. There are four subtypes of PLCA: lichen amyloidosis (LA), macular amyloidosis (MA), biphasic amyloidosis (BA), and nodular amyloidosis (NA). PLCA occurs most frequently in Latin Americans and Asians. Treatment is not standardized. OBJECTIVES: To identify subtypes, demographic and clinical features and treatment efficacy in patients with histopathologically confirmed PLCA. MATERIALS AND METHODS: Data of PLCA patients were extracted from the electronic hospital database and included if diagnosis of PLCA was histopathologically confirmed and if sufficient information regarding treatment and follow-up was available. The evaluation of the treatment efficacy was based on a novel score to assess the reduction of itch and skin lesions. RESULTS: In this retrospective, monocentric study, 37 cases of PLCA diagnosed between 2000 and 2020 were included (21 females) with a mean age of 52 years. LA was the most frequent subtype found in 21 patients (56.8%), followed by MA in 10 patients (28%) and BA in 6 patients (16.2%). No cases of NA were included. 22 patients (59.4%) had skin phototype II or III. Regarding treatment, a combination of UVA1 phototherapy with high-potency topical corticosteroids seemed to show the highest efficacy with complete clearance of symptoms in 4 patients (10.8%). A substantial improvement of symptoms was found in 5 patients (12.7%) treated with high-potency topical corticosteroids alone or in combination either with UVA1 or bath PUVA or monotherapy with UVA1 phototherapy or capsaicin (0.075%) cream. Low-/medium-potency topical corticosteroids alone or in combination with UVBnb (311 nm) phototherapy showed a lower efficacy. CONCLUSION: Our data show that PCLA is a rare disease in central Europe but can also be expected in a predominantly Caucasian population. The best treatment response was achieved with a combination of UVA1 phototherapy and high-potency topical corticosteroids.

Primary Localized Cutaneous Amyloidosis of Keratinocyte Origin: An Update with Emphasis on Atypical Clinical Variants.

Amyloid is a protein derived from at least 20 different substances. Once misfolded, it results in a group of cutaneous and systemic conditions. Primary localized cutaneous amyloidosis of keratinocyte origin is a very common subtype that can manifest either as lichen or macular amyloidosis, lacking systemic involvement. Lichen amyloidosis often presents as multiple hyperpigmented papules on the lower extremities whereas macular amyloidosis is classically characterized by dark brown rippled macules on the interscapular area. Review of the literature reveals that in addition to the classical presentation of primary localized cutaneous amyloidosis there exists a plethora of various manifestations that can be grouped into either geographic or morphologic categories. This review provides clinicians with the intimate knowledge of these presentations and summarizes the available treatment modalities.

Highly branched poly(ß-amino ester)s for gene delivery in hereditary skin diseases.

Non-viral gene therapy for hereditary skin diseases is an attractive prospect. However, research efforts dedicated to this area are rare. Taking advantage of the branched structural possibilities of polymeric vectors, we have developed a gene delivery platform for the treatment of an incurable monogenic skin disease - recessive dystrophic epidermolysis bullosa (RDEB) - based on highly branched poly(ß-amino ester)s (HPAEs). The screening of HPAEs and optimization of therapeutic gene constructs, together with evaluation of the combined system for gene transfection, were comprehensively reviewed. The successful restoration of type VII collagen (C7) expression both in vitro and in vivo highlights HPAEs as a promising generation of polymeric vectors for RDEB gene therapy into the clinic. Considering that the treatment of patients with genetic cutaneous disorders, such as other subtypes of epidermolysis bullosa, pachyonychia congenita, ichthyosis and Netherton syndrome, remains challenging, the success of HPAEs in RDEB treatment indicates that the development of viable polymeric gene delivery vectors could potentially expedite the translation of gene therapy for these diseases from bench to bedside.

Advances in gene therapy and their application to skin diseases: A review.

With recent advances in genetic engineering technology, gene therapy is now being considered as a treatment not only for congenital diseases but also acquired diseases, such as cancer. Gene therapeutic agents for hereditary immune disorders, haemophilia, retinal diseases, neurodegenerative diseases, and lymphoma have been approved in the United States and Europe. In the field of dermatology, clinical trials of gene therapy have been conducted, because the skin is an easily accessible organ that represents an attractive tissue for gene therapy. In recent years, gene therapy has been attempted for a variety of skin diseases, such as genodermatoses (including epidermolysis bullosa and Netherton syndrome), cutaneous lymphoma, and malignant melanoma. As a result, it is difficult to grasp the current status of gene therapy in dermatology. This review focuses on each of the gene-transfer techniques currently in use and describes the current status of gene therapy for skin diseases using each technology.

Segmental stiff skin syndrome (SSS): Clinical case and a brief review.

Stiff skin syndrome (SSS) is a rare, scleroderma-like condition that is commonly characterised by stony hard skin and limited joint mobility, in the absence of visceral involvement or immunologic abnormalities. Depending on the distribution of the disease, this disorder can be further categorised into classic (widespread) SSS or its newly described segmental variant. Additional features of this syndrome may include hypertrichosis, lipodystrophy, dysmetria and scoliosis. In this report, we present the case of a patient with segmental SSS and we briefly review the current literature about the topic.

Ex vivo gene modification therapy for genetic skin diseases-recent advances in gene modification technologies and delivery.

Genetic skin diseases, also known as genodermatoses, are inherited disorders affecting skin and constitute a large and heterogeneous group of diseases. While genodermatoses are rare with the prevalence rate of less than 1 in 50,000 - 200,000, they frequently occur at birth or early in life and are generally chronic, severe, and could be life-threatening. The quality of life of patients and their families are severely compromised by the negative psychosocial impact of disease, physical manifestations, and the lack or loss of autonomy. Currently, there are no curative treatments for these conditions. Ex vivo gene modification therapy that involves modification or correction of mutant genes in patients' cells in vitro and then transplanted back to patients to restore functional gene expression has being developed for genodermatoses. In this review, the ex vivo gene modification therapy strategies for genodermatoses are reviewed, focusing on current advances in gene modification and correction in patients' cells and delivery of genetically modified cells to patients with discussions on gene therapy trials which have been performed in this area.

Arterial Tortuosity Syndrome: An Ascorbate Compartmentalization Disorder?

Significance: Cardiovascular disorders are the most important cause of morbidity and mortality in the Western world. Monogenic developmental disorders of the heart and vessels are highly valuable to study the physiological and pathological processes in cardiovascular system homeostasis. The arterial tortuosity syndrome (ATS) is a rare, autosomal recessive connective tissue disorder showing lengthening, tortuosity, and stenosis of the large arteries, with a propensity for aneurysm formation. In histopathology, it associates with fragmentation and disorganization of elastic fibers in several tissues, including the arterial wall. ATS is caused by pathogenic variants in SLC2A10 encoding the facilitative glucose transporter (GLUT)10. Critical Issues: Although several hypotheses have been forwarded, the molecular mechanisms linking disrupted GLUT10 activity with arterial malformations are largely unknown. Recent Advances: The vascular and systemic manifestations and natural history of ATS patients have been largely delineated. GLUT10 was identified as an intracellular transporter of dehydroascorbic acid, which contributes to collagen and elastin cross-linking in the endoplasmic reticulum, redox homeostasis in the mitochondria, and global and gene-specific methylation/hydroxymethylation affecting epigenetic regulation in the nucleus. We revise here the current knowledge on ATS and the role of GLUT10 within the compartmentalization of ascorbate in physiological and diseased states. Future Directions: Centralization of clinical, treatment, and outcome data will enable better management for ATS patients. Establishment of representative animal disease models could facilitate the study of pathomechanisms underlying ATS. This might be relevant for other forms of vascular dysplasia, such as isolated aneurysm formation, hypertensive vasculopathy, and neovascularization. Antioxid. Redox Signal. 34, 875-889.

Type 1 Plasminogen Deficiency With Pulmonary Involvement: Novel Treatment and Novel Mutation.

Type 1 plasminogen deficiency is a rare genetic disorder. Type 1 plasminogen deficiency is characterized by fibrin-rich pseudomembrane formation on mucosal surfaces, particularly the conjunctiva. Tracheobronchial tree involvement is a less common reported manifestation of type 1 plasminogen deficiency. Pseudomembranes in the tracheobronchial tree may result in respiratory compromise and ultimately fail if not recognized and treated. Currently, there is no specific replacement therapy approved for the treatment of congenital plasminogen deficiency. In the present paper, we report that type 1 plasminogen deficiency with novel frameshift mutation and pulmonary involvement was treated initially with systemic fresh frozen plasma followed by pulmonary lavage with fresh frozen plasma and tissue plasminogen activator.

Actinic prurigo in a dermatological reference center in Colombia: 108 cases / Prurigo actínico en un centro dermatológico de referencia en Colombia: 108 casos.

Introduction: Actinic prurigo is a chronic photodermatosis. It affects the Latin American population more frequently, predominantly women, and involves the sun-exposed areas of the skin, conjunctiva, and lips. Objective: To update the information on the clinical-epidemiological characteristics and treatment of patients with actinic prurigo in Colombia. Materials and methods: We conducted a cross-sectional study including the medical records of patients with actinic prurigo treated in the Photodermatology Service of Hospital Universitario Centro Dermatológico Federico Lleras Acosta between 2011 and 2016. We described the demographic, clinical, histopathological, and treatment characteristics of the patients. Results: We included 108 patients, 77 (71.3%) were women and 31 (28.7%) men, mainly with phototypes III-IV (70%). The disease had begun during the first decade of life in 66.4% of the cases and 25% of the patients had a family history with the condition. The lesions predominated on the face (93.5%), forearms (79.6%), and back of the hands (70.4%). Ocular (87.9%) and lip (88.8%) involvement was also documented. A photo-provocation test with UVA was performed in 25% of the cases and skin biopsies in 19.4%. Physical and chemical photoprotection was indicated in all patients. Mild to moderate cases were treated with topical corticosteroids (91.7%) and calcineurin inhibitors (65.7%) while severe cases received thalidomide (33.3%) and pentoxifylline (14.8%). Conclusion: The characteristics of actinic prurigo patients in Colombia are similar to those reported in other Latin American countries: early onset of the disease, predominance in women, frequent involvement of conjunctiva and lips, and adequate response to topical and systemic treatment.

Introducción. El prurigo actínico es una fotodermatosis crónica. Afecta con mayor frecuencia a la población latinoamericana, predomina en mujeres y compromete la piel expuesta al sol, las conjuntivas y los labios. Objetivo. Actualizar la información sobre las características clínico-epidemiológicas y el tratamiento de pacientes con prurigo actínico en Colombia. Materiales y métodos. Se hizo un estudio de corte transversal que incluyó los registros clínicos de pacientes con prurigo actínico atendidos en el Servicio de Fotodermatología del Hospital Universitario Centro Dermatológico Federico Lleras Acosta entre el 2011 y el 2016, y se describieron sus características demográficas, clínicas e histopatológicas, así como su tratamiento. Resultados. Se incluyeron 108 pacientes, el 71,3 % de ellos mujeres y el 28,7% hombres, con predominio de los fototipos III-IV (70 %). La enfermedad se había iniciado durante la primera década de vida en el 66,4% de los casos y el 25 % de los pacientes tenía antecedentes familiares de la enfermedad. Las lesiones predominaban en el rostro (93,5 %), los antebrazos (79,6 %) y el dorso de las manos (70,4 %). También, se documentó compromiso ocular (87,9 %) y de los labios (88,8 %). Se hizo la prueba de fotoprovocación con radiación ultravioleta A en el 25 % de los casos y biopsia cutánea en el 19,4 %. Todos los pacientes se trataron con protección solar química y física. En los casos leves a moderados, se formularon corticoides tópicos (91,7 %) e inhibidores de la calcineurina (65,7 %), y en los graves, talidomida (33,3 %) y pentoxifilina (14,8 %). Conclusión. Las características de los pacientes colombianos con prurigo actínico son similares a las reportadas en otros países latinoamericanos: inicio temprano de la enfermedad, predominio en mujeres, compromiso frecuente de conjuntivas y labios, y adecuada respuesta al tratamiento tópico y sistémico.

Genodermatoses with malignant potential.

The hereditary nature of some forms of cancer was recognized long ago. Over time, recognition of associated findings led to the delineation of numerous hereditary cancer syndromes. Many of these syndromes also have cutaneous manifestations, the recognition of which can lead to their early identification. Recognition of these syndromes allows vigilant surveillance and preemptive treatment, which can dramatically impact the risks of morbidity and mortality for affected patients. The rise of rapid and accurate genetic testing now allows the early identification of asymptomatic at risk family members so that monitoring can be initiated as early as possible. The dermatologist plays a critical role in early identification of these syndromes and, in many cases, their treatment. This review summarizes many known hereditary cancer syndromes with cutaneous findings, their etiology, identification, evaluation, and management. Importantly, this is an ever evolving topic and new findings and syndromes will continue to be recognized. The dermatologist must be always alert to ensure they are detected.

Emerging therapies in genodermatoses.

The human genome project yielded a compendium of genetic material that has allowed rapid advancement both in the technique of whole exome sequencing and also in the ability to identify single gene defects. The next generation of genetics has investigated how these genes interact in the development of disease, identifying pathways of illness and end organ tissue abnormal development. From the knowledge of single genes and pathways of genodermatosis development arises the opportunity to produce genetic therapies. This contribution reviews some of the exciting, emerging genetic therapies in genodermatoses.

[Stiff skin syndrome in a pediatric patient: a therapeutic challenge. Clinical case]. / Síndrome de piel indurada en un paciente pediátrico: un desafío terapéutico. Presentación de un caso.

Stiff skin syndrome is a chronic, rare sclerosing disorder that occurs in childhood, characterized by progressive induration of the skin that can cause thoracic restrictions and respiratory distress, limitations in joint mobility and gait difficulties, with significant deterioration of the quality of life. Because their therapeutic options are scarce and ineffective it is essential to start an early physical therapy to prevent these complications and to continue studying this condition to be able to offer patients more and better treatments. We present the case of a 9-year-old patient with indurated skin syndrome and its therapeutic challenge.

El síndrome de la piel indurada es un trastorno esclerosante crónico, infrecuente, que se presenta en la infancia, caracterizado por la induración progresiva de la piel. Esta afección puede provocar restricciones torácicas y dificultad respiratoria, limitaciones en la movilidad articular y trastornos en la marcha, con importante deterioro de la calidad de vida. Debido a que sus opciones terapéuticas son escasas y poco eficaces, es fundamental que el paciente inicie precozmente una terapia física para prevenir estas complicaciones y que se continúe estudiando esta enfermedad a fin de poder ofrecer a los pacientes más y mejores tratamientos. Se presenta el caso de una paciente de 9 años con síndrome de la piel indurada y su desafío terapéutico.

Is there a role for blood purification therapies targeting cytokine storm syndrome in critically severe COVID-19 patients?

The coronavirus disease-19 (COVID-19) has spread over many countries and regions since the end of 2019, becoming the most severe public health event at present. Most of the critical cases developed multiple organ dysfunction, including acute kidney injury (AKI). Cytokine storm syndrome (CSS) may complicate the process of severe COVID-19 patients. This manuscript reviews the different aspects of blood purification in critically ill patients with AKI and increased inflammatory factors, and examines its potential role in severe COVID-19 treatment. Continuous renal replacement therapy (CRRT) has been practiced in many sepsis patients with AKI. Still, the timing and dosing need further robust evidence. In addition to the traditional CRRT, the high-throughput membrane with adsorption function and cytokine adsorption column are two representatives of recently emerging novel membrane technologies. Their potential in removing inflammatory factors and other toxins prospects for the treatment of severe COVID-19.