Novel Management of Ocular Surface Inflammation in Patients With Ocular Graft-Versus-Host Disease in the Setting of Cataract Surgery.

PURPOSE: To report the outcomes of cataract surgery in patients with ocular graft-versus-host disease (oGVHD) using a novel preoperative immunomodulatory regimen in a collaborative subspecialty care setting. METHODS: Retrospective case series of patients with oGVHD who underwent cataract surgery using a novel preoperative immunomodulatory regimen in a collaborative care setting. A preoperative regimen consisting of pooled human immune globulin 1%, autologous serum 50%, and methylprednisolone 1% eye drops was prescribed. Outcome measures included visual acuity (VA), ocular surface disease index (OSDI) score, lissamine green staining, and complications with a minimum of 2 years of follow-up. RESULTS: Thirty-five eyes from 20 patients with oGVHD were studied. The mean age was 59 years (range 30-70 years). A healthy comparison group included 35 eyes from 24 patients with a mean age of 63 years (range 44-74 years). At the 2-year follow-up, the mean corneal staining score was 2.3/15, the mean OSDI score was 37.5, and the mean VA was 20/30 (logarithm of the minimal angle of resolution 0.17). The global complication rate was 2.8% at the last follow-up with no difference versus a healthy comparison group. CONCLUSIONS: A collaborative care model improving ocular surface health before cataract surgery with dry eye and cataract subspecialists can optimize outcomes in patients with oGVHD.

Oral squamous cell carcinoma arising from areas of Graft-versus-host disease: A systematic review.

BACKGROUND: Graft-versus-host disease (GVHD) is an immune system reaction that occurs in patients with a history of hematopoietic stem cell transplantation (HSCT), in which the grafted donor's cells attack those of the host. The objective of this systematic review was to present a study on oral squamous cell carcinoma (OSSC) that developed from GVHD areas in patients undergoing HSCT. MATERIAL AND METHODS: An electronic search was conducted in the databases PUBMED, WEB OF SCIENCE, SCOPUS, MEDLINE and SCIENCE DIRECT, according to PRISMA guidelines. RESULTS: Of the 1582 results, 23 articles were included, resulting in 81 cases. The most common underlying disease for performing the transplant was Myeloid Leukemia (55.6%). The mean age was 39 years, with a predilection for males (64.2%). The tongue was the site of GVHD that most frequently underwent transformation to SCC (59.3%). The average time between transplantation and the development of GVHD was of approximately of 8 months, while the average period of development between transplantation and the development of OSCC was of approximately of 111 months. The most common treatment to GVHD was cyclosporine associated with corticosteroids. CONCLUSIONS: OSCCs arising from areas of GVHD present a different evolution from conventional oral carcinomas, since they affect younger patients, smoking and alcohol are not important etiological factors and finally because they present good prognosis, but further studies with larger number cases followed are needed to confirm our findings.

Superficial mucoceles in cancer patients: a retrospective series from a Stomatology unit.

BACKGROUND: The aim of this study is to relate all the superficial mucoceles found in a cancer center, described the association with oncological conditions, and discuss its etiology and pathology that we found in the past few years. MATERIAL AND METHODS: Sixteen cases of superficial mucocele were retrieved from the patients' records of the Stomatology Department of the A. C. Camargo Cancer Center, São Paulo, Brazil, and demographic and clinical data were collected from electronic medical records. RESULTS: There were 16 patients, 8 patients were men and 8 women, with ages varying from 26 to 70 years old. Superficial mucoceles were observed in patients submitted to head and neck radiotherapy (n=6), graft versus host disease (n=4), one associated with oral mucositis related to allogenic bone marrow stem cells transplantation (n=1), systemic lupus (n=1), Sjögren's syndrome (n=1), oral lichenoid lesion associated with pembrolizumab (n=1) and no local or systemic inflammatory associated found (n=2). CONCLUSIONS: This study reports a series of superficial mucoceles from a single stomatology unit. Most patients had superficial mucoceles secondary to head and neck radiotherapy and graft versus host diseases. However, two patients (12.5%) had mucoceles related to systemic inflammatory conditions (Sjögren's Syndrome and Systemic Lupus).

Immunopathological insights into villitis of unknown etiology on the basis of transplant immunology.

Villitis of unknown etiology (VUE) is an inflammatory disease characterized by the infiltration of maternal CD8 +T cells into the placental villi. Although the pathogenesis of VUE is still debated, dysregulation of the immune system appears to be an important factor in the development of the disease. Interaction of maternal T cells with the fetal antigens seems to be the trigger for the VUE onset. In this context, graft vs host disease (GVHD) and allographic rejection seem to share similarities in the VUE immunopathological mechanism, especially those related to immunoregulation. In this review, we compared the immunological characteristics of VUE with allograft rejection, and GVHD favoring a better knowledge of VUE pathogenesis that may contribute to VUE therapeutics strategies in the future.

Risk of oral cancer in patients with graft-vs-host disease: A systematic review and meta-analysis.

OBJECTIVE: This systematic review was undertaken to determine the risk of oral cancer in patients with chronic graft-vs-host disease (cGvHD). STUDY DESIGN: The search was conducted in 6 electronic databases (PubMed/MEDLINE, EMBASE, LILACS, Web of Science, Scopus, and LIVIVO) and gray literature (Google Scholar, Open Gray, and ProQuest) for studies published up to November 2021. RESULTS: Of the 13 cohorts included in qualitative synthesis, 9 were eligible for the quantitative analysis. The meta-analysis showed that the presence of cGvHD increased the risk of developing oral cancer (risk ratio [RR] = 2.78; 95% CI, 1.27-6.08; I2 = 46%; P = .01). A subgroup meta-analysis revealed a higher risk of oral cancer in Asian samples exposed to cGvHD (RR = 2.50; 95% CI, 1.54-4.04; I2 = 0%; P = .0002), which was not seen in the pooled analysis of European samples (P = .24). The overall methodological quality of most studies included was "good." The cumulative evidence (Grading of Recommendations Assessment, Development and Evaluation) was considered moderate and of very low confidence for Asian and European studies, respectively. CONCLUSIONS: Patients with cGvHD resulting from allogenic hematopoietic stem cell transplantation run an increased risk of developing oral cancer. Hence, it is recommended that patients with cGvHD be monitored to allow for the early detection and treatment of secondary malignant disease.

Total Resorption of a Chronic L4-L5 Disc Extrusion After Application of the Atlasprofilax Method: A Case Report.

BACKGROUND The intervertebral disc extrusion resorption has been described in the literature by various authors. It occurs in up to 75% of patients with symptomatic extruded lumbar discs. The Atlasprofilax method favors osteo-musculo-articular rehabilitation processes, mainly impacting on 2 levels: the first is the bone anatomy of the atlanto-occipital joint, and the second is the fasciae located in the cervical region. CASE REPORT A 42-year-old male patient diagnosed by MRI with dehydration of L2-L3 to L5-S1 intervertebral discs, disc bulging at L2-L3 and L3-L4, and disc extrusion at L4-L5, received a one-time neuromuscular treatment, called the Atlasprofilax method, to the suboccipital region. In a repeat MRI 6 months later, the disc extrusion at L4-L5 was totally resorbed and improvement in the L3-L4 and L4-L5 disc bulges was seen. The patient's symptoms prior to the Atlasprofilax treatment included bilateral trapezius pain, right brachialgia, constant chronic low back pain, right sciatica, gait claudication, and paresthesia and dysesthesias in the lower limbs with associated pain and numbness in the calves. These symptoms were ameliorated after the treatment. The sciatica disappeared 1 week after the treatment and did not recur. In a follow-up 5 years later, the remaining symptoms had improved even further. CONCLUSIONS We propose that alterations of the cervical musculature and deep fascia could predispose to the development of lumbar disc abnormalities. We therefore also propose that improvements in this patient, both in symptoms and in imaging findings, are due to a reduction of the asymmetric distribution of forces and elastic loading as a result of the Atlasprofilax treatment.

Ocular Manifestations in Patients with Fanconi Anemia: A Single-Center Experience Including 106 Patients.

OBJECTIVES: To describe the prevalence of acquired ocular manifestations in patients with Fanconi anemia (FA) and to describe and correlate the congenital ocular malformations with the genetic subtypes of the disease. STUDY DESIGN: This is a cross-sectional observational study of 106 consecutive patients with confirmed diagnosis of FA who were followed at the Hematopoietic Stem Cell Transplantation (HSCT) Service at the Federal University of Paraná, Curitiba, Parana, Brazil. Participants underwent a complete ophthalmologic evaluation and 84 patients underwent ocular ultrasound examination. This study was conducted between November 2014 and August 2017. RESULTS: The patients ranged in age from 6 months to 43 years of age. Microphthalmia was the most common congenital ocular abnormality (95.2%). A decrease in anthropometric measurements was observed, including palpebral fissure length (78/103 patients [76.5%]), microcornea (48/103 patients [46.6%]), and ptosis (31/103 patients [30.1%]). We identified a new ophthalmic condition in 15 patients with FA, that is, epiretinal tissue on the optic disc. The genetic subtype was identified in 78 patients (79.6%), the FA-A subtype was most prevalent (50%). The most common acquired ocular manifestation (non-graft-versus-host disease [GVHD] related) in patients who did not undergo HSCT (n = 44) was limbal neovascularization (13.6%), whereas in patients who underwent HSCT (n = 62), the GVHD-related manifestation was ocular GVHD (51.6%). The most frequent symptom of ocular GVHD was keratoconjunctivitis sicca (29%). CONCLUSIONS: Several ocular manifestations were identified in patients with FA.

[Cutaneous manifestations of graft versus host disease in a population of pediatric and young adults patients]. / Manifestaciones cutáneas de la enfermedad injerto versus huésped en una población pediátrica y de adultos jóvenes.

Bone marrow transplant is a potentially curative therapy for several diseases, and allogeneic bone marrow transplant is the most commonly indicated type for leukemias. Graft versus host disease (GVHD) is the main complication of allogeneic bone marrow transplant. In both acute and chronic GVHD, the skin is the most frequently involved organ. The objective of this study was to analyze cutaneous manifestations of this disease. Retrospective and descriptive study that included 59 transplanted patients aged 0 to 20 years. In 50 cases allogeneic bone marrow transplant was performed. Twenty-five patients developed GVHD (17 acute disease and 8 chronic disease) and 24 of them had cutaneous involvement. According to the literature, skin compromise was the commonest clinical manifestation of GVHD. Main finding in acute GVHD in our series was the erythematous maculopapular rash, while in chronic GVHD they were sclerotic lesions resembling morphea.

El trasplante de médula ósea es una terapia potencialmente curativa para múltiples enfermedades; el alogénico es el más indicado en leucemias. La enfermedad injerto versus huésped (EIVH) constituye la principal complicación del trasplante de médula ósea alogénico. Tanto en la EIVH aguda como crónica, la piel es el órgano más frecuentemente comprometido. El objetivo fue analizar las manifestaciones cutáneas de esta entidad. Trabajo retrospectivo y descriptivo, que incluyó a 59 pacientes trasplantados de edades entre 0 y 20 años. En 50 casos, se realizó trasplante de médula ósea alogénico. Veinticinco pacientes desarrollaron EIVH (17, la forma aguda, y 8, la forma crónica), y 24 tuvieron compromiso cutáneo. En concordancia con lo comunicado se encontró que las manifestaciones cutáneas fueron la manifestación clínica más común de EIVH. El hallazgo principal en EIVH aguda en nuestra serie fue el rash eritematoso maculopapular y, en EIVH crónica, las lesiones escleróticas símil morfea.

Afectación ocular en la enfermedad injerto contra huésped / Ocular damage in graft-versus-host disease

RESUMEN El trasplante alogénico de precursores hematopoyéticos está indicado en el tratamiento de diversos trastornos de la sangre, sobre todo en las neoplasias malignas. La enfermedad injerto contra huésped es la complicación principal de los trasplantes alogénicos de órganos hematopoyéticos. Es una enfermedad inmunológica provocada por la interacción entre el donante y el receptor, mediante respuestas innatas y adaptativas. Con gran frecuencia afecta la piel y el sistema gastrointestinal. Diferentes pueden ser las manifestaciones oculares, pero son las alteraciones de la superficie ocular las más frecuentes. Los cambios en la superficie ocular pueden provocar ceguera. El diagnóstico y el tratamiento precoz mejoran el pronóstico. Además del tratamiento general de la enfermedad es necesario instaurar medidas específicas para controlar las alteraciones oculares. Se realizó una revisión sobre los artículos publicados con el objetivo de conocer sobre la enfermedad injerto contra huésped y su afectación ocular(AU)

ABSTRACT Allogeneic transplantation of hematopoietic precursors is indicated in the treatment of various blood disorders, particularly malignant neoplasms. Graft-versus-host disease is the main complication of allogeneic transplants of hematopoietic organs. GVHD is an immunological condition caused by the interaction between the donor and the recipient manifested as innate and adaptive responses. It very often affects the skin and the gastrointestinal system. A variety of ocular manifestations may also occur, the most common of which are ocular surface alterations. Changes in the ocular surface may cause blindness. Early diagnosis and treatment improve prognosis. Besides the general treatment of the disease it is necessary to implement specific measures to control ocular alterations. A review was conducted of published papers on the topic to become acquainted with graft-versus-host disease and the ocular damage it causes(AU)

Evaluación de formulaciones inmunoterapéuticas experimentales en el modelo hibrido murino de Reaccion del Injerto contra el Hospedador / Evaluation of experimental immunotherapeutic formulations in the hybrid murine model of Graft-versus-Host Reaction

Introducción: La Enfermedad del Injerto Contra el Hospedador es la complicación más frecuente de los Trasplantes de Células Madre Hematopoyéticas y de todos los trasplantes que contengan células inmunocompetentes alogénicas, el 100 por ciento la padecen y cerca del 30 por ciento mueren por su causa; una proporción alta de casos son esteroide-refractarios, asimismo otras medidas inmunosupresoras modernas fracasan. En los campos de la Inmunoterapia y la Vaccinología también existe una escasez preocupante de inmunomoduladores de origen biológico potentes, efectivos, seguros y de amplio espectro. Existe un modelo híbrido murino de gran utilidad metodológica para estudios experimentales. Objetivo: Evaluar dos formulaciones novedosas de origen biotecnológico, una de ellas inmunopotenciadora y otra inmunosupresora, desarrolladas como cocleatos. Material y Métodos: Mediante Microscopia Electrónica y RT-PCR se caracterizaron las formulaciones como nanopartículas y su capacidad de regular la expresión del ARNm de linfoquinas definitorias de sus perfiles, respectivamente. Empleando el modelo de Enfermedad del Injerto Contra el Hospedador en ratón híbrido F1 (CBAxC57BL), se evaluó su carácter inmunomodulador in vivo . Resultados: Partiendo de los proteoliposomas de Neisseria meningitidis, se obtuvieron dos formulaciones en forma de cocleatos, ambas con diámetros de partícula inferior a 100nm. La Formulación 1mostró un perfil proinflamatorio con potente capacidad de aumentar el IFNγ y el TNFα y potenció el Índice de Bazo hasta 2,05 en el modelo EICH con p=0,0002. La Formulación 2 mostró un perfil supresor-regulatorio con potente capacidad de aumentar la IL-10 y el TGFβ y además de suprimir la producción de TNFα. En el modelo usado, esta formulación, suprimió el Índice de Bazo de manera dosis dependiente y con alta significación estadística. Se corroboró el conocido perfil de seguridad y ausencia de reactogenicidad de ambas formulaciones. Conclusiones: Ambas formulaciones tienen potencial aplicación en los campos de la terapia de Enfermedad del Injerto Contra el Hospedador en otras patologías y en Vaccinología. Los resultados obtenidos en el presente trabajo fundamentan la conveniencia de continuar el desarrollo farmacéutico y completar la preclínica de ambas formulaciones(AU)

Introduction: Graft-versus-host disease is the most frequent complication of Hematopoietic Stem Cell Transplants and all transplants containing allogeneic immunocompetent cells; 100 percent of patients suffer from this complication and about 30 percent die for this particular cause. A high proportion of cases are steroid-refractory; likewise, other modern immunosuppressive measures fail. In the fields of Immunotherapy and Vaccinology, there is also a worrying shortage of powerful, effective, safe and broad spectrum immunomodulators of biological origin. There is a hybrid murine model of great methodological utility for experimental studies. Objective: To evaluate two novel formulations of biotechnological origin: an immunopotentiator formulation and an immunosuppressive one, which were developed as cochleates. Material and Methods: The formulations assayed by Electron Microscopy and RT-PCR were characterized as nanoparticles and for their capacity to regulate lymphokine mRNA expression profile, respectively. The immunomodulatory character was evaluated in vivo using Graft-versus-host disease in (CBAxC57BL) F1 hybrid mice. Results: Starting from the proteoliposomes derived from Neisseria meningitides, two cochleate formulations were obtained, both with particle diameters below 100 nm. Formulation 1 showed a proinflammatory profile with potent capacity to increase IFNγ and TNFα, and potentiated the Spleen Index up to 2.05 in the GVDH model with p = 0.0002. Formulation 2 showed a suppressor/regulatory profile with potent capacity to increase IL-10 and TGFβ and suppress the production of TNFα. In the model used, this formulation suppressed the Spleen Index in a dose-dependent manner with high statistical significance. The known safety profile and absence of reactogenicity of both formulations was corroborated. Conclusions: Both formulations have potential application in the fields of GVHD therapy and other pathologies as well as in Vaccinology. The results obtained in the present work suggest the usefulness to continue with the pharmaceutical development and complete the preclinical studies of both formulations(AU)

Características Clínicas e Complicações do Transplante Haploidêntico com Ciclofosfamida Pós-Transplante: Implicações para a Enfermagem / Clinical Characteristics and Complications of the Haploidentical Transplantation with Post-Transplant Cyclophosphamide: Implications for Nursing / Características Clínicas y Complicaciones del Trasplante Haploidéntico con Ciclofosfamida Post-Trasplante: Implicaciones para la Enfermería

Introdução: O transplante haploidêntico (haplo) vem crescendo em números e se tornando uma alternativa viável para pacientes sem doadores compatíveis. Uma assistência de enfermagem qualificada também é muito importante para o seu sucesso. Portanto, torna-se necessário adquirir conhecimentos e habilidades no assunto. Objetivo: Descrever as características clínicas e complicações do haplo com ciclofosfamida pós-transplante e discutir suas implicações para a assistência de enfermagem. Método: Revisão integrativa da literatura publicada a partir de 2014, pesquisada nas bases da Biblioteca Virtual em Saúde com o descritor "haploidentical transplantation" e selecionada com critérios pré-definidos. Resultados: Vinte e cinco textos foram revisados; todos da área médica e compostos principalmente de estudos de coorte retrospectivos com amostras pequenas. Entre as características mais prevalentes, destacaram-se: a mãe como principal doadora para crianças (5/7 estudos); regime não mieloablativo (52%); e enxerto de sangue periférico (56%). Além da doença enxerto versus hospedeiro e da rejeição, as complicações mais descritas foram: cistite hemorrágica por vírus BK (56%) e reativação do citomegalovírus (48%); e as com maiores variações nas frequências foram mucosite (8% a 100%) e febre não infecciosa (22% a 100%). As principais causas de mortalidade foram a recaída da doença (3% a 35%) e as infecções (3% a 32%). Conclusão: Esta revisão alertou para a necessidade de aprimoramento da assistência na administração da ciclofosfamida pós-transplante, no suporte aos doadores e no manejo da febre não infecciosa, das infecções virais e da cistite hemorrágica, para que haja melhora na qualidade de vida dos pacientes e diminuição na morbidade e na mortalidade relacionadas ao haplo.

Introduction: Haploidentical Transplantation (haplo) has been growing in numbers and becoming a viable alternative for patients without compatible donors. Qualified nursing care is also very important for its success. Therefore, it becomes necessary to acquire knowledge and skills about the subject. Objective: To describe clinical characteristics and complications of haplo with post-transplant cyclophosphamide and discuss its implications for nursing care. Method: Integrative literature review published from 2014, searched in the bases of the "Biblioteca Virtual em Saúde" with the descriptor "haploidentical transplantation" and selected with predefined criteria. Results:Twenty-five texts were reviewed, all of them of the medical area and consisting mainly of retrospective cohort studies with small samples. Among the most prevalent characteristics, the following were outstanding: the mother as the main donor for children (5/7 studies); non-myeloablative regimen (52%) and peripheral blood graft (56%). In addition to graft versus host disease and rejection, the most described complications were: BK virus hemorrhagic cystitis (56%) and reactivation of cytomegalovirus (48%); and the ones with the highest variations in frequencies were mucositis (8% to 100%) and non-infectious fever (22% to 100%). The main causes of mortality were relapse of the disease (3% to 35%) and infections (3% to 32%). Conclusion: This review warned about the necessity of improving the care in the administration of post-cyclophosphamide, the support to donors and management of non-infectious fever, viral infections and hemorrhagic cystitis to improve the quality of life of patients and reduce haplo-related morbidity and mortality.

Introducción: El diagnóstico precoz del riesgo nutricional puede mejorar el pronóstico de los pacientes onco-hematológicos. Objetivo: Describir el estado nutricional en los pacientes onco-hematológicos y evaluar los factores asociados al riesgo nutricional en los pacientes onco-hematológicos de un Hospital Universitario Terciario de Fortaleza - Ceará. Método: Estudio transversal que incluyó a 127 pacientes adultos internados. Los datos de diagnóstico clínico y demográfico fueron recolectados a través de análisis de prontuarios. El estado nutricional fue evaluado por el índice de masa corporal (IMC), circunferencia braquial (CB) y por la aplicación de la herramienta de clasificación de riesgo nutricional - NRS-2002. Resultados: Diferentes parámetros, hubo divergencias en el estado nutricional. La mayoría de la muestra presentaba riesgo nutricional de acuerdo con la evaluación de la NRS-2002 70,1% (n=89), seguida por la CB 33,9% (n=43) y por IMC 8,7% (n=11). Se observó una correlación positiva significativa entre el IMC y la edad [r=0,313, p<0,001] y CB [r=0,846, p<0,001]. Se observó una asociación significativa NRS-2002≥3, e IMC<18,5 kg/m² (p=0,023) y CB desnutrida (p=0,001). Hubo asociación significativa entre IMC<18,5kg/m² y CB desnutrida (p=0,001), y entre residir en zona urbana y presentar CB adecuado (p=0,023). Conclusión: Alta prevalencia de riesgo nutricional, así como una asociación significativa entre riesgo nutricional y bajos valores de IMC y CB, y residir en zonas rurales. Hay la necesidad de utilizar una combinación de indicadores para diagnosticar de forma más precisa y precoz el estado nutricional de estos pacientes.

Pulmonary restriction secondary to cutaneous sclerosis caused by chronic graft versus host disease: Case Report / [Restricción pulmonar secundaria a esclerosis cutánea por enfermedad injerto contra huésped crónica: Reporte de Caso.]

Chronic graft versus host disease (GVHD) is a major complication of the allogeneic stem cell transplant. One of most frequent manifestations of GVHD is the cutaneous compromise with the sclerodermatous variety being the most severe. We considered that the restrictive respiratory compromise and its evolution are not well characterized. We described the functional respiratory alterations of a patient with sclerodermatous chronic GVHD and considered differential diagnosis of pulmonary restriction in this type of patient. We reported the case of a 21-year-old woman with pulmonary restriction secondary to cutaneous sclerosis which was caused by chronic GVHD. This report illustrates the importance of utilizing both functional respiratory tests and diagnosis images to accurately characterize the cause of the respiratory compromise. We believe that the functional alterations described in this case could be caused by the cutaneous disorder found.

La enfermedad injerto contra huésped crónica (EICH) es una complicación mayor del trasplante de células progenitoras alogénico. Una de sus manifestaciones más frecuentes es el compromiso cutáneo, siendo su variedad esclerodermiforme la más severa. El compromiso respiratorio, predominantemente restrictivo y su evolución no han sido bien caracterizados. El caso describe las alteraciones funcionales respiratorias de una paciente con EICH cutánea crónica tipo esclerodermiforme en dos momentos de su evolución y considera los diagnósticos diferenciales que producen restricción en estos pacientes. Se presenta el caso de una mujer de 21 años con restricción pulmonar secundaria a esclerosis cutánea por EICH. Este caso ilustra la relevancia de la utilización conjunta de las pruebas funcionales respiratorias y de los métodos diagnósticos por imágenes para caracterizar adecuadamente el compromiso respiratorio de estos pacientes. A nuestro juicio las alteraciones funcionales respiratorias descriptas pueden ser explicadas por el trastorno cutáneo hallado.

Doença do Enxerto-versus-hospedeiro ocular: Revisão / Graft-versus-Host Disease: Review

Resumo Doença do Enxerto-versus-hospedeiro (do inglês Graft-versus-Host Disease - GVHD) é uma complicação importante e com altas taxas de morbidade e mortalidade nos pacientes submetidos ao transplante alogênico de células-tronco hematopoiéticas. O acometimento ocular, denominado GVHD ocular, pode acometer todas as estruturas dos olhos, porém a unidade lacrimal (glândulas lacrimais e superfície ocular) é o principal alvo da resposta inflamatória mediada por células T doadas. O desenvolvimento de doença do olho seco grave é a principal manifestação clínica ocular, e a associação de diversas opções terapêuticas se faz necessário. O objetivo desta revisão é descrever as manifestações clínicas, os critérios diagnósticos, o impacto na qualidade de vida, o tratamento atual e as perspectivas desta doença, que precisa de um acompanhamento multidisciplinar.

Abstract Graft-versus-host Disease (GVHD) is a major complication with high morbidity and mortality rates on patients undergoing hematopoietic stem cell transplantation. The ocular involvement, named ocular GVHD, may affect all structures of the eyes, but the lacrimal unit (lacrimal glands and ocular surface) is the main target of the inflammatory response mediated by the donor T cells. The development of dry eye disease is the main clinical ocular manifestation, and the association of a variety of therapeutics options is necessary. The aim of the review is to describe the clinical manifestations, diagnostic criteria, impact in quality of life, the current treatment and future perspectives of this disease that demands a multidisciplinary follow-up.

Vitiligo type cutaneous manifestation of chronic graft-versus-host disease. Case report. / Enfermedad injerto contra huésped cutánea crónica tipo vitiligo. Caso clínico.

INTRODUCTION: Graft-versus-host disease (GVHD) is caused by a pathologic and destructive response of the organism as a result of the interaction between donor immunocompetent T lymphocytes and the recipient tisular antigens. It's considered the most serious complication of hematopoietic stem cell transplantation, most frequently described after bone marrow transplantation (BMT). The skin is usually the first and most commonly affected organ, in both acute and chronic, with a variable clinical spectrum of presentation. OBJECTIVE: To report a case of vitiligo as a manifestation of cutaneous chronic GVHD, a low prevalence sign, which recognition could help to suspect this severe compli cation. CASE REPORT: 8 years old male, diagnosed with acute lymphoblastic leukemia (ALL) at 3 years old, had a combined medullary and central nervous system (NCS) relapse with minimal positive disease 3 years afterwards. After 4 years ALL was diagnosed, he received an allogeneic bone marrow transplant. Seven months after the BMT he presented multiple melanocytic nevi with peripheral hypopigmentation, and some isolated asymptomatic, confluent achromic macules on the face, trunk and limbs. The skin biopsy was compatible with chronic vitiligo and sclerodermiform type GVHD. He received topical treatment with Tacrolimus, achieving clinical stabilization. CONCLUSIONS: GVHD leads to the appearance of autoantibodies that could act as a trigger in the onset of autoimmune diseases, such as vitiligo. Consequently it could explain this poorly described manifestation in the literature of chronic cutaneous GVHD.

Enfermedad injerto contra huésped cutánea crónica tipo vitiligo. Caso clínico / Vitiligo type cutaneous manifestation of chronic graft-versus-host disease. Case report

Resumen: Introducción: La enfermedad injerto contra huésped (EICH) se produce por una respuesta patoló gica y destructiva del organismo, como resultado de la interacción entre linfocitos T inmunocompetentes del donante y los antígenos del tejido receptor. Se considera la complicación más grave del trasplante de células madres hematopoyéticas, descrito con mayor frecuencia posterior al trasplante de médula ósea (TMO). La piel suele ser el primer órgano y el más comúnmente afectado, tanto en su forma aguda como crónica, con un espectro clínico de presentación variable. Objetivo: Reportar un caso de vitiligo como manifestación de EICH cutánea crónica, signo de baja prevalencia, cuyo reconocimiento podría ayudar a la sospecha de esta grave complicación. Caso clínico: Escolar de sexo masculino de 8 años de edad, con antecedente de leucemia linfoblástica aguda (LLA) diagnosticada a los 3 años de edad, con recaída combinada medular y del sistema nervioso central (SNC) con enfer medad mínima positiva en los 3 años siguientes. Cuatro años posterior al diagnóstico de LLA, recibió TMO alogénico y siete meses después presentó múltiples nevos melanocíticos con hipopigmentación perilesional y máculas acrómicas en cara, tronco y extremidades, asintomáticas. La biopsia de piel fue compatible con EICH crónica tipo vitiligo y esclerodermiforme. Recibió tratamiento tópico con Tacrolimus, logrando estabilización del cuadro. Conclusiones: La EICH conlleva a la aparición de autoanticuerpos que podrían actuar como un factor desencadenante en la aparición de enfermedades autoinmunes, como lo es el vitiligo. En consecuencia podría explicar esta manifestación, poco descri ta en la literatura, de la EICH cutánea crónica.

Abstract: Introduction: Graft-versus-host disease (GVHD) is caused by a pathologic and destructive response of the organism as a result of the interaction between donor immunocompetent T lymphocytes and the recipient tisular antigens. It's considered the most serious complication of hematopoietic stem cell transplantation, most frequently described after bone marrow transplantation (BMT). The skin is usually the first and most commonly affected organ, in both acute and chronic, with a variable clinical spectrum of presentation. Objective: To report a case of vitiligo as a manifestation of cutaneous chronic GVHD, a low prevalence sign, which recognition could help to suspect this severe compli cation. Case report: 8 years old male, diagnosed with acute lymphoblastic leukemia (ALL) at 3 years old, had a combined medullary and central nervous system (NCS) relapse with minimal positive disease 3 years afterwards. After 4 years ALL was diagnosed, he received an allogeneic bone marrow transplant. Seven months after the BMT he presented multiple melanocytic nevi with peripheral hypopigmentation, and some isolated asymptomatic, confluent achromic macules on the face, trunk and limbs. The skin biopsy was compatible with chronic vitiligo and sclerodermiform type GVHD. He received topical treatment with Tacrolimus, achieving clinical stabilization. Conclusions: GVHD leads to the appearance of autoantibodies that could act as a trigger in the onset of autoimmune diseases, such as vitiligo. Consequently it could explain this poorly described manifestation in the literature of chronic cutaneous GVHD.

Enfermedad injerto contra huesped: sus manifestaciones bucales / Graft-versus-host disease: its oral manifestations

La enfermedad injerto contra huésped es la principal complicación que sufren los pacientes que han recibido trasplante alogénico. Se produce como consecuencia de una reacción inflamatoria exagerada mediada por los linfocitos del donante y estimulada por aquellos tejidos que han sido lesionados por la enfermedad de base, por las infecciones previas o por el tratamiento de acondicionamiento. El diagnóstico es clínico e histopatológico. Los pacientes presentan rash maculopapular pruriginoso y doloroso que puede extenderse por toda la superficie corporal, fiebre, vómito, náuseas, diarrea y anorexia. En la mucosa bucal se observan erosiones ulceradas, extremamente dolorosas y pueden ser la primera o la única manifestación detectable clínicamente de esta enfermedad. El objetivo es presentar un caso de enfermedad de injerto contra huésped. Se trata de una mujer de 54 años de edad con linfoma no-Hodgking, que recibió tratamiento con quimioterapia, radioterapia y trasplante de células madre hematopoyéticas en el 2009. Tres meses después, presentó lesiones en la piel diagnosticadas como enfermedad injerto contra huésped y tratadas con corticoesteroides, a los seis meses fue remitida al odontólogo porque se quejaba de ardor en la boca, xerostomía y dificultad para masticar, tenía úlceras en la mucosa bucal y en la lengua. En la ocasión recibió tratamiento con corticoesteroides, clorhexidina, orientaciones de higiene bucal y controles clínicos permanentes. Aunque existen protocolos para la prevención y el tratamiento de la enfermedad injerto contra el huésped, su frecuencia ha aumentado en los últimos años debido al incremento en el número de trasplantes. Por esta razón, es fundamental que el odontólogo forme parte del grupo multidisciplinario que asiste al paciente y que esté familiarizado con los signos y síntomas de esta enfermedad en la mucosa bucal, pues las manifestaciones clínicas pueden ser las únicas para realizar el diagnóstico(AU)

Graft-versus-host disease is the main complication following an allogeneic tissue transplant. It is caused by an exaggerated inflammatory reaction mediated by donor lymphocytes and stimulated by tissues lesioned by the underlying disease, by previous infection or by the conditioning treatment. The diagnosis is clinical and histopathological. Patients have itchy and painful maculopapular rash that can spread throughout the entire body surface, fever, vomiting, nausea, diarrhea and anorexia. Extremely painful ulcerated erosions occur in the oral mucosa, which may be the first or the only clinically detectable manifestation of the disease. The objective is to report a case of graft-versus-host disease. A 54 year-old woman with non-Hodgkin lymphoma was treated with chemotherapy, radiation therapy and hematopoietic cell transplantation in 2009. After three months, she presented skin lesions diagnosed as graft-versus-host disease and received corticosteroids. Six months later, she was referred to the dentist because of complaints of xerostomia, a burning sensation in her mouth and difficulty chewing. She also had ulcers in the oral mucosa and tongue. This time she received topical corticosteroid therapy, chlorhexidine, oral hygiene instructions and permanent clinical control. Despite some protocols for the prevention and treatment of graft-versus-host disease, its frequency has recently risen due to the increasing number of transplants. For this reason, it is essential for the dentist to be part of the multidisciplinary team treating the patient, and familiar with the signs and symptoms of the disease, since clinical manifestations may be the only ones at hand to make the diagnosis(AU)

Clinical and histological study of permanent alopecia after bone marrow transplantation

Abstract: BACKGROUND: Permanent alopecia after bone marrow transplantation is rare, but more and more cases have been described, typically involving high doses of chemotherapeutic agents used in the conditioning regimen for the transplant. Busulfan, classically described in cases of irreversible alopecia, remains associated in recent cases. The pathogenesis involved in hair loss is not clear and there are few studies available. In addition to chemotherapeutic agents, another factor that has been implicated as a cause is chronic graft-versus-host disease. However, there are no histopathological criteria for defining this diagnosis yet. OBJECTIVE: the study aims to evaluate clinical and histological aspects in cases of permanent alopecia after bone marrow transplantation, identifying features of permanent alopecia induced by myeloablative chemotherapy and alopecia as a manifestation of chronic graft-versus-host disease. METHODS: data were collected from medical records of 7 patients, with description of the clinical features and review of slides and paraffin blocks of biopsies. RESULTS: Two distinct histological patterns were found: one similar to androgenetic alopecia, non-scarring pattern, and other similar to lichen planopilaris, scarring alopecia. CONCLUSION: The first pattern corroborates the literature cases of permanent alopecia induced by chemotherapeutic agents, and the second is compatible with manifestation of chronic graft-versus-host disease on scalp, that has never been described yet. The results contribute to the elucidation of the factors involved in these cases, including the development of therapeutic methods.

cGVHD-Related Caries and Its Shared Features with Other 'Dry-Mouth'-Related Caries.

Several systemic diseases and their medical treatment may predispose the development of aggressive dental caries. Head and neck radiotherapy, chemotherapy, Sjögren's syndrome and long-standing treatment with drugs that induce hyposalivation are some of these conditions. The aim of this article is to describe the clinical features of five patients who developed chronic graft-versus-host-disease (cGVHD) as a complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and, in spite of close dental follow-up, subsequently developed rampant caries. In these cases, the restorations showed early failure and the caries still progressed until generalized teeth destruction. The majority of the teeth therefore had to be extracted due to advanced dental caries and rapid clinical progression. Herein the term "cGVHD-related caries" is proposed to describe this under-recognized complication of cancer treatment that may evolve in allo-HSCT recipients that develop cGVHD. This condition is poorly recognized in the literature and may represent the final result of the clustering of oral complications in cGVHD patients, including mucositis, oral pain, hyposalivation, taste loss and oral infections, leading to rampant caries due to impaired oral hygiene and increased intake of highly cariogenic food. Consequently, the knowledge of this oral complication should improve the medical and dental management of cGVHD oral manifestations and improve the quality of life of patients with this post allo-HSCT complication.

cGVHD-Related Caries and Its Shared Features with Other 'Dry-Mouth'-Related Caries

Several systemic diseases and their medical treatment may predispose the development of aggressive dental caries. Head and neck radiotherapy, chemotherapy, Sjögren's syndrome and long-standing treatment with drugs that induce hyposalivation are some of these conditions. The aim of this article is to describe the clinical features of five patients who developed chronic graft-versus-host-disease (cGVHD) as a complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and, in spite of close dental follow-up, subsequently developed rampant caries. In these cases, the restorations showed early failure and the caries still progressed until generalized teeth destruction. The majority of the teeth therefore had to be extracted due to advanced dental caries and rapid clinical progression. Herein the term "cGVHD-related caries" is proposed to describe this under-recognized complication of cancer treatment that may evolve in allo-HSCT recipients that develop cGVHD. This condition is poorly recognized in the literature and may represent the final result of the clustering of oral complications in cGVHD patients, including mucositis, oral pain, hyposalivation, taste loss and oral infections, leading to rampant caries due to impaired oral hygiene and increased intake of highly cariogenic food. Consequently, the knowledge of this oral complication should improve the medical and dental management of cGVHD oral manifestations and improve the quality of life of patients with this post allo-HSCT complication.

Diversas doenças sistêmicas e seus tratamentos podem predispor ao desenvolvimento de cáries dentárias agressivas. A radioterapia de cabeça e pescoço, quimioterapia, síndrome de Sjögren e tratamentos prolongados com as drogas que induzem a hipossalivação são algumas destas condições. O objetivo deste artigo é descrever as características clínicas de cinco pacientes que desenvolveram doença do enxerto contra hospedeiro crônica (DECHc) como uma complicação do transplante alogênico de células-tronco hematopoiéticas (aloTCTH) e, apesar do acompanhamento periódico com dentistas, desenvolveram cáries rampantes. Nestes casos relatados, as restaurações mostraram falhas precoces e as cáries continuaram progredindo até a destruição generalizada dos dentes. A maioria dos dentes, portanto, foi extraída devido à cárie avançada e rápida progressão clínica. Neste artigo, o termo "cáries relacionadas à DECHc" é proposto para descrever esta complicação pouco conhecida do tratamento do câncer, que se manifesta em receptores de TCTH que desenvolvem DECHc. Esta condição é pouco reconhecida na literatura e pode representar o resultado final do agrupamento das complicações bucais em pacientes com DECHc, incluindo mucosite, dor oral, hipossalivação, perda de paladar e infecções orais, levando à cárie rampante devido à dificuldade de higiene oral e aumento da ingestão de alimentos altamente cariogênicos. Por consequência, o conhecimento desta complicação oral deve melhorar os tratamentos médico e odontológico das manifestações bucais da DECHc e melhorar a qualidade de vida dos pacientes com esta complicação após o TCTH.