[Suspected vascular ehlers danlos syndrome. Case report]. / Sospecha diagnóstica de síndrome de Ehlers Danlos tipo vascular: reporte de un caso y revisión de literatura.

Ehlers Danlos Syndrome comprises a heterogeneous group of genetic disorders of the connective tissue, due to defects in collagen or its modifying enzymes. We report a 21 years old male presenting with translucent skin revealing the subcutaneous venous pattern. He had a thin face, large-appearing eyes, thin lips, thin nose, joint hypermotility and history of hip dysplasia. A vascular Ehlers Danlos Syndrome was suspected. However, the genetic study to confirm the diagnosis was not done.

[Effect of copper sulphate on the lung damage induced by chronic intermittent exposure to ozone]. / Efecto del sulfato de cobre en el daño pulmonar inducido por la exposición crónica intermitente a ozono.

BACKGROUND: Ozone exposure could increase lung damage induced by airborne particulate matter. Particulate matter lung toxicity has been attributed to its metallic content. AIM: To evaluate the acute effect of intratracheal administration of copper sulfate (CuSO4) on rat lungs previously damaged by a chronic intermittent ozone exposure. MATERIAL AND METHODS: Two-months-old male Sprague-Dawley rats were exposed to 0.5 ppm ozone four h per day, five days a week, during two months. CuSO4 was intratracheally instilled 20 h after ozone exposure. Controls breathed filtered air or were instilled with 0.9% NaCl or with CuSO4 or were only exposed to ozone. We evaluated lung histopathology. F2 isoprostanes were determined in plasma. Cell count, total proteins, γ glutamyl-transpeptidase (GGT) and alkaline phosphatases (AP) were determined in bronchoalveolar lavage fluid (BALF). RESULTS: Ozone increased total cell count, macrophages, proteins and AP in BALF (p < 0.05), and induced pulmonary neutrophil inflammation. CuSO4 plus air increased plasma F2 isoprostane levels and total cell count, neutrophils and proteins in BALF (p < 0.05). Histopathology showed foamy macrophages. Ozone plus CuSO4 exposed animals showed a neutrophil inflammatory lung response and an increase in total cell count, proteins, GGT and AP in BALF (p < 0.05). Foamy and pigmented alveolar macrophages were detected in all lungs of these animals (p < 0.001). CONCLUSIONS: Intratracheal instillation of a single dose of CuSO4 in rats previously subjected to a chronic and intermittent exposure to ozone induces a neutrophil pulmonary inflammatory response and cytoplasmic damage in macrophages.

[Detection of HTLV-1 DNA in biopsies of Chilean patients with cutaneous T-cell lymphoma]. / Búsqueda del ADN del virus HTLV-1 en biopsias de pacientes con linfoma cutáneo de células T.

BACKGROUND: Human T-lymphotropic virus-1 (HTLV-1) infection has been associated with the pathogenesis of cutaneous T cell lymphomas (CTCL). AIM: To search for HTLV-1 DNA in skin biopsies of patients with CTCL. MATERIAL AND METHODS: A retrospective study was conducted using 25 biopsies of patients with CTCL. DNA was extracted from lymphoid tissue by microdissection. A nested PCR was conducted to detect HTLV-1 genome using primers for the tax region. As negative controls, four cases of superficial perivascular dermatitis were chosen. As positive controls, five cases of T-cell leukemia/lymphoma (ATCL) were studied. RESULTS: A positive reaction was found in 3 of 25 cases. These biopsies corresponded to a case of Mycosis Fungoides, a case of CD30 (-) T-cell lymphoma and a case of lymphomatoid papulosis. Search was negative in the four cases of superficial perivascular dermatitis and positive in four cases of adult T-cell leukemia/lymphoma (ATCL). CONCLUSIONS: HTLV-1 DNA search in tissues is a useful tool recommended to study T-cell lymphomas. HTLV-1 infection only occurs in sporadic cases but may contribute to tumor aggressiveness and prognosis.

[AA amyloidosis with cutaneous manifestations. Report of one case]. / Manifestaciones cutáneas de amiloidosis sistémica como clave diagnóstica. Caso clínico.

BACKGROUND: Systemic amyloidosis is a rare disease that can affect any organ. Its clinical manifestations are varied and nonspecific. The skin involvement of this disease is common and can be easily recognized on physical examination. We report a 57-year-old male presenting with a two years history of malaise, dyspnea and myalgias. On physical examination, ungueal dystrophy, orange pigmentation of eyelids with periocular petechiae and mild macroglossia were observed. Incisional biopsies of the eyelids, cheeks and hands were obtained. The pathological study demonstrated amyloid deposits. Since protein electrophoresis was normal, the diagnosis of AA amyloidosis was postulated.

[Sweet's syndrome associated with acute myeloid leukemia. Report of one case]. / Síndrome de Sweet asociado a leucemia mieloide aguda y factor estimulante de colonias de granulocitos. Caso clínico.

Sweet's syndrome, also known as acute febrile neutrophilic dermatosis, is characterized by fever, neutrophilia, erythematous and tender skin lesions that typically show a diffuse infiltrate of neutrophils in the upper dermis. This disorder has been associated with myeloproliferative syndromes. We report the case of a 53-year-old woman with an acute myeloid leukemia, presenting a Sweet's syndrome. A worsening of cutaneous lesions injuries was observed when granulocyte colony stimulating factor was added to treatment.

[Bronchiolar disorders: clinical-radiological assessment and classification]. / Evaluación clínico-radiológica y clasificación de la bronquiolitis del adulto.

Bronchiolar disorders are generally difficult to diagnose. A detailed clinical history may point toward a specific diagnosis. Pertinent clinical questions include history of smoking, collagen vascular disease, inhalation injury, medication use and organ transplantation. It is important also to evaluate possible systemic and pulmonary signs of infection, evidence of air trapping, and high-pitched expiratory wheezing, which may suggest small airways involvement. Pulmonary function tests and plain chest radiography may demonstrate abnormalities; however, they rarely prove sufficiently specific to obviate bronchoscopic or surgical biopsy. High-resolution CT (HRCT) scanning of the chest is often an important diagnostic tool to guide diagnosis in these difficult cases, because different subtypes of bronchiolar disorders may present with characteristic image findings. Some histopathologic patterns of bronchiolar disease may be relatively unique to a specific clinical context but others are nonspecific with respect to either etiology or pathogenesis. Primary bronchiolar disorders include acute bronchiolitis, respiratory bronchiolitis, follicular bronchiolitis, mineral dust airway disease, constrictive bronchiolitis, diffuse panbronchiolitis, and other rare variants. Prominent bronchiolar involvement may be seen in several interstitial lung diseases, including hypersensitivity pneumonitis, collagen vascular disease, respiratory bronchiolitis-associated interstitial lung disease, cryptogenic organizing pneumonia, and pulmonary Langerhans' cell histiocytosis. Large airway diseases that commonly involve bronchioles include bronchiectasis, asthma, and chronic obstructive pulmonary disease. The clinical and prognostic significance of a bronchiolar lesion is best determined by identifying the etiology, underlying histopathologic pattern and assessing the correlative clinic-physiologic-radiologic context.

[Combined periampullary adenocarcinoma and neuroendocrine tumor in type 1 neurofibromatosis: report of one case]. / Carcinoma mixto adenocarcinoma y neuroendocrino periampular en un paciente con neurofibromatosis tipo 1: Caso clínico.

Neurofibromatosis is a hereditary autosomal-dominant disease with high rates of de novo mutations, and carries a high risk of neoplasms. It affects both sexes and all races and ethnic groups. It is characterized by multiple cutaneous lesions and tumors, both benign and malignant, especially in the nervous system. We report a 52-year-old woman with a type 1 neurofibromatosis, presenting with fever, jaundice and weight loss. On physical examination, the patient was jaundiced and had "café au lait" spots in the skin. A magnetic resonance imaging showed bile duct dilation and a possible ampullar carcinoma. The patient was operated, during the exploration she presented a periampullary tumor and multiple small nodular lesions in the stomach, the tumor was resected with a pancreaticoduodenectomy and the nodular gastric lesions were biopsied. The pathological study revealed a combined adenocarcinoma and neuroendocrine duodenal tumor. The study of the stomach lesions revealed a gastrointestinal stromal tumor. Four months after surgery, the patient is in good condition.

[Cutaneous tuberculosis: two case reports and review]. / Tuberculosis cutánea: reporte de dos casos y revisión de la literatura.

Cutaneous tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis. It is uncommon (1% of all cases of tuberculosis), but has increased due to the human immunodeficiency virus epidemic and to pharmacologic immunosuppression. It presents a wide variety of clinical forms depending on how bacteria reach the skin and on the immune status of the patient. We present two cases of cutaneous tuberculosis diagnosed in the Hospital Clínico de la Pontificia Universidad Católica de Chile. We emphasize the difficulty in diagnosis and classification of this disease and briefly discuss on the different diagnostic and therapeutic approaches.

Bullous systemic lupus erythematosus: An uncommon manifestation in pediatric population. / Lupus eritematoso sistémico buloso: Una manifestación infrecuente en población pediátrica.

INTRODUCTION: Bullous systemic lupus erythematosus (BSLE) is an autoimmune subepidermal blistering disease se condary to the presence of autoantibodies against type VII collagen of the basement membrane zone. It is considered a variant of Systemic Lupus Erythematosus (SLE) and is uncommon in the pediatric population. OBJECTIVE: To describe the case of a pediatric patient with a bullous eruption compati ble with BSLE. CLINICAL CASE: A 16-year-old female patient of Mapuche descent with history of SLE diagnosed at age 10, undergoing treatment. She consulted due to a six-week history of a generalized bullous eruption with no systemic symptoms. Biopsy for histology and direct immunofluorescence (DIF) confirmed the diagnosis of BSLE. The patient responded favorably to dapsone 100 mg/day (associated with her baseline treatment), without new reactivations after 8 years of follow-up. Con clusion: BSLE is an infrequent manifestation of SLE. The clinical presentation is similar to other bullous dermatoses, but the histopathology and DIF in correlation with the presence of SLE confirm the diagnosis. Although indigenous ancestry is associated with SLE high-risk alleles, studies regarding the association of BSLE in this ethnic group are still lacking.

[Hansen's disease: case report and review of literature]. / Enfermedad de Hansen: Revisión a propósito de un caso.

Leprosy is a granulomatous disease affecting the skin and peripheral nerves caused by Mycobacterium leprae. The range of clinical forms varying from tuberculoid to lepromatous leprosy results from variations in the cellular immune response to the mycobacterium. Despite available combined drug-therapy, it continues to be a significant public health problem, carrying a strong stigma. Although recently there has been no native cases in Chile, a few imported cases have been diagnosed. We present a 56-year-old man who had lived in Paraguay for 8 years, and presented with leprosy 6 years after returning to Chile. The biology of leprosy, clinical features of the disease, current diagnostic criteria and approaches to treatment are discussed.

[Granulomatous amoebic meningoencephalitis by Balamuthia mandrillaris: case report and literature review]. / Meningoencefalitis granulomatosa por Balamuthia mandrillaris: reporte de un caso y revisión de la literatura.

The free-living amebas Naegleria and Acanthamoeba are recognized as causal agents of central nervous system infections. Recently a third free-living ameba, Balamuthia mandrillaris, was identified as the causal agent of granulomatous encephalitis in humans. We report a case of Balamuthia encephalitis in an immunocompetent school-age girl who presented cutaneous lesions that compromised the central portion of the face. The skin biopsy revealed granulomatous lesion with positive PCR for non-tuberculous Mycobacterium. We started treatment for atypical extrapulmonary mycobacteriosis. Nevertheless, the child was readmitted six months later, with progressive neurological involvement, dying about one year after the onset of cutaneous symptoms. The brain necropsy showed the presence of B. mandrillaris cysts and trophozoites. Balamuthia mandrillaris infection should be considered in the differential diagnosis of a patient with chronic granulomatous disease with neurologic symptoms.

Sospecha diagnóstica de síndrome de Ehlers Danlos tipo vascular: reporte de un caso y revisión de literatura / Suspected vascular ehlers danlos syndrome: case report

Ehlers Danlos Syndrome comprises a heterogeneous group of genetic disorders of the connective tissue, due to defects in collagen or its modifying enzymes. We report a 21 years old male presenting with translucent skin revealing the subcutaneous venous pattern. He had a thin face, large-appearing eyes, thin lips, thin nose, joint hypermotility and history of hip dysplasia. A vascular Ehlers Danlos Syndrome was suspected. However, the genetic study to confirm the diagnosis was not done.

Efecto del sulfato de cobre en el daño pulmonar inducido por la exposición crónica intermitente a ozono / Effect of copper sulphate on the lung damage induced by chronic intermittent exposure to ozone

Background: Ozone exposure could increase lung damage induced by airborne particulate matter. Particulate matter lung toxicity has been attributed to its metallic content. Aim: To evaluate the acute effect of intratracheal administration of copper sulfate (CuSO4) on rat lungs previously damaged by a chronic intermittent ozone exposure. Material and Methods: Two-months-old male Sprague-Dawley rats were exposed to 0.5 ppm ozone four h per day, five days a week, during two months. CuSO4 was intratracheally instilled 20 h after ozone exposure. Controls breathed filtered air or were instilled with 0.9% NaCl or with CuSO4 or were only exposed to ozone. We evaluated lung histopathology. F2 isoprostanes were determined in plasma. Cell count, total proteins, γ glutamyl-transpeptidase (GGT) and alkaline phosphatases (AP) were determined in bronchoalveolar lavage fluid (BALF). Results: Ozone increased total cell count, macrophages, proteins and AP in BALF (p < 0.05), and induced pulmonary neutrophil inflammation. CuSO4 plus air increased plasma F2 isoprostane levels and total cell count, neutrophils and proteins in BALF (p < 0.05). Histopathology showed foamy macrophages. Ozone plus CuSO4 exposed animals showed a neutrophil inflammatory lung response and an increase in total cell count, proteins, GGT and AP in BALF (p < 0.05). Foamy and pigmented alveolar macrophages were detected in all lungs of these animals (p < 0.001). Conclusions: Intratracheal instillation of a single dose of CuSO4 in rats previously subjected to a chronic and intermittent exposure to ozone induces a neutrophil pulmonary inflammatory response and cytoplasmic damage in macrophages.

[Pilomatrixoma: unusual clinical presentation]. / Pilomatrixoma: una presentación clínica inusual.

Pilomatrixoma is a rare, benign neoplasm that is derived from hair matrix cells. It is more frequent during childhood, especially between the ages of 5 and 15 years. Pilomatrixoma is usually a hard, well circumscribed, solitary lesion, and can be located on any part of the body, except palms and soles, with a predilection for maxillofacial region. Multiple pilomatrixomas are rare and they have been associated with various systemic syndromes, of which myotonic dystrophy has been the most described. The diagnosis of pilomatrixoma is fundamentally clinical. Complementary studies such as ultrasound can be useful to confirm the diagnosis. Excisional surgery is the standard curative treatment. We present a 17-year-old female patient with an extremely uncommon clinical presentation of pilomatrixoma: multiple lesions, anetodermic, and rapid growth.

[Acquired reactive perforating collagenosis: report of two cases]. / Colagenosis perforante reactiva adquirida: Caso clínico.

Acquired reactive perforating collagenosis is a perforating dermatosis characterized by transepidermal elimination of collagen. It is frequently associated to diabetes mellitus and chronic renal insufficiency, but it is also related to other systemic diseases. The lesions tend to resolve once the underlying condition is treated. We report two patients with the condition. A 65 year-old diabetic female on hemodialysis consulted for multiple itching cutaneous ulcers lasting one year. On physical examination, hyperpigmented papules and nodules were observed. A 65 year-old female with chronic renal failure in hemodialysis consulted for itching lesions in hands, forearms and arms. On physical examination, hyperpigmented lesions with ulcers, erosions and crusts were observed. In both cases, the pathological study of the lesions disclosed a reactive perforating collagenosis.

Bap1 y neoplasias melanocíticas / Bap1 and melanocytic neoplasms

El melanoma maligno cutáneo (MMC) es un cáncer genéticamente heterogéneo, en cuya patogénesis participarían varios genes. Algunos de estos activan la vía MAP kinasa (BRAF, NRAS, KIT, NF1), mientras que otros confieren una mayor susceptibilidad a melanoma familiar, como CDKN2A, CDK4, MITF y BAP1. BAP1 (BRCA1-associated-protein 1) ha sido descrito como una proteína que se une a BRCA1 para inhibir el crecimiento celular. Actualmente se sabe que es producto de un gen supresor de tumores (denominado BAP1) y que actúa como una enzima con actividad deubiquitinasa, la cual se asocia a varios complejos de proteínas, regulando diversas vías celulares relacionadas con el ciclo celular, diferenciación y muerte celular, así como también gluconeogénesis y respuesta a daño del ADN. Tanto su actividad deubiquitinasa como su localización nuclear son relevantes para su función en la supresión de tumores.

Malignant cutaneous melanoma (MMC) is a genetically heterogeneous cancer and various genes participate in its pathogenesis. Some of these genes activate the MAP kinase pathway (BRAF, NRAS, KIT, NF1) and others are related to a higher susceptibility to familial melanoma like CDKN2A, CDK4, MITF y BAP1. BAP1 (BRCA1-associated –protein 1) has been described as a BRCA1-binding protein inhibiting cell growth. This protein is a product of a gene with tumor suppressor activity, the protein being a deubiquitinase associated to multiple protein complexes regulating various cellular pathways, including the cell cycle, differentiation and cell death, as well as gluconeogenesis and DNA damage response. Both deubiquitinase activity and location to the nucleus are relevant to its tumor suppressor function.

Liquen escleroso y atrófico: revisión de una dermatosis con múltiples manifestaciones / Lichen sclerosus and atrophic: review of a dermatosis with multiple manifestations

El liquen escleroso y atrófico (LEA) es una enfermedad inflamatoria crónica poco frecuente, de causa desconocida, con tendencia a la atrofia epidérmica y cicatrización destructiva. Predomina en mujeres, en la región anogenital, asociándose a un importante deterioro funcional y, en ocasiones, transformación maligna a carcinoma espinocelular. El tratamiento de elección es aún controvertido, siendo los corticoides tópicos de alta potencia y los inhibidores tópicos de la calcineurina los más utilizados. Se presentan cuatro casos clínicos de LEA; uno en una niña de 8 años, con una placa blanquecina atrófica localizada en tórax anterior; un segundo caso, un paciente de sexo masculino de 31 años con una placa blanquecina atrófica localizada en el glande, prepucio y cuerpo del pene; un tercer caso, un paciente de sexo masculino de 24 años con pápulas blanquecinas de 1 mm de diámetro, localizadas en el cuerpo del pene; y finalmente, una paciente de sexo femenino de 53 años con placas blanquecinas, atróficas e induradas en la axila derecha. Todos con hallazgos histopatológicos característicos que permitieron confirmar el diagnóstico de LEA. A partir de estos casos destacamos las diferentes localizaciones y edades de presentación que puede tener esta enfermedad junto con la importancia de un diagnóstico e inicio precoz del tratamiento. Esta revisión tiene como objetivo actualizar los conocimientos sobre los datos demográficos, clínicos, fisiopatológicos y terapéuticos en torno a LEA. Para ello, se realizó una búsqueda exhaustiva de la literatura utilizando los buscadores de PubMed y la Colaboración Cochrane. Resultados de la búsqueda incluyen bibliografía publicada hasta julio de 2014.

Lichen sclerosus et atrophicus (LSA) is an uncommon chronic inflammatory disease of unknown cause, prone to produce epidermal atrophy and destructive scarring. It predominates in women, in the anogenital region, usually associated with significant functional impairment and sometimes malignant transformation to squamous cell carcinoma (SCC). The treatment of choice is still controversial, with topical high potency steroids and topical calcineurin inhibitors being actually the most used. Four clinical cases are presented: one from an 8 year-old girl with a whitish atrophic plaque located on the chest; another is a male patient, aged 31, with a whitish atrophic plaque located on the glans, foreskin and body of the penis; a third case, 24 year-old male, with whitish papules of 1 mm in diameter located on the body of the penis and; finally, a female patient aged 53, with white atrophic and indurated plaques at the right axilla. All of them had characteristic histopathologic findings, confirming the diagnosis of LSA. From these cases we pretend to highlight the different locations and ages of presentation of LSA, and the importance of an early diagnosis and treatment. This review update the current understanding of the demographic, clinical, pathogenic and therapeutic data on LSA. For this, a comprehensive search of the literature was conducted using PubMed and Cochrane Library. Search results include published references until july 2014.

Granulomatosis eosinofílica con poliangeítis: reporte de caso yrevisión de la literatura / Eosinophilic granulomatosis with polyangiitis: case report and review of the literature

La granulomatosis eosinofílica con poliangeítis (Síndrome de Churg-Strauss) es una enfermedad vasculítica primaria poco frecuente. El diagnóstico actualmente se define a partir de la presencia de al menos cuatro de seis criterios propuestos por la Sociedad Americana de Reumatología, los cuales incluyen: asma bronquial, eosinofilia mayor que 10 por ciento, sinusitis paranasal, infiltración pulmonar, evidencia histológica de vasculitis y compromiso neurológico ya sea mono o polineuropático. En el presente artículo se reporta el caso de un paciente de 56 años con antecedentes de asma bronquial, rinitis alérgica y poliposis nasal operada, derivado a nuestro centro por cuadro de aumento de volumen doloroso en ambas extremidades inferiores, baja de peso, parestesias y debilidad muscular. Asociado a esto desarrolló lesiones purpúricas palpables cuya biopsia resultó compatible con granulomatosis eosinofílica con poliangeítis. El paciente posteriormente recibió tratamiento inmunosupresor con prednisona y un pulso de ciclofosfamida con buena respuesta clínica. Se presenta una revisión bibliográfica a propósito del caso.

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss Syndrome) is an uncommon primary vasculitis. The diagnosis is currently defined by the presence of at least four of six criteria proposed by the American College of Rheumatology, which include: asthma, eosinophilia less than 10 percent, paranasal sinusitis, pulmonary infiltration, histologic evidence of vasculitis and neurologic compromise as mono or polyneuropathy. In the present article, we report the case of a 56 year-old man with history of asthma, allergic rhinitis and operated nasal polyposis, referred to our center with painful bulking in both lower extremities, weight loss, paresthesias and muscle weakness. It also developed palpable purpura. Biopsy of skin lesions was compatible with eosinophilic granulomatosis with polyangiitis. The patient subsequently received immunosuppressive therapy with prednisone and a cyclophosphamide bolus with good clinical response. A review on the subject is also presented.

[Pulmonary and gastric sarcoidosis. Report of one case]. / Sarcoidosis pulmonar y gástrica. Caso clínico.

We report a 66 year-old woman with a history of pulmonary sarcoidosis, diagnosed with a lung biopsy in 1993 and treated with prednisone for 2 years. She presented at our institution in 1999 with a stage IV disease and important functional and clinical impairment. A bronchial biopsy disclosed non caseating granulomas. Tuberculosis was intensively studied and persistently negative. Due to frequent nausea and vomiting an endoscopic gastric biopsy was performed which revealed non caseating granulomas involving the gastric mucosa. There was no evidence of Helicobacter pylori and stains for fungi and acid-fast bacilli were negative. Treatment with prednisone relieved digestive symptoms, although a control biopsy of the gastric mucosa revealed persistence of non caseating granulomas. Both lung stage IV and gastric sarcoidosis are uncommon forms of the disease.

Búsqueda del ADN del virus HTLV-1 en biopsias de pacientes con linfoma cutáneo de células T / Detection of HTLV-1 DNA in biopsies of Chilean patients with cutaneous T-cell lymphoma

Background: Human T-lymphotropic virus-1 (HTLV-1) infection has been associated with the pathogenesis of cutaneous T cell lymphomas (CTCL). Aim: To search for HTLV-1 DNA in skin biopsies of patients with CTCL. Material and Methods: A retrospective study was conducted using 25 biopsies of patients with CTCL. DNA was extracted from lymphoid tissue by microdissection. A nested PCR was conducted to detect HTLV-1 genome using primers for the tax region. As negative controls, four cases of superficial perivascular dermatitis were chosen. As positive controls, five cases of T-cell leukemia/lymphoma (ATCL) were studied. Results: A positive reaction was found in 3 of 25 cases. These biopsies corresponded to a case of Mycosis Fungoides, a case of CD30 (-) T-cell lymphoma and a case of lymphomatoid papulosis. Search was negative in the four cases of superficial perivascular dermatitis and positive in four cases of adult T-cell leukemia/lymphoma (ATCL). Conclusions: HTLV-1 DNA search in tissues is a useful tool recommended to study T-cell lymphomas. HTLV-1 infection only occurs in sporadic cases but may contribute to tumor aggressiveness and prognosis.