Medicamentos según riesgo de desencadenar crisis en pacientes con porfirias agudas / Drugs according to risk of to unchain crisis in patients with acute porphyries

Las variedades agudas de porfirias suelen presentar episodios conocidos como crisis agudas, que pueden ser muy graves y aún fatales. La causa desencadenante más frecuente de estas crisis es el consumo de ciertos medicamentos. Así como algunos fármacos están identificados como productores de estas crisis, otros no tienen ese riesgo. Se puede así distinguir medicamentos sin peligro o "seguros", otros que conllevan el riesgo de desencadenar crisis o "no seguros" y otros en que la información es contradictoria. Esta publicación tiene por objeto facilitar, tanto a pacientes como a médicos tratantes, el listado de principios activos, incluyendo los fármacos que los contienen, ordenados según sean "seguros", "no seguros" y con "información contradictoria" y clasificados según acción farmacológica. A fin de facilitar aún más la selección de medicamentos a usar, se incorpora una segunda lista de productos farmacéuticos que se expenden en el mercado chileno, ordenados también según su riesgo de producir crisis agudas. El mercado de medicamentos es muy dinámico, constantemente están incorporándose nuevos y retirando otros que se dejan de usar, por lo que nuestra Unidad mantiene actualizadas estas listas en nuestra página Web (http://porfiria.med.uchile.cl)

[Hepatitis C virus and resulting diseases]. / El virus C de la hepatitis y las enfermedades que produce.

In 1989, the main agent causing non A non B hepatitis was identified as a RNA virus of the flavivirus family, with several serotypes, and was denominated virus C. At the present moment, the knowledge about the infection features and diseases that it causes has expanded thanks to the availability of reliable laboratory techniques to detect the antibody and the virus. The prevalence of infection and the frequency of serotypes varies in different regions of the world. Chile is a country with a low prevalence. The detection of infected blood in blood banks has reduced the spreading of the disease. Other means of infection such as the use of intravenous drugs, hemodialysis and transplantation have acquired greater importance. Sexual, maternal and familial transmission is exceptional. Infected people develop an acute hepatitis, generally asymptomatic. Eighty percent remain with a chronic hepatic disease, that can be mild or progressive, evolving to cirrhosis or hepatic carcinoma. Chronic hepatitis, closely resembling an autoimmune disease, can be caused by the virus. Alcohol intake increases viral activity causing severe hepatic diseases, refractory to treatments. Several non hepatic diseases are associated to hepatitis C virus infection such as essential mixed cryoglobulinemia, mesangiocapillary glomerulonephritis, porphyria cutanea tarda, dysglobulinemias and probably type 2 diabetes mellitus. The only available treatment is interferon, that is successful in a minority of patients, frequently causing a transient improvement. The use of Ribaravine associated to interferon improve the effectiveness of therapy. Liver transplantation is the only therapy for severe hepatic disease. The use of new antiviral drugs should improve the prognosis of the disease.

[Acquired characteristics of porphyria cutanea tarda in patients infected with hepatitis C virus]. / Carácter adquirido de la porfiria cutánea tarda en pacientes infectados con virus C de la hepatitis.

BACKGROUND: Porphyria cutanea tarda (PCT) is due to a partial defect of hepatic uroporphyrinogen decarboxylase (URO-D). In the hereditary form, both hepatic and erythrocytic enzymes are altered, whereas in the acquired form, only the hepatic enzyme fails. There is a high prevalence of hepatitis C virus infection in patients with PCT, specially in those without family history of the disease. AIM: To study erythrocytic URO-D activity in order to find out whether hepatitis C virus infection is associated to the acquired form of PCT or unveils an inactive hereditary form. PATIENTS AND METHODS: URO-D activity was measured in red blood cells of normal controls, hepatitis C virus carriers without symptoms of PCT and patients with PCT, with and without family history of the disease, with and without anti hepatitis C virus antibodies. RESULTS: URO-D activity was similar in normal controls, patients with chronic liver disease associated to hepatitis C virus, and in patients with PCT without family history of the disease with and without hepatitis C virus antibodies. URO-D activity was lower in patients with PCT and family history of the disease, with and without hepatitis C virus antibodies. CONCLUSIONS: PCT in patients with hepatitis C virus infection is due to an acquired alteration of hepatic URO-D. Hepatitis C virus does not modify erythrocytic URO-D.

Genotipo del virus C de la hepatitis en pacientes con porfiria cutanea tarda / Genotype of the hepatitis virus C in patients with porphyria cutanea tarda

En pacientes con porfiria cutánea tarda (PCT) se ha demostrado alta prevalencia del anticuerpo del virus C de la hepatitis (anti-VCH) y del propio virus. Previamente hemos informado una prevalencia de anti-VCH de 53 por ciento, y de 80 por ciento entre aquellos pacientes con PCT esporádica. La PCT se asocia frecuentemente a daño hepático crónico,desconociéndose su origen. Se ha postulado que el VCH, directa o imdirectamente, modificaría la actividad de la uroporfirinógeno decarboxilasa(URO-D) hepática, alteración carterística de la PCT, y por lo tanto la enfermedad sería adquirida y no genética. Podría esperarse que la frecuencia e intensidad de la hepatopatías en los pacientes con PCT fuera mayor en aquellos pacientes portadores del Anti-VCH

Genotipo del virus C de la hepatitis en pacientes con porfiria cutanea tarda / Genotype of the hepatitis virus C in patients with porphyria cutanea tarda

En pacientes con porfiria cutánea tarda (PCT) se ha demostrado alta prevalencia del anticuerpo del virus C de la hepatitis (anti-VCH) y del propio virus. Previamente hemos informado una prevalencia de anti-VCH de 53 por ciento, y de 80 por ciento entre aquellos pacientes con PCT esporádica. La PCT se asocia frecuentemente a daño hepático crónico,desconociéndose su origen. Se ha postulado que el VCH, directa o imdirectamente, modificaría la actividad de la uroporfirinógeno decarboxilasa(URO-D) hepática, alteración carterística de la PCT, y por lo tanto la enfermedad sería adquirida y no genética. Podría esperarse que la frecuencia e intensidad de la hepatopatías en los pacientes con PCT fuera mayor en aquellos pacientes portadores del Anti-VCH(AU)

[Porphyrin excretion in patients with chronic hepatitis C virus infection]. / Excreción de porfirinas e infección crónica por virus C de la hepatitis.

BACKGROUND: The high prevalence of chronic hepatitis C virus infection in patients with porphyria cutanea tarda, specially in those without family history of the disease, suggests that this could be an acquired disease and one of the most frequent extra hepatic manifestations of hepatitis C virus infection. AIM: To study the excretion of porphyrins and its precursors in cirrhotic patients with and without hepatitis C virus infection. PATIENTS AND METHODS: Eighteen patients with cirrhosis Child-Pough A, eight infected with hepatitis C virus, were studied. Urinary excretion of [symbol see text] aminolevulinic acid, porphobilinogen, coproporphyrins, uroporphyrins and fecal excretion of coproporphyrins and protoporphyrins were measured. Red blood cell protoporphyrin was also measured. RESULTS: There were no differences in the measured parameters between patients with or without hepatitis C virus infection. No patient had uroporphyrin excretion values over the normal range. Some patients had slight elevations in some parameters, but always below the values observed in porphyrias. CONCLUSIONS: In these group of patients, hepatitis C virus infection of its associated liver disease, do not cause detectable alterations in porphyrin metabolism.

[Treatment of porphyria cutanea tarda with chloroquine and its effect on associated liver disease: retrospective analysis]. / Tratamiento de la porfiria cutánea tarda con cloroquina y su efecto sobre la hepatopatía asociada: análisis retrospectivo.

BACKGROUND: Chloroquine may improve cutaneous symptoms and liver disease manifestations in patients with porphyria cutanea tarda. AIM: To retrospectively analyze the effects of choloroquine in patients with porphyria cutanea tarda. PATIENTS AND METHODS: Five patients (one female), aged 45 to 65 years old, were studied. The duration of the disease ranged from 2 to 15 years. One patient was alcoholic and other was a hepatitis C virus carrier. All patients received chloroquine 125 mg twice weekly. Before, during and after treatment, cutaneous signs, serum bilirubin, hepatic enzymes and urine copro and uroporphyrin were assessed. Four patients were subjected to a liver biopsy before starting chloroquine. RESULTS: All patients had increased levels of urine porphyrins, four had abnormal serum liver enzymes. All liver biopsies showed variable hemosiderosis, two patients had a chronic active hepatitis (one with cirrhosis), one a chronic persistent hepatitis and one had mild rague alterations. During chloroquine treatment, cutaneous symptoms improved in all patients, transaminases and gamma glutamyl transferase decreased. In three, urine uroporphyrin increased initially and normalized afterwards. Choloroquine was well tolerated. CONCLUSIONS: Chloroquine improved cutaneous symptoms, urine uroporphyrin and serum liver enzyme levels in treated patients.

Tratamiento de la porfiria cutánea tarda con cloroquina y su efecto sobre la hepatopatía asociada: análisis retrospectivo / Porphyria cutanea tarda treatment with chloroquine and it effect on associated hepatopathy: retrospective analysis

Chloroquine may improve cutaneous symptoms and liver disease manifestations in patients with porphyria cutanea tarda. To retrospectively analyze the effects of chloroquine in patients with porphyria cutanea tarda. Five patients (1 female), aged 45 to 65 years old, were studied. The duration of the disease ranged from 2 to 15 years. All patients received chloroquine 125 mg twice weekly. Before, during and after treatment, cutaneous signs, serum bilirubin, hepatic enzymes and urine copro and uroporphyrin were assessed. Four patients were subjected to a liver biopsy before starting chloroquine. All patients had increased levels of urine porphyrins, four had abnormal serum liver enzymes. All liver biopsies showed variable hemosiderosis, 2 patients had a chronic active hepatitis (1 with cirrhosis), one a chronic persistent hepatitis and one had a mild vague alterations. During chloroquine treatment, cutaneous symptoms improved in all patients, transaminases and gamma glutamyl transferase decreased. In 3, urine uroporphyrin increased initially and normalized afterwards. Chloroquine was well tolerated. Chloroquine improved symptoms, urine uroporphyrins and serum liver enzyme levels in treated patients

[Hepatitis C virus infection in patients with porphyria]. / Infección por virus C de la hepatitis en pacientes con porfiria.

Hepatitis C virus antibodies were studied in sera coming from 39 patients with porphyria (cutanea tarda in 17, variegate in 8, intermittent acute in 4, coproporphyria in 2 and protoporphyria in 8). Nine of 17 patients with porphyria cutanea tarda had positive antibodies, but none of the patients with other types of porphyria. All subjects with porphyria cutanea tarda had histological or laboratory liver abnormalities. There was no relationship between the presence of antibodies and frequency of alcoholism, diabetes, or carbohydrate intolerance. Family background of porphyria was significantly less frequent among patients with positive hepatitis C virus antibodies. In 13 patients, a liver biopsy was performed, always showing signs of chronic hepatitis, whose magnitude was higher in those with positive antibodies. It is concluded that, as reported previously, hepatitis C virus may be an activating factor for porphyria cutanea tarda or may potentiate its accompanying liver disease.

[Drugs and porphyric crisis]. / Fármacos y crisis porfírica.

Life threatening crisis may accompany some varieties of porphyria like the acute intermittent form, coproporphyria, porphyria variegata and that associated to deficiency of porphobilinogen synthetase. Drugs are commonly involved as precipitating factors. A classification of drugs according to their proven or probable triggering effect is offered in this paper. Insufficient information precludes the classification of some drugs.

[The hepatic porphyrias: experience with 105 cases]. / Las porfirias hepáticas: experiencia con 105 casos.

Hepatic porphyria is a rare metabolic syndrome caused by abnormal enzyme activity in heme biosynthesis. Between 1974 and 1991; 105 patients have met criteria for diagnosis of hepatic porphyria based on typical clinical findings and/or laboratory abnormalities. According to type, 42% had porphyria cutanea tarda, 21% porphyria variegate, 15% protoporphyria, 6.7% acute intermittent porphyria, 6.7% coproporphyria and 1.9% porphyria due to porphobilinogen deficit. A proper classification was not established in 6.7% of patients. Porphyria cutanea tarda was more common in males (70%) and porphyria variegata, in females (90%). A family history of the disease was present in 33% of patients; 20% of patients were of European descent and 4% of Mapuche descent. Diagnosis was usually established in the third decade, somewhat later in porphyria cutanea tarda (45 years of age) and very early in protoporphyria. 10% of patients were asymptomatic and 29 patients developed at least one porphyric crisis. These were related to pregnancy in 6 patients, to hormone administration in 7, to antibiotics in 5. No cause was established in 21 cases. Severe crisis were successfully treated with Hematin. Venipuncture was used to treat 50% of patients with porphyria cutanea tarda with 95% success. Thus, hepatic porphyria is recognized with increasing frequency and can be treated successfully in most cases.

[One hour xylose test blood in the diagnosis of celiac disease]. / Prueba de xilosa sanguinea en una hora en el diagnóstico de enfermedad celiaca.

Plasma levels of d-xylose one hr after a standard 5 g oral dose were measured in 82 children suspected of having celiac disease. Duodenal mucosa was obtained by intestinal biopsy in all. Among patients with normal mucosa, 95% had xylose levels above 20 mg/dl; 100% of patients with a flat mucosa had levels under 20 mg/dl. Results were independent of patients age. We conclude that this is a reliable test to screen patients suspected of having celiac disease, prior to intestinal biopsy.

Porfirias hepáticas / Hepatic porphyrias

Las porfirias hepáticas son afecciones metabólicas de baja prevalencia. Sin embargo, en Chile se ha ido conformando una casuística importante y creciente, en la medida que se ha divulgado el conocimiento y los recursos diagnósticos de estas afecciones. En nuestro país se han descrito casos de las 6 principales variedades de porfiria. La sintomatología de estas afecciones es abundante y multisistémica. Ella puede ser limitante de una vida normal e incluso invalidante y con compromiso estético si existe un componente cutáneo externo. En las variedades que se acompañan de crisis agudas puede haber amenaza de muerte si no se diagnostican y tratan oportuna y adecuadamente. Las variedades cutánea tarda y protoporfiria cursan frecuentemente con daño hepático y con notable gravedad. El diagnóstico de porfiria se sospecha clínicamente , pero por la inespecificidad de de sus síntomas y signos bebe confirmarse con los correspondientes exámenes de laboratorio. Los pacientes portadores de porfiria pueden excretar cantidades normales de porfirias o de sus precursores, pero raramente de todas ellas. En ocaciones, un paciente en estado de su enfermedad puede tener secreción normal de todas las porfirias y precursores. Por otra parte, es posible observar hiperporfirinuria en afecciones distintas de las prorfirias. Medidas preventivas y terapias simples pero oportunas pueden aliviar los síntomas y evitar la muerte. Entre estas es posible destacar la sobrecarga de hidratos de carbono y la infusión de hematina en las crisis agudas y la práctica de sangrías o la administración de cloroquina en las formas con compromiso cutáneo

Valor diagnostico de las pruebas de laboratorio en los sindromes de malabsorcion. / Diagnostic value of laboratory tests in malabsorption syndromes

Se analizan los resultados obtenidos en nuestro laboratorio para las determinaciones de carotinemia, absorcion de vitamina A y D-xilosa. En 102 determinaciones de carotinemia despues de una carga de 50.000 unidades de vitamina A por tres dias, se observa que el 96,7% de los casos con SMA presentan valores inferiores a lo normal (55 mcgr/100ml) sin presentar diferencias notorias de este porcentaje de absorcion entre celiacos (93,6%) y no celiacos (100%). En 94 determinaciones de porcentaje de absorcion a las 4 horas de una dosis de 300.000 unidades de vitamina A tras una carga de 50.000 unidades diarias por 3 dias, se observa que el 75% de los casos con SMA tienen valores inferiores a lo normal (5% de absorcion), existiendo una clara diferencia de esta deficiencia entre celiacos (89,3%) y no celiacos (60,7%). En 20 pruebas de absorcion de D-xilosa tras la administracion de 25 gr de esta pentosa en 250 ml de agua se observan valores plasmaticos inferiores al normal (20 mg%) en 38,9% de los casos con SMA y valores urinarios inferiores al normal (4 gr/5 horas) en 61,7% de los casos, existiendo una diferencia notoria entre celiacos (87,7%) y no celiacos (45,5%)