Case for diagnosis. Sclerodermiform manifestations of porphyria cutanea tarda secondary to hepatitis C

Abstract: A 63-year-old black female patient with blisters and exulcerations on the face, neck, upper limbs, and subsequent evolution with hypochromic sclerotic areas and alopecia, is reported. Chronic hepatitis C and presence of high levels of porphyrins in urine were demonstrated. There was complete remission with the use of hydroxychloroquine, photoprotection, and treatment of hepatitis. Significant sclerodermoid involvement of the skin as a manifestation of porphyria cutanea tarda secondary to hepatitis C emphasizes the importance of diagnostic suspicion regarding skin manifestation in order to indicate the appropriate therapy, and to minimize the hepatic morbidity.

Porfiria cutánea tarda como manifestación extrahepática de hepatitis C crónica: reporte de un caso / Porphyria cutanea tarda as extrahepatic manifestation of chronic hepatitis C: a case report

Se presenta el caso de un paciente varón de 56 años quien es evaluado por presentar a nivel del dorso de ambas manos cicatrices hiperpigmentadas e hipopigmentadas, asociadas a quistes de milia. Se le realizó estudios del metabolismo de las porfirinas y biopsia cutánea de las lesiones los cuales resultaron compatibles con porfiria cutánea tarda. En el laboratorio inicial se encontró elevación de los valores de transaminasas, identificándose posteriormente infección crónica por virus de hepatitis C. Con la finalidad de tratar la infección viral y resolver el compromiso dérmico, considerado como manifestación extrahepática del virus hepatitis C, se inició tratamiento con interferón pegilado y ribavirina evolucionando favorablemente con respuesta viral rápida, carga viral no detectable hasta la actualidad (36 semanas de tratamiento), disminución del nivel de transaminasas séricas y mejoría de las lesiones dérmicas.

The present case is a 56 year old male who present hyperpigmented and hypopigmented scars in both hands, associated with the presence of milia cysts. It was studied the metabolism of porphyrins and skin biopsy of the lesions which were compatible with porphyria cutanea tarda. In the initial laboratory, elevated transaminases values were found and subsequently identified chronic infection of hepatitis C virus. In order to treat viral infection and resolve the dermal commitment; considered extrahepatic manifestation of hepatitis C virus, treatment was started with pegylated interferon and ribavirin, with favorably development and rapid viral response, with undetectable viral load until now (24 weeks of treatment), decreased level of serum transaminases and improvement of skin lesions.

Manifestaciones dermatólogicas asociadas al virus de la hepatitis C / Dermatological diseases associated with hepatitis C virus

Objetivo: Realizar una revisión bibliografíca del virus de la hepatitis C (VHC) y de las manifestaciones dermatológicas que pueden desencadenarse en los pacientes afectados por este virus. Observaciones: El VHC es actualmente reconocido como uno de los principales agentes causales de enfermedad hepática crónica. La infección viral suele acompañarse de manifestaciones dermatológicas en un gran número de casos. La patogénesis de estos cuadros cutáneos puede estar asociada directamente a la presencia viral, tal como ocurre en el eritema necrolítico acral, considerado actualmente como una patología específica del VHC. Otros cuadros, como la crioglobulimenia mixta, el liquen plano, la sialoadenitis, la urticaria crónica, la enfermedad de Behcet, el eritema polimorfo y nodoso (entre otras patologías), responden a mecanismos inmunológicos. Un segundo grupo, representado por la porfiria cutánea tarda y prurito, responde a mecanismos no inmunológicos. Tambien debemos incluir como manifestaciones dermatológicas del VHC a las farmacodermias generadas por la terapia antiviral con interferón, que desencadena patologías como psoriasis, liquen plano, síndrome de Sjögren, y la asociación del interferón con ribavirina, responsables de reacciones fotoalérgicas. Presentamos una nueva clasificación de la manifestaciones cutáneas del VHC, que facilita la compresión de las mismas desde el punto de vista etiopatogénico, a partir de la revisión bibliográfica realizada

Haem biosynthesis and human porphyria cutanea tarda: effects of alcohol intake.

The review describes the structural and biochemical properties of the haem biosynthetic enzyme, uroporphyrinogen decarboxylase (UROD), which sequentially catalyzes the removal of the four carboxyl groups from the acetate side chains of octacarboxylic uroporphyrinogen to form coproporphyrinogen, and the possible biochemical mechanism of the genesis of porphyria cutanea tarda (PCT). The disease is caused when the activity of UROD is significantly reduced. PCT is a multifactorial disease where both inherent and environmental factors such as alcohol, estrogens, halogenated aromatic hydrocarbons and viral infection (mainly hepatitis C) are involved in biochemical and clinical expression. In PCT, hepatic iron plays a key role. Alcohol intake could induce mobilization of iron from protein-bound ferritin. PCT should be managed by avoidance of these toxins and removal of iron by vigorous phlebotomy. Such iron-reduction therapy would provide additional benefit for hepatitis C patients by interferon therapy.

El virus C de la hepatitis y las enfermedades que produce / Hepatitis C virus and the diseases that it produces

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

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

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 wether 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

Experimental porphyria cutanea tarda and photosensitivity

FUNDAMENTOS - A porfiria cutânea tardia é uma doença metabólica da via porfirina-heme, resultante da deficiência da enzina uroporfirinogênio descarboxilase, que induz ao acúmulo de porfirinas, principalmente no fígado e na pele, responsáveis por lesöes cutâneas em áreas expostas ao sol. OBJETIVOS - Determinar a espécie animal que melhor corresponda ao modelo experimental da PCT, para o estudo de lesöes cutâneas relacionadas à fotossensibilidade. MÉTODO - Ratos, cobaias e camundongos foram submetidos a uma dieta contendo um dos fatores desencadeantes da PCT, o hexaclorobenzeno (HCB), na concentraçäo de 0,25 porcento. Após o surgimento da PCT, os animais foram expostos à radiaçäo ultravioleta, as porfirinas uninárias dosadas e as manifestaçöes cutâneas de fotossensibilidade anotadas, e, comparadas ao grupo controle. RESULTADOS - Somente os ratos apresentaram aumento da excreçäo de porfirinas urinárias, principalmente de uroporfirinas: 60,81ug/24h, comparados aos controles: 0,9ug/24h, neurotoxicidade e lesöes cutâneas em àreas fotoexpostas. CONCLUSÄO - Considerando-se as três espécies de animais estudadas, os ratos apresentaram quadro semelhante à PCT encontrada no homem. Em relaçäo às cobaias, sugere-se administrar dieta contendo menor concentraçäo de HCB e prolongar o tempo do experimento. Os camundongos näo se adequaram ao modelo experimental

Manifestaciones esclerodermiformes en porfiria cutánea tarda secundaria a hemodiáliasis / Sclerodemiform manifestations in porphyria tarda cutanea secondary to hemodyalisis

A case report of a 28 years old, woman with chronic hemodialisis due to chronic renal failure and cutaneous porphyria-sclerodermic syndrome is presented.The diagnosis and the treatment of the disease are comented

Porfiria cutánea tarda asociada a virus de la hepatitis c / Porphyria cutanea tarda associated with hepatitis c virus

La porfiria cutánea tarda es la más frecuente de las porfirias. Los cambios esclerodermiformes, si bien conocidos, no son habituales. Al virus de la hepatitis C se lo ha encontrado asociado a las porfirias cutáneas tardas. Algunos autores consideran que puede ser el factor causal de la disfunción hepática, afectando el metabolismo de las porfirias; otros en cambio consideran que actuaría como un co-factor, al igual que el alcohol, los estrógenos, ciertos tóxicos, etc. Presentamos un varón de 55 años de edad, que presentó una porfiria cutánea tarda con cambios esclerodermiformes cutáneos, asociada al virus de la hepatitis C. Se discute su asociación a este virus y el rol patogénico del mismo en la porfiria

Alteraciones en el camino metabólico del hemo en pacientes diabéticos / Changes in the heme metabolic pathway in diabetic patients

In the last decades several authors have observed a frequent association between diabetes mellitus and porphyria, mainly porphyria cutanea tarda. In previous studies, it has been demonstrated that both d delta d-aminolevulic acid dehydratase (ALA-D) and porphobilinogen deaminase (PBG-D), enzymes of the heme pathway, are inhibited by high concentrations of glucose in vitro in crude preparations of erythrocytes. The activity of these same enzymes was diminished in different tissues obtained from streptozotocin induced diabetic mice. Therefore, we decided to investigate the incidence of heme metabolism alterations in diabetes mellitus in a population of 100 non selected adult patients. The activities of erythrocytic ALA-D and PBG-D were measured. Rhodanese, an enzyme of the sulfocompounds pathway closely related to the regulation of heme biosynthesis, was also studied. Urine porphyrin content as well as the chromatographic pattern of esterified porphyrins were determined. ALA-D and PBG-D activities were diminished in diabetic patients (40 and 20 respectively), while rhodanese was only slightly increased (Fig. 1). ALA-D activity was subnormal in a 92 of the complete diabetic population, while PBG-D activity was less than normal in a 79 of the same population. No significative differences between enzymic activities were observed in the groups insulin and non-insulin dependent (Fig. 3). Urine porphyrin content was increased in 5 of the diabetic population. Chromatographic pattern of urinary porphyrins was notably altered in diabetic patients irrespectively of their porphyrin content (Fig. 4), suggesting an alteration in the enzyme uroporphyrinogen decarboxylase resembling the primary enzymic defect observed in porphyria cutanea tarda.(ABSTRACT TRUNCATED AT 250 WORDS)

Porfiria cutánea tarda en dos pacientes con trasplante renal / Cutanea tarda porphyria in 2 patients with kidney transplantation

Two patients who developed porphyria cutanea tarda, six and eight years after a successful renal transplantation are reported. There was no history, in either of them, of alcohol abuse, blood transfusion, iron or estrogen therapy and any hemodialysis in the last years. There is no evidence to support that a renal allograft is capable to develop porphyria cutanea tarda. Nevertheless, it would be interesting to consider its possible influence, due to the longer survival of these patients.