Porphyria cutanea tarda in a HIV- positive patient

Abstract: This is a case report about Porphyria cutanea tarda (PCT) and its relationship with the infection caused by the human immunodeficiency virus (HIV). Cutaneous porphyria is an illness caused by enzymatic modification that results in partial deficiency of uroporphyrinogen decarboxylase (Urod), which may be hereditary or acquired. Several studies suggest that HIV infection associated with cofactors might trigger the development of porphyria cutanea tarda. In this case report, we present a patient infected with HIV, who after the introduction of antiretroviral therapy (ART) enjoyed clinical improvement of porphyria cutanea tarda symptoms.

Estudo da imunofluorescência direta, imunomapeamento e microscopia ótica na porfiria cutânea tardia / Study of direct immunofluorescence, immunofluorescence mapping and light microscopy in porphyria cutanea tarda

FUNDAMENTO: Apesar de a porfiria cutânea tardia ser a mais frequente das porfirias, há poucos estudos que abordam sua fisiopatologia cutânea. OBJETIVO: Avaliar as alterações cutâneas na porfiria cutânea tardia utilizando a microscopia ótica e a imunofluorescência direta, antes e depois do tratamento com cloroquina. Realizar o imunomapeamento antigênico da bolha para estudo do seu nível de clivagem. MÉTODOS: Relata-se a microscopia ótica e imunofluorescência direta de 28 pacientes em três fases diferentes: 23 pacientes com porfiria ativa antes do tratamento (Fase A), sete pacientes com remissão clínica durante o tratamento (Fase B) e oito pacientes com remissão bioquímica (Fase C). O imunomapeamento foi realizado em sete pacientes. RESULTADOS: Na porfiria ativa, a imunofluorescência direta demonstrou fluorescência homogênea e intensa no interior e na parede dos vasos e na junção dermoepidérmica. Na remissão clínica (Fase B) e na remissão bioquímica (Fase C), o depósito de imunoglobulinas se manteve, mas o depósito de complemento apresentou diminuição na maioria. O imunomapeamento não demonstrou plano de clivagem fixo. CONCLUSÃO: Não houve correlação entre a resposta clínica e os depósitos de imunoglobulinas. A diminuição do complemento favorece a hipótese de que a ativação da cascata do complemento representa uma via adicional que leva à lesão endotelial.

BACKGROUND: Even though porphyria cutanea tarda is the most frequent type of porphyria, there are few studies about its cutaneous physiopathology. OBJECTIVE: To evaluate skin changes in porphyria cutanea tarda using light microscopy and direct immunofluorescence before and after treatment with chloroquine. To perform antigen immunomapping of bullae to study their level of cleavage. METHODS: Light microscopy and direct immunofluorescence of 28 patients are reported in three different phases: 23 patients with active porphyria before treatment (Phase A), 7 patients with clinical remission during treatment (Phase B), and 8 patients with biochemical remission (Phase C). Immunomapping was performed on 7 patients. RESULTS: In active porphyria, direct immunofluorescence showed homogenous and intense fluorescence on the inside and on the walls of blood vessels as well as in the dermal-epidermal junction. In clinical remission (Phase B) and biochemical remission (Phase C), the deposit of immunoglobulins was maintained, but the deposit of complement was reduced in most cases. Immunomapping revealed no standard cleavage plane. CONCLUSION: No correlation was observed between clinical response and immunoglobulin deposits. The reduction of complement favors the hypothesis that activation of the complement cascade represents an additional pathway that leads to endothelial damage.

Aparición de porfiria cutánea tarda durante el tratamiento con peg-interferón más ribavirina en un paciente con hepatitis C crónica con viremia indetectable / Development of porphyria cutanea tarda in a chronic hepatitis C patient with indetectable viremia under treatment with peg-interferon plus ribavirin

La porfiria cutánea tarda (PCT) es considerada una manifestación extrahepática de la infección por el virusde la hepatitis C (HCV). La frecuencia de esta asociación es variable y no es claro el mecanismo por el cual el virus la desencadena. Se presenta un hombre de 47 años con hepatitis C, genotipo-1b, que durante el tratamiento con peg-interferón alfa-2b más ribavirinasin viremia detectable en las semanas 12, 24 y 48, en la semana 44 consulta por presentar lesiones dermatológicasfotosensibles. Con el diagnóstico presuntivo de PCT se realizó biopsia cutánea y el dosaje de porfirinasurinarias fue 4185 ug/24hs (vn: < 250). El análisis cromatográfico reveló el típico patrón de PCT, confirmando el diagnóstico. El gen HFE de la hemocromatosis mostró mutaciones de carácter heterocigoto (H63D y C282Y), asociación frecuente en los pacientescon sobrecarga de hierro y PCT. El tratamiento antiviral de la infección por HCV puede mejorar las manifestacionesde la PCT. La ocurrencia de novo de éstafue reportada recientemente durante el tratamiento de la hepatitis C crónica con interferón y ribavirina pero no hay casos relatados de aparición tardía de PCT enpacientes HCV con viremia no detectable. La presencia de la mutación del gen HFE y la posibilidad de unaumento de oferta de hierro por la acción hemolítica de la ribavirina podrían explicar un exceso de hierrocapaz de desencadenar la crisis de PCT. Tampoco sonconcluyentes los estudios con respecto al aumento o no de la concentración de hierro en hígado en pacientes con anemia que reciben ribavirina.

Porphyria cutanea tarda (PCT) is considered an extra-hepatic manifestation of HCV infection. The frequency of this association varies according to different authors and the mechanism by which the virus can trigger this disease is not yet clear. We present a 47-year-old-man with chronic hepatitis C genotype 1b who, during the treatment with peg-interferón alfa 2b plus ribavirina, with no detectable viremia at weeks 12th, 24th, and 48th, developed dermatological photosensitive lesions at week 44th. With a presumptive diagnosis of PCT a cutaneous/skin biopsy was performed as well as a porphyrin dosage with urine porphyirins of 4185 microg/24 hs (nv<250). The chromatographic analysis revealed the typical PCT pattern thus confirming the diagnosis. The hemochromatosis HFE gen evaluation showed heterozigotus character mutations (H63D and C282Y) a frequent association in patients with iron overload and PCT. The antiviral treatment of the HCV infection can improve the clinical-humoral manifestations of PCT. The novo occurrence of PCT was recently reported during chronic hepatitis C treatment with interferón and ribavirin, but no cases of late appearance of PCT in patients with no detectable viremia were reported. The mutation of the gen HFE in our patient and the hemolysis caused by ribavirin can be related to the development of the disease, but the iron overload because of ribavirin use is also controversial. This is another example of the complexity of this association.

Porfiria cutanea tarda esclerodermiforme, secundaria a hemodiálisis / Sclerodermiform porphyria cutanea tarda

La porfiria cutanea tarda (PCT) es un desorden del metabolismo del hemo que condiciona la acumulación y eliminación aumentada de porfirinas y/o sus precursores. La enzima deficiente es la uroporfirinógeno decarboxilasa (URO-D). Presentamos una paciente de sexo femenino, de 58 años de edad, que cursa insuficiencia renal crónica secundaria a nefropatía lúpica, en tratamiento dialítico trisemanal, que nos consulta por la aparición de lesiones ampollares en zonas foroexpuestas ante mínimos traumatismos. Nos referimos a la porfiria cutanea tarda, haciendo hincapié en la variante esclerodermiforme

Porfiria cutánea tarda esclerodermiforme: presentación de cuatro casos y revisión de la literatura / Sclerodermic porphyria cutanea tarda: report of 4 casis and a review of the literature

La porfiria cutánea tarda esclerodermiforme (PCTE) es una forma poco frecuente de la presentación de la porfiria cutánea tarda (PCT), representando el 18-33 por ciento de los casos. Se caracteriza por manifestarse con placas esclerodermiformes de aparición insidiosa y tardía en el curso de la enfermedad. El déficit de la actividad de la enzima uroporfirinógeno decarboxilasa (UPDC), lleva a la acumulación de metabolitos intermedios responsables de las manifestaciones clínicas y bioquímicas. Se presentan cuatro pacientes con PCTE estudiados en nuestro Servicio, en un período de cuatro años (1992-1996)

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

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

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

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.