Porphyria cutanea tarda: an under-recognised manifestation of haemochromatosis.

We present a case of a woman who presented with a photosensitive skin rash and blisters on her extremities which did not improve with steroids. These were associated with polyarthralgia and a deranged liver function test on her admission. Further workup revealed that the patient has an undiagnosed porphyria cutanea tarda (PCT) and hereditary haemochromatosis. The patient later underwent regular venesections which improved her condition. This case report not only illustrates the challenge in diagnosing PCT but also aims to highlight the association between PCT and hereditary haemochromatosis.

A Case Report of Porphyria Cutanea Tarda with Hepatitis-C Virus Co-infection.

Porphyria cutanea tarda is a rare disorder of heme metabolism due to deficiency of the enzyme uroporphyrinogen decarboxylase which is manifested as some typical dermatological features and hepatic dysfunction. The Hepatitis-C virus co-infection is common and it can be aggravated by other environmental factors. We report a case of porphyria cutanea tarda in a 37-year-old woman, who presented with recurrent skin blisters and has concomitant Hepatitis-C virus infection. She was taking oestrogen containing oral contraceptive pill for a long duration. The diagnosis of porphyria cutanea tarda was considered on the basis of clinical features and high level of urine porphyrin level. She was put on hydroxychloroquine and combination drugs for Hepatitis-C virus with significant improvement after 3 months of therapy.

Case 304: Porphyria Cutanea Tarda.

HISTORY: In 2017, a 72-year-old woman was seen in the gastroenterology department with a 2-month history of mild and intermittent abdominal pain without other accompanying symptoms. Her medical history was unremarkable, except for a previous visit due to facial photodermatitis 3 years earlier. Diazepam for a sleeping disorder was the only chronic medication recorded. Results of physical examination, blood count, and basic metabolic panels including assessment of renal and liver function were normal; only the ferritin level was slightly elevated (265 ng/mL [595 pmol/L]; normal range, 10-120 ng/mL [22-269 pmol/L]). Abdominal US was performed, followed by multiphasic contrast-enhanced CT and liver MRI due to the findings of the first study. A diagnosis was not established in that moment, and acetaminophen was prescribed for pain relief. As the symptoms continued, laboratory tests and imaging studies were repeated 2 years later, with similar findings and no notable changes.

Between a rock and a hard place: management of systemic lupus erythematosus and porphyria cutanea tarda.

Porphyria cutanea tarda (PCT), the most common porphyria, is a rare photodermatosis characterized by fragile, hemorrhagic bullae and erosions with associated milia, hyperpigmentation, and hypertrichosis. SLE is a systemic connective tissue disease with approximately 80% of those affected manifesting cutaneous findings. These include malar and discoid rashes, photosensitivity, bullae, oral ulcerations, as well as a variety of other nonspecific findings. In this case, we illustrate a rare but established association between these two pathologic entities, and the resulting therapeutic challenge in treating a patient with both conditions. The concurrence of these two diseases poses therapeutic challenges with a paucity of evidence-based recommendations. Management with low dose weekly antimalarial therapy may be the appropriate middle ground in effectively treating the two co-morbid conditions especially in a patient with other underlying systemic conditions.

Evolution of HCV associated porphyria cutanea tarda after HCV sustained virologic response by direct acting antivirals / Evolución de la porfiria cutánea tarda asociada al VHC tras obtenerse respuesta virológica sostenida del VHC mediante el uso de antivirales de acción directa

Objectives: Porphyria cutanea tarda (PCT) is common and usually associated with HCV chronic infection and HFE polymorphisms. Since DAA IFN-free regimens availability, SVR for HCV is nearly a constant and we wonder whether HCV SVR determine PCT evolution.Methods: Retrospective observational study including patients with HCV associated PCT from the Gastroenterology and Infectious Diseases Departments at our Hospital, treated with DAA (Apr/2015–Apr/2017). Clinical variables of PCT were collected at PCT diagnosis, after PCT treatment, before DAA use and after SVR achievement. UROD activity and C282Y/H63D polymorphisms were registered. SPSS 22.0.Results: 13 HCV-PCT patients included: median age 52.5 years; 4 females; 8 HCV/HIV co-infected (all on undetectable viral load). Classical PCT factors: 12 smoked, 9 alcohol abuse, 6 former IDU. 10 type I PCT and 1 type II PCT. HFE polymorphism: 2 cases with C282Y/H63D; H63D polymorphism in 8. PCT manifestations resolved with PCT treatment in 4 patients, almost completely in 7 patients, 1 patient referred stabilization and one worsened. After DAA treatment all the residual lesions resolved, what always led to specific treatment interruption.Conclusions: Our series of cases of HCV-associated PCT shows that SVR after DAA treatment leads to PCT resolution. Porphyrin levels are not needed after ending PCT specific treatment interruption when there are no residual skin lesions in HCV-associated PCT.(AU)

Objetivos: La porfiria cutánea tarda (PCT) es un trastorno frecuentemente asociado con la infección por VHC y los polimorfismos HFE. Desde la aparición de los AAD en regímenes libres de IFN, la RVS para el VHC es casi universal. Nos preguntamos si la RVS del VHC determina la evolución de la PCT asociada al VHC.Métodos: Estudio observacional retrospectivo con pacientes con PCT asociada al VHC atendidos en Gastroenterología y Enfermedades Infecciosas en nuestro centro, tratados con AAD (abril 2015 - abril 2017). Se registra información relacionada con la PCT en el momento del diagnóstico, tras iniciar tratamiento para la PCT, antes de AAD y tras RVS. Analizamos la actividad UROD y los polimorfismos C282Y/H63D. SPSS 22.0.Resultados: Se incluyen 13 pacientes con PCT asociada al VHC: edad mediana 52,5 años; 4 mujeres; 8 coinfectados VHC/VIH (todos con VIH indetectable). Factores asociados a PCT: 12 fumadores, 9 alcohol, 6 ADVP. Hubo 10 PCT clasificadas como tipo I y una PCT tipo II. HFE: 2 casos C282Y/H63D; H63D presente en 8. Tras iniciar tratamiento clásico para PCT los síntomas se resolvieron completamente en 4 casos, casi completamente en 7, se estabilizaron en un paciente y empeoraron en un paciente. Tras la RVS con AAD desaparecieron las lesiones residuales en los pacientes que las presentaban, lo que llevó a interrumpir todos los tratamientos para la PCT.Conclusiones: Nuestra serie de casos de PCT asociada al VHC muestra que la RVS para el VHC tras AAD conduce siempre a la curación de la PCT. Según esto no sería necesaria la determinación de porfirinas tras finalizar la terapia específica para la PCT cuando no haya lesiones cutáneas residuales en la PCT asociada al VHC.(AU)

Porphyria cutanea tarda and patterns of long-term sick leave and disability pension: a 24-year nationwide matched-cohort study.

BACKGROUND: Porphyria cutanea tarda (PCT) is a skin disorder caused by a defect in the liver enzyme uroporphyrinogen decarboxylase and is associated with hepatitis C virus infection, high alcohol intake, smoking and iron overload. Data on the long-term morbidity of PCT is lacking. METHODS: We conducted a nationwide matched cohort study over a 24-year period. The study sample included 534 persons aged 18-67 years with a biochemically confirmed PCT diagnosis and a sample of 21,360 persons randomly selected from the working age population, matched on age, sex and educational attainment. We investigated if persons with sporadic and familial PCT had an increased risk of long-term sick leave (LTSL) or disability pension. We further assessed risk before (pre-PCT), during (during-PCT) and after (post-PCT) the typical period of first onset to diagnosis, treatment and remission. RESULTS: Overall, persons with PCT had a 40% increased risk (hazard ratio [HR] = 1.4, 95% confidence interval [CI] = 1.3, 1.5) of LTSL and a 50% increased risk (HR = 1.5, CI = 1.3, 1.7) of disability pension. Risk of disability pension was increased pre-PCT (HR = 1.3, CI 1.3 (1.0, 1.6), during-PCT (HR 1.5, CI 1.0, 2.2) and post-PCT (HR = 2.0, CI 1.5, 2.6). For LTSL, risk was increased pre-PCT (HR = 1.3, CI 1.1, 1.4) and during-PCT (HR = 1.5, CI 1.1, 2.1), but not post-PCT. Risk was greatest in persons with sporadic than familial PCT. Diagnostic reasons for disability pension that were increased compared to matched controls were PCT or skin disease in 11 of 199 cases (PCT: n = 7, incident rate ratios [IRR] = 49.2, CI = 38.8, 62.4; diseases of the skin and subcutaneous tissue, n = 4, IRR = 4.2, CI = 1.6, 11.0). The vast majority of diagnostic reasons for accessing disability pension were related to comorbidities, PCT susceptibility factors and more general health issues such as: malignant neoplasms (n = 12, IRR = 2.4, CI = 1.4, 4.2), substance and alcohol dependence (n = 7, IRR = 5.0, CI = 2.5, 10.1), neurotic and mood-disorders (n = 21, IRR = 1.7, CI = 1.1, 2.6), and diseases of the musculoskeletal system and connective tissue (n = 71, IRR = 2.5, CI = 1.9, 3.2). CONCLUSIONS: Persons with PCT have an increased risk of LTSL and disability pension indicating significant morbidity in this patient group. Appropriate long-term follow-up and monitoring for relapses and co-morbid diseases are recommended.

Evolution of HCV associated porphyria cutanea tarda after HCV sustained virologic response by direct acting antivirals.

OBJECTIVES: Porphyria cutanea tarda (PCT) is common and usually associated with HCV chronic infection and HFE polymorphisms. Since DAA IFN-free regimens availability, SVR for HCV is nearly a constant and we wonder whether HCV SVR determine PCT evolution. METHODS: Retrospective observational study including patients with HCV associated PCT from the Gastroenterology and Infectious Diseases Departments at our Hospital, treated with DAA (Apr/2015-Apr/2017). Clinical variables of PCT were collected at PCT diagnosis, after PCT treatment, before DAA use and after SVR achievement. UROD activity and C282Y/H63D polymorphisms were registered. SPSS 22.0. RESULTS: 13 HCV-PCT patients included: median age 52.5 years; 4 females; 8 HCV/HIV co-infected (all on undetectable viral load). Classical PCT factors: 12 smoked, 9 alcohol abuse, 6 former IDU. 10 type I PCT and 1 type II PCT. HFE polymorphism: 2 cases with C282Y/H63D; H63D polymorphism in 8. PCT manifestations resolved with PCT treatment in 4 patients, almost completely in 7 patients, 1 patient referred stabilization and one worsened. After DAA treatment all the residual lesions resolved, what always led to specific treatment interruption. CONCLUSIONS: Our series of cases of HCV-associated PCT shows that SVR after DAA treatment leads to PCT resolution. Porphyrin levels are not needed after ending PCT specific treatment interruption when there are no residual skin lesions in HCV-associated PCT.

Multiple focal fatty changes in the liver in patients with porphyria cutanea tarda: A case series and review of the literature.

Porphyria cutanea tarda (PCT) is commonly diagnosed in cases where multiple hyperechoic nodules are observed in the liver. Pathologically, these nodules associated with PCT are focal fatty deposits. We report here, seven cases of PCT with fatty changes over multiple foci in the liver. Furthermore, the characteristics of ultrasonography (US) findings of 32 previously reported cases are summarized. The US features of these nodules showed a homogenous hyperechoic or hyperechoic rim pattern, partial confluence, and no mass effect in the vascular structures. Because multiple hyperechoic liver nodules occasionally mimic malignancies, and because their diagnosis can be challenging, clinicians should consider checking urine porphyrin levels to rule out PCT when such nodules are observed on US.

Sight-threatening progressive corneo-scleral involvement in porphyria cutanea tarda.

Porphyria cutanea tarda is the most common type of porphyria. It is associated with a deficiency of uroporphyrinogen decarboxylase enzyme responsible for heme synthesis. Clinical manifestations are predominantly dermatological and very rarely present with ocular involvement. Although scleral thinning in the interpalpebral area is a well-documented entity, sight-threatening corneal involvement is rarely described. We, herein report a case of a 58-year-old man who presented with ocular surface dryness, photophobia and mild redness. Slit-lamp biomicroscopy revealed corneo-scleral thinning in both eyes. The diagnosis was confirmed with a urine porphyrin test, serum iron and serum ferritin levels. We started him on conservative management after which he was lost to follow-up. He presented again after 6 years with total corneal opacification and progressive loss of vision in the right eye.

Chronic blistering rash on hands.

The location of the patient's lesions and multiple risk factors suggested that an uncommon disorder was at work.

Porphyria Cutanea Tarda Associated With Acute Hemorrhagic Pancreatitis.

Porphyria cutanea tarda (PCT) is a condition of dysregulated heme synthesis that leads to accumulation of photosensitizing precursors with resultant fragility and blistering of the skin. It can be hereditary or acquired and has been known to be associated with hepatic C virus, alcohol, HIV, and estrogen. In this article, we report an unusual presentation of PCT associated with acute hemorrhagic pancreatitis in a 57-year-old man. He presented initially to a community hospital with acute onset of epigastric abdominal pain and new-onset ascites. Lipase was elevated. Diagnostic paracentesis was grossly bloody. He was then transferred to our institution for concern for acute hemorrhagic pancreatitis. On arrival, physical examination demonstrated vesicles and bullae with erythematous bases, in different stages of healing seen over the dorsal aspects of both hands with scaling, scarring, and hypopigmentation and hyperpigmentation of the skin. Laboratory evaluation and skin biopsy confirmed the diagnosis of PCT. Search for an underlying etiology failed to reveal typical predisposing factors. This report illustrates that acute hemorrhagic pancreatitis may be an underlying etiology for PCT.

Porphyria cutanea tarda increases risk of hepatocellular carcinoma and premature death: a nationwide cohort study.

BACKGROUND: Porphyria cutanea tarda (PCT) is a skin disorder originating from a deficit of the liver enzyme uroporphyrinogen decarboxylase. PCT may be a risk factor for hepatocellular carcinoma (HCC) and other cancers, but the evidence is unclear. We aimed to investigate cancer and premature mortality risk in persons with PCT. METHODS: The cohort study consisted of all Norwegian residents from 18 years between 2000 and 2016 (n = 5.4 million). 612 persons with PCT, and all cancer diagnoses and causes of death were identified through record linkage between national registries. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were adjusted for age, sex, education and calendar years. We additionally compared persons with PCT to persons with a history of chronic alcohol abuse (n = 30,468). RESULTS: Persons with PCT were more likely to be diagnosed with HCC [adjusted HR (aHR) = 19.7, CI = 8.8-44.0) and gallbladder and biliary tract cancer (aHR = 6.8, CI = 2.2-21.0) than the reference population. A moderate increased risk for HCC (aHR = 3.1, CI = 1.2-7.7) and gallbladder and biliary tract cancer (aHR = 4.0, CI = 1.1-14.4) remained when compared to persons with a history of chronic alcohol abuse. Additionally, compared to the reference population, persons with PCT had an increased risk of premature death (aHR = 1.5, CI = 1.2-1.7), due to the following causes of death: malignant neoplasms (aHR = 1.4, CI = 1.0-1.9), diseases of the liver (HR = 5.5, CI = 2.5-12.2), and drug and alcohol overdose (HR = 9.9, CI = 4.7-20.8). CONCLUSIONS: Persons with PCT had an increased risk of HCC and cancer of the gallbladder and biliary tract, as well as premature death. Although most of our findings can likely be explained by common lifestyle risk factors, something inherent in PCT may contribute to the development of HCC.

Porphyria cutanea tarda: Recent update.

Porphyria cutanea tarda (PCT) is the most common human porphyria, due to hepatic deficiency of uroporphyrinogen decarboxylase (UROD), which is acquired in the presence of iron overload and various susceptibility factors, such as alcohol abuse, smoking, hepatitis C virus (HCV) infection, HIV infection, iron overload with HFE gene mutations, use of estrogens, and UROD mutation. Patients with familial or type II PCT due to autosomal dominant UROD mutation also require other susceptibility factors, as the disease phenotype requires hepatic UROD deficiency to below 20% of normal. PCT clinically manifests with increased skin fragility and blistering skin lesions on sun exposed areas. The common age of presentation is 5th to 6th decade and occurs slightly more commonly in males. Although mild liver biochemical profile are common, advanced fibrosis and cirrhosis with hepatocellular carcinoma (HCC) can occasionally develop. Screening for HCC using ultrasound examination is recommended in PCT patients, especially with cirrhosis and advanced fibrosis. PCT is effectively and readily treatable with the use of either repeated phlebotomy or use of 100 mg hydroxychloroquine orally twice a week, and both the treatments are equally effective and safe. With the advent of new or direct antiviral agents for HCV infection, treatment of concomitant HCV has become safer and effective. Data are emerging on the benefit of these drugs as monotherapy for both PCT and HCV. After the achievement of remission of PCT, there remains a potential for relapse, especially when the susceptibility factors are not adequately controlled. Scanty data from retrospective and observational studies shows the relapse rate to be somewhat higher after remission with low-dose hydroxychloroquine as compared to phlebotomy induced remission. Future studies are needed on exploring mechanism of action of 4-aminoquinolines, understanding interaction of HCV and PCT, and relapse of PCT on long-term follow-up.