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.
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.
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).
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.

BACKGROUND: Porphyria cutanea tarda (PCT) is a rare, photosensitive disease characterized by skin fragility and blistering on sun-exposed areas. There is little previous research on how this condition affects health-related quality of life (HRQoL) and to the best of our knowledge this is the largest sample of PCT patients surveyed about their HRQoL. The aims of this study were to describe HRQoL, symptoms, susceptibility factors, disease activity and treatment in patients with PCT, and investigate the associations between these factors.
METHODS: This is a cross-sectional, retrospective study based on patient-reported outcome and laboratory data. The Norwegian Porphyria Centre diagnoses all patients with PCT in Norway, all of whom are invited to participate in the Norwegian Porphyria Registry. Between December 2013-2015, 111 patients received a postal questionnaire and invitation to participate.
RESULTS: Sixty-eight persons responded, with seven being excluded due to prolonged response time or missing information, resulting in 61 participants in the final analyses (55%). Median age was 60 years and 33 were female. We found a moderate negative relationship between the type and localisation of PCT symptoms and both mental (r = -.354 p < 0.01) and physical (r = -.441, p < 0.01) aspects of HRQoL. Participants who had started treatment when answering the questionnaire reported significantly better physical functioning and less bodily pain than those who had not started treatment. We did not observe an association between biochemical markers of disease activity and symptoms or HRQoL. Itching, a symptom that has received little attention in PCT was reported by 59% of the participants.
CONCLUSIONS: Our results show that reduced HRQoL is associated with more symptoms and not having started treatment. PCT is a rare disease, and there is a need for the development of best-practice guidelines to facilitate good patient care.

BACKGROUND: Porphyria cutanea tarda (PCT) is a rare hepatocutaneous disease for which the prognosis is largely unknown.
OBJECTIVE: To compare all-cause and cause-specific mortality between a nationwide cohort of patients with PCT and a matched population sample.
METHODS: We included all Danish patients who received a diagnosis of PCT from 1989 through 2012. Each patient was matched by age and sex to 10 random population control individuals. We compared survival and cause-specific mortality between patients and control individuals and adjusted for confounding from alcohol-related diseases, hepatitis, hemochromatosis, HIV, diabetes, acute myocardial infarction, stroke, cancer, chronic obstructive pulmonary disease, and cirrhosis.
RESULTS: The 20-year survival was 42.9% (95% confidence interval [CI], 36.9-48.7) for patients with PCT compared with 60.5% (95% CI, 58.6-62.4) for matched control individuals. All-cause mortality hazard ratio (HR) was 1.80 (95% CI, 1.56-2.07) before adjustment and 1.22 (95% CI, 1.04-1.44) after adjustment. The cause-specific mortality was markedly increased for nonmalignant gastrointestinal diseases (HR, 5.32; 95% CI, 2.71-10.43) and cancers of the gut (HR, 2.05; 95% CI, 1.24-3.39), liver/gallbladder (HR, 11.24; 95% CI, 4.46-28.29), and lungs (HR, 2.17; 95% CI, 1.41-3.33).
CONCLUSIONS: We had no data on lifestyle factors.
CONCLUSIONS: Patients with PCT have increased mortality, primarily explained by an increased mortality from gastrointestinal diseases and from cancers of the gut, liver/gallbladder, and lungs.

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.
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).
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).
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 has a complex etiology with genetic factors not completely elucidated. The miscegenation of the Brazilian population has important implications in the predisposition to diseases. There are no studies concerning the genetic ancestry of patients with porphyria cutanea tarda from a mixed population. Thirty patients living in Rio de Janeiro with sporadic porphyria cutanea tarda were studied for the genetic ancestry through informative markers - INDELS. There was a significant predominance of European ancestry across the sample of patients with porphyria cutanea tarda (70.2%), and a small contribution of African and Amerindian ancestry, 20.1% and 10.9%, respectively.

BACKGROUND: Porphyria cutanea tarda (PCT) is characterized by fragile skin with blistering on sun-exposed areas. Symptoms typically develop in late adulthood and can be triggered by iron overload, alcohol intake, oestrogens and various liver diseases. Treatment consists of phlebotomy to reduce iron, or increasing urinary porphyrin excretion by administering chlorochin. To optimize patient care, health personnel need to understand the subjective experiences of PCT.
OBJECTIVE: To explore the experiences of persons with PCT with regard to symptoms, treatment, follow-up and prevention of the disease.
METHODS: Interpretive description was used as a qualitative approach. Twenty-one participants attended three focus groups. All participants had experienced PCT symptoms during the last 5 years.
RESULTS: Participants\' experiences varied from trivializing symptoms and fragile skin to what was described as a desperate situation, with huge blisters, skin falling off and feeling as if one was in a \'horror movie\'. For some, itching was very troublesome, preventing sleep and delaying skin healing. In managing PCT a shift in focus from skin to blood was described. PCT was perceived as a chronic and systemic disease causing a range of health problems. Strategies for preventing symptoms ranged from doing nothing to frequent controls and check-ups.
CONCLUSIONS: Participants had a systemic perception of PCT, and a tendency to attribute a range of health problems to the condition. This study adds insight into the experiences patients have with PCT.

BACKGROUND: Porphyria cutanea tarda is the most common form of porphyria, characterized by the decreased activity of the uroporphyrinogen decarboxylase enzyme. Several reports associated HFE gene mutations of hereditary hemochromatosis with porphyria cutanea tarda worldwide, although up to date only one study has been conducted in Brazil.
OBJECTIVE: Investigation of porphyria cutanea tarda association with C282Y and H63D mutations in the HFE gene. Identification of precipitating factors (hepatitis C, HIV, alcoholism and estrogen) and their link with HFE mutations.
METHODS: An ambispective study of 60 patients with PCT was conducted during the period from 2003 to 2012. Serological tests for hepatitis C and HIV were performed and histories of alcohol abuse and estrogen intake were investigated. HFE mutations were identified with real-time PCR.
RESULTS: Porphyria cutanea tarda predominated in males and alcohol abuse was the main precipitating factor. Estrogen intake was the sole precipitating factor present in 25% of female patients. Hepatitis C was present in 41.7%. All HIV-positive patients (15.3%) had a history of alcohol abuse. Allele frequency for HFE mutations, i.e., C282Y (p = 0.0001) and H63D (p = 0.0004), were significantly higher in porphyria cutanea tarda patients, compared to control group. HFE mutations had no association with the other precipitating factors.
CONCLUSIONS: Alcohol abuse, hepatitis C and estrogen intake are prevalent precipitating factors in our porphyria cutanea tarda population; however, hemochromatosis in itself can also contribute to the outbreak of porphyria cutanea tarda, which makes the research for HFE mutations necessary in these patients.

OBJECTIVE: To determine the efficacy and safety of deferasirox (an oral iron-chelating agent approved to reduce iron stores in patients with chronic iron overload due to blood transfusions) in a pilot trial for the treatment of patients with porphyria cutanea tarda (PCT), the most common of the porphyrias and often difficult to treat.
METHODS: Prospective, open-label, noncomparative study.
METHODS: University-affiliated tertiary health care center in Dallas, Texas.
METHODS: Ten patients with PCT were enrolled in this 6-month study. The diagnosis was established by documenting the presence of elevated porphyrin level in the urine and a history of developing 3 or more blisters per month for at least 3 months prior to enrollment. Patients were treated with 250 mg/d of deferasirox, with an increase to 500 mg/d after 2 months if new blisters continued to develop.
METHODS: The improvement in number of blisters at the end of the 6-month treatment period was assessed.
RESULTS: Of 10 patients, 8 completed the study. Seven had resolution of blistering, 6 had a reduction in urinary porphyrin levels, and 7 had a reduction in ferritin levels. The treatment was well tolerated.
CONCLUSIONS: In this small pilot study, deferasirox induced improvement in cutaneous findings of PCT in 8 patients who completed 6 months of treatment. Most patients also had a substantial reduction in urinary porphyrin and ferritin levels. Future larger controlled studies are needed to confirm these findings. Deferasirox may be a useful alternative to existing treatment modalities for PCT.
BACKGROUND: clinicaltrials.gov Identifier: NCT00599326.

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.
CONCLUSIONS: 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.

Most rodent models of porphyria cutanea tarda (PCT) share in common the administration of iron and agents that induce transcription of cytochrome P450s. Dissection of changes related to porphyrin accumulation required generation of a genetic model free from exogenous precipitants. Mice heterozygous for a null Urod mutation and homozygous for null Hfe alleles spontaneously develop major increases in hepatic and urinary porphyrins several months after weaning but the high % uroporphyrin signature of PCT is established earlier, before total hepatic and urinary porphyrins rise. Total porphyrin levels eventually plateau at higher levels in females than in males. Porphyrinogens were the dominant tetrapyrroles accumulating in hepatocytes. Hepatic Urod activity is markedly reduced but total hepatic heme content does not diminish. Microsomal heme, however, is reduced and in vitro metabolism of prototype substrates showed that some but not all cytochrome P450 activities are reduced. High hepatic levels of uroporphyrinogen are also associated with increased glutathione S-transferase activity and elevated mRNA of 2 transporters, Abcc1 and Abcc4. This murine model of familial PCT affords the opportunity to study changes in porphyrinogen and porphyrin accumulation and transport in the absence of exogenous factors that alter P450 activity and transmembrane transporters.