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.

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.

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.

The devil's in the dosing: severe drug-induced liver injury in a hydroxychloroquine-naive patient with subacute cutaneous lupus erythematosus and porphyria cutanea tarda.

A 29-year-old woman with a 1.5 year history of photosensitive skin lesions on her hands presented with a malar rash, bullous lesions on her hands, and was diagnosed with subacute lupus erythematosus after serologies revealed a positive antinuclear antibody test (1:2560), and antibodies to Ro/SSA and dsDNA. Hydroxychloroquine (400 mg/day) was prescribed and the patient developed severe drug-induced liver injury. Biopsy of her bullous skin lesions was consistent with porphyria cutanea tarda, as were her serological and urinary exams. She was successfully treated with therapeutic phlebotomy. This case identifies porphyria cutanea tarda as an important differential diagnosis for the rheumatologist to consider when evaluating patients with bullous skin lesions. Hydroxychloroquine in lower doses is an effective treatment for porphyria cutanea tarda; at doses used to treat systemic lupus erythematosus and subacute cutaneous lupus, there is a potentially life-threatening complication of hepatotoxicity.

Radiation and chemotherapy with no excessive toxicity in a patient with human papillomavirus-related tonsillar cancer and porphyria cutanea tarda: Case report and literature review.

BACKGROUND: Porphyria is a condition of cutaneous photosensitivity. It is unclear if radiotherapy (RT) is safe in patients with porphyria. METHODS: We report a patient case with uncontrolled porphyria cutanea tarda treated with chemoradiation for p16-positive oropharyngeal cancer. Given the scarcity of data on this subject, we also conducted a literature review on the topic of radiation in patients with porphyria. RESULTS: The patient in our study did not experience any unusual acute or late toxicity, despite receiving a high dose of cutaneous radiation. We also found the majority of the literature supports the safe use of therapeutic radiation in patients with porphyria. CONCLUSION: In this patient, and in the majority of the literature, radiation seems safe in patients with porphyria; however, there are few reports on the subject in the literature, therefore, caution is warranted.

[Porphyria cutanea tarda: the benefit of additional diagnostics]. / Porphyria cutanea tarda: Nut van aanvullende diagnostiek.

The porphyrias are a clinically and genetically heterogeneous group of relatively rare metabolic diseases that result from disorders in the biosynthesis of haeme. Porphyria cutanea tarda (PCT) is the most common type, accounting for 80-90% of all porphyrias, and is essentially an acquired disease, although PCT can also occur on a familial basis. We describe a 71-year-old female and a 62-year-old male patient, both of whom had several risk factors for developing PCT, ranging from iron overload due to a mutation in the hereditary haemochromatosis protein (HFE) gene, alcohol use, smoking, and exogenous oestrogen, to persistent hepatitis C infection. The clinical relevance of the several diagnostic modalities is important in PCT. Diagnostic evaluation is important in order to confirm the diagnosis, but also to evaluate the treatment response in the context of long-term follow-up in the prevention of late complications of PCT, i.e. hepatocellular carcinoma.

Porphyria cutanea tarda and Sjogren's syndrome.

Porphyria cutanea tarda is prevalent in connective tissue disease, common in systemic lupus erythematosus. However, the co-existence of primary sjogren's syndrome and porphyria cutanea tarda is rare and poses diagnostic and therapeutic challenges. We report a case of porphyria cutanea tarda associated with primary sjogren's syndrome.

Porphyria cutanea tarda and Sjogren's syndrome

Porphyria cutanea tarda is prevalent in connective tissue disease, common in systemic lupus erythematosus. However, the co-existence of primary sjogren's syndrome and porphyria cutanea tarda is rare and poses diagnostic and therapeutic challenges. We report a case of porphyria cutanea tarda associated with primary sjogren's syndrome.

[Sclerodermatous changes in porphyria cutanea tarda: six cases]. / Lésions sclérodermiformes dans la porphyrie cutanée tardive : six observations.

BACKGROUND: The clinical features of porphyria cutanea tarda (PCT) are usually distinctive and include blistering on sun-exposed areas, fragile skin, hypertrichosis and hyperpigmentation. Sclerodermatous changes are much less common, and may either reveal PCT or else appear later. We carried out a retrospective study of the files of six female patients presenting such lesions. PATIENTS AND METHODS: Six women (age: 45 to 72 years) were referred for sclerodermatous lesions on sun-exposed areas of the upper body. In four patients, these lesions revealed PCT and in the remaining two patients they were indicative of previously treated but relapsing PCT. Four had sclerodermatous skin changes mimicking morphea of the neck and neckline, the top of the back and the face, while one presented more diffuse facial and cervical sclerosis. Associated alopecia was seen in three patients. The last patient presented isolated sclerodermiform alopecia. Associated malar hypertrichosis was seen in five cases and facial hyperpigmentation was noted in three cases. Four exhibited no blisters, cutaneous fragility, milia or photosensitivity. Histological findings were consistent with morphea or scleroderma in all cases. All patients presented abnormal liver tests: cirrhosis was present in four cases (primitive biliary cirrhosis, alcoholic cirrhosis and hepatitis C) and fatty liver in two cases. In four cases, there was excessive alcohol intake. Uroporphyrin levels were above the normal range in all cases. Local corticosteroid therapy associated with phlebotomy and/or low-dose hydroxychloroquine resulted in complete normalisation of porphyrin levels in four patients, with complete resolution of the cutaneous lesions in two patients and partial improvement in the other two. DISCUSSION: Sclerodermatous changes are uncommon in PCT. They are not always late and secondary to the process of healing of blisters but can in fact constitute the first cutaneous symptom of the disease while revealing the underlying liver disease. Even in the absence of blisters, photosensitivity or cutaneous fragility, a diagnosis of PCT must be suspected in a setting of sclerodermatous changes distributed on the neck and face, or the neckline, or scarring alopecia, if associated with abnormal liver tests. Skin biopsy to confirm the diagnosis of scleroderma may delay the diagnosis, which is in fact based on porphyrin level. Normalization of the latter parameter under treatment allows regression of lesions.

Boston keratoprosthesis for visual rehabilitation in porphyria cutanea tarda.

A 56-year-old man, presented with bilateral chronic visual loss associated with generalised skin lesions. He had undergone multiple penetrating keratoplasties in his right eye for recurrent corneal infections and perforations. On ocular examination, his left eye was phthisical and his right eye had light perception vision owing to a failed and vascularised corneal graft. Dermatological evaluation revealed multiple hyperpigmented and hypopigmented lesions along with thickening of skin on nose, scalp and dorsum of hands. Skin biopsy showed focal areas of deposition of faint periodic acid Schiff-positive diastase-resistant perivascular material. The high-performance liquid chromatography assessment revealed increased presence of porphyrins in blood and urine, thus confirming a diagnosis of porphyria cutanea tarda. The patient's vision in the right eye improved after undergoing Boston type 1 keratoprosthesis along with general photoprotective measures for the exposed parts of the body.

Fotossensibilidade amplificada? Relato de porfiria cutânea tarda associada a lúpus eritematoso sistêmico / Increased photosensitivity? Case report of porphyria cutanea tarda associated with systemic lupus erythematosus

A associação de porfiria cutânea tarda (PCT) e lúpus eritematoso sistêmico (LES) é rara. O LES, de fisiopatologia complexa e manifestações clínicas pleomórficas, assemelha-se à PCT pela fotossensibilidade. Um achado que pode diferenciar as duas doenças são as lesões cutâneas bolhosas, raras no LES, mas características da PCT. Descrevemos um caso de associação de PCT e LES e revisamos a literatura, enfatizando questões fisiopatológicas, clínicas e terapêuticas. Um dado relevante para a prática clínica concerne ao tratamento do lúpus com antimaláricos, o que pode oferecer riscos para a PCT.

The association of porphyria cutanea tarda (PCT) and systemic lupus erythematosus (SLE) is rare. Systemic lupus erythematosus, of complex pathophysiology and pleomorphic clinical manifestations, is similar to PCT regarding photosensitivity. One finding that can differentiate both diseases is the presence of cutaneous blisters, which are rare in SLE, but characteristic of PCT. We report one case of the association of PCT and SLE and revise the literature, emphasizing pathophysiological, clinical and therapeutic aspects. One relevant information for clinical practice relates to the treatment of SLE with antimalarials, which is a risk for PCT.