Treatment Of Porphyria Cutanea Tarda Research Articles

Porphyria cutanea tarda in Scotland: underlying associations and treatment approaches.

Despite its rarity, porphyria cutanea tarda (PCT) is globally recognized as the most common form of cutaneous porphyria. This study aims to review the underlying associations and treatment of PCT in Scotland. We retrospectively reviewed data on 27 patients diagnosed with PCT between 1987 and 2022 at the Scottish Cutaneous Porphyria Service. Males slightly predominated (66.7%). The mean ± standard deviation (SD) age at diagnosis was 55.6 ± 12.5 years. Common associated factors were heavy alcohol intake (88.5%), genetic hemochromatosis (72%), smoking (45.5%), and hepatitis C virus infection (16%). Most had multiple associated factors (70.4%). Patients with genetic hemochromatosis with the C282Y genotype exhibited higher median transferrin saturation (69.5 vs. 35, P = 0.004) and ferritin levels (observed in males only) (1175 vs. 339; P = 0.014) than those with the H636D genotype. Most (52%) received combination therapy of venesection and antimalarials, followed by venesection monotherapy (32%) and antimalarial monotherapy (16%). Overall, 95.2% achieved biochemical improvement. Median time to improvement was 7, 5, and 9 months with venesection, antimalarial, and combined treatments, respectively (P = 0.173). Biochemical remission was achieved in 50% of patients. Remission occurred in 2/4 of patients with antimalarial monotherapy (median time 19 months) and 9/13 patients with combined treatment (median time 26 months). Biochemical relapse was found in three patients, all of whom received combination therapy. Excess alcohol intake and genetic hemochromatosis were the most common underlying associations with PCT in our Scottish cohort. Treatment for PCT should be individualized, and long-term follow-up is needed to monitor for disease relapse.

Ledipasvir/Sofosbuvir Is Effective as Sole Treatment of Porphyria Cutanea Tarda with Chronic Hepatitis C.

Chronic hepatitis C [CHC] is a risk factor for porphyria cutanea tarda [PCT]. To assess whether ledipasvir/sofosbuvir is effective for treating both PCT and CHC, we treated patients with CHC + PCT solely with ledipasvir/sofosbuvir and followed them for at least 1year to assess cure of CHC and remission of PCT. Between September 2017 and May 2020, 15 of 23 screened PCT + CHC patients were eligible and enrolled. All were treated with ledipasvir/sofosbuvir at recommended doses and durations, according to their stage of liver disease. We measured plasma and urinary porphyrins at baseline and monthly for the first 12months and at 16, 20, and 24 mos. We measured serum HCV RNA at baseline, 8-12, and 20-24 mos. Cure of HCV was defined as no detectable serum HCV RNA ≥ 12weeks after the end of treatment (EOT). Remission of PCT was defined clinically as no new blisters or bullae and biochemically as urinary uro- plus hepta-carboxyl porphyrins ≤ 100 mcg/g creatinine. All 15 patients, 13 of whom were men, were infected with HCV genotype 1. 2/15 withdrew or were lost to follow-up. Of the remaining 13, 12 achieved cure of CHC; 1 had complete virological response, followed by relapse of HCV after ledipasvir/sofosbuvir but was subsequently cured by treatment with sofosbuvir/velpatasvir. Of the 12 cured of CHC, all achieved sustained clinical remission of PCT. Ledipasvir/sofosbuvir [and likely other direct-acting antivirals] is an effective treatment for HCV in the presence of PCT and leads to clinical remission of PCT without additional phlebotomy or low-dose hydroxychloroquine treatment. ClinicalTrials.gov NCT03118674.

S1362 Direct-Acting Antivirals [DAA] Are Effective as Sole Treatment of Porphyria Cutanea Tarda (PCT) With Chronic Hepatitis C [CHC

S1362 Direct-Acting Antivirals [DAA] Are Effective as Sole Treatment of Porphyria Cutanea Tarda (PCT) With Chronic Hepatitis C [CHC

Relapse of porphyria cutanea tarda after treatment with phlebotomy or 4-aminoquinoline antimalarials: a meta-analysis.

Porphyria cutanea tarda (PCT) is the most common human porphyria. It is caused by hepatic deficiency of uroporphyrinogen decarboxylase activity, which is acquired in the presence of multiple susceptibility factors. PCT presents clinically with cutaneous blistering photosensitivity and is readily treatable with either repeated phlebotomy or 4-aminoquinoline antimalarials. To perform a systematic review and meta-analysis to compare the effectiveness of these quite different treatment approaches, especially on relapse rates (RRs) after achieving remission. Published studies that included follow-up for at least 1year after treatment of PCT were included. The primary study outcome was PCT relapse. Pooled data are reported as the RRs per person-year of follow-up with 95% confidence intervals (CIs). Of 375 articles identified as pertaining to PCT treatment, 12 were eligible for analysis. Of these, five used high-dose 4-aminoquinoline regimens (two combined with phlebotomy and three without phlebotomy), five used low-dose 4-aminoquinoline regimens and three used phlebotomy. RRs during the year after treatment were similar for the high- and low-dose 4-aminoquinoline groups (35-36%) and lower in the phlebotomy group (20%). The pooled RRs with their 95% CIs were 8·6 (3·9-13·3) per 100 person-years in the high-dose 4-aminoquinoline group, 17·1 (8·9-25·3) per 100 person-years in the low-dose 4-aminoquinoline group and 5·1 (0·5-10·6) per 100 person-years in the phlebotomy group. Subgroup and sensitivity analyses showed similar results. Clinical or biochemical RRs ranged from 5 to 17 per 100 person-years after remission of PCT. Relapses were somewhat more frequent after remission with 4-aminoquinoline regimens than after remission following phlebotomy. Prospective studies are needed to define better how often relapses occur with these treatments after documenting both clinical and biochemical remission of PCT.

Hepatitis C Treatment in Patients With Porphyria Cutanea Tarda

BackgroundHepatitis C virus (HCV) infection is a common susceptibility factor for porphyria cutanea tarda (PCT). Experience on HCV treatment in patients with PCT is limited. Recently, HCV treatment has improved with direct-acting antivirals (DAA). We review our experience on HCV treatment in patients with PCT with older and newer regimens. Materials and MethodsA retrospective chart review was conducted. HCV treatment was attempted 22 times in 13 patients with PCT (5 attempts in 1, 2 in 5 and 1 in the other 7 patients). ResultsBefore starting HCV treatment, PCT was in complete remission in 16, partial remission in 2, unknown status in 2 and active in 2 instances. PCT relapsed during therapy 6 times (all interferon-based regimens and 2 including telaprevir), 4 requiring treatment interruption. Treatment was interrupted for reasons other than PCT relapse in 2 patients treated with interferon-based regimens. To prevent PCT recurrence, hydroxychloroquine was continued during HCV therapy 6 times (3 interferon regimens, 2 ribavirin regimens without interferon and 1 DAA alone). Twelve patients achieved sustained viral response, 3 with interferon regimens and 9 with DAA. Two patients with active PCT were treated with DAA, with reduction of plasma porphyrins in 1 and normalization in the other at the end of HCV therapy. ConclusionsHCV treatment regimens including interferon or ribavirin may precipitate PCT relapse. Hydroxychloroquine may be useful to prevent such relapses. In this limited experience, DAA were not associated with PCT relapse. Studies are needed to examine DAA as a primary PCT treatment in HCV-infected patients.

The Role of Polypodium leucotomos Extract in the Treatment of Porphyria Cutanea Tarda

The dermatologic manifestations of porphyrias result from localized cutaneous formation of reactive oxygen species. The significance of these inflammatory mediators may extend beyond the skin, as increased oxidative stress may play a role in the systemic manifestations of porphyrias. Polypodium leucotomos is a tropical fern that has demonstrated antioxidant, anti-inflammatory and photoprotective properties. Although it has proven effective in the treatment of various photoaggravated dermatoses, we are unaware of any prior reports citing Polypodium leucotomos as a beneficial treatment option in the setting of porphyria cutanea tarda. We describe a patient with refractory porphyria cutanea tarda, who demonstrated dramatic improvement in cutaneous lesions following the initiation of Polypodium leucotomos extract. Due to its low toxicity and demonstrated direct interference in the production of inflammatory mediators are central to cutaneous manifestations of porphyrias, we propose consideration of Polypodium leucotomos as a potential therapeutic option for patients with porphyria cutanea tarda.

Desferrioxamine treatment of porphyria cutanea tarda in a patient with HIV and chronic renal failure

Porphyria cutanea tarda (PCT) can occur in HIV patients. Current evidence suggests that HIV infection may interfere with the hepatic cytochrome oxidase system, leading to porphyrin metabolism impairment. Moreover, chronic hemodialysis in renal failure may be a risk factor for PCT. In addition to the contributory factors for PCT associated to HIV infection, it is possible that porphyrin accumulation secondary to renal failure may play a role in the expression of this disease. We report a case of PCT in an HIV-1 infected patient under blood dialysis, refractory to antimalarials and controlled with desferrioxamine.

Improvement in ocular cicatricial pemphigoid following treatment for porphyria cutanea tarda

A 64-year-old Caucasian male complaining of redness and tearing for 3 years in both eyes was referred for evaluation of cicatricial conjunctivitis. Ocular cicatricial pemphigoid was suspected and this diagnosis was confirmed through biopsy. The patient’s condition showed moderate improvement following treatment with methotrexate and mycophenolate mofetil. The patient was later diagnosed with porphyria cutanea tarda and phlebotomy treatments were subsequently initiated. The patient’s ocular symptoms improved further after he began receiving these phlebotomy treatments, and conventional treatment was discontinued. The authors hypothesize that circulating porphyrins activated by ultraviolet light could be the cause of the ocular cicatricial pemphigoid in this patient.

Improved Drug Modification to Treat Porphyria Cutanea Tarda

Porphyria cutanea tarda (PCT) also known as the “vampire disease” is the most common type of porphyritic diseases. This disease occurs 1 in 50,000 people. Symptoms involve hyperpigmentation (tanning of skin) and hypertrichosis (skin manifestations mainly on top of cheeks). This disease is contributed mainly by deficiency of uroporphyrinogen decarboxylase (UROD), an enzyme that is present in the cytoplasm which aids in the synthesis of heme. The commercial drug available that is used to treat PCT is Plaquenil chemically known as Hydroxychloroquinone. This drug has shown to be effective in patients. But, in many cases it even worsens the condition of PCT in addition to its side effects. Gumweed extract shows antiporphyric activity. Quercertin, a phytochemical present in guweed bestows the wonder to treat porphyria. This experiment is dedicated to make the drug hydroxychloroquinone safer and more efficient in the treatment of porphyria. It is manifested by combining it with a gumweed phytochemical quercertin which is originally a flavinoid. This new modified drug can be used in the treatment of porphyria cutanea tarda and also to reduce the harmful effects of plaquenil in addition to unveiling the health benefits of gumweed.

Pilot trial of deferasirox in the treatment of porphyria cutanea tarda

Pilot trial of deferasirox in the treatment of porphyria cutanea tarda

Effective treatment for porphyria cutanea tarda with oral cimetidine

Effective treatment for porphyria cutanea tarda with oral cimetidine

Treatment of porphyria cutanea tarda with chloroquine.

SUMMARY Twenty men and one woman with porphyria cutanea tarda were treated with oral chloroquine, 125 mg twice weekly. In nineteen of the patients chloroquine was taken for 8–5 months on average before complete clinical and biochemical remission occurred. Initially, treatment led to a considerable increase in urinary uroporphyrin and a mild increase in serum transaminases, but no adverse clinical reactions were observed. As the mechanism of chloroquine action in porphyria cutanea tarda has not yet been clarified, special caution must be observed when it is used therapeutically.

Management of hepatitis C virus in patients with porphyria cutanea tarda

Extrahepatic manifestations associated with chronic hepatitis C virus (HCV) infection are increasingly recognized and often complicate HCV therapy. Porphyria cutanea tarda (PCT), an uncommon phenotypic expression of a defect in the uroporphyrinogen decarboxylase enzyme, is 12 times more likely to occur in those with HCV compared with the general population in the United States. It is hypothesized that increased free intrahepatic iron levels and chronic HCV infection can accelerate the pathogenesis of liver injury in patients with phenotypic expression of PCT. Symptomatic treatment of PCT has traditionally revolved around phlebotomy to control total body iron levels. However, phlebotomy for PCT management poses a challenge to concomitant treatment of HCV with combination therapy, ribavirin, and interferon. This article highlights the pathogenesis of PCT and discusses its impact on the management of HCV in individuals with this uncommon extrahepatic disease.

A 32‐Year‐Old Man with Skin Lesions

Diagnosis: Porphyria cutanea tarda (PCT). The diagnosis was based on the photodistributed pattern of blistering, chronic pruritic skin lesions, increased skin fragility, and bruising (figure 1). Serological tests for hepatitis detected antibody to hepatitis C virus (HCV), with an HCV RNA load of copies/mL and an HCV-1b genotype. The patient 6 1.18 10 tested negative for HIV, and results of iron studies were normal. The clearance rate of urinary uroporphyrin was 891 mg/day (normal range, 10-50 mg/day). Urinary uroporphyrin clearance rates of 1800 mg/day have been associated with photosensitivity [1]. PCT is the most common form of porphyria and is commonly found in adults with liver disease and hepatic iron overload (figure 2) [2–4]. In both familial and sporadic forms of this disease, the primary abnormal condition appears to be the reduced activity of uroporphyrinogen decarboxylase. Studies involving large groups of patients with PCT have found a high frequency of HCV infection [5]. The pathogenesis of the skin lesions remains unknown. The differential diagnosis of skin lesions in patients with HCV includes PCT, mixed cryoglobulinemia, lichen planus, leukocytoclastic vasculitis, polyarteritis nodosa, erythema multiforme, and erythema nodosum [6]. Treatment of PCT involves avoidance of precipitating factors, such as alcohol use, sun exposure, and estrogen therapy, together with treatment of HCV infection (if present). Phlebotomy can be attempted, because iron depletion—even in the absence of iron overload—often leads to improvement in both dermatological and hepatic manifestations [7, 8]. Chloroquine therapy has also been used successfully in cases of PCT that are refractory to phlebotomy [9, 10]. There is increasing evidence of the efficacy of IFN-a therapy in patients with chronic HCV infection, and case reports document successful treatment of HCV-associated PCT with INF-a [11, 12]. Our patient was advised to avoid triggering factors—namely, to cease consuming alcohol—and is being evaluated for combination IFN-a– ribavirin therapy for treatment of HCV infection.

Effect of Chloroquine Wash-out Period of Photosensitizers in the Skin and Selected Organs in Rats.

In the last decade, photodynamic therapy has become an alternative method for the diagnosis and therapy of tumors. In human medicine hematoporphyrin derivatives, sulfonated hydrophilic meso-tetraphenylporphyrin (TPPS4) and an oligomer of hematoporphyrin (Photosan 3), are widely used. Chloroquine is used for the treatment of porphyria cutanea tarda for its power to release porphyrins from the liver tissue. The kinetics of two porphyrin photosensitizers TPPS4 and Photosan 3 in the skin and some organs as well as the effect of chloroquine on the porphyrin excretion and their accumulation in skin and organs of Wistar rats were studied. TPPS4 exhibited maximum fluorescence in skin 48 h after application with decreasing to basal level from the 8th to the 14th day. Maximum fluorescence was reached at 72 hours after Photosan 3 application and it decreased to basal level during 96 hours after application. TPPS4 caused significantly higher fluorescence compared to Photosan 3. Chloroquine after oral administration did not change the fluorescence of skin, but it significantly decreased the TPPS4 concentration in rat organs if chloroquine treatment started 3 days or 2 weeks after TPPS4 application. Chloroquine significantly decreased the serum TPPS4 concentration during the period of 28 days. Fluorescence of skin was significantly higher and lasted longer after application of TPPS4 compared to Photosan 3. Chloroquine after oral administration did not influence the fluorescence of the skin, but it significantly decreased the TPPS4 concentration in rat organs. This effect could be useful in photodynamic therapy for mobilizing exogenous porphyrins from tissues after parenteral photodynamic therapy.

Antioxidant inhibition of porphyrin-induced cellular phototoxicity

Porphyrins such as protoporphyrin IX (PP IX) and uroporphyrin I (UP I) can be phototoxic to human cells. To study the protective ability of antioxidants (β-carotene, lycopene, ascorbic acid and α-tocopherol), against such porphyrin phototoxicity, membrane destruction experiments (Jurkat cells) and human cell cultures (fibroblasts) were performed. Both β-carotene and lycopene and also the combination of β-carotene, ascorbic acid and α-tocopherol offered cell protection against PP IX phototoxicity. Investigations of both cell membrane protection and of cell growth showed differences in terms of the protection afforded by the anti-oxidants. Thus, for PP IX, carotenoids alone, and in combination with ascorbic acid and α-tocopherol, showed higher protection factors in general than UP I. However, for membrane protection there was significant protection against UP I by the combination of β-carotene, ascorbic acid and α-tocopherol but not by any of these anti-oxidants alone. The membrane protection against PP IX by β-carotene, and especially lycopene, is significant presumably because of the high lipophilicity of all these molecules. However, the hydrophilic UP I will cause phototoxicity mainly via H 2O 2, radical or singlet oxygen production in the aqueous phase, and these reactive species may be generated some distance from the cell membrane. This may lead to the little or no protection observed for UP I by the individual antioxidants. Nevertheless, a combination of β-carotene, ascorbic acid and α-tocopherol offers membrane protection against the phototoxicity of both porphyrins. This is believed to occur as a result of synergistic processes. Our results suggest that the treatment of porphyria cutanea tarda and erythropoietic protoporphyria may be improved by the use of a combination of the antioxidants studied.

Treatment of porphyria cutanea tarda with phlebotomy in a patient on peritoneal dialysis

Porphyria cutanea tarda (PCT) is frequently described among patients with chronic renal failure undergoing hemodialysis. One patient who was receiving peritoneal dialysis and had PCT develop has been described in the literature. However, it was later determined that the patient's PCT was related to the hepatotoxic drug she was receiving rather than her peritoneal dialysis. Our patient is the first reported case, to our knowledge, of a patient with end-stage renal disease with negative hepatitis serology who was not receiving a hepatotoxic drug, or on hemodialysis, who had PCT develop while receiving peritoneal dialysis. (J Am Acad Dermatol 2001;44:336-8.)

Management of porphyria cutanea tarda in the setting of chronic renal failure: A case report and review

The treatment of porphyria cutanea tarda (PCT) in patients with chronic renal failure poses a therapeutic challenge. In the absence of renal failure, phlebotomy and oral antimalarials have been the standard of care for PCT. However, in the presence of renal failure, associated chronic anemia often precludes the use of phlebotomy, and oral antimalarials are usually ineffective. We describe a patient with severe symptomatic PCT and chronic renal failure whose disease was successfully managed with a combination of high-dose erythropoietin and small volume phlebotomy. We also review several previously reported approaches to management of PCT in the setting of renal failure, which include small repeated phlebotomy, erythropoietin, deferoxamine, chloroquine, plasma exchange, high-efficiency/high-flux hemodialysis, cholestyramine, charcoal hemoperfusion, and kidney transplantation. An algorithm for the management of these patients is proposed. (J Am Acad Dermatol 2000;42:645-52.)

Treatment of Porphyria cutanea tarda with Oral Thalidomide

Eight male patients with overt clinical and biochemical features of porphyria cutanea tarda (PCT) were orally treated with 300 mg/day thalidomide for 1 week and with 200 mg/day for 3 more weeks. Already after the first week of treatment no new vesicles and/or bullae could be observed. Spontaneous blisters completely disappeared, increased skin fragility subsided and skin hyperpigmentation receded about 2 months after completion of therapy, whereas hypertrichosis persisted. There was a rapid decrease in the urinary total porphyrin excretion which reached normal levels in all patients by the end of the fourth week of therapy, whereas the posttreament chromatographic pattern of urinary porphyrins revealed a slight reduction of higher carboxylated porphyrin metabolites and an increase in the amount of the excreted coproporphyrin, as compared to the pretreatment period. Somnolence, intermittent constipation and dry mouth occurred in all patients, 2 patients additionally experienced dizziness. No evidence of peripheral neuropathy could be detected and laboratory investigations revealed no abnormalities, as compared to the pretreatment period. During the 16- to 28-month follow-up of the patients, no clinical or biochemical relapse was observed. In view of the encouraging results of the present investigation, further studies are now warranted in order to definitely answer the question whether oral thalidomide may be regarded as an effective alternative approach to the treatment of PCT.

Hepatic multi-nodular focal fatty metamorphosis in acquired porphyria cutanea tarda: Sonographic, CT, and mri features

The authors report the sonographic, computed tomography (CT), and magnetic resonance imaging (MRI) findings in a patient with acquired porphyria cutanea tarda and hepatic multi-nodular focal fatty metamorphosis. There has only been one previous description of an association between these two conditions. The diagnosis was confirmed by histological analysis of a liver biopsy specimen. Symptomatology related to the hepatic abnormality may be due to an inflammatory reaction induced by the presence of uroporphyrin crystals in the liver. Each of the radiological techniques demonstrated unusual hepatic abnormalities and, in particular, MRI showed poorly defined areas in the liver which, on T2-weighted sequences, exhibited a hypersignal with fat saturation. Treatment of porphyria cutanea tarda led to clinical remission and resolution of radiological abnormalities.