Version May 2024
INTRODUCTION — Porphyrias are metabolic disorders in which altered activity of enzymes in the heme biosynthetic pathway leads to accumulation of toxic metabolic intermediates or byproducts.
Porphyria cutanea tarda (PCT; previously called symptomatic porphyria, chemical porphyria, toxic porphyria) is the most common and the most readily treated porphyria. PCT is a cutaneous porphyria caused by deficient activity of uroporphyrinogen decarboxylase (UROD) in the liver. Hepatoerythropoietic porphyria (HEP) is an extremely rare condition caused by biallelic pathogenic variants in the UROD gene.
This topic discusses the management and prognosis of PCT and HEP. The pathogenesis, clinical manifestations, and diagnostic evaluation are presented separately. (See "Porphyria cutanea tarda and hepatoerythropoietic porphyria: Pathogenesis, clinical manifestations, and diagnosis".)
Management of PCT is highly specific. Additional topics discuss management of other cutaneous porphyrias:
●Erythropoietic porphyrias – Congenital erythropoietic porphyria (CEP) and erythropoietic protoporphyria (EPP).
•CEP – (See "Congenital erythropoietic porphyria", section on 'Management'.)
•EPP – (See "Erythropoietic protoporphyria and X-linked protoporphyria", section on 'Management'.)
●Acute hepatic porphyrias that can affect the skin – Variegate porphyria (VP) and hereditary coproporphyria (HCP) can cause skin and/or neurovisceral manifestations.
•VP – (See "Variegate porphyria", section on 'Management'.)
•HCP – (See "Hereditary coproporphyria", section on 'Management'.)
An overview of porphyrias is also presented separately. (See "Porphyrias: An overview".)
OVERVIEW OF MANAGEMENT — PCT is an iron-related, readily treated and nonfatal condition. The figure illustrates key management decisions (algorithm 1).
●Indications for treatment – All individuals with PCT and active skin lesions should be considered for treatment [1]. (See 'Indications for treatment' below.)
Individuals with subclinical PCT (porphyrin elevations that are diagnostic for PCT but without skin manifestations) may be treated or monitored and advised to avoid modifiable susceptibility factors. (See "Porphyria cutanea tarda and hepatoerythropoietic porphyria: Pathogenesis, clinical manifestations, and diagnosis", section on 'Susceptibility factors'.)
●Primary therapies – The preferred initial treatment for PCT associated with chronic hepatitis C virus (HCV) infection is treatment with direct-acting antiviral (DAA) therapy. (See 'Treatment for HCV infection' below.)
All other patients with PCT and active skin lesions who can tolerate phlebotomy or low-dose hydroxychloroquine should be considered for one of these therapies. Evaluation of iron status is important in determining which of these therapies to pursue. (See 'Indications for treatment' below and 'Choice of primary therapy' below and 'Postdiagnostic testing' below.)
●Skin protection – Protection from sunlight is recommended until porphyrin levels have normalized with treatment. (See 'Sunlight avoidance until porphyrins normalize' below.)
●Susceptibility factors – Individual PCT patients have different combinations of overt or underlying susceptibility factors that may influence choice of treatment [2]. Modifiable factors include smoking, alcohol and nonalcoholic fatty liver disease, chronic HCV infection, HIV infection, estrogens, and iron supplements. Genetic susceptibility factors may include heterozygosity for a pathogenic variant in UROD (found in approximately 20 percent of patients) and the HFE C282Y variant. (See 'Postdiagnostic testing' below and 'Counseling regarding susceptibility factors' below and 'Treatment for HCV infection' below.)
●Monitoring – After treatment and disease remission, plasma or urine porphyrin levels can be monitored. Porphyrin elevations are an early sign of recurrence and can prompt retreatment without waiting for skin lesions to redevelop. (See 'Monitoring after phlebotomy' below and 'Monitoring with hydroxychloroquine' below.)
●Genetic testing and counseling – Genetic testing of the UROD and HFE genes is recommended, in part to determine the risk to first-degree relatives, particularly for HFE C282Y. (See 'Considerations for relatives' below.)
Patients without a pathogenic variant in UROD are classified as having type 1 (sporadic) PCT, and those with a pathogenic variant in UROD as having type 2 (familial) PCT. Most type 2 patients present sporadically (with no family history of PCT). Type 3 refers to patients with relatives with PCT but without a UROD mutation; some may have HFE mutations. (See 'Disease classification (sporadic versus familial)' below.)
●Hepatoerythropoietic porphyria (HEP) – PCT-related susceptibility factors may play a role and should be evaluated in the exceedingly rare patients with HEP. HEP resembles CEP clinically, and avoidance of sun exposure is often the only reliable treatment. (See 'HEP (biallelic UROD variants)' below.)
CONSIDERATIONS BEFORE STARTING THERAPY
Postdiagnostic testing — Additional testing is indicated once the diagnosis of PCT is established biochemically. Full diagnostic evaluations for PCT (and HEP, which usually presents in childhood) are presented separately. (See "Porphyria cutanea tarda and hepatoerythropoietic porphyria: Pathogenesis, clinical manifestations, and diagnosis", section on 'Diagnostic evaluation'.)
●Tests used in decision-making about treatment of PCT – Assessment of severity of liver disease, iron status and recognized susceptibility factors helps to determine which therapy is most appropriate (algorithm 1). The following laboratory testing is indicated:
•Complete blood count (CBC) including platelet count
•Serum ferritin
•Serum chemistries and creatinine
•Liver function tests
-Bilirubin
-Alkaline phosphatase
-Transaminases (alanine aminotransferase [ALT], aspartate aminotransferase [AST])
-Albumin
-Prothrombin time
•Hepatitis C virus (HCV) testing – (See "Screening and diagnosis of chronic hepatitis C virus infection".)
•HIV testing – (See "Screening and diagnostic testing for HIV infection".)
•UROD genetic testing is part of determining the multiple susceptibility factors that differ among individual patients. Patients who are heterozygous for a UROD mutation are classified as having type 2 (familial) PCT [3]. Erythrocyte UROD activity is expected to be half-normal in such individuals with PCT who may experience disease onset at an earlier age and have fewer additional susceptibility factors. Patients with HEP have biallelic UROD variants and erythrocyte UROD activity is more markedly decreased (typically, <20 percent of normal). (See "Porphyria cutanea tarda and hepatoerythropoietic porphyria: Pathogenesis, clinical manifestations, and diagnosis", section on 'Disease classification' and "Porphyria cutanea tarda and hepatoerythropoietic porphyria: Pathogenesis, clinical manifestations, and diagnosis", section on 'Significance of pathogenic variants in the UROD gene'.)
•HFE genetic testing – Onset of PCT may be earlier in patients with biallelic HFE mutations and fewer additional susceptibility factors may be present. Finding of HFE mutations enables screening of relatives for unrecognized hemochromatosis before onset of symptoms. (See 'Asymptomatic UROD variants' below and "Gene test interpretation: HFE (hereditary hemochromatosis gene)".)
•For patients who will be receiving low-dose hydroxychloroquine, a baseline retinal examination. (See 'Monitoring with hydroxychloroquine' below.)
●Liver imaging – Almost all patients with PCT have abnormalities in liver chemistries as well as susceptibility factors that themselves may cause progressive liver damage. Therefore, imaging to assess for underlying advanced liver disease is important for all patients with PCT. (See "Epidemiology, clinical features, and diagnosis of nonalcoholic fatty liver disease in adults", section on 'Radiographic examinations' and "Clinical manifestations and diagnosis of alcohol-associated fatty liver disease and cirrhosis", section on 'Imaging studies'.)
●HCC surveillance – Surveillance for hepatocellular carcinoma (HCC) is appropriate for any patient with evidence of advanced hepatic fibrosis or cirrhosis after treatment of PCT. (See 'HCC surveillance' below and "Surveillance for hepatocellular carcinoma in adults".)
Indications for treatment
●Active skin lesions – All patients with active skin lesions from PCT (picture 1 and picture 2 and picture 3) should be treated with one of the three primary therapies (direct-acting antivirals [DAAs] for HCV, phlebotomy, or low-dose hydroxychloroquine), skin should be protected, and any other identified susceptibility factors should be addressed. The figure summarizes considerations in choice of primary therapy (algorithm 1).
●Subclinical PCT – PCT causes elevation in porphyrins in urine and plasma, with a predominance of uroporphyrin (octacarboxyl porphyrin) and heptacarboxyl porphyrin, and in the absence of skin lesions may represent PCT that is presymptomatic or in partial remission. This pattern of increased porphyrins is not completely specific for PCT, and other porphyrias such as variegate porphyria (VP) should be considered [4].
Longitudinal observations to determine how many of individuals found to have subclinical PCT will develop overt PCT without treatment are lacking. However, susceptibility factors should be identified and reduced when possible, and porphyrin levels monitored at intervals of three to six months to determine if further increases or decreases are occurring. Patients previously treated for active PCT who have recurrent elevations in porphyrins may be retreated before skin lesions reappear.
●Heterozygosity for UROD pathogenic variant without porphyrin elevation – Individuals identified as heterozygous for a pathogenic variant in UROD who lack porphyrin elevations can be counseled to avoid factors associated with overt PCT and their porphyrin levels monitored perhaps yearly, but these individuals do not require primary therapy. This applies to individuals who have genetic testing for any reason (first-degree relative identified with PCT and a UROD pathogenic variant, secondary finding from genetic testing done for another reason) (see 'Considerations for relatives' below). However, longitudinal observations of such individuals are lacking.
Choice of primary therapy — The following considerations influence the choice of primary therapy (algorithm 1):
●HCV status – For individuals with chronic HCV infection, growing experience suggests that DAA treatment is effective primary therapy for PCT and is the treatment of choice rather than phlebotomy or low-dose hydroxychloroquine [1]. (See 'Treatment for HCV infection' below.)
If there is substantial iron overload, therapeutic phlebotomies can also be started concurrently or (preferably) after cure of HCV infection. Because inflammation in the liver due to HCV can contribute to ferritin elevation by inducing an acute phase response, the degree of iron overload can be more meaningfully assessed after successful antiviral therapy.
●Institutional preference – Phlebotomy is preferred at most centers for treatment of PCT not associated with chronic HCV, based on greater experience.
●Iron status – Phlebotomy is also attractive because PCT is an iron-related disease.
•Iron overload or homozygous HFE C282Y or H63D – For individuals with iron overload, phlebotomy is clearly preferred because it treats PCT and prevents organ injury from excess iron. We feel most strongly about using phlebotomy in individuals with substantially elevated ferritin (>600 ng/mL) or with biallelic HFE mutations that have been associated with hemochromatosis.
•No iron overload – For individuals who are heterozygous or negative for HFE C282Y and have lower ferritin levels, either phlebotomy or low-dose hydroxychloroquine is reasonable. Details of these therapies are provided below. (See 'Phlebotomy' below and 'Low-dose hydroxychloroquine' below.)
Phlebotomies and low-dose hydroxychloroquine are both considered effective primary therapy for PCT and are almost always able to produce a complete remission. Although controlled trials are lacking, either of these treatments appears to result in faster improvements than removal of susceptibility factors such as discontinuation of alcohol alone.
-Advantages of phlebotomy include proven efficacy based on uncontrolled observations over many decades and a strong rationale for treating an iron-related disease. However, phlebotomy may be expensive, inconvenient, and uncomfortable, and may cause syncope or anemia in some patients. As a result, compliance with phlebotomy can be challenging [5].
-Advantages of hydroxychloroquine include greater ease of use and lower cost.
●Pregnancy – Experience with treatment of PCT during pregnancy is lacking. However, low-dose hydroxychloroquine for treatment of any condition is contraindicated during pregnancy. Likewise, antiviral therapy for HCV infection during pregnancy is not an option, since the safety and efficacy of DAA agents in pregnancy have not been evaluated. Phlebotomy may be feasible if PCT is associated with marked iron overload, but in general it is preferred to address treatment of PCT after delivery. Given that PCT is readily treated, therapy is ideally instituted if needed prior to pregnancy.
●Comorbidities – Hydroxychloroquine should not be used in the following individuals:
•Pregnant or breastfeeding
•Advanced liver disease, regular alcohol use, or hepatotoxic medications
•Glucose-6-phosphate dehydrogenase (G6PD) deficiency
•Psoriasis
•Retinal disease (unless cleared by an ophthalmologist)
•End-stage kidney disease (ESKD)
●Patient preference – Phlebotomy and low-dose hydroxychloroquine are very different treatments, and patient circumstances and preferences must be considered.
●Supporting evidence — Phlebotomy and low-dose hydroxychloroquine were compared in a 2012 prospective pilot study involving 48 consecutive patients with PCT, which found that time needed to normalize plasma porphyrin levels, which predicts clinical improvement, was similar for both treatments [5]. In this study, patients underwent phlebotomy (one unit of blood every two weeks) or treatment with low-dose hydroxychloroquine (100 mg twice a week). Most patients were either ineligible for one of these treatments or preferred to choose the type of treatment and therefore were not randomly assigned to treatment. Nevertheless, clinical features, including frequency of HCV, were comparable in both treatment groups.
Time to achieving a normal plasma porphyrin concentration in 30 evaluable patients was similar at 6.9 months for phlebotomy and 6.1 months for hydroxychloroquine. Normalization of plasma porphyrin levels rather than skin findings was used to define remission because resolution of skin lesions was highly variable and difficult to assess. Costs were lower and compliance was better with hydroxychloroquine.
With both therapies, a longer time is needed to reverse the predominance of highly carboxylated porphyrins in urine and for skin lesions to heal and skin friability to resolve. Studies comparing recurrence rates after each of these treatments and as related to various susceptibility factors are needed.
Experience in the DAA era supports initial treatment of PCT with DAAs when a patient's susceptibility factors include chronic HCV. Improvement of PCT occurs as rapidly with DAA treatment as with phlebotomy or low-dose hydroxychloroquine [1]. PCT is the only type of porphyria that can be cured by successful treatment of concurrent HCV.
Evidence is lacking for other treatments such as thalidomide, plasmapheresis, vitamin E, N-acetylcysteine, anastrozole, urinary alkalization, or cimetidine [6-11]. These should not be considered alternatives to DAAs, phlebotomy, or low-dose hydroxychloroquine.
Sunlight avoidance until porphyrins normalize — Patients may not appreciate that the skin manifestations are due to sun exposure. Sunlight should be avoided at least until plasma porphyrin levels are normal but is generally not needed once plasma porphyrin levels normalize.
Skin fragility and blistering may continue for some time after porphyrin levels are normal, probably due to slow healing of previously damaged skin.
Skin protection measures include:
●Cloth gloves
●Broad-brimmed hats
●Sunglasses
●Long trousers and long-sleeved shirts
●Shoes
●Other protective clothing
●Inorganic sunscreens (eg, zinc oxide, titanium dioxide)
Details are presented separately. (See "Overview of cutaneous photosensitivity: Photobiology, patient evaluation, and photoprotection", section on 'Photoprotection' and "Selection of sunscreen and sun-protective measures", section on 'Selection of sunscreen products'.)
Pain control and infection prevention — The skin lesions associated with PCT may be painful and require oral analgesics. Affected areas should be kept clean and skin infections treated with antibiotics; topical steroids are of little or no benefit. Skin fragility, which can persist for some time after biochemical remission, is not itself an indication that treatment was not successful.
Counseling regarding susceptibility factors — Most patients with PCT have multiple susceptibility factors, which may include alcohol use, smoking, estrogen use, HCV infection, HIV infection, UROD mutations, and/or HFE mutations. (See "Porphyria cutanea tarda and hepatoerythropoietic porphyria: Pathogenesis, clinical manifestations, and diagnosis", section on 'Susceptibility factors'.)
Patients are advised to favorably alter the factors they can control by stopping alcohol, estrogen use, and smoking. Early involvement of a hepatologist is advisable because PCT is a liver disease and many of the associated susceptibility factors affect the liver.
Limited experience suggests that these behavioral changes alone are not sufficient for remission but may hasten response to phlebotomy or hydroxychloroquine and prevent recurrences. It is not clear why recurrences occur in some patients and not others; in many individuals, resumption of excess alcohol intake is often implicated.
●Alcohol – Patients are advised to abstain from use of alcohol, and many do so at least for a period of time. Additional strategies for alcohol cessation for individuals with an alcohol use disorder are presented separately. (See "Alcohol use disorder: Psychosocial management" and "Brief intervention for unhealthy alcohol and other drug use: Efficacy, adverse effects, and administration".)
●NAFLD – Nonalcoholic fatty liver disease (NAFLD) is another modifiable risk factor. Management is discussed separately. (See "Management of nonalcoholic fatty liver disease in adults".)
●Smoking – Patients are also advised to discontinue smoking, including marijuana. For many patients, this is more difficult than stopping alcohol use. Strategies are discussed separately. (See "Overview of smoking cessation management in adults" and "Pharmacotherapy for smoking cessation in adults".)
●Estrogen – Patients receiving estrogen therapy are advised to discontinue use at least until remission is achieved, after which an estrogen patch may be used safely, if necessary [12].
●Iron – Patients should be counseled to avoid potential sources of excessive iron intake such as dietary and nutritional supplements or multivitamins containing iron; however, avoidance of normal dietary sources of iron such as red meat is not required.
●Medications – Estrogens are the only drugs that are commonly implicated in causing PCT in adults. PCT is very rare in children, and most cases have been associated with cancer treatment with multiple chemotherapeutic agents [13]. Drugs known to exacerbate acute porphyrias are seldom reported to precipitate PCT (table 1); however, they should be avoided when possible.
Little induction of ALAS1 is needed to account for the large amounts of porphyrins excreted in urine in PCT (in contrast with the much larger amounts of delta-aminolevulinic acid [ALA] and porphobilinogen [PBG] that are excreted in the acute hepatic porphyrias) [14]. However, medications that induce hepatic ALAS1 may sometimes contribute in PCT and should be avoided [15].
Additional information on drugs that are considered harmful in acute hepatic porphyrias based on existing (but often limited) evidence can be accessed online:
•American Porphyria Foundation (https://porphyriafoundation.org/)
•International Porphyria Network (IPNET; https://porphyrianet.org/en/content/worldwide-network)
PHLEBOTOMY
Overview of phlebotomy — Phlebotomy is appealing because PCT is an iron-related disorder, and iron depletion presumably prevents formation of the uroporphomethene UROD inhibitor. (See "Porphyria cutanea tarda and hepatoerythropoietic porphyria: Pathogenesis, clinical manifestations, and diagnosis", section on 'UROD inhibitor'.)
Repeated phlebotomy is highly effective for treating PCT associated with iron overload as well as in patients with normal iron stores [16-24].
●Phlebotomy is clearly preferred in patients with substantial iron overload, such as with ferritin >600 ng/mL or with homozygosity for HFE C282Y or H63D or compound heterozygosity (C282Y/H63D), since iron overload can cause other health issues.
●Phlebotomy is not effective for treating other porphyrias; thus, it is important before starting treatment to be sure that the diagnosis of PCT is confirmed and other less common cutaneous porphyrias are excluded. Patients with variegate porphyria (VP), hereditary coproporphyria (HCP), mild congenital erythropoietic porphyria (CEP), or hepatoerythropoietic porphyria (HEP) are frequently misdiagnosed initially as having PCT and treated inappropriately. (See "Porphyria cutanea tarda and hepatoerythropoietic porphyria: Pathogenesis, clinical manifestations, and diagnosis", section on 'Differential diagnosis'.)
Phlebotomy procedure — Phlebotomy involves removal of one unit of whole blood (approximately 450 mL) at intervals of approximately every two weeks. It can be performed in a medical office, blood bank or other hospital facility, or at the patient's home by a trained phlebotomist. Patients should be encouraged to maintain hydration and avoid vigorous exercise within 24 hours of the procedure to avoid volume depletion or dehydration. This phlebotomy interval is more frequent than allowed by blood collection facilities that collect donated blood for transfusion. (See "Blood donor screening: Overview of recipient and donor protections", section on 'Donation frequency'.)
●Ferritin assessment – We use an initial target ferritin of approximately 25 ng/mL, which assures depletion of excess iron without causing anemia. It is not necessary to maintain this ferritin long term, especially if other susceptibility factors can be addressed.
Serum ferritin and hemoglobin are measured with each procedure and the results are used to determine whether the next procedure should occur on schedule or should be delayed. Phlebotomies are continued until the ferritin level from two weeks earlier is <30 ng/mL, at which point phlebotomies are stopped and a ferritin level is drawn to document a level of approximately 25 ng/mL.
Ferritin is an acute phase reactant that can increase with inflammation (see "Acute phase reactants"). However, a predictable downward trend to a target value of approximately 25 ng/mL is observed in almost all patients with PCT treated by phlebotomy.
●Hemoglobin assessment – Phlebotomy is deferred and rescheduled if the hemoglobin is too low; the threshold is individualized according to the individual's baseline and other health conditions that might be adversely affected by anemia. This approach leads to remission of PCT while avoiding development of symptomatic anemia.
Phlebotomy is often difficult in patients with end-stage kidney disease (ESKD) due to anemia. Stopping iron supplementation, initiating erythropoietin (or increasing the erythropoietin dose if the patient is already taking erythropoietin), and performing small-volume phlebotomies can be effective [25,26].
Specific recommendations on the use of erythropoietin as well as relative contraindications in patients with ESKD are presented separately. (See "Hyporesponse to erythropoiesis-stimulating agents (ESAs) in chronic kidney disease".)
Iron chelation and hydroxychloroquine are other options for individuals who cannot tolerate phlebotomy due to anemia. (See 'Iron chelation for individuals who cannot tolerate phlebotomy' below and 'Low-dose hydroxychloroquine' below.)
●Porphyrin and skin assessment – Plasma porphyrins are also monitored at each phlebotomy. Porphyrins are almost always decreased from baseline during treatment but remain elevated when the target ferritin is reached and phlebotomies are stopped [18]. Porphyrins can then be measured monthly to document gradual normalization. Resolution of skin lesions may also be delayed and should not be used as a basis for continuing or discontinuing phlebotomy.
Expected response to phlebotomy
●Number of phlebotomies needed – Most patients will require only six to eight phlebotomies to reach the target ferritin level because severe iron overload is not common in PCT.
An exception is an individual with iron overload and HFE C282Y/C282Y or C282Y/H63D; these individuals have hereditary hemochromatosis and may require substantially more phlebotomy procedures to remove excess iron. They should also undergo periodic maintenance phlebotomies to prevent reaccumulation of excess iron stores, as discussed separately. (See "Management and prognosis of hereditary hemochromatosis", section on 'Phlebotomy'.)
In a case series of 147 patients with PCT, C282Y/C282Y and C282Y/H63D genotypes were found in 6 and 8 percent, respectively [27].
●Changes in the liver – The large amounts of porphyrins in the liver are gradually mobilized and excreted, and porphyrin levels will continue to decrease [19]. Improvement in liver function and histology are reported but are inconsistent, reflecting the role of commonly associated susceptibility factors that also cause liver damage [23].
●Skin changes – Phlebotomy is generally highly effective in treating skin lesions of PCT, although recovery is gradual. Hypertrichosis and hyperpigmentation also improve slowly. Pseudo-sclerodermatous skin changes improve in some patients [19]. Patients often have minor continuing skin symptoms.
Monitoring after phlebotomy — Once phlebotomy is stopped, plasma or urine porphyrins can be monitored at 6- to 12-month intervals, and phlebotomy can be reinitiated if porphyrin levels again become elevated. For a patient who has repeated recurrences of PCT, limited experience suggests that maintaining the ferritin level <100 ng/mL may prevent further recurrences.
Iron chelation for individuals who cannot tolerate phlebotomy — Iron chelation is much less efficient for removing iron than phlebotomy and is only used for individuals with PCT and substantial iron overload who cannot tolerate phlebotomies due to anemia or other reasons such as inadequate venous access, symptoms of iron deficiency (restless legs syndrome), or symptoms related to volume depletion at the time of phlebotomy (significant fatigue or lightheadedness). Phlebotomy-related symptoms can be treated with a fluid bolus after completion of phlebotomy to replete intravascular volume more rapidly. Several studies in individuals with PCT have documented that iron chelation is less useful than standard of care treatment by phlebotomy or low-dose hydroxychloroquine:
●Phlebotomy versus deferoxamine – An observational study compared phlebotomy (15 patients) versus deferoxamine (DFO, Desferal; 10 patients); the patients treated with DFO had various contraindications to phlebotomy [17]. Both treatments were effective; remission occurred in 6 to 14 months with chelation. However, the number of phlebotomies needed for the comparison group was unusually large (15 to 32 phlebotomies per patient, 300 mL each), and times to remission were unusually long (9 to 19 months). Times to reaching target ferritin levels were not compared. Deferoxamine was given as 1.5 g by subcutaneous pump five days a week, which was more expensive and required a greater time commitment than phlebotomy.
●Hydroxychloroquine versus deferoxamine – A well-designed trial randomly assigned 40 patients with PCT and heavy alcohol use to hydroxychloroquine (200 mg twice a week) versus deferoxamine (30 mg/kg daily administered subcutaneously for one week every three months) and found improvement in both groups [28]. However, decreases in ferritin with chelation (55 ng/mL at six months) were not comparable to what is generally seen with phlebotomy (20 ng/mL). Urine porphyrins were normal at one year with hydroxychloroquine and had decreased but remained elevated with chelation. The authors concluded that hydroxychloroquine rather than chelation should be the preferred alternative to phlebotomy.
●Deferasirox – In a pilot study of deferasirox (Exjade), skin blistering decreased in all eight evaluable patients, but ferritin decreased by only 41 percent to 226 ng/mL, which is not comparable with the target ferritin levels generally seen with phlebotomy [29]. Two patients did not initially have uroporphyrin elevations as expected in PCT. Therapy was given for six months at an initial dose of 250 mg daily (equivalent to approximately 5 mg/kg daily) and was increased to 500 mg daily at two months due to continued new blister formation in all patients. This dose of 500 mg daily (equivalent to approximately 10 mg/kg daily) is lower than doses used for patients with transfusional iron overload. (See "Iron chelators: Choice of agent, dosing, and adverse effects".)
Chelation therapy also requires additional monitoring (eg, audiology examination, ophthalmology evaluation, liver function testing), which is different for each chelating agent. (See "Iron chelators: Choice of agent, dosing, and adverse effects" and "Transfusion in sickle cell disease: Management of complications including iron overload", section on 'Monitoring for adverse events'.)
LOW-DOSE HYDROXYCHLOROQUINE
Overview of low-dose hydroxychloroquine — Hydroxychloroquine and chloroquine are 4-aminoquinoline antimalarial drugs that are considered interchangeable. Hydroxychloroquine is preferred because it is thought to be safer in terms of retinal toxicity [30]. (See 'Monitoring with hydroxychloroquine' below.)
●Indications – Low-dose hydroxychloroquine is an effective treatment for PCT, either for initial therapy or as a suitable alternative when phlebotomies are difficult to perform or poorly tolerated. Direct-acting antivirals (DAAs) are preferred therapy in patients with PCT and hepatitis C virus (HCV) infection. (See 'Treatment for HCV infection' below.)
Low-dose hydroxychloroquine is an appropriate choice for patients without iron overload (with ferritin in the normal range), including individuals who are heterozygous for HFE C282Y and H63D.
Advantages of hydroxychloroquine include ease of use, low cost, and low incidence of toxicities of the recommended low-dose regimen. Disadvantages include the need for ophthalmologic examinations and the need for assistance in cutting pills.
●Contraindications – Contraindications include:
•Pregnancy or lactation
•Advanced liver disease
•End-stage kidney disease (ESKD)
•Regular use of alcohol or hepatotoxic drugs such as acetaminophen, isoniazid, or valproic acid
•Glucose-6-phosphate dehydrogenase (G6PD) deficiency
•Psoriasis
•Retinal disease (unless cleared by an ophthalmologist)
For individuals with iron overload, low-dose hydroxychloroquine is not a means of removing excess iron. Patients with marked iron overload or HFE-related hemochromatosis should be treated by phlebotomy rather than hydroxychloroquine.
Low-dose hydroxychloroquine should not be used to treat PCT in patients with ESKD because mobilized porphyrins are poorly dialyzed.
Hydroxychloroquine dosing and duration of therapy
●Dosing – The preferred regimen is hydroxychloroquine, 100 mg (one-half of a 200 mg tablet), orally twice per week [5]. Half-pills are used because pills containing the preferred dose for PCT are not available.
This regimen of hydroxychloroquine has been shown to achieve a normal plasma porphyrin level as quickly as phlebotomy [5]. Higher doses have been used but have not been shown to lead to more rapid remission and are likely to cause more frequent side effects [31-37].
●Duration of therapy – The optimal duration of treatment is not established, but we and others continue treatment until plasma or urine porphyrin levels have been normal for at least several months [32].
●Re-treatment – PCT recurrences after treatment with low-dose hydroxychloroquine can be re-treated in the same manner. However, the safety and efficacy of continuing hydroxychloroquine during remission to prevent recurrence of PCT has not been studied and is not advisable.
●Adverse effects – Even with a regimen of hydroxychloroquine, 100 mg twice per week, mild transaminase and porphyrin elevations may occur initially but these increases are not usually accompanied by symptoms, and they typically resolve with continued treatment. Hydroxychloroquine rather than chloroquine is recommended because hydroxychloroquine may have less potential for adverse effects than chloroquine [30].
This treatment causes a noticeable initial increase in photosensitivity in some patients. Further, even minor hepatotoxicity is a concern if the patient has advanced liver disease, is consuming large amounts of alcohol, or is being treated with a hepatotoxic drug.
There is a risk of retinopathy with hydroxychloroquine (or chloroquine) treatment that appears to be dose dependent [38,39]. Although retinopathy is unlikely to occur with the low doses described herein, ophthalmological examination should be performed according to standard guidelines (eg, before treatment, at the end of treatment, or after one year if continued treatment is needed to achieve remission, which is unusual).
Adverse effects are discussed in more detail separately. (See "Antimalarial drugs in the treatment of rheumatic disease", section on 'Adverse effects'.)
●Supporting evidence – A retrospective review observed responses to hydroxychloroquine in all individuals with PCT except those who were homozygous for HFE C282Y [40]. This included responses with sustained resolution of skin lesions in 59 individuals (nine who were heterozygous for HFE C282Y, 18 who were homozygous for HFE H63D, eight who were compound heterozygous for HFE C282Y and H63D, and 24 who lacked either HFE variant). Outcomes in three individuals who were homozygous for HFE C282Y included failure of lesions to improve in one and transient improvement followed by recurrence in two.
Evidence demonstrating better responses with hydroxychloroquine versus iron chelation is discussed above. (See 'Iron chelation for individuals who cannot tolerate phlebotomy' above.)
●Historical background and mechanism of action – The role of hydroxychloroquine and chloroquine in PCT has an interesting history.
•It was noted initially that patients treated with higher doses of these drugs for other diseases such as rheumatoid arthritis who also had PCT developed fever, malaise, nausea, and marked increases in urinary uroporphyrin and heptacarboxyl porphyrin, plasma porphyrins, serum transaminases, other liver function tests, and ferritin levels. A usual dose of chloroquine for malaria prophylaxis can even unmask previously unrecognized PCT [41,42].
•This initial toxicity was followed by complete remission of PCT [43]. The dose-related acute increases in porphyrin levels and cutaneous manifestations of PCT are manifestations of acute hepatic damage and the release of large amounts of porphyrins stored in hepatocytes.
•These drugs are weak bases and are mostly taken up in hepatocytes and especially in lysosomes, where excess porphyrins are stored in PCT. They may complex with porphyrins in these subcellular organelles, and cell damage may occur as porphyrins are released. However, the mechanism by which these drugs mobilize porphyrins is not well understood [5]. They may lower hepatocyte iron uptake but do not lower ferritin levels significantly, so they do not appear to act by causing iron depletion.
•Subsequently, it was found that a low-dose regimen was preferred compared with standard doses because porphyrins are mobilized from the liver more gradually with little increase in plasma porphyrins or hepatocellular damage.
Monitoring with hydroxychloroquine — Treatment efficacy is monitored by measuring plasma and urine porphyrins monthly. The drug is stopped after the levels have been normal for at least several months [5].
Retinal examinations are required before initiating treatment with hydroxychloroquine. Examinations should be repeated after one year, or at the end of treatment (which is usually before one year). (See "Antimalarial drugs in the treatment of rheumatic disease", section on 'Ocular effects'.)
Once the drug is discontinued, longer-term monitoring for PCT recurrence consists of clinical assessment and porphyrin measurement at 6- to 12-month intervals.
Re-treatment may be based on porphyrin elevations as an early sign of recurrence rather than waiting for skin lesions to develop.
Monitoring of ferritin is not helpful during treatment with hydroxychloroquine; even low-dose hydroxychloroquine may cause transient hepatocellular damage accompanied by an acute phase response and a transient increase in ferritin. Additionally, this treatment is expected to mobilize and remove porphyrins rather than iron.
LIVER DISEASE
Treatment for HCV infection — Hepatitis C virus (HCV) infection is an important susceptibility factor for PCT.
Direct-acting antiviral (DAA) agents are highly effective for treating chronic HCV infection and have excellent safety profiles. All individuals with chronic HCV infection should be offered DAA as initial treatment rather than phlebotomy or low-dose hydroxychloroquine [1]; delays in treating HCV should be avoided. Supporting evidence for DAA therapy comes from observational studies and our experience [44-46].
Specific HCV treatment recommendations are discussed in detail separately:
●Overview and selection of therapy – (See "Overview of the management of chronic hepatitis C virus infection".)
●Initial antiviral therapy – (See "Management of chronic hepatitis C virus infection: Initial antiviral therapy in adults".)
●Antiviral retreatment following relapse – (See "Management of chronic hepatitis C virus infection: Antiviral retreatment following relapse in adults".)
●HCV and HIV coinfection – (See "Treatment of chronic hepatitis C virus infection in the patient with HIV".)
HCC surveillance — The risk for hepatocellular carcinoma (HCC) is increased in individuals with chronic liver disease and advanced fibrosis or cirrhosis. (See "Epidemiology and risk factors for hepatocellular carcinoma".)
Surveillance for HCC is appropriate after age 50 years for any patient with advanced hepatic fibrosis or cirrhosis, including patients who have been successfully treated for PCT. (See "Surveillance for hepatocellular carcinoma in adults".)
PROGNOSIS
●Quality of life – Evidence from a Norwegian registry suggests that PCT negatively affects health-related quality of life, especially among untreated patients [47]. After successful treatment of PCT, quality of life is expected to return to normal.
●Disease course – PCT may relapse following successful treatment, especially in patients who resume excess alcohol intake, but the frequency of relapses and relationship to other susceptibility factors are unclear.
In a meta-analysis of 12 studies involving 525 patients with PCT, relapse rates after treatment with phlebotomy or antimalarial drugs were approximately 20 to 35 percent over a median follow-up of 1 to 11 years [37]. The pooled relapse rate per person-year of follow-up was 5.1 percent after initial remission with phlebotomy, 8.6 percent with high-dose hydroxychloroquine, and 17.1 percent after low-dose hydroxychloroquine. However, most of the series were single-arm and did not directly compare relapse rates with different therapies. This study preceded the availability of highly effective treatments for hepatitis C.
Such estimates may be affected by adequacy of follow-up, which may be better in those who relapse, and by inclusion of cases where initial treatment was incomplete. Many other considerations factor into the choice of therapy, as discussed above. (See 'Choice of primary therapy' above.)
●Survival – PCT is a readily treated, nonfatal condition; a normal life expectancy should be expected.
However, there is often underlying liver disease and other concurrent conditions, and some patients have developed hepatocellular carcinoma (HCC). This is the rationale for surveillance in individuals who have liver disease with advanced fibrosis or cirrhosis. (See 'HCC surveillance' above.)
In a case-control study in Denmark, patient survival at 20 years was lower in PCT versus matched control individuals (43 versus 61 percent), with the higher mortality mainly due to gastrointestinal diseases and cancers of the gut, liver, gallbladder, and lungs [48].
Prognosis for hepatoerythropoietic porphyria (HEP) is discussed below. (See 'HEP (biallelic UROD variants)' below.)
SPECIAL POPULATIONS
HEP (biallelic UROD variants) — Hepatoerythropoietic porphyria (HEP) is an extremely rare condition caused by biallelic pathogenic variants in UROD, which encodes uroporphyrin decarboxylase (UROD). (See "Porphyria cutanea tarda and hepatoerythropoietic porphyria: Pathogenesis, clinical manifestations, and diagnosis", section on 'Disease classification'.)
●Protection from sunlight – The cornerstone of management for HEP is protection from sunlight; this is the only intervention known to improve symptoms reliably. (See 'Sunlight avoidance until porphyrins normalize' above.)
●Susceptibility factors – In contrast with PCT, reduction of hepatic iron does not appear to be effective in managing HEP, likely because in the absence of a normally functioning gene, hepatic UROD activity remains low from birth [49,50]. (See 'Counseling regarding susceptibility factors' above.)
However, it is reasonable to evaluate these patients for the susceptibility factors that are important in PCT because it is possible that generation of a UROD inhibitor could sometimes contribute to further lowering of hepatic UROD activity. (See "Porphyria cutanea tarda and hepatoerythropoietic porphyria: Pathogenesis, clinical manifestations, and diagnosis", section on 'UROD inhibitor'.)
●Hydroxychloroquine – Low-dose chloroquine was apparently useful in one case [50]. Low-dose hydroxychloroquine might be tried, with appropriate dose reduction for a pediatric patient and careful observation to assess efficacy and safety.
●Charcoal – Oral charcoal, which can bind porphyrins in the gastrointestinal tract, was helpful in a case of severe disease that resembled congenital erythropoietic porphyria (CEP) but had UROD deficiency and dyserythropoiesis [51].
●Management of complications – Additional aspects of dermatologic and eye care, dental care, and the importance of vitamin D supplementation in patients practicing strict sun avoidance, are similar to those for patients with CEP; these are presented separately. (See "Congenital erythropoietic porphyria", section on 'Skin and eye care' and "Congenital erythropoietic porphyria", section on 'Vitamin D' and "Congenital erythropoietic porphyria", section on 'Dental care'.)
Anemia is unusual in HEP, but in one case, severe anemia was successfully treated with erythropoietin [52]. Other potential causes of anemia should also be investigated and addressed if present (eg, iron deficiency, hemolytic anemia). (See "Approach to the child with anemia" and "Diagnostic approach to anemia in adults".)
●Stem cell or liver transplantation – There is no evidence that hematopoietic stem cell transplantation is an effective therapy for HEP.
It is presumed that most of the excess porphyrins in this disease are produced by the liver, and it is unlikely that restoration of UROD activity in hematopoietic cells alone would overcome the hepatic UROD deficiency and excessive hepatic porphyrin production [53]. Strategies utilizing gene therapy may be effective in the future [54].
Liver transplantation has not been reported.
●Prognosis – HEP can be disfiguring, but life-threatening complications are rare and life expectancy appears to be normal [55].
●Genetic/reproductive counseling – Genetic and reproductive counseling may be more complex for individuals or families with HEP than for those with PCT.
Full siblings have a 25 percent chance of inheriting a UROD variant from both parents and developing HEP, a 50 percent chance of inheriting a UROD variant from one parent, and a 25 percent chance of not inheriting a UROD variant. Individuals who only have one UROD variant are at low risk to develop PCT because penetrance is low. (See "Porphyria cutanea tarda and hepatoerythropoietic porphyria: Pathogenesis, clinical manifestations, and diagnosis", section on 'Significance of pathogenic variants in the UROD gene'.)
In addition to discussing the inheritance pattern, counseling may include information regarding the possible use of preimplantation genetic testing, prenatal testing, or donor gametes [56]. (See "Preimplantation genetic testing" and "Donor insemination" and "In vitro fertilization: Overview of clinical issues and questions", section on 'When are donor oocytes used?' and "Diagnostic amniocentesis" and "Chorionic villus sampling".)
HIV — Optimal therapy for HIV is important in patients with PCT who have HIV infection. It is not clear if optimal HIV therapy alone will lead to improvement of PCT, but the two conditions should be treated concurrently. Concurrent HCV infection should also be treated if present, and this may lead to resolution of PCT; however, experience is limited. Patients with PCT and HIV infection who are not coinfected with HCV may be considered for treatment with phlebotomy or low-dose hydroxychloroquine. The choice of primary therapy is similar to patients without HIV. (See 'Choice of primary therapy' above.)
PCT has not been found to be an indication for altering treatment for HIV. Recommendations for HIV therapy are presented separately. (See "Primary care of adults with HIV" and "Acute and early HIV infection: Treatment" and "Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach".)
Asymptomatic UROD variants — Individuals who are heterozygous for a pathogenic variant in UROD who do not have skin lesions or porphyrin elevations are considered to have latent familial disease. The disease has very low penetrance, and patients may be monitored and treated if they develop elevations in porphyrin levels. (See 'Indications for treatment' above.)
CONSIDERATIONS FOR RELATIVES
Disease classification (sporadic versus familial) — This discussion is also presented separately. (See "Porphyria cutanea tarda and hepatoerythropoietic porphyria: Pathogenesis, clinical manifestations, and diagnosis", section on 'Disease classification'.)
●Sporadic (type 1) disease – In sporadic (type 1) PCT, there is no identified UROD variant and no familial inheritance pattern. Approximately 80 percent of individuals with PCT have sporadic disease. (See "Porphyria cutanea tarda and hepatoerythropoietic porphyria: Pathogenesis, clinical manifestations, and diagnosis", section on 'Pathogenesis'.)
●Familial (type 2) disease (UROD pathogenic variant) – In familial type 2 disease, heterozygosity for a pathogenic variant in UROD is present. Approximately 20 percent of individuals with PCT have type 2 disease. Because penetrance is low in such families, overt PCT often presents in a sporadic fashion (with a negative family history for PCT).
●Familial (type 3) disease (no UROD pathogenic variant) – In familial type 3 disease, more than one member of a kindred has PCT, but a pathogenic variant in UROD cannot be identified. These kindreds may share a variant in HFE that increases iron absorption or an inherited variant in an unknown gene that contributes to development of PCT.
Counseling for at-risk relatives
●Components of counseling – First-degree relatives of a patient with PCT who is heterozygous for a pathogenic UROD variant can be counseled about the genetics of PCT, the low penetrance, and the appropriate diagnostic testing. (See "Porphyria cutanea tarda and hepatoerythropoietic porphyria: Pathogenesis, clinical manifestations, and diagnosis".)
Approximately 80 percent of PCT cases are not associated with pathogenic variants in UROD; this is referred to as type 1 or "sporadic" PCT. If the index patient in a kindred has type 1 disease (tested negative for pathogenic variants in UROD) and does not have HFE C282Y, their first-degree relatives can be counseled that they are not at increased risk for PCT due to known genetic risk factors. (See "Porphyria cutanea tarda and hepatoerythropoietic porphyria: Pathogenesis, clinical manifestations, and diagnosis", section on 'Significance of pathogenic variants in the UROD gene'.)
PCT has a genetic component if the patient has inherited a pathogenic variant in UROD, and first-degree relatives have a 50 percent chance of inheriting that variant. However, most individuals who inherit the variant will not develop PCT due to low disease penetrance. If a patient with PCT has HFE C282Y, relatives may be at risk for developing PCT or hemochromatosis. (See "Inheritance patterns of monogenic disorders (Mendelian and non-Mendelian)", section on 'Penetrance and expressivity'.)
A porphyria expert or genetic counselor can explain the inheritance of type 2 PCT to the family (autosomal dominant with limited penetrance). Testing of children usually can be deferred until they reach an age of consent, since disease manifestations generally occur in mid to late adulthood. (See "Genetic testing", section on 'Ethical, legal, and psychosocial issues'.)
●Testing of relatives – Testing of relatives is optional and can generally be delayed until adulthood to allow informed consent, unless a child has skin lesions, in which case they should be tested. PCT is very rare in children and when present in a child is usually associated with familial (type 2) disease.
When possible, before testing relatives, genetic testing of the UROD and HFE genes should be performed on the index patient first. Relatives do not require testing if no disease variants are identified in the index patient. Testing the index patient first is also important so that if a genetic component exists, relatives can be tested for the correct gene and the correct variant in that gene. (See "Genetic testing", section on 'Questions to consider before testing'.)
●Advice for relatives who test positive – Relatives who test positive for the familial UROD variant but do not have overt disease (asymptomatic heterozygotes) can be tested periodically for porphyrin levels. In a study that measured porphyrin levels in 16 unaffected relatives of patients with PCT who carried the familial UROD variant, six (38 percent) had increased urinary porphyrins [57].
The likelihood of developing symptomatic disease and the benefit of treating asymptomatic carriers with elevated porphyrin levels is unknown, but primary therapy is unlikely to be needed. We advise these individuals (or those awaiting testing or test results) to avoid acquired susceptibility factors, especially heavy alcohol use and smoking. (See 'Counseling regarding susceptibility factors' above.)
If the index patient has tested positive for HFE C282Y or another gene variant associated with iron overload, relatives can be counseled regarding the inheritance, advantages and disadvantages of testing, optimal age for testing, and clinical implications. (See "Gene test interpretation: HFE (hereditary hemochromatosis gene)" and "Clinical manifestations and diagnosis of hereditary hemochromatosis", section on 'Diagnostic evaluation' and "Management and prognosis of hereditary hemochromatosis".)
●Advice for relatives who test negative – If more than one PCT case occurs in a kindred in the absence of a UROD pathogenic variant, which is referred to as type 3 PCT, an effort should be made to identify shared environmental susceptibility factors or other genetic risk factors such as HFE C282Y or H63D. Counseling of family members can be tailored to these identified factors.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Porphyria" and "Society guideline links: Photosensitivity disorders (photodermatoses)".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Porphyria cutanea tarda (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Pathogenesis – Porphyria cutanea tarda (PCT) is a blistering cutaneous porphyria caused by reduced activity of hepatic uroporphyrinogen decarboxylase (UROD) (figure 1). (See "Porphyria cutanea tarda and hepatoerythropoietic porphyria: Pathogenesis, clinical manifestations, and diagnosis", section on 'Pathogenesis'.)
•Approximately 80 percent is sporadic (type 1). Susceptibility factors include alcohol, smoking, hepatitis C virus (HCV), nonalcoholic fatty liver disease (NAFLD), HIV, estrogen, and iron overload, which may be from hereditary hemochromatosis (HH).
•Approximately 20 percent is familial (type 2), with heterozygosity for a pathogenic variant in UROD. Penetrance is low; additional susceptibility factors are present in those with overt disease.
•PCT in >1 relative in the absence of a UROD variant (type 3) may be due to other genetic factors (HFE variants) or shared environmental factors.
•Hepatoerythropoietic porphyria (HEP) is due to biallelic UROD pathogenic variants.
●Diagnostic evaluation – (See "Porphyria cutanea tarda and hepatoerythropoietic porphyria: Pathogenesis, clinical manifestations, and diagnosis", section on 'Diagnostic evaluation'.)
●PCT management
•Overview – PCT is the most readily treatable porphyria. Confirmed diagnosis is important because PCT therapies are ineffective for other porphyrias. The figure summarizes major treatment decisions (algorithm 1).
All individuals with active skin lesions should avoid sunlight, reduce modifiable susceptibility factors (smoking, alcohol), and be treated with one of the following (see 'Overview of management' above):
-Direct-acting antiviral agents (DAAs) for HCV
-Phlebotomy
-Low-dose hydroxychloroquine
Testing for HCV, iron overload (ferritin and transferrin saturation [TSAT]), and comorbidities is used to guide selection of therapy. (See 'Considerations before starting therapy' above.)
•Choice of therapy
-For patients with HCV, DAA therapy should be provided first; testing for iron overload can be repeated and addressed later if needed.
-For patients with iron overload (ferritin above reference range), we recommend phlebotomy (Grade 1B).
-For patients with HFE C282Y/C282Y, H63D/H63D, or C282Y/H63D without HCV infection or iron overload, we suggest phlebotomy (Grade 2C). Low-dose hydroxychloroquine is reasonable if the ferritin is <100 ng/mL.
-For all others, phlebotomy and low-dose hydroxychloroquine are both good options. Phlebotomy is preferred at most centers, but the choice should consider patient circumstances and preferences.
•Therapy details
-Phlebotomy – Similar procedure to blood donation, every two weeks; monitor hemoglobin, porphyrins, and ferritin. Porphyrins gradually decline once target ferritin (<25 ng/mL) is reached. Chelation is reserved for individuals with iron overload who cannot tolerate phlebotomy. (See 'Phlebotomy' above.)
-Low-dose hydroxychloroquine – Dosing is 100 mg twice weekly; higher doses may be harmful. Avoid in individuals who are pregnant, lactating, use alcohol or hepatotoxic medications, or have advanced liver or kidney disease, glucose-6-phosphate dehydrogenase (G6PD) deficiency, psoriasis, or retinal disease (unless cleared by an ophthalmologist). Measure porphyrins monthly and continue therapy for several months after normalization. Retinal examinations are required. (See 'Low-dose hydroxychloroquine' above.)
●HEP and latent PCT – Sunlight avoidance is the main HEP treatment. Heterozygous UROD variant without symptoms or porphyrin elevations can be monitored without treatment. Avoiding susceptibility factors is prudent in both cases. (See 'Special populations' above.)
●Prognosis – PCT does not alter life expectancy but can affect quality of life. Liver disease and perhaps untreated PCT are risk factors for hepatocellular cancer and other complications. Skin lesions that recur can be retreated. (See 'Prognosis' above and 'HCC surveillance' above.)
●Relatives – Relatives of patients with pathogenic variants in UROD or HFE can be counseled about the genetics of PCT and HH, the low penetrance of both, appropriate testing, and avoidance of susceptibility factors if appropriate. Genetic testing can generally be delayed until adulthood. (See 'Considerations for relatives' above.)
ACKNOWLEDGMENT — UpToDate gratefully acknowledges Stanley L Schrier, MD (deceased), who contributed as Section Editor on earlier versions of this topic review and was a founding Editor-in-Chief for UpToDate in Hematology.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
