AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

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Background

Porphyria cutanea tarda (PCT) is a term encompassing a group of disorders in which activity of the heme synthetic enzyme uroporphyrinogen decarboxylase (UROD) is deficient. PCT includes familial types with UROD gene mutations and acquired types that may occur in individuals with a genetic predisposition (sporadic PCT) after exposure to hepatotoxins or in the context of hepatic tumors. Familial PCT most often reflects the presence of 1 mutation at the UROD locus. A rare familial type with 2 such mutations has been termed hepatoerythropoietic porphyria.

Clinical expression of both familial and acquired PCT often follows exposure to agents or conditions that adversely affect hepatocytes and lead to hepatosiderosis. These agents or conditions include ethanol, estrogen, hepatitis and human immunodeficiency viruses, and hemochromatosis genes. Excess iron enhances the formation of toxic oxygen species and increases oxidative stress and apparently facilitates porphyrinogenesis by catalyzing the formation of oxidation products that inhibit UROD. Reduction of UROD activity to approximately 25% of normal leads to clinical expression of the disease. Environmental exposure to polyhalogenated aromatic hydrocarbon compounds has caused acquired toxic porphyric disorders in large populations, which is referred to as epidemic porphyria. Hepatic tumors producing excess porphyrins are rare causes of PCT-like disorders.

Pathophysiology

When hepatic UROD activity falls below a critical threshold, porphyrin by-products of the heme biosynthetic pathway with 4-8 carboxyl group substituents are overproduced. These porphyrins are reddish pigments that accumulate in the liver and are disseminated in plasma to other organs. Porphyrins with high carboxyl group numbers are water soluble and excreted primarily by renal mechanisms. The porphyrin with 8 carboxyl groups is termed uroporphyrin; 4-carboxyl porphyrins include coproporphyrin and isocoproporphyrin, which are chiefly excreted in feces. Porphyrins are photoactive molecules that efficiently absorb energy in the visible violet spectrum. Photoexcited porphyrins in the skin mediate oxidative damage to biomolecular targets, causing cutaneous lesions.

The most common photocutaneous manifestations of PCT are due to increased mechanical fragility after sunlight exposure; erosions and blisters form painful indolent sores that heal with milia, dyspigmentation, and scarring (see Image 2). Other common features of PCT include hypertrichosis, sclerodermalike plaques that may develop dystrophic calcification, and excretion of discolored urine that resembles port wine or tea due to the porphyrin pigments present.

Frequency

United States

No porphyria registry is available in the United States; thus, the prevalence of PCT is not accurately known but is estimated at 1 case in 25,000-50,000 population. It is the most common porphyria.

International

Higher prevalences of PCT have been reported in some European populations. A high prevalence among South African Bantu people has been linked with a propensity for hepatic siderosis.

Mortality/Morbidity

• The major morbidity of PCT is due to skin fragility and blistering, which preclude manual labor and hamper daily activities. The subsequent erosions represent full-thickness epidermal loss; they are painful and often become thickly crusted and secondarily infected. Healing is slow and leaves pigmentary changes, milia, and atrophic scars.
• PCT has been associated with the development of hepatocellular carcinoma, chiefly in populations of older men with long-standing active disease, heavy ethanol intake, and cirrhosis. Most studies predate recognition of hepatitis C prevalence in populations with PCT or hepatocellular carcinoma; many reported cancers may have been, at least in part, sequelae of chronic hepatitis viral infection.

Race

PCT occurs in persons of all ethnic groups.

Sex

PCT occurs in both sexes. Older reports indicated a great preponderance of men; more recent surveys include many women.

Age

• Sporadic PCT typically manifests in adulthood.
• Symptoms of familial PCT typically first appear in adults heterozygous for a UROD gene mutation, but they have also been reported in heterozygote children. When 2 mutations are present (homozygotes or compound heterozygotes), onset is typically in childhood.
• PCT-like disorders resulting from exposure of large numbers of people to hepatotoxic chemicals have afflicted people of all ages.

CLINICAL

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History

• The most common initial symptoms are cutaneous fragility and blistering of the hands, forearms, and, sometimes, the face. Discolored urine may also be reported, but this information may need to be elicited. Changes in hair growth and pigmentation may be noted spontaneously or only after inquiry. Patients often do not realize the role of sunlight exposure in the subsequent appearance of lesions.
• In familial PCT, other affected relatives may be known. However, most related carriers of the mutant gene remain silent, and patients are unaware of the familial nature of their disease.
• In both familial and sporadic PCT, a history of exposure to environmental inducers (eg, ethanol, estrogens, hepatitis) can often be elicited. In symptomatic familial PCT, none of the common inducing agents may be discoverable. Paradoxically, proven carriers of the same mutation may remain clinically and biochemically silent despite exposure to such agents.
• Childhood onset of PCT should suggest either heterozygous or homozygous familial forms of the disease, unless observed in the context of environmental exposure to a chemical hepatotoxin.
• PCT-like disease in multiple members of populations exposed to polyhalogenated aromatic hydrocarbons should suggest epidemic toxic porphyria.

Physical

• The most common presenting sign of PCT is fragility of sun-exposed skin after mechanical trauma, leading to erosions and bullae, typically on hands and forearms and occasionally on face or feet. Healing of crusted erosions and blisters leaves milia, hyperpigmented patches, and hypopigmented atrophic scars.
• Hypertrichosis is often observed over temporal and malar facial areas and may also involve arms and legs.
• Pigmentary changes include melasmalike hyperpigmentation of the face. An erythematous suffusion or plethora of the central face, neck, upper chest, and shoulders may be present.
• Scarring alopecia and separation of nail plates from their beds (photo-onycholysis) can be seen in more severely affected patients.
• Indurated, waxy, yellowish plaques that resemble lesions of scleroderma can develop over the chest and the back but are most prominent in the preauricular and nuchal areas. These plaques may develop dystrophic calcification. Rarely, the only physical sign of PCT is a hyperpigmented sclerodermoid appearance.
• In severely affected individuals, particularly familial hepatoerythropoietic or toxic epidemic cases in children, digital shortening, atrophy, and contractures resembling those of dystrophic epidermolysis bullosa have occurred.
• A urine sample is often, but not always, grossly discolored with a tea- or wine-colored tint.

Causes

The unifying underlying cause of all forms of PCT is reduction of UROD activity to a critical point during hepatic heme synthesis.

Exposure to hepatitis viruses A, B, or C has been reported to be associated with PCT. Hepatitis C appears to be the most commonly associated viral infection, with a rate of greater than 50% in populations studied in several European countries and in the United States. In some other regions, the concordance has been found to be lower.

Association with human immunodeficiency virus infection has also been reported.

DIFFERENTIALS

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Other Problems to be Considered

Hereditary coproporphyria

WORKUP

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Lab Studies

• Urinary porphyrin levels are abnormally high, with several hundred to several thousand micrograms excreted in a 24-hour period. The excess porphyrin pigment is often grossly evident in visible light and yields a pink fluorescence under Wood lamp (black light) radiation (see Image 4). Chromatographic separation by carboxyl number of increased porphyrins present reveals a predominance of 8- and 7-carboxyl porphyrin fractions, with lesser amounts of 6-, 5-, and 4-carboxyl porphyrins, reflecting a UROD defect. A similar array of polycarboxylated porphyrins can be found in serum or plasma specimens. The fecal coproporphyrin fraction is often abnormally high and largely consists of isocoproporphyrin. Erythrocyte porphyrin levels are in the reference range, except in hepatoerythropoietic porphyria, in which zinc protoporphyrin is elevated.
• UROD enzyme activity assay is commercially available in at least one laboratory in the United States. Enzyme activity data may help determine patterns of inheritance in familial PCT and confirm the diagnosis in cases with confusing biochemical data.
• Mutation analysis of genes encoding UROD is now commercially available in a United States laboratory for individuals with biochemically confirmed PCT.
• A thorough evaluation requires determination of the hematologic and iron profile, including serum ferritin level, liver function profile, and screening for hepatitis viruses and the human immunodeficiency virus.
• Abnormal glucose tolerance and serum antinuclear antibodies are found more frequently among PCT populations.
• Assessment for 1 or more hemochromatosis genes may be informative.
• Ascorbic acid (vitamin C) serum levels are deficient in some patients with PCT.
• Alpha-fetoprotein presence in serum is useful to screen for hepatocellular carcinoma.

Imaging Studies

• Evaluation of the liver for size, iron content, or the presence of tumors is indicated in selected cases.

Procedures

• Skin biopsy findings by light microscopy and direct immunofluorescence techniques may be consistent with a diagnosis of PCT but are not unequivocally diagnostic. Similar findings can be observed in other porphyrias and in pseudoporphyrias associated with certain drugs, intensive use of tanning beds or cabinets, or long-term dialysis therapy for renal failure. Direct immunofluorescence examination can help differentiate PCT from immunobullous diseases with dermoepidermal junction cleavage (epidermolysis bullosa acquisita, lupus erythematosus) in which the perivascular immunoglobulin deposition found in PCT is not observed.
• Liver biopsy may be appropriate in selected cases to evaluate iron burden or damage due to ethanol abuse, viral infections, hemochromatosis, or suspected tumors.

Histologic Findings

Skin biopsy specimens of fresh blisters show subepidermal bullae with minimal dermal inflammatory infiltrate and dermal papillae protruding upward into the blister cavity (festooning). Thickened upper dermal capillary walls and dermoepidermal basement membrane zones are evident in routinely stained sections and accentuated with the periodic acid-Schiff stain. Elastosis, sclerosis of dermal collagen, and hyaline deposits may be seen in the dermis. Linear, eosinophilic, periodic acid-Schiff–positive globules composed of basement membrane material and degenerating keratinocytes ("caterpillar bodies") may be observed in the blister roof.

Ultrastructural examination of dermal vascular walls and the basement membrane zone reveals replication of basal laminae, reflecting multiple episodes of damage and repair.

Direct immunofluorescence examination shows deposition of immunoglobulins and complement in and around the dermal capillaries and at the basement membrane zone. These deposits do not indicate that PCT is an autoimmune disorder; they are believed to be immunoproteins leaked from the damaged vasculature.

Liver biopsy abnormalities range from minimal to severe. Increased iron deposition is frequently present. Other abnormalities may include steatosis, chronic inflammatory infiltrates, fibrosis, cirrhosis, and necrosis. Needlelike intracytoplasmic inclusions believed to be uroporphyrin crystals occur near ferritin iron deposits in hepatocytes.

TREATMENT

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Medical Care

• Sunlight avoidance is the main defense for photosensitivity until clinical remission can be induced. Alcohol must be proscribed. Estrogen use should be discontinued unless its need outweighs its adverse effects on porphyrin metabolism. After achievement of remission, estrogen therapies may be cautiously reinstituted; however, the duration of remissions may be shortened. Remissions may last from several months to many years. If symptoms recur, re-treatment can restore remissions.
• Therapeutic phlebotomy reduces iron stores, which improves heme synthesis disturbed by ferroinhibition of UROD. The goal of therapy is to reduce serum ferritin levels to the lower limit of the reference range. Venesections are scheduled at intervals ranging from a unit of whole blood removed twice weekly to every 2-3 weeks as tolerated by the patient. Care is given to not induce anemia. Phlebotomy is the preferred therapy for individuals with a heavy iron burden. Efficacy of antihepatitis C therapy appears to be enhanced if hepatosiderosis is first reduced by phlebotomy.
• In patients in whom phlebotomy is not convenient or is contraindicated and in those who have relatively mild iron overload, oral chloroquine phosphate (125-250 mg PO twice weekly) or hydroxychloroquine sulfate (200-400 mg PO 2-3 times/wk), doses much lower than those used for antimalarial or photoprotective indications, is often effective. Larger doses can cause severe hepatotoxicity. Even low-dose regimens can occasionally produce hepatic toxicity, and careful monitoring is indicated. Some clinicians begin with a single, small test dose.
• Chelation with desferrioxamine is an alternative means of iron mobilization when venesections are not practical.
• For patients with PCT who are anemic due to other chronic diseases (eg, renal failure, human immunodeficiency viral infection), human recombinant erythropoietin can be used to stimulate erythropoiesis. This mobilizes tissue iron and may increase the circulating erythrocyte mass to a degree that permits therapeutic phlebotomies to be performed at judicious volumes and intervals.

Consultations

• Consultation with a gastroenterologist or a hepatologist for evaluation and treatment of viral hepatitis, liver damage due to alcohol abuse or hemochromatosis, and hepatic tumors may be warranted.
• Consultation with a hematologist may be helpful in cases of suspected hemochromatosis or for management of phlebotomy or iron chelation therapies.
• Consultation with a gynecologist for alternative forms of treatment for female patients in whom therapeutic use of estrogenic hormones is a probable inducing factor is often helpful.
• For male patients treated with estrogen for prostatic carcinoma, consultation with the treating oncologist regarding the need for continued therapy is indicated.

Diet

Iron-rich foods should be consumed in moderation; strict avoidance is not usually necessary.

Activity

Patients should avoid sunlight exposure until biochemical and clinical remission has been induced. Manual labor should be curtailed to minimize mechanical trauma that will cause erosions and blistering.

MEDICATION

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Medical therapy may be used alone or in combination with phlebotomy.

Drug Category: Antimalarials

These agents are believed to form complexes with porphyrin molecules within hepatocytes that are then discharged into the circulation and excreted by renal mechanisms. Increased urinary iron excretion has also followed their use. Reported experience in treating children with PCT with antimalarials is limited.

Drug Category: Bone marrow stimulants

In patients with anemia of chronic disease in whom venesections are relatively contraindicated, stimulation of erythropoiesis can mobilize tissue iron and may even enable low-volume phlebotomies to be performed at judicious intervals.

FOLLOW-UP

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Further Outpatient Care

• Levels of hemoglobin, serum ferritin, and plasma/serum or urinary porphyrins should be monitored during the course of treatment to guide the frequency of venesections and to determine the point of discontinuation of therapies.
• • Phlebotomy should be continued until the serum ferritin level has reached the lower border of reference range values. Clinical remission may not be complete until several weeks to months after biochemical remission has been reached.
  • Urinary and plasma/serum porphyrin levels may continue to decrease for several weeks to months after the ferritin level has reached the target range for discontinuation of phlebotomy.
  • Interval monitoring of serum ferritin and porphyrin levels is recommended every 3 months for a year and then every 6 months to a year thereafter to ensure maintenance of remissions.

Patient Education

• Patients should be educated about the role of sunlight in eliciting the skin lesions.
• The need to avoid iron-containing dietary supplements and alcohol should be stressed.
• Dietary iron is not usually a significant problem, but some patients may benefit from guidance about the iron content of foods from a nutritionist. Adequate dietary vitamin C should be consumed.

MISCELLANEOUS

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Medical/Legal Pitfalls

• Other porphyrias, pseudoporphyrias, and photoaggravated bullous dermatoses can manifest with clinical features indistinguishable from those of PCT. Failure to obtain sufficient biochemical confirmation of the diagnosis can lead to inappropriate treatment of non-PCT disorders.

Special Concerns

• Pregnancy in women with PCT has been followed by safe delivery of healthy infants. Mobilization of maternal excess tissue iron stores to support the growing fetus may actually be beneficial to pregnant women with PCT. Supplemental iron should be withheld during gestation unless iron deficiency is evident. Increased cutaneous photosensitivity in the first trimester, preeclampsia, and gestational diabetes have been noted in a few cases.
• Reinstitution of estrogenic hormone therapies in women with PCT who have achieved remissions may be completed in some cases without inducing the return of overt disease, but the risk of doing so must be balanced against the benefits of such therapies. If a patient accepts the risk (presently unquantifiable) of possibly reactivating her PCT in the hope of regaining the benefits of estrogen therapies, the use of transdermal delivery systems is recommended to mitigate the first-pass effects of oral estrogens reaching the liver from the enteric tract.
• The risks of PCT patients using plant-derived, estrogenlike compounds are not well established, but these agents probably should be avoided.
• The estrogen-receptor antagonist tamoxifen has been associated with the development of PCT in a few women treated with this agent for breast carcinoma.

MULTIMEDIA

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Media file 1:  Thickened skin with blisters, scars, and milia. Courtesy of Dirk Elston, MD.
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Media file 2:  Close-up image of blisters, scarring, and milia. Courtesy of Dirk Elston, MD.
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Media type:  Photo

Media file 3:  Subepidermal bulla, festooning of rete ridges, hyalinization of blood vessel walls, solar elastosis, and caterpillar bodies. Courtesy of Dirk Elston, MD.
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Media type:  Photo

Media file 4:  Fluorescence of urine with a Wood light examination. Courtesy of Brooke Army Medical Center Teaching File.
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Media type:  Photo

REFERENCES

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• Agarwal R, Peters TJ, Coombes RC, Vigushin DM. Tamoxifen-related porphyria cutanea tarda. Med Oncol. 2002;19(2):121-3. [Medline].
• Anderson KE, Goeger DE, Carson RW, et al. Erythropoietin for the treatment of porphyria cutanea tarda in a patient on long-term hemodialysis. N Engl J Med. Feb 1 1990;322(5):315-7. [Medline].
• Badcock NR, O''Reilly DA, Zoanetti GD, et al. Childhood porphyrias: implications and treatments. Clin Chem. Jun 1993;39(6):1334-40. [Medline].
• Battle AM, Stella AM, De Kaminsky AR, et al. Two cases of infantile porphyria cutanea tarda: successful treatment with oral S-adenosyl-L-methionine and low-dose oral chloroquine. Br J Dermatol. Mar 1987;116(3):407-15. [Medline].
• Blauvelt A. Hepatitis C virus and human immunodeficiency virus infection can alter porphyrin metabolism and lead to porphyria cutanea tarda. Arch Dermatol. Dec 1996;132(12):1503-4. [Medline].
• Bonkovsky HL, Poh-Fitzpatrick M, Pimstone N, et al. Porphyria cutanea tarda, hepatitis C, and HFE gene mutations in North America. Hepatology. Jun 1998;27(6):1661-9. [Medline].
• Bonkovsky HL, Lambrecht RW, Shan Y. Iron as a co-morbid factor in nonhemochromatotic liver disease. Alcohol. Jun 2003;30(2):137-44. [Medline].
• Bruce AJ, Ahmed I. Childhood-onset porphyria cutanea tarda: successful therapy with low-dose hydroxychloroquine (Plaquenil). J Am Acad Dermatol. May 1998;38(5 Pt 2):810-4. [Medline].
• Can C, Nigogosyan G. Acquired toxic porphyria cutanea tarda due to hexachlorobenzene. Report of 348 cases caused by this fungicide. JAMA. Jan 12 1963;183:88-91. [Medline].
• Edwards CQ, Griffen LM, Goldgar DE, et al. HLA-linked hemochromatosis alleles in sporadic porphyria cutanea tarda. Gastroenterology. Oct 1989;97(4):972-81. [Medline].
• Elder GH, Roberts AG. Uroporphyrinogen decarboxylase. J Bioenerg Biomembr. Apr 1995;27(2):207-14. [Medline].
• Elder GH, Smith SG, Herrero C, et al. Hepatoerythropoietic porphyria: a new uroporphyrinogen decarboxylase defect or homozygous porphyria cutanea tarda?. Lancet. Apr 25 1981;1(8226):916-9. [Medline].
• Epstein JH, Tuffanelli DL, Epstein WL. Cutaneous changes in the porphyrias. A microscopic study. Arch Dermatol. May 1973;107(5):689-98. [Medline].
• Fernández I, Castellano G, de Salamanca RE, et al. Porphyria cutanea tarda as a predictor of poor response to interferon alfa therapy in chronic hepatitis C. Scand J Gastroenterol. Mar 2003;38(3):314-9. [Medline].
• Fung MA, Murphy MJ, Hoss DM, et al. The sensitivity and specificity of "caterpillar bodies" in the differential diagnosis of subepidermal blistering disorders. Am J Dermatopathol. Aug 2003;25(4):287-90. [Medline].
• Gisbert JP, García-Buey L, Alonso A, et al. Hepatocellular carcinoma risk in patients with porphyria cutanea tarda. Eur J Gastroenterol Hepatol. Jul 2004;16(7):689-92. [Medline].
• Grossman ME, Bickers DR, Poh-Fitzpatrick MB, et al. Porphyria cutanea tarda. Clinical features and laboratory findings in 40 patients. Am J Med. Aug 1979;67(2):277-86. [Medline].
• Ippen H. Treatment of porphyria cutanea tarda by phlebotomy. Semin Hematol. Apr 1977;14(2):253-9. [Medline].
• Kappas A, Sassa S, Galbraith RA, et al. The porphyrias. In: CR Scriver, et al, eds. The Metabolic Basis of Inherited Disease. New York: McGraw-Hill; 1995:. 2103-59.
• Kordac V, Semrádová M. Treatment of porphyria cutanea tarda with chloroquine. Br J Dermatol. Jan 1974;90(1):95-100. [Medline].
• Lambrecht RW, Bonkovsky HL. Hemochromatosis and porphyria. Semin Gastrointest Dis. Apr 2002;13(2):109-19. [Medline].
• Lefkowitch JH, Grossman ME. Hepatic pathology in porphyria cutanea tarda. Liver. Feb 1983;3(1):19-29. [Medline].
• Linde Y, Harper P, Floderus Y, Ros AM. The prevalence of hepatitis C in patients with porphyria cutanea tarda in Stockholm, Sweden. Acta Derm Venereol. 2005;85(2):164-6. [Medline].
• Loret de Mola JR, Muise KL, Duchon MA. Porphyria cutanea tarda and pregnancy. Obstet Gynecol Surv. Aug 1996;51(8):493-7. [Medline].
• Malkinson FD, Levitt L. Hydroxychloroquine treatment of porphyria cutanea tarda. Arch Dermatol. Oct 1980;116(10):1147-50. [Medline].
• Poh-Fitzpatrick MB, Honig PJ, Kim HC, Sassa S. Childhood-onset familial porphyria cutanea tarda: effects of therapeutic phlebotomy. J Am Acad Dermatol. Nov 1992;27(5 Pt 2):896-900. [Medline].
• Ramsay CA, Magnus IA, Turnbull A, Baker H. The treatment of porphyria cutanea tarda by venesection. Q J Med. Jan 1974;43(169):1-24. [Medline].
• Ratnaike S, Blake D, Campbell D, et al. Plasma ferritin levels as a guide to the treatment of porphyria cutanea tarda by venesection. Australas J Dermatol. Apr 1988;29(1):3-8. [Medline].
• Rocchi E, Cassanelli M, Borghi A, et al. Liver iron overload and desferrioxamine treatment of porphyria cutanea tarda. Dermatologica. 1991;182(1):27-31. [Medline].
• Sinclair PR, Gorman N, Shedlofsky SI, et al. Ascorbic acid deficiency in porphyria cutanea tarda. J Lab Clin Med. Aug 1997;130(2):197-201. [Medline].
• Stölzel U, Köstler E, Schuppan D, et al. Hemochromatosis (HFE) gene mutations and response to chloroquine in porphyria cutanea tarda. Arch Dermatol. Mar 2003;139(3):309-13. [Medline].
• Taljaard JJ, Shanley BC, Stewart-Wynne EG, et al. Studies on low dose chloroquine therapy and the action of chloroquine in symptomatic porphyria. Br J Dermatol. Sep 1972;87(3):261-9. [Medline].
• Toll A, Celis R, Ozalla M, et al. The prevalence of HFE C282Y gene mutation is increased in Spanish patients with porphyria cutanea tarda without hepatitis C virus infection. J Eur Acad Dermatol Venereol. Nov 2006;20(10):1201-6. [Medline].
• Wolff K, Hönigsmann H, Rauschmeier W, et al. Microscopic and fine structural aspects of porphyrias. Acta Derm Venereol Suppl (Stockh). 1982;100:17-28. [Medline].

Article Last Updated: Feb 22, 2007