AUTHOR INFORMATION

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Authored by Maureen B Poh-Fitzpatrick, MD, Columbia University College of Physicians and Surgeons, Professor Emerita and Special Lecturer, Department of Dermatology, Professor of Medicine, Division of Dermatology, University of Tennessee College of Medicine

Maureen B Poh-Fitzpatrick, MD, is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and New York Academy of Medicine

Edited by Craig A Elmets, MD, Director of Dermatology, Departments of Dermatology, Professor, Pathology, Environmental Health Sciences, The Kirklin Clinic, University of Alabama at Birmingham; Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA; Julia R Nunley, MD, Associate Professor, Program Director, Department of Dermatology, Virginia Commonwealth University Medical Center; Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University; and Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center

Author's Email:	Maureen B Poh-Fitzpatrick, MD
Editor's Email:	Craig A Elmets, MD

eMedicine Journal, February 22 2007, VOLUME 8, Number 2

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:

• In the US: 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.

• Internationally: 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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Epidermolysis Bullosa
Epidermolysis Bullosa Acquisita
Erythropoietic Porphyria
Hydroa Vacciniforme
Lupus Erythematosus, Bullous
Pseudoporphyria
Variegate Porphyria

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.

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 Name	Chloroquine (Aralen) -- Anti-inflammatory activity by suppressing lymphocyte transformation and may have photoprotective effect. Use in porphyria requires small doses once a week. Larger doses may cause severe hepatic necrosis and death. Binds porphyrins and enhances excretion. Available as 250-mg tab and 500-mg scored tab; not available as a syr. Crush tab and mask bitter taste in jam, applesauce, or other soft food.
Adult Dose	125-250 mg PO twice a week; alternatively, 250 mg PO qwk
Pediatric Dose	Safe and effective pediatric dosing schedules not well established; doses reported as tolerated yet effective have ranged from 12.5 mg PO twice weekly over 2 y in a child aged 4-6 y to 100 mg PO twice weekly over a 5 mo in a child aged 12 y; mg/kg dosing not been reported
Contraindications	Absolute: Hypersensitivity, retinopathy from any cause Relative: Pregnancy/lactation, retinal/visual-field changes, severe blood dyscrasias, psoriasis, G-6-PD deficiency (caution advocated but routine screening not recommended; associated with hemolysis but not in usual dosage range), significant hepatic dysfunction, myasthenia gravis, significant neurologic disease, long-term therapy in children (listed in Physician’s Desk Reference as contraindication; main concern is overdose/toxicity; chronic toxicity risk, however, is thought to be no greater than in adults)
Interactions	Cimetidine increases levels; kaolin and magnesium trisilicate decrease levelsIncreases digoxin levels with coadministration; increased retinal toxicity with coadministration of hydroxychloroquine (do not coadminister)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Large cumulative doses can cause irreversible retinopathy; higher or more frequent dosing schedules may precipitate clinical hepatotoxicity with elevated serum liver transaminase levels and constitutional symptoms; while some authorities indicate that 4-aminoquinoline compounds should be administered with caution for increased hemolysis in patients with G-6-PD deficiency, others indicate that these agents do not cause increased hemolysis in such cases; pretreatment assessment of visual-field acuity, G-6-PD level, and CBC count is recommended, as well as periodic monitoring of blood cell counts and visual-field changes with long-term use

Drug Name	Hydroxychloroquine (Plaquenil) -- Inhibits chemotaxis of eosinophils, inhibits locomotion of neutrophils, and impairs complement-dependent antigen-antibody reactions. Hydroxychloroquine sulfate 200 mg is equivalent to 155 mg hydroxychloroquine base and 250 mg chloroquine phosphate. Available as 200-mg tab; not available as a syr. Crush tab and mask bitter taste in jam, applesauce, or other soft food.
Adult Dose	200-400 mg PO 2-3 times/wk
Pediatric Dose	Not established; 3 mg/kg PO twice weekly over 14 mo reported as safe and effective in a child aged 4 y
Contraindications	Absolute: Hypersensitivity, retinopathy from any cause Relative: Pregnancy/lactation, retinal/visual-field changes, severe blood dyscrasias, psoriasis, G-6-PD deficiency (caution advocated but routine screening not recommended; associated with hemolysis but not in usual dosage range), significant hepatic dysfunction, myasthenia gravis, significant neurologic disease, long-term therapy in children (listed in Physician’s Desk Reference as contraindication; main concern is overdose/toxicity; chronic toxicity risk, however, is thought to be no greater than in adults)
Interactions	Cimetidine increases levels; kaolin and magnesium trisilicate decrease levels Increases digoxin levels with coadministration; increased retinal toxicity with coadministration of chloroquine (do not coadminister)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Large cumulative doses can cause irreversible retinopathy; higher or more frequent dosing schedules may precipitate clinical hepatotoxicity with elevated serum liver transaminase levels and constitutional symptoms; while some authorities indicate that 4-aminoquinoline compounds should be administered with caution for increased hemolysis in patients with G-6-PD deficiency, others indicate that these agents do not cause increased hemolysis in such cases; pretreatment assessment of visual-field acuity, G-6-PD level, and CBC count is recommended, as well as periodic monitoring of blood cell counts and visual-field changes with long-term use

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.

Drug Name	Epoetin alfa (Epogen, Procrit) -- Stimulates division and differentiation of committed erythroid progenitor cells. Induces release of reticulocytes from bone marrow into blood stream.
Adult Dose	50-100 U/kg IV/SC 3 times/wk
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; uncontrolled hypertension
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution with hypertension and history of seizures; decrease dose if hematocrit increase exceeds 4 points in any 2-wk period

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.

TEST QUESTIONS

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CME Question 1: What is the defective enzyme responsible for all forms of porphyria cutanea tarda?

A: Uroporphyrinogen III synthase in bone marrow cells
B: Uroporphyrinogen III synthase in hepatocytes
C: Uroporphyrinogen decarboxylase in erythrocyte precursor cells
D: Uroporphyrinogen decarboxylase in hepatocytes
E: Uroporphyrinogen deaminase in hepatocytes

The correct answer is D: All disorders in the porphyria cutanea tarda group, whether inherited or acquired, are characterized by reduced activity of hepatic uroporphyrinogen decarboxylase. Deficient activity of hepatic uroporphyrinogen decarboxylase results in overproduction of porphyrin by-products of the heme biosynthetic pathway that have 4-8 carboxyl group substituents. These porphyrins are photoactive molecules that absorb light energy strongly in the visible violet spectrum. Photoexcited porphyrins in the skin mediate oxidative damage to biomolecular targets, causing cutaneous photosensitivity reactions.

CME Question 2: Clinical features consistent with porphyria cutanea tarda (PCT) include which of the following?

A: Mechanical fragility and blistering of skin exposed to sunlight
B: Hypertrichosis
C: Sclerodermoid plaques with calcification
D: Cutaneous dyspigmentation
E: All of the above

The correct answer is E: Clinical features consistent with PCT include all of the above. The most common manifestation of PCT is fragility of sun-exposed skin after mechanical trauma, leading to erosions and bullae, which are worst on the dorsal aspects of the hands, the forearms, and the face. Hypertrichosis is often observed and is most florid over the temporal and malar facial areas, but it is also sometimes present on the arms and the legs. Indurated, waxy, yellowish plaques that resemble lesions of scleroderma can develop over the chest and the back but are most often prominent in the preauricular and nuchal areas. Pigmentary changes include melasmalike hyperpigmentation of the face and an erythematous suffusion or plethora of the central face, neck, upper chest, and shoulders.

Pearl Question 1 (T/F): A 40-year-old man presents with fragility and blistering of the skin exposed to sunlight. His urine is tea-colored and fluoresces upon Wood light examination. This information is sufficient to establish a diagnosis of porphyria cutanea tarda.

The correct answer is False: Although the most likely diagnosis is porphyria cutanea tarda, other possibilities include variegate porphyria, hereditary coproporphyria, and late-onset congenital erythropoietic porphyria. A laboratory profile of porphyrins present in urine, stool, and blood is needed to ascertain the precise diagnosis.

Pearl Question 2 (T/F): A 40-year-old man presents with recent onset of cutaneous fragility and blistering of the skin exposed to sunlight. His urine does not fluoresce upon Wood light examination, and his serum porphyrin levels are in the reference range; therefore, a diagnosis of variegate porphyria rather than porphyria cutanea tarda should be suspected.

The correct answer is False: In the absence of elevated plasma or serum porphyrin levels, the cutaneous photosensitivity cannot be ascribed to any porphyria. A differential diagnosis of pseudoporphyria due to drugs or other associated factors or due to other bullous dermatoses resembling porphyria cutanea tarda should be considered.

Pearl Question 3 (T/F): The hepatitis virus infection most frequently associated with porphyria cutanea tarda is hepatitis A.

The correct answer is False: Exposure to hepatitis viruses A, B, and C have all been reported in association with porphyria cutanea tarda. Hepatitis C appears to be the most commonly associated viral infection, with rates of more than 50% in several populations of patients with porphyria cutanea tarda studied in European countries and in the United States.

Pearl Question 4 (T/F): Isocoproporphyrin is characteristically accumulated in excess in fecal specimens of patients with porphyria cutanea tarda.

The correct answer is True: Isocoproporphyrin is a tetracarboxylic by-product of heme biosynthesis that is excreted in large amounts when uroporphyrinogen decarboxylase activity is deficient, and the rate of enzymatic conversion of pentacarboxylic porphyrinogen to coproporphyrinogen is thereby significantly reduced. Excess fecal isocoproporphyrin is typically associated with porphyria cutanea tarda.

PICTURES

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Caption: Picture 1. Thickened skin with blisters, scars, and milia. Courtesy of Dirk Elston, MD.
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Caption: Picture 2. Close-up image of blisters, scarring, and milia. Courtesy of Dirk Elston, MD.
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Caption: Picture 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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Caption: Picture 4. Fluorescence of urine with a Wood light examination. Courtesy of Brooke Army Medical Center Teaching File.
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BIBLIOGRAPHY

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