645

From the Department of Internal Medicine, Case Western ReserveUniversity, Cleveland,a and the Department of Dermatology,Henry Ford Hospital and Medical Centers, Detroit.b

Reprint requests: Henry W. Lim, MD, Department of Dermatology,Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI 48202-2689.E-mail: hlim1@hfhs.org.

Copyright © 2000 by the American Academy of Dermatology, Inc.0190-9622/2000/$12.00 + 0 16/1/105504doi:10.1067/mjd.2000.105504

P orphyria cutanea tarda (PCT) is a vesiculobul-

lous skin disorder characterized by an

acquired or inherited autosomal dominant

defect in heme biosynthesis, involving a deficiency in

the enzyme uroporphyrinogen decarboxylase.

Patients present with increased skin fragility, subepi-

dermal bullae, erosions, hypertrichosis, hyperpig-

mentation, hypopigmentation, milia, and scarring.1

The laboratory diagnosis of PCT is based on a pre-

dominance of plasma uroporphyrin, urine uropor-

phyrins I and III, heptacarboxyl porphyrin, and ele-

vated fecal heptacarboxyl porphyrin and isocopro-

porphyrin.1

Acquired PCT is by far the most common form. In

most cases, this occurs in the setting of hepatic

injury precipitated by the ingestion of alcohol, estro-

gens, or chlorinated hydrocarbons such as hexa-

chlorobenzene.2 Virtually all patients with PCT have

evidence of iron overload.1 PCT has also been asso-

ciated with hepatitis C virus infection, HIV infection,

and hemochromatosis.3-5

During the past two decades, PCT has been

reported in patients with chronic renal failure being

treated with hemodialysis; the prevalence ranges

from 1.2% to 18% of patients receiving maintenance

hemodialysis.6 This condition should be differentiat-

ed from bullous dermatosis of hemodialysis (also

known as pseudoporphyria),2 a condition which

clinically resembles PCT but does not exhibit an

abnormal porphyrin profile.

Although the precise origin of PCT in hemodia-

lyzed patients is unknown, several pathophysiologic

mechanisms have been proposed: (1) Azotemia

decreases the activity of uroporphyrinogen decar-

boxylase.7 (2) These patients have an impaired abili-

ty to excrete porphyrins, and porphyrins are poorly

dialyzed because of binding with high-molecular-

weight proteins.8 (3) Aluminum intoxication (less

common today with aluminum-free dialysis water)

may interfere with heme synthesis by inhibiting fer-

rochelatase or by binding transferrin and preventing

the incorporation of iron into heme.9

We describe a patient with chronic renal failure

and PCT, whose PCT successfully responded to small

volume phlebotomy and high-dose erythropoietin.

CASE REPORTA 38-year-old Mexican woman with end-stage

renal disease secondary to chronic pyelonephritis,

on dialysis for the past 17 years (hemodialysis with

the exception of chronic ambulatory peritoneal dial-

ysis from 1993-1995), was referred to the Dermato-

THERAPY

Management of porphyria cutanea tardain the setting of chronic renal failure:

A case report and review

Sherry Shieh, MD,a Joel L. Cohen, MD,b and Henry W. Lim, MDb

Cleveland, Ohio, and Detroit, Michigan

The treatment of porphyria cutanea tarda (PCT) in patients with chronic renal failure poses a therapeutic

challenge. In the absence of renal failure, phlebotomy and oral antimalarials have been the standard of care

for PCT. However, in the presence of renal failure, associated chronic anemia often precludes the use of

phlebotomy, and oral antimalarials are usually ineffective. We describe a patient with severe symptomatic

PCT and chronic renal failure whose disease was successfully managed with a combination of high-dose

erythropoietin and small volume phlebotomy. We also review several previously reported approaches to

management of PCT in the setting of renal failure, which include small repeated phlebotomy,

erythropoietin, deferoxamine, chloroquine, plasma exchange, high-efficiency/high-flux hemodialysis,

cholestyramine, charcoal hemoperfusion, and kidney transplantation. An algorithm for the management of

these patients is proposed. (J Am Acad Dermatol 2000;42:645-52.)

line phosphatase, 296 IU/L (normal, 39-117 IU/L);

serum glutamic-oxaloacetic transaminase, 37 IU/L

(normal, 0-31 IU/L); lactate dehydrogenase, 346

IU/L (normal, 94-250 IU/L); iron, 29 µg/dL (normal,

30-160 µg/dL); total iron-binding capacity, 269

µg/dL (normal, 259-388 µg/dL); transferrin satura-

tion, 11% (normal, 20-55%); ferritin, 441 ng/mL

(normal, 5-146 ng/dL); total plasma porphyrins,

260.4 µg/dL (normal, 0-0.9 µg/dL), with a fluores-

cence maximum at 618 nm, a finding characteristic

of PCT; serum porphobilinogen, 0.22 µg/mL (nor-

mal, 0.0-0.1 µg/mL); erythrocyte porphobilinogen

deaminase, 49 nmol/mL/h (normal, 20-50 nmol/

ml/h); total erythrocyte porphyrin, 997 µg/dL (nor-

mal, 20-80 µg/dL) with a predominance of zinc pro-

toporphyrin; erythrocyte uroporphyrinogen decar-

boxylase, 62.1 nmol/mL of red blood cells per hour

(normal, 30-60 nmol/mL of red blood cells per

hour); fecal total porphyrins, 206 nmol/g dry

weight (normal, 0-200 nmol/g) with elevated isoco-

proporphyrin, heptacarboxyl and pentacarboxyl

porphyrins, and isocoproporphyrin/copropor-

phyrin ratio. Skin biopsy findings revealed a

subepidermal vesicle with minimal inflammation

consistent with PCT. Direct immunofluorescence

showed IgG and C3 at the dermoepidermal junc-

tion and IgG in blood vessel walls. Indirect

immunofluorescence was negative.

logy Clinic at Henry Ford Hospital in June 1998 with

a 2-year history of recurrent blisters on her face,

hands, forearms, and feet, which appeared during

the summer and resolved by winter. Her medical his-

tory includes the following: numerous blood trans-

fusions for severe anemia, hepatitis C virus infection,

secondary hyperparathyroidism, and a seizure disor-

der. She has had two unsuccessful living and cadav-

eric kidney transplants in 1982 and 1985 as well as a

parathyroidectomy. Her medications included

phenytoin, 500 mg daily; propoxyphene, napsylate,

and acetaminophen (Darvocet N-100), 200 mg 4

times a day; and erythropoietin, 4000 U 3 times

weekly. There was no family history of porphyria,

seizures, or cutaneous photosensitivity.

On examination the patient had multiple, tense

blisters and superficial erosions with crusting dis-

tributed on the face, forearms, dorsum of the

hands, fingers, legs, feet, and toes (Fig 1). There

was also onycholysis of most fingernails, wide-

spread hyperpigmentation of sun-exposed areas,

and lanugo hair growing on the temples and later-

al cheeks. Laboratory findings included the follow-

ing: phenytoin, 6.0 µg/mL (normal, 10-20 µg/mL);

hemoglobin, 7.9 g/dL (normal, 12.0-16.0 g/dL);

hematocrit, 22.6% (normal, 37.0%-47.0%); blood

urea nitrogen, 72 mg/dL (normal, 6-19 mg/dL); cre-

atinine, 10.7 mg/dL (normal, 0.4-1.1 mg/dL); alka-

646 Shieh, Cohen, and Lim J AM ACAD DERMATOL

APRIL 2000

Fig 1. Erosions, crusting, and blisters on dorsum of hands. Onycholysis should also be noted.

On the basis of the porphyrin profile, biopsy find-

ings, and immunofluorescence findings, the clinical

diagnosis of PCT was confirmed. The patient contin-

ued on high-flux hemodialysis with a polysulfone F-60

dialyzer. She remained on a regimen of phenytoin. In

September 1998, erythropoietin was increased to

10,000 U (200 U/kg) 3 times weekly. It was estimated

that 50 mL of blood was lost weekly during hemodial-

ysis. The patient also received one dose of hydroxy-

chloroquine (400 mg) at this time. After 1 month, a

slight decrease in the frequency of blisters was noted;

repeat ferritin value was 100 ng/dL. Because skin

lesions continued to be active, hydroxychloroquine

(400 mg weekly 2 days before the first dialysis for that

week) was given for a total of 5 doses. In December

1998, laboratory test results were as follows: ferritin,

646 ng/mL; alkaline phosphatase, 393 IU/L; and serum

glutamic-oxaloacetic transaminase, 74 IU/L. At that

time, the erosions on her fingers continued to

progress. Erythropoietin was increased to 18,000 U 3

times per week, and small repeated phlebotomies of

100 mL weekly were started. In January 1999, a

marked decrease in the activity of skin lesions was

observed, ferritin levels had decreased to 302 ng/mL,

but her fingertips showed evidence of necrosis with

eventual mutilation of the distal right index finger.

Erythropoietin was further increased to 20,000 U 3

times per week and phlebotomies of 100 mL weekly

were continued through April 1999. At that time, skin

fragility was markedly improved, ferritin had

decreased to 39 ng/mL, and transferrin saturation was

8%; however, hemoglobin had decreased to 5.8 g/dL.

Two units of blood were transfused; phlebotomy was

subsequently discontinued.

The patient was last seen in November 1999, and

her PCT was in clinical remission. Examination of the

skin showed no active blisters, although she contin-

ued to have mild sclerodermoid changes of the face

and neck line; temporal and preauricular hypertri-

chosis; hyperpigmentation involving the face, neck,

forearms, and hands; and mild tightening of the skin

on the fingertips associated with destruction of the

nail beds. At that time, her serum ferritin remained

within the normal range (63 ng/mL), and total plas-

ma porphyrins had decreased to 23.9 µg/dL (approx-

imately one tenth of the pretreatment level), with a

predominance of uroporphyrin.

DISCUSSIONThe management of PCT in patients with renal

failure focuses on the reduction of iron stores and

plasma porphyrins; in refractory cases, kidney trans-

plantation may be a consideration. In this section,

we review some of the available therapeutic options

and summarize treatment outcomes.

Treatment of iron overload

As reflected by serum iron or serum ferritin levels,

virtually all patients with PCT have iron overload.1 In

a study of 111 patients without clinical PCT on long-

term hemodialysis, elevated serum ferritin levels

were associated with the HLA antigens A3, B7, and

B1410; HLA-A3 and B7 alleles are known to occur

with increased frequency in hemochromatosis. In a

review of 74 patients with elevated serum ferritin lev-

els, 17.5% had hemochromatosis, and 6.7% had PCT;

all tested patients with PCT had either HLA-B7 or

both A-3 and B-7.11 Furthermore, many patients with

sporadic and familial PCT are now known to have the

hemochromatosis mutations (Cys282Tyr, His63Asp)

in the hemochromatosis HFE gene.4,5 In patients

with renal failure, chronic anemia frequently results

in multiple blood transfusions, precipitating or exac-

erbating iron overload.

The porphyrinogenic role of iron has been well

studied.2 Iron increases the inducibility of 5-aminole-

vulinate synthase, a major regulatory enzyme in

heme biosynthetic pathway. It suppresses the activi-

ty of uroporphyrinogen decarboxylase, the defective

enzyme in PCT. In addition, it participates in the oxi-

dation of porphyrinogens to their corresponding

porphyrins, which are not able to be metabolized.

Therefore reduction of total body iron load is an

important step in the management of PCT, including

PCT associated with chronic renal failure. Reports of

treatment of iron overload in the latter condition are

summarized below and in Table I.

Phlebotomy. Phlebotomy has been shown to be

safe and effective in depleting total body iron stores;

it is the treatment of choice in PCT not associated

with renal failure, leading to remission in many

cases.12,13 Most patients with renal failure are unable

to tolerate the standard removal of 250 to 500 mL of

blood once to twice per week because of the associ-

ated anemia. Nevertheless, standard volume phle-

botomy and, more frequently, small volume phle-

botomy have been reported to be efficacious for the

treatment of PCT in these patients.8,14,15

Erythropoietin. Erythropoietin is a glycoprotein

that stimulates erythrogenesis and mobilizes excess

iron stores. When used in doses ranging from 20 to

50 U/kg 2 to 3 times a week, erythropoietin has been

effective in improving lesions of PCT in at least 4

reported cases. Improvement in the appearance of

skin lesions was accompanied by a rise in hemoglo-

bin and fall in serum iron, ferritin, and plasma por-

phyrins in most instances.16-19

Combined phlebotomy and erythropoietin.High-dose erythropoietin, more than 150 U/kg 3

times per week, can be used in conjunction with

phlebotomy in chronic renal failure to help correct

Shieh, Cohen, and Lim 647J AM ACAD DERMATOL

VOLUME 42, NUMBER 4

observed increased plasma porphyrin levels and

decreased excretion in 62 patients on long-term

hemodialysis; 5 patients had plasma porphyrin val-

ues in the range of patients with clinical PCT.25

Various treatment modalities have been used to

reduce the level of plasma porphyrins (Table II). The

mechanism of induction of persistent remission in

the absence of correction of hepatic enzymatic

defect is unclear.

Chloroquine. Chloroquine is an antimalarial that

chelates and removes hepatic-bound porphyrins by

forming a water-soluble complex that is renally

excreted.26 However, in patients on dialysis, chloro-

quine-porphyrin complexes are inefficiently cleared

and no treatment successes have been reported.27,28

Similarly, in our patient, we were unable to achieve

improvement with 5 doses of hydroxychloroquine

400 mg weekly.

Plasma exchange. Plasma exchange consists of

the removal of large volumes of plasma and replac-

ing it with exogenous plasma or plasma substitutes.

In the case of PCT, plasma exchange results in

removal of plasma porphyrins and amelioration of

the disease. In addition to a successful report by

anemia and reduce iron stores. This method has

been successfully utilized in the management of our

patient, in addition to two other previously reported

cases.20,21 Combination of phlebotomy with lower

dose erythropoietin (50 U/kg 2 to 3 times a week)

was not successful in one patient.22

Deferoxamine. Deferoxamine is an alternative

means of reducing hepatic iron stores in patients

with severe anemia who are unable to tolerate phle-

botomy. This agent acts by chelating iron, and to a

lesser extent, aluminum. Several investigators have

explored the use of deferoxamine in treating dialysis-

related PCT. At least two groups reported excellent

results with deferoxamine 2 to 4 g administered

intravenously with each dialysis,23,24 whereas 4 other

groups observed no improvement with lower doses

of the medication (0.5-1.5 g intravenously with each

dialysis).17-19,21

Treatment of porphyrinemiaIn the presence of impaired renal function,

patients are unable to efficiently excrete porphyrins

and thus may be more predisposed to the develop-

ment of PCT. Poh-Fitzpatrick, Sosin, and Bemis25

648 Shieh, Cohen, and Lim J AM ACAD DERMATOL

APRIL 2000

Table I. Summary of treatment outcomes in PCT associated with chronic renal failure: Reduction ofiron overload*

Method/No. of Hgb, pre/post Ferritin, pre/postcases Investigators (Nl, 12-16 g/dL) (Nl, 0.005-0.146 µg/dL)

Standard phlebotomy/1 Lichtenstein, Babb, Felsher8 8.0/NR 1.92/1.92Small repeated phlebotomy/2 Riccioni et al15 9.8/8.6 NR/NR

Ruggian et al14 13.1/NR 1.77/0.091Erythropoietin/4 Sarkell & Patterson16 5.3/9.9 0.505/0.144

Piazza et al17 6.6/11.0 0.388/0.420Peces et al18 NR/10.0 0.831/0.063Yaqoob et al19 8.0/5.6 0.870/0.086

Combined erythropoietinand phlebotomy/4 Poux et al20 7.0/11.0 2.50/<0.025

Anderson et al21 8.6/NR 0.050/NR

Stevens et al22 7.3/NR NR/NR

Shieh (current study) 7.9/5.5 0.441/0.039

Deferoxamine/6 Stockenhuber et al23 6.67/NR 2.05/1.22Praga et al24 8.0/13.3 1.54/NRPiazza et al17 6.6/NR 0.388/NRPeces et al18 NR/NR 0.831/NRYaqoob et al19 8.0/NR 0.870/0.870Anderson et al21 8.6/NR 0.050/NR

CAPD, Chronic ambulatory peritoneal dialysis; Epo, erythropoietin; HD, hemodialysis; Hgb, hemoglobin; IV, intravenous; Nl, normal;NR, not reported; SC, subcutaneous.*English-language reports only.

Disler et al,29 two Japanese investigators have also

reported improvement in patients with PCT treated

with plasma exchange therapy. Suga and Ikezawa30

described 9 Japanese patients with PCT on

hemodialysis and one patient with PCT on long-term

ambulatory peritoneal dialysis treated successfully

with combined plasma exchange, high-performance

hemodialysis membranes, and hemodiafiltration.

Toriyama and Kawahara31 used small volume plasma

exchange therapy on a patient with PCT on mainte-

nance hemodialysis.

Hemodialysis. In most reported cases, signifi-

cant dialysis of porphyrins has not been possible

with conventional hemodialysis. This suggests that

porphyrins may bind to high-molecular-weight pro-

teins and form undialyzable complexes32 since the

lower molecular weight of porphyrin alone should

allow it to pass easily. Another possible explanation is

that the negatively charged dialysis membranes

oppose the negatively charged uroporphyrin mole-

cules.32 In the early 1990s, Carson et al33 showed

that dialysis with high-efficiency and high-flux mem-

branes allowed increased removal of plasma por-

phyrins because of larger membrane surface area

and pore size. In the same study, polysulfone mem-

branes were shown to be more effective than high-

efficiency cellulose membranes. Furthermore, they

achieved this result using a high blood flow rate of

300 mL/min (vs <250 mL/min), performing dialysis 3

times a week for 4 hours over 4 weeks. Two other

groups also found that high-efficiency dialysis more

effectively cleared porphyrins compared with con-

ventional dialysis,18,27 whereas another investigator

found no significant difference.19 Today, most dialy-

sis patients receive high flux hemodialysis, but PCT

still occurs, suggesting that high-flux hemodialysis

alone may not be sufficient to prevent the develop-

ment of PCT.

Cholestyramine. Cholestyramine is a basic

anion exchange resin that binds bile salts and is used

for reduction of hypercholesterolemia. In vitro,

cholestyramine binds carboxylated porphyrins

and thus may have a beneficial role in PCT by block-

ing the enterohepatic circulation of porphyrins.

Cholestyramine, 12 g in daily divided doses with

meals, has been used successfully in PCT patients

without renal failure, resulting in rapid resolution of

cutaneous lesions, but with no significant change in

Shieh, Cohen, and Lim 649J AM ACAD DERMATOL

VOLUME 42, NUMBER 4

Time to ReportedTotal successes/ achieve duration

Treatment protocol Remission failures remission of remission

500 mL × 3 courses Yes 1/0 NR NR100 mL 2×/wk for 8 mo with HD; then 50 mL/wk × 1 y Yes 2/0 8 mo 2 y250-350 mL biweekly × 4 mo Yes 4-5 mo NR50 U/kg 3 ×/wk post HD Yes 4/0 16 mo NR40 U/kg IV 2×/wk post HD Yes 4 mo NR20 U/kg SC 3×/wk post HD Yes 1 mo 9 mo50 U/kg IV 3×/wk post HD + iron 100 mg/wk Yes 3.5 mo 18 mo

Epo 200 U/kg IV 3×/wk 4 mo later: Phlebotomy 50 mL Yes 3/1 4 mo NRq2wk × 9 mo = 900mL

Epo 150 U/g IV post HD + iron 300 mg tid; 3 1⁄2 weeks later: Yes 4 mo NRPhlebotomy 120-180 mL × 3 wk = 900 mL

Epo 50 U/kg 2-3×/wk; 2 mo later: No NR NRPhlebotomy 7 intermittent = 1475 mL

Epo >200 U/kg 3×/wk; 4 mo later: Phlebotomy 100 mL/wk Yes 4 mo NR× 4 mo

4 g IV with HD 3×/wk × 12 mo Yes 2/4 12 mo NR2 g IV with HD ×2 courses; 1 g IV × 1 course, over 18 mo Yes 18 mo NR500 mg IV at 1st h of HD for 30 sessions during 3 mo No NR NR1 g with HD × 1 mo, then 500 mg × 9 mo No NR NRSingle 1 g dose No NR NR1500 mg every other HD (time course NR) No NR NR

was made, she received a cadaveric kidney trans-

plant and discontinued erythropoietin therapy.

Immediate resolution of cutaneous lesions as well as

a gradual clearance of porphyrins occurred. She was

reportedly free of skin lesions for at least 2 years

despite graft rejection 1 year after the transplant.

CONCLUSIONThe treatment of PCT in the setting of chronic

renal failure and hemodialysis remains a therapeutic

challenge despite the numerous treatment modali-

ties that have been tried. Overall, as demonstrated

in our patient, efforts aimed at reducing the iron

overload state are more uniformly effective than

those attempting to reduce plasma porphyrins.

Phlebotomy, erythropoietin, and to a lesser extent,

deferoxamine have been reported to be effective,

porphyrin excretion.34 However, two cases of

hemodialysis-associated PCT treated with cholestyra-

mine showed no improvement.21,27

Charcoal hemoperfusion. In vitro experiments

demonstrated that charcoal hemoperfusion could

remove uroporphyrin from plasma.35,36 However, as

reported by McColl et al,37 this treatment was not

successful in a patient with hemodialysis-related

PCT.

PCT refractory to medical treatmentKidney transplantation. Stevens et al22

achieved a complete clinical and laboratory resolu-

tion of PCT in a woman on long-term peritoneal dial-

ysis whose PCT had been refractory to topical

steroids, erythropoietin, and phlebotomy treatments

(Table III). Eleven months after the diagnosis of PCT

650 Shieh, Cohen, and Lim J AM ACAD DERMATOL

APRIL 2000

Table II. Summary of treatment outcomes in PCT associated with chronic renal failure: Porphyrin reduction*

Method/ Plasma porphyrinNo. of Hgb pre/post pre/postcases Investigators (Nl, 12-16 g/dL) (Nl, 0-0.9 µg/dL) Treatment protocol

Chloroquine/3 Parrilla et al27 NR/NR 121.1/NR (total)† 75 mg weekly × 2 moKing et al28 8.0/NR 53.0/54.0 (URO) 100 mg 3×/wk × 2 wkShieh (current study) 7.9/NR 260.4/NR (total) 400 mg weekly × 5 doses

Plasma exchange/1 Disler et al29 NR/NR 44.25/20.0 (URO) 4 L of plasma over 1 h × 2treatments, 48 h apart

High-flux hemodialysis/1 Carson et al33 NR/NR 202/128 (total) HFHD with polysulfonemembranes, 4 h 3×/wk× 4 wk; flow rate300 mL/min

Cholestyramine/2 Anderson et al21 8.6/NR NR/NR NRParrilla et al27 NR/NR NR/NR NR

Charcoal hemoperfusion/1 McColl et al37 NR/NR 37.43/35.26 (URO)† 100 g activated charcoalcolumn 4-h sessions× 3 over 6 days

HFHD, High-flux hemodialysis; Hgb, hemoglobin; Nl, normal; NR, not reported; URO, uroporphyrin.*English-language reports only.†Conversion from nanomoles per liter based on the weighted average of molecular weights for fractionated porphyrins: uroporphyrin,831.7 g; heptacarboxyl, 787.7 g; hexacarboxyl, 743.7 g; pentacarboxyl, 696.7 g; and coproporphyrin, 655.6 g.

Table III. Summary of treatment outcomes in PCT associated with chronic renal failure: Refractory tomedical treatment*

Ferritin Plasma porphyrinMethod/No. Hgb pre/post pre/post pre/post

of cases Investigators (Nl, 12-16 g/dL) (µg/mL) (Nl, 0-0.9 µg/dL) Treatment protocol

Kidney transplant/ 1 Stevens et al22 7.3/NR NR/NR 13.75/NR (total)† Cadaveric kidney transplant11 mo after diagnosis

Hgb, Hemoglobin; Nl, normal; NR, not reported.*English language reports only.†Conversion from nanomoles per liter based on the weighted average of molecular weights for fractionated porphyrins: uroporphyrin,831.7 g; heptacarboxyl, 787.7 g; hexacarboxyl, 743.7 g; pentacarboxyl, 696.7 g; and coproporphyrin, 655.6 g.

whereas chloroquine, cholestyramine, and charcoal

hemoperfusion have not. Plasma exchange has been

useful in several cases, but the procedure is complex

and expensive; it also incurs risk of infection with

blood products. As a last resort, kidney transplanta-

tion was immediately effective in one reported case.

On the basis of composite of therapeutic trials

reported in the literature, an algorithmic approach

to the management of these difficult patients can be

proposed. First, discontinuation of precipitating

agents and sun protection are crucial to successful

treatment. The next important step involves evalua-

tion of the hematologic status of the patient. No crit-

ical number exists above which phlebotomy is war-

ranted and below which it is contraindicated. In the

3 phlebotomy studies reported, pretreatment hemo-

globin ranged from 8.0 to 13.1 g/dL, whereas pre-

treatment hemoglobin ranged from 5.3 to 8.6 g/dL

for those receiving erythropoietin, erythropoietin/

phlebotomy, and deferoxamine therapy. If a patient

is clinically stable and hemoglobin is greater than or

equal to 10 g/dL, then phlebotomy alone may be

helpful, eliminating the need for additional treat-

ment modalities. Otherwise, if hemoglobin is less

than 8.0 g/dL, erythropoietin (20-50 U/kg 3 times per

week) can be started alone to ameliorate the anemia

and treat the PCT. Failure of either modality alone is

an indication for combination therapy with high-

dose erythropoietin (>150 U/kg) and small volume

phlebotomy (100 mL weekly). If remission occurs

with combination therapy, then erythropoietin can

be continued with close monitoring of serum ferritin

levels, and phlebotomy repeated as needed.

Deferoxamine should probably be considered a sec-

ond-line agent because of its relative lack of efficacy

and prolonged time to remission. Plasma exchange

and kidney transplantation should be reserved for

treatment-resistant cases.

REFERENCES1. Bickers DR, Pathak MA, Lim HW. The porphyrias. In: Freedberg

IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz SI, et al, edi-tors. Fitzpatrick’s Dermatology in general medicine; vol 2. 5thed. New York: McGraw-Hill; 1999. p. 1766-803.

2. Kim JJ, Lim HW. Hexachlorobenzene and porphyria cutaneatarda. Arch Dermatol 1999;135:459-60.

3. Lim HW. Role of viral infection in porphyria cutanea tarda.Photodermatol Photoimmunol Photomed 1997;13:75-7.

4. Bonkovsky HL, Poh-Fitzpatrick M, Pimstone N, Obando J, DiBisceglie A, Tattrie C, et al. Porphyria cutanea tarda, hepatitis C,and HFE gene mutations in North America. Hepatology 1998;27:1661-9.

5. Elder GH, Worwood M. Mutations in the haemochromatosis(HFE) gene, porphyria cutanea tarda and iron overload.Hepatology 1998;27:289-91.

6. Poh-Fitzpatrick MB, Masullo AS, Grossman ME. Porphyriacutanea tarda associated with chronic renal disease andhemodialysis. Arch Dermatol 1980;116:191-5.

7. Day RS, Eales L. Porphyrins in chronic renal failure. Nephron1980;26:90-5.

8. Lichtenstein JR, Babb EJ, Felsher BF. Porphyria cutanea tarda ina patient with chronic renal failure on haemodialysis. Br JDermatol 1981;104:575.

9. Rosenlof K, Fyhrquist F, Tenhunen R. Erythropoietin, aluminum,and anaemia in patients on haemodialysis. Lancet 1990;335:247-9.

10. Quereda C, Teruel JL, Lamas S, Marcen R, Matesanz R, Ortuno J.HLA antigens and serum ferritin in hemodialysis patients.Nephron 1987;45:104-10.

11. O’Reilly FM, Darby C, Fogarty J, Tormey W, Kay EW, Leader M, etal. Screening of patients with iron overload to identifyhemochromatosis and porphyria cutanea tarda. Arch Dermatol1997;133:1098-101.

12. Ippen H.Treatment of porphyria cutanea tarda by phlebotomy.Semin Hematol 1977;14:253-60.

13. Grossman ME, Bickers DR, Poh-Fitzpatrick MB, DeLeo VA, HarberLC. Porphyria cutanea tarda: clinical features and laboratoryfindings in 40 patients. Am J Med 1979;67:277-86.

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Total Time to Reportedsuccesses/ achieve duration

Remission failures remission of remission

No 0/3 NR NRNo NR NRNo NR NRYes 1/0 Days 4 mo

No 0/1 NR NR

No 0/2 NR NRNo NR NRNo 0/1 NR NR

Total Time to Reportedsuccesses/ achieve duration

Remission failures remission of remission

Yes 1/0 Immediate 2 y

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