Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

no phlebotomy contraindications

1st line – repeated phlebotomy until a target serum ferritin is reached

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ACUTE
|
no phlebotomy contraindications
1st line – 

repeated phlebotomy until a target serum ferritin is reached

PCT results from reduced (<20% of normal) activity of uroporphyrinogen decarboxylase (UROD) in the liver. This occurs when uroporphyrinogen is partially oxidized to form uroporphomethene, which is a competitive inhibitor of hepatic UROD. This in turn results in accumulation in the liver of uroporphyrin and other highly carboxylated porphyrins that are the oxidized substrates and intermediates of UROD. These porphyrins circulate in plasma and are excreted renally.[3] Because PCT is an iron-related disease, reduction of iron stores by repeat phlebotomy is effective, and is standard treatment in most centers.

Phlebotomy is also preferred by some patients because it does not involve potential adverse effects of drug administration.

However, it is costly, inconvenient, and sometimes poorly tolerated. It is contraindicated in patients with anemia due to concurrent medical conditions, those with a cardiopulmonary disease that might be compromised by a modest drop in hemoglobin, those with poor venous access, or patients with frequent presyncope after phlebotomies.

Phlebotomy of approximately 450 mL every 2 weeks is usually performed until the desired serum ferritin target of 15 to 20 nanograms/mL is achieved, then phlebotomy is stopped. In patients with chronic renal failure/end-stage renal failure on hemodialysis, if phlebotomies are administered they are small in volume (approximately 100 mL) and supported by the administration of erythropoietin.

Plasma (and urine) porphyrins fall less rapidly than ferritin. Therefore, treatment is usually completed before porphyrins are normal and skin lesions completely resolved.

Monitor ferritin, plasma total porphyrins, and hematocrit or hemoglobin while the patient is having repeated phlebotomy.[16] If the hematocrit or hemoglobin levels are too low, allow about 2 weeks for the hematocrit or hemoglobin to increase before continuing phlebotomy.

Primary options

phlebotomy: approximately 450 mL every 2 weeks until target ferritin of 15-20 nanograms/mL is achieved

Plus – removal of susceptibility factors

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ACUTE
|
no phlebotomy contraindications
Plus – 

removal of susceptibility factors

Treatment recommended for ALL patients in selected patient group

Management includes identification and, when possible, removal of susceptibility factors for PCT (excessive alcohol intake, smoking, and estrogen therapy).

Advise patients to avoid sunlight until plasma total porphyrins are normal. Beta-carotene and sun blockers are not effective.

Stopping drinking alcohol, smoking, and estrogen treatment may hasten remission but these are generally not sufficient on their own.

Estrogen therapy can be resumed if clinically indicated after PCT is in remission.

Plus – erythropoietin and low-volume phlebotomy

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ACUTE
|
no phlebotomy contraindications
|
chronic renal failure/end-stage renal failure on hemodialysis
Plus – 

erythropoietin and low-volume phlebotomy

Treatment recommended for ALL patients in selected patient group

In PCT patients with chronic renal failure/end-stage renal failure on hemodialysis or peritoneal dialysis, iron reduction is accomplished by administration of erythropoietin (to correct erythropoietin deficiency and restore red cell production by the bone marrow) to support small volume (approximately 100 mL) phlebotomies at each hemodialysis session.

Hydroxychloroquine and chloroquine are contraindicated in this group of patients due to inefficacy. If the patient has any contraindications to phlebotomy, erythropoietin is given and a decision to perform further low-volume phlebotomy will be based on the specialist opinion and will take into account the patient's current hemoglobin or hematocrit levels.

Primary options

epoetin alfa: consult specialist for guidance on dose

OR

darbepoetin alfa: consult specialist for guidance on dose

Plus – antiviral therapy

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ACUTE
|
no phlebotomy contraindications
|
with hepatitis C
Plus – 

antiviral therapy

Treatment recommended for ALL patients in selected patient group

Direct-acting antivirals (DAAs) are highly effective for treatment of hepatitis C, and limited evidence suggests that this treatment should be initiated in PCT patients with hepatitis C without first treating with phlebotomies or low-dose hydroxychloroquine.[29] Studies are under way to compare times to remission and durability of DAA therapy when compared with phlebotomy or low-dose hydroxychloroquine.[30] While there is a lack of evidence, some experts may recommend DAAs alone for PCT patients with hepatitis C.

See Hepatitis C (Treatment Algorithm).

Plus – antiretroviral therapy

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ACUTE
|
no phlebotomy contraindications
|
with HIV
Plus – 

antiretroviral therapy

Treatment recommended for ALL patients in selected patient group

HIV infection is potentially life-threatening, especially if treatment is interrupted. Therefore it is important to continue treatment for HIV concurrently with treatment of PCT. However, if patients are newly diagnosed with both PCT and HIV, specialist guidance should be sought from infectious diseases specialists regarding decision and timing to start antiretroviral therapy.

See HIV infection (Treatment Algorithm).

phlebotomy contraindicated or poorly tolerated

1st line – low-dose hydroxychloroquine or chloroquine

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ACUTE
|
phlebotomy contraindicated or poorly tolerated
1st line – 

low-dose hydroxychloroquine or chloroquine

Low doses of hydroxychloroquine or chloroquine are recommended for patients in whom phlebotomy is contraindicated, difficult, or poorly tolerated.[23][24][25][26][27]

Usual doses are not used because they can cause transient but sometimes severe liver damage and worsening of photosensitivity. Hydroxychloroquine has a better safety profile than chloroquine.

The treatment is contraindicated in patients with end-stage renal disease, substantial serum ferritin elevations (>500 nanograms/mL), advanced liver disease, continuing heavy alcohol intake, glucose-6-phosphate dehydrogenase (G6PD) deficiency, or intolerance to these medications.

Ophthalmological evaluation is recommended before and at 12-month intervals during treatment.

The low-dose regimen is continued until plasma porphyrins have been normal for about 3 months, after which they can be discontinued.

Low-dose hydroxychloroquine is generally as effective as phlebotomy for treatment of PCT, but longer studies are needed to compare relapse rates.[23][28]

Primary options

hydroxychloroquine sulfate: 100 mg orally twice weekly

OR

chloroquine phosphate: 150 mg orally twice weekly

Plus – removal of susceptibility factors

Back
ACUTE
|
phlebotomy contraindicated or poorly tolerated
Plus – 

removal of susceptibility factors

Treatment recommended for ALL patients in selected patient group

Management includes identification and, when possible, removal of susceptibility factors for PCT (excessive alcohol intake, smoking, and estrogen therapy).

Patients are advised to avoid sunlight until plasma total porphyrins are normal. Beta-carotene and sun blockers are not effective.

Stopping alcohol, smoking, and estrogen treatment may hasten remission but these are generally not sufficient on their own.

Estrogen therapy can be resumed if clinically indicated after PCT is in remission.

Plus – antiviral therapy

Back
ACUTE
|
phlebotomy contraindicated or poorly tolerated
|
with hepatitis C
Plus – 

antiviral therapy

Treatment recommended for ALL patients in selected patient group

Direct-acting antivirals (DAAs) are highly effective for treatment of hepatitis C, and limited evidence suggests that this treatment should be initiated in PCT patients with hepatitis C without first treating with phlebotomies or low-dose hydroxychloroquine.[29] Studies are under way to determine whether initial treatment of hepatitis C-associated PCT with these agents leads to remission as quickly as phlebotomy or low-dose hydroxychloroquine.[30] While there is a lack of evidence, some experts may recommend DAAs alone for PCT patients with hepatitis C.

See Hepatitis C (Treatment Algorithm).

Plus – antiretroviral therapy

Back
ACUTE
|
phlebotomy contraindicated or poorly tolerated
|
with HIV
Plus – 

antiretroviral therapy

Treatment recommended for ALL patients in selected patient group

HIV infection is potentially life-threatening, especially if treatment is interrupted. Therefore it is important to continue treatment for HIV concurrently with treatment of PCT. However, if patients are newly diagnosed with both PCT and HIV, specialist guidance should be sought from infectious diseases specialists regarding decision and timing to start antiretroviral therapy.

See HIV infection (Treatment algorithm).

ONGOING

relapse after remission

1st line – repeated treatment

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ONGOING
|
relapse after remission
1st line – 

repeated treatment

According to the patient's sensitivities to treatment, recurrences of PCT should be treated with either phlebotomies or low-dose hydroxychloroquine.

Plus – removal of susceptibility factors

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ONGOING
|
relapse after remission
Plus – 

removal of susceptibility factors

Treatment recommended for ALL patients in selected patient group

Management includes identification and, when possible, removal of susceptibility factors for PCT (excessive alcohol intake, smoking, and estrogen therapy).

Patients are advised to avoid sunlight until plasma total porphyrins are normal. Beta-carotene and sun blockers are not effective.

Stopping alcohol, smoking, and estrogen treatment may hasten remission but these are generally not sufficient on their own.

Estrogen therapy can be resumed if clinically indicated after PCT is in remission.

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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