MANAGEMENT OF PORPHYRIA CUTANEA TARDA

Read this page in conjunction with Porphyria cutanea tarda.

The management of porphyria cutanea tarda differs from that of the other porphyrias in that the condition is reversible. Porphyria cutanea tarda is in most cases secondary to precipitating conditions, principally:

• iron overload, which is in many cases related to heterozygosity or homozygosity for haemochromatosis-related mutations
• exposure to alcohol
• exposure to oestrogens
• hepatitis C
• HIV infection
• renal failure
• and rarely, SLE or lymphoma.

For optimal management, it is necessary to assess and manage these conditions independently.

INVESTIGATION

Take a full history of exposure to alcohol, drugs, iron-containing preparations, oestrogen and industrial toxins. Examine the patient, looking for evidence of liver disease, HIV infection, haemochromatosis or systemic illness. Request the following: liver function tests, tests of iron status including serum ferritin and transferrin saturation, and DNA analysis for the C282Y and H63D mutations. (These are the common mutations in the HFE gene associated with hereditary haemochromatosis, and will be positive in some patients with porphyria cutanea tarda.), HIV and HCV serology. A liver biopsy is frequently useful as an indicator of both iron loading and of the degree of liver abnormality associated with the porphyria cutanea tarda.

It is important that patients are seen as primarily having a "medical" rather than a "skin" problem: though it is the photosensitive skin damage which brings them to medical attention, the primary, underlying problem is frequently non-trivial, e.g. haemochromatosis, hepatitis C, HIV infection.

MANAGEMENT

Symptomatic therapy: skin disease

Manage the skin disease with sun protection and wound care (See Management of skin disease).

Specific therapy for porphyria cutanea tarda

Remove precipitating factors

Alcohol consumption should be drastically reduced or ceased. Oestrogen therapy should cease.

Reduce iron loading

Commence venesection. Remove 500 ml of blood fortnightly and continue until serum ferritin and transferrin saturation are at the lower end of the normal range.

Oral chloroquine therapy

Prescribe chloroquine 125 mg three times weekly. This has the effect of mobilising porphyrins from the liver. Introduction of therapy is frequently associated with a temporary aggravation of skin disease and reddening of the urine from an increase porphyrin concentration; these features pass as the disease comes into remission. Do not use higher doses: this can lead to severe hepatitis. Refer for expert management of severe liver disease, haemochromatosis, hepatitis C or HIV infection. Preliminary evidence suggests that suppression of hepatitis C and HIV by appropriate antiviral drug regimens may induce remission in patients with porphyria cutanea tarda associated with these infections.

MANAGEMENT OF HIV-ASSOCIATED PCT

This association accounts for an increasing number of patients referred to us for assessment. It is our impression that these patients frequently do not seem to have the other risk factors typical of PCT in HIV-negative patients; in particular, there may be no evidence of iron overload or of alcohol exposure.

It is our practice to commence venesection - even if there is no apparent iron overload, and to continue this provided the patient does not become iron deficient. We prescribe chloroquine, and commence antiretroviral therapy as soon as convenient. It is however wise to wait until the liver enzymes, if disturbed, have stabilised, so as not to mask an antiretroviral-associated liver injury. This regimen has proved very effective in our patients.

REMISSION

Typically venesection is followed by biochemical in clinical remission of the porphyria cutanea tarda after approximately 5 to 6 venesections (3 to 4 months). Clinical resolution is speeded up by the addition of chloroquine. Use of chloroquine alone as described in the older literature is not recommended, as this does not improve the associated iron loading which is deleterious for the liver.

MAINTENANCE OF REMISSION

Once in remission, serum ferritin and transferrin saturation should be checked once or twice annually. Should any tendency to rise be shown, further venesections should be carried out. If hormone replacement therapy is strongly indicated, it is acceptable to reintroduce the lowest possible dose of oestrogen once the patient is in remission. In our experience, this has not resulted in relapse of PCT. Urine and plasma porphyrins should be checked from time to time to ensure that the porphyria is not reactivating.

Typically remission is durable, and it may be 10-15 years before iron levels have reaccumulated sufficiently for the PCT to recur. If so, it responds well to further venesection.