Medical Care
Sunlight avoidance is the main defense for photosensitivity until clinical remission can be induced. Alcohol must be proscribed. Cessation of tobacco smoking should be recommended, not only for potential beneficial effect on porphyria, but for overall good health. 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 [56, 57, 58] reduces iron stores, which improves heme synthesis disturbed by ferro-mediated inhibition of uroporphyrinogen decarboxylase (UROD). The goal of therapy is to reduce serum ferritin levels to the lower limit of the reference range. [59] Venesections may be scheduled at intervals ranging from a unit of whole blood removed twice weekly to every 2-3 weeks as tolerated by the patient. Care should be taken to not induce anemia (hemoglobin < 10-11 g/dL). Phlebotomy is the preferred therapy for individuals with a heavy iron burden. Efficacy of antihepatitis C therapy appears to be enhanced if hepatic siderosis is first reduced by phlebotomy. [60]
For patients in whom phlebotomy is not convenient or is contraindicated or for patients with relatively mild iron overload, oral chloroquine phosphate (125-250 mg PO twice weekly) or hydroxychloroquine sulfate (100-200 mg PO 2-3 times/wk), doses much lower than those used for antimalarial or photoprotective indications, can be effective. [61, 62, 63, 64, 65, 66] 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. Hepatic transaminases and urinary porphyrin output may rise transiently after institution of therapy, returning to normal levels as treatment continues. Low-dose chloroquine and phlebotomy therapies may be used concomitantly to more rapidly reach clinical and biochemical remissions. [67]
Chelation with desferrioxamine is an alternative means of iron mobilization when venesections are not practical. [68] A pilot study of the oral iron-chelating agent desferasirox in 10 patients with porphyria cutanea tarda found that 7 who completed the 6-month trial noted resolution of blistering, 6 had lesser urinary porphyrin content, and 7 had reduced serum ferritin levels. [69] A larger controlled study may confirm this agent as a useful alternative treatment. In patients who are not tolerant of therapeutic phlebotomy, iron chelation with deferoxamine has been discussed as an alternative treatment for PCT. Studies suggest subcutaneous infusions of 40-50 mg/kg for 8-10 hours daily for the first 5 days and then subsequently reduced to 5-10 days per month. In addition to being an iron chelator, deferoxamine may reduce the compensatory increase of intestinal iron absorption often seen in remission induced by the greater degree of iron reduction achieved by phlebotomies. [2]
For patients with porphyria cutanea tarda who are anemic due to other chronic diseases (eg, renal failure, human immunodeficiency viral infection), human recombinant erythropoietin can be used to stimulate erythropoiesis. [70] 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.
A tabular outline of management recommendations published in 2012 offers additional details. [71]
In patients with PCT-associated with hepatitis C viral infection, effective treatment of the hepatitis C viral infection has resulted in a cure of the PCT as well. Earlier regimens that involved the use of interferon or ribavirin had been associated with severe flares of the cutaneous disease. Pretreatment with phlebotomy realized this issue. However, newer regimens that use direct-acting antivirals do not seem to result in a similar exacerbation of cutaneous fragility and blistering and are thus preferable. Singal et al also suggest that antimalarial therapy might be beneficial as an adjunctive therapy for PCT in the hepatitis C–infected patient. [66]
Special concerns
Pregnancy in women with porphyria cutanea tarda has been followed by safe delivery of healthy infants. [72] Mobilization of maternal excess tissue iron stores to support the growing fetus may actually be beneficial to pregnant women with porphyria cutanea tarda. 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 porphyria cutanea tarda 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 porphyria cutanea tarda 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 estrogen-receptor antagonist tamoxifen has been associated with the development of porphyria cutanea tarda in women treated with this agent for breast carcinoma. [73] The risks posed by plant-derived, estrogenlike compounds to individuals with porphyria cutanea tarda are not well established.
Porphyria cutanea tarda may appear for the first time in patients with end-stage renal disease after several months of long-term dialysis. [74] Anuric individuals can be readily diagnosed by assaying a plasma or serum specimen for the characteristic elevated levels of polycarboxylated porphyrins. Quantitative plasma porphyrin levels are often much higher than those of patients with normal renal function, who excrete large amounts of these water-soluble porphyrins in urine. These patients may be very photosensitive.
Chronic anemia is often present in end-stage renal disease despite increased iron stores, limiting treatment by phlebotomy. Erythropoietin may be used to reduce excess iron stores by stimulating erythropoiesis, which may result in sufficient erythrocyte mass to permit judicious low-volume serial phlebotomy. Chloroquine or hydroxychloroquine should not be used, as porphyrins liberated from hepatocytes by these agents enter the plasma, but cannot be cleared through the kidney, resulting in even higher circulating levels and increased cutaneous photosensitivity. Deferoxamine and ferric carboxymaltose have been used in the setting of renal failure. [75]
Surgical Care
Renal transplantation has been effective in reducing porphyrin levels and in improving cutaneous photosensitivity in porphyria cutanea tarda occurring in patients with end-stage kidney disease. [76, 77]
Consultations
Consultation with a dermatologist for a skin examination as well biopsies sent for hematoxylin and eosin (H&E) staining and direct immunofluorescence is indicated.
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 such as red meats should be consumed sparingly. Adequate levels of vitamin C may retard oxidation reactions in the liver; consumption of vitamin C‒rich fresh fruits and vegetables, their juices, or an iron-free multivitamin containing vitamin C are recommended.
Activity
Patients should avoid sunlight exposure until biochemical and clinical remission has been induced. Manual labor should be curtailed to minimize the mechanical trauma that causes erosions and blistering. Use of light-exclusive clothing and lifestyle alterations are usually necessary to alleviate photocutaneous reactions until remissions can be achieved.
Long-Term Monitoring
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.
For patients who have achieved posttherapy clinical and biochemical remissions, checking levels of serum or plasma porphyrins at progressively longer intervals (3, 6, 12 months) and tracking serum ferritin levels similarly may detect any trend toward recurrence prior to reappearance of cutaneous photosensitivity. A progressive rise in levels of porphyrins and of ferritin would herald a potential reemergence of symptoms. Reinstitution of therapy to again reduce iron load (as reflected by serum ferritin levels diminishing to a low-normal range) would be expected to prevent reappearance of symptoms. Thereafter, surveillance of serum or plasma porphyrin levels and of serum ferritin should again be carried out periodically.
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Thickened skin with blisters, scars, and milia. Courtesy of Dirk Elston, MD.
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Close-up image of blisters, scarring, and milia. Courtesy of Dirk Elston, MD.
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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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Fluorescence of urine with a Wood light examination. Courtesy of Brooke Army Medical Center Teaching File.
