Protoporphyria Treatment & Management

Updated: Apr 11, 2016
  • Author: Maureen B Poh-Fitzpatrick, MD; Chief Editor: William D James, MD  more...
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Treatment

Medical Care

For protoporphyria uncomplicated by hepatobiliary disease, the major problem is lifelong cutaneous photosensitivity. Anemia, if present in erythropoietic protoporphyria (EPP), typically is mild but may have features of iron deficiency. Iron supplementation has both improved [50, 51, 52] and worsened [53, 54] EPP. In one X-linked dominant protoporphyria (XLP) patient, iron therapy was followed by improvements in protoporphyrin overload, liver damage, and anemia. [29] Cholelithiasis is managed surgically. Liver dysfunction is an ominous development for which medical remedies are not consistently effective. Progressive intractable liver insufficiency is an indication for liver transplantation. [21, 23, 61]

Note the following treatment measures for photosensitivity:

  • Shield skin from sunlight by using protective clothing and lifestyle adjustments.
  • Because the wavelengths of light causing porphyrin-sensitized phototoxicity are chiefly in the visible spectrum, window glass is not an effective barrier. Plastic films that attenuate transmission of portions of the visible light and long UV spectra are available and can be applied to window or windshield glass. [62]
  • Topical sunscreens are not effective unless transmission of long UV and visible light rays is reduced by their use. Sun-blocking formulations containing zinc oxide or titanium dioxide reflect visible light and may be helpful. [62]
  • Topical sunless tanning gels or creams containing dihydroxyacetone produce superficial pigmentation that blocks some of the offending wavelengths. [62]
  • Induction of endogenous melanin by exposure of skin to broad- or narrow-band UV-B lamps or to UV-A in conjunction with a psoralen UV-A photosensitizer also may increase tolerance to natural sunlight. [63]
  • Afamelanotide, an alpha-melanocyte–stimulating hormone analogue that increases melanin production in the skin, is a novel subcutaneously implantable photoprotective agent [64] currently in clinical trials in the United States. It is available by prescription in Europe.
  • Oral beta-carotene reduces photosensitivity in some, but not all, patients. [3, 65, 66]
  • Attenuation of photosensitivity using oral cysteine [67] or pyridoxine [68] has been reported but not widely confirmed.
  • H1-receptor antagonists can mitigate histamine-mediated components of the acute reaction, but they rarely suppress all signs and symptoms. [69] Suppression of heme synthesis by inhibition of cytochrome P-450 formation and of heme oxygenase activity is a mechanism proposed for transient improvement of isolated cases of various porphyrias after H2-receptor antagonist use that remains unproven. [70]
  • A pilot study of the oral enteric sorbent colestipol found less photosensitivity in 3 subjects with EPP after its use, but reductions in erythrocyte protoporphyrin levels were not significant. [71]

Although adverse reactions to porphyrinogenic drugs known to exacerbate acute hepatic porphyrias are not characteristic of protoporphyria, avoid or administer with caution drugs with cholestatic properties, such as estrogenic hormones. Assess the risk-to-benefit ratio for each individual with protoporphyria when considering use of cholestatic therapies.

Immunization against viral hepatitis agents should be offered.

Supplementation with cholecalciferol (vitamin D3) should be given if serum vitamin D levels are low and/or bone density studies reveal osteopenia or osteoporosis.

Medical approaches to reversing protoporphyric liver dysfunction are not well established, owing to inconsistent or uncertain efficacy and experience in relatively few cases. These include the following:

  • Orally administered cationic exchange resins or activated charcoal aimed at reducing enterohepatic recirculation of porphyrin and/or bile acids to enhance hepatic porphyrin excretion may have some level of efficacy in selected patients. [43, 72, 73, 71]
  • Hypertransfusion to slow erythropoiesis [74] and intravenous infusion of heme analogues to repress endogenous porphyrin production [75, 76] have been beneficial in some cases.
  • Reduction in erythrocyte protoporphyrin levels and improved liver function followed administration of vitamin E to a protoporphyric patient with cirrhosis. [77]
  • Plasmapheresis [76] or exchange transfusion [78] to reduce the circulating protoporphyrin burden appeared helpful in a small number of advanced cases.
  • Medical regimens are often used in combination or rapid sequence in progressively deteriorating patients and are best instituted by experts in a referral center for advanced liver disease.
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Surgical Care

Failure of medical reversal of protoporphyrin-induced hepatic decompensation warrants liver transplantation. Operating room illumination has caused acute phototoxic damage to skin and internal organs during liver transplantation for protoporphyric liver failure. [79, 80, 58, 81] This procedure requires several hours' exposure of skin and internal organs to intense visible light at a time when the patient's accumulated protoporphyrin levels are typically extremely high, causing severe photosensitivity. Preoperative exchange transfusions, plasmapheresis, and/or infusion of a heme analogue may lower the circulating burden of protoporphyrin in the blood, reducing intraoperative phototoxic potential. [82] These treatments may also aid postoperatively in retarding the development of protoporphyrin hepatotoxicity in the engrafted liver. [75, 76]

Wahlin et al recommended a specific flexible yellow filter excluding wavelengths below 470 nm for use over operating room lamps to optimally attenuate phototoxic damage to patients with erythropoietic protoporphyria during liver transplantation, yet provide acceptable illumination for the surgeons. [83] They found the risk of phototoxic injury in endoscopic, laparoscopic, and non–liver transplant surgery in such patients to be low and recommended that protective measures, including filters for operating room lamps, should be reserved for liver transplantation or for other prolonged surgical procedures in cholestatic patients.

Biliary complications (stones, sludge, strictures) are more frequent after liver transplantation for erythropoietic protoporphyria compared with the general population of transplant patients; therefore, consideration of Roux loop reconstruction is recommended. [33, 58]

Adverse reactions to anesthetic agents problematic in acute hepatic porphyrias are not characteristic of protoporphyria.

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Consultations

Consultation with a hematologist should be sought for management of anemia, particularly before instituting iron supplementation, or if hypertransfusion, exchange transfusion, or plasmapheresis is considered. Rarely, bone marrow transplantation may have a role in the management of selected patients with severe manifestations. [32, 57]

Referral to specialists at a comprehensive liver center should be arranged at the earliest signs of liver decompensation for assistance in evaluation and management of progressive liver dysfunction. If liver transplantation becomes necessary, a successful outcome is more likely if the procedure is performed before the patient is gravely debilitated.

Referral to a medical geneticist can aid in counseling patients and families about risks of inheriting or transmitting the mutations and polymorphisms associated with the disease. [84, 85]

Preoperative consultation with anesthesiologists and biomedical engineers is essential concerning use of appropriate filters over operating room lighting during liver transplantation or for other procedures for protoporphyria patients who have high circulating protoporphyrin levels and/or anticipated severe photosensitivity.

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Diet

Do not severely curtail carbohydrate intake; a "glucose effect" may beneficially modulate abnormal heme synthesis. [86] Limit use of ethanol; alcohol excess has been implicated in fatal protoporphyria associated with liver failure. [87] Vitamin D and calcium-rich foods or supplements may reduce the incidence of osteopenia or osteoporosis associated with chronic sunlight avoidance.

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Activity

Sunlight avoidance is mandatory. Recommend adjustment of outdoor activities to avoid midday sunlight. Stylish and comfortable sun-protective clothing is commercially available that can reduce time constraints on many outdoor sports or activities. Specialized programs for photosensitive children can be found that offer safe and healthy recreational experiences, even a summer camp organized by the Xeroderma Pigmentosum Society. See Camp Sundown.

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Complications

Severe neurological dysfunction (eg, encephalopathy, axonal polyneuropathy, respiratory failure) characteristic of attacks of acute porphyrias has been observed in persons with end-stage hepatic failure associated with erythropoietic protoporphyria (EPP). [79, 80, 88]

Pregnancy does not cause worsening of EPP; photosensitivity may actually improve during gestation. [26]

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