The study, “Erythropoietic Protoporphyria: Initial Diagnosis With Cholestatic Liver Disease,” appeared in the journal Pediatrics.
EPP patients typically have skin manifestations in sun-exposed areas, evident as skin pain, burning, stinging and itching, often associated with redness and swelling.
Up to 20% of these patients have hepatobiliary disease — a group of liver and biliary systems disorders — and 5% develop advanced liver disease with reduced flow of bile, or cholestasis. An EPP diagnosis usually precedes signs of liver disease, but skin lesions may not be recognized as early disease manifestations.
The scientists described the case of an 8-year-old boy with chronic skin changes in the eyes, worsening pruritus (itching) and jaundice, or yellowed skin and eyes. His medical history included a facial rash with blistering, hypo- and/or hyperpigmentation (coloring abnormalities), and a burning sensation in the toes during the summer. He also had heart defects, including a hypoplastic (interrupted) aortic arch, as well as asthma.
Six weeks before arriving at a hospital, the patient’s lost his fingernails and developed intense itching on his hands and feet. His height and weight were below average for his age.
Physical examination revealed prominent scleral icterus, a condition characterized by yellowing of the white part of the eye, as well as a palpable and enlarged spleen and liver. In addition to healed blisters and areas of altered pigmentation, the boy showed scarring and widespread jaundice.
Blood biochemistry tests revealed exaggerated levels of liver enzymes, bilirubin — a substance generated during the normal breakdown of red blood cells and whose elevated levels may indicate liver disease — and of the protein albumin, which is made by the liver. The boy also had higher-than-normal levels of total cholesterol, triglyceride, LDL, as well as low level of HDL, all of which are well-reported in EPP.
Liver biopsy revealed diverse alterations related to inflammation, as well as dark-brown pigment accumulation typical of EPP. Electron microscopy revealed multiple pigment crystals in liver cells called hepatocytes and Kupffer cells consistent with protoporphyrin, which collects to toxic levels in EPP. In agreement, total and red blood cells levels of protoporphyrin were markedly high.
The patient was started with a twice-a-day oral solution of ursodeoxycholic acid, a naturally occurring bile acid used for cholestatic liver disease, and later 2 g of twice daily cholestyramine, a medication used to lower cholesterol and itching. He was also prescribed oral beta-carotene capsules (90 mg per day) to neutralize the chemical compounds formed by protoporphyrin, and vitamin E to help with wound healing and provide antioxidant defenses.
Six months later, the boy was hospitalized again with influenza type A. His liver enzyme levels remained high as he had not complied with therapy. Medications to treat EPP were restarted, leading to a quick decrease in liver enzymes and bilirubin.
“This case illustrates that undiagnosed, chronic, recurring skin manifestations of EPP may precede the development of clinically apparent liver disease, confirming that a delay in diagnosis may be due to the often subtle and unrecognized cutaneous [skin] symptoms,” the researchers wrote.
“We hope to alert pediatricians, hepatologists, and pathologists to consider EPP in patients who present with a recent onset of cholestasis and chronic cutaneous symptoms,” they added.