Erythropoietic Protoporphyria: Initial Diagnosis With Cholestatic Liver Disease

Abstract

The porphyrias are a group of rare metabolic disorders that result from defects in heme biosynthesis. Erythropoietic protoporphyria (EPP) is the most common inherited porphyria in children and is diagnosed in most individuals after the onset of cutaneous manifestations. Hepatobiliary disease affects the minority of individuals with EPP and usually manifests in patients with an established diagnosis of EPP. We report on a classic but rare case of EPP that masqueraded as cholestasis. An 8-year-old boy was referred to the Hepatology Clinic after an abrupt onset of jaundice with a longstanding history of dermatitis. The diagnosis of EPP was established with liver biopsy, which revealed dense, dark-brown pigment in hepatocytes and Kupffer cells that, on polarization, displayed bright-red birefringence and centrally located Maltese crosses. Plasma total porphyrins and erythrocyte protoporphyrin were elevated and confirmed a diagnosis of EPP. We hope to raise awareness of this diagnosis among pediatricians, hepatologists, and pathologists and increase the consideration of EPP in patients with cholestatic liver disease and chronic dermatitis.

Erythropoietic protoporphyria‐ associated hepatopathy: expanding the spectra of brown pigments encountered in hepatic specimens

“…The accumulation of excess protoporphyrin further exacerbates cholestasis and reduces the excretion of protoporphyrin. Taken together, these changes lead to hepatic disease of varying severity ranging from mild parenchymal liver disease to progressive hepatocellular disease including end‐stage liver disease and acute liver failure 1‐5 . Protoporphyrin deposits in bile may also crystallize forming gallstones, 1 as seen in our patient as well.…”

“…FECH deficiency is associated with increased concentrations of protoporphyrin in erythrocytes, skin and liver 1‐3 . Up to 20% of patients may develop hepatobiliary disease; however only a small subset (about 5%) would develop severe liver disease with cholestasis and liver failure 1,4 …”

“…Typically, the usual initial clinical manifestation of EPP is acute painful photosensitivity. However, EPP‐associated hepatopathy as the initial presentation has been described in the literature, and is certainly a possibility in cases where the skin symptoms are not recognized as manifestations of EPP or may be dismissed as chronic non‐specific dermatitis 4 . Given the rarity of EPP, it is conceivable that this diagnosis could be overlooked by the clinician as well as the pathologist.…”

Recognized and Emerging Features of Erythropoietic and X-Linked Protoporphyria

“…A mild accumulation of α1-antitrypsin has also been reported in Kupffer cells, but not in hepatocytes. However, no hemosiderin or copper was detectable by special stains [ 42 ]. A recent study demonstrated the unique property of porphyrins to cause organelle-selective protein oxidation and aggregation, which is thought to be a major mechanism of cellular injury in porphyria [ 43 ].…”

Hematopoietic cell transplant for reversal of liver fibrosis in a pediatric patient with erythropoietic protoporphyria

“…Subsequently, there is accumulation of the photoactive, toxic compound PPIX in plasma, erythrocytes, bone marrow, skin, and sometimes liver 1 . Severity of EPP phenotype varies considerably between affected individuals due to incomplete penetrance and allelic heterogeneity in FECH mutations and has contributed to significant diagnostic delays 2‐4 . The most common presentation includes dermatologic features, such that within minutes of exposure to sunlight and some artificial light patients develop rash, pruritis, blisters, or even second‐degree burns.…”