Delayed photosensitivity in a child with erythropoietic protoporphyria : a case report

Abstract

Erythropoietic protoporphyria (EPP) is a genetically inherited disease that causes protoporphyrin accumulation in erythrocytes, skin, liver, bile, and stool. Clinically this manifests as photosensitivity with painful, edematous cutaneous porphyria. We present the case of a four-year-old boy with a delayed photosensitivity reaction to sunlight. In the evening following sun exposure, he would develop swelling and a violaceous rash on the dorsal surface of his hands and occasionally the helix of his ears. His reactions were severe, requiring morphine on more than one occasion prior to diagnosis. He later developed waxy depressed scars on his nose and cheeks. On laboratory investigation, both total and free protoporphyrin were elevated. Photosensitivity in EPP usually occurs minutes after sun exposure, but our patient had significantly delayed reactions. Genetic testing revealed mutation in the FECH gene that confirmed the diagnosis of EPP. Although rare, presentations of photosensitivity in the pediatric population should be carefully evaluated.

Cimetidine Does Not Inhibit 5-Aminolevulinic Acid Synthase or Heme Oxygenase Activity: Implications for Treatment of Acute Intermittent Porphyria and Erythropoietic Protoporphyria

“…This triggers reactive oxygen species production and complement activation, both of which lead to inflammatory changes [48,49]. It has been reported that a daily oral regimen of cimetidine markedly improved cutaneous photosensitivity in four pediatric patients with EPP [37,38]. However, the EPP-causing FECH mutations were documented in only one of these patients [37], and PPIX was measured before and after cimetidine administration in another single patient [38].…”

“…Given recent reports that cimetidine improved cutaneous photosensitivity in patients with EPP, presumably by inhibiting ALAS activity in erythroid cells [36][37][38], we investigated whether cimetidine inhibits ALAS2 activity, first in vitro and then in bone marrow cells isolated from cimetidine-treated mice. Human ALAS2 enzyme (NP_001033057.3) was prokaryotically expressed and purified, and its activity was measured in the presence of increasing concentrations (0 to 240 µmol/L) of cimetidine (Table 1).…”

“…In EPP, the primary phenotype is skin photosensitivity due to decreased ferrochelatase activity that leads to accumulation of the photoreactive porphyrin protoporphyrin IX (PPIX) in bone marrow erythroid cells, where heme synthesis is mainly driven by the erythroid-specific ALAS2 isozyme (Supplemental Figure S1A). A notable improvement in cutaneous photosensitivity was reported in these studies that included 4 pediatric and 15 adult EPP patients administered cimetidine daily (30-40 mg/kg/day in children; 800-1600 mg/day in adults) [36][37][38]. While it has been speculated that cimetidine leads to clinical benefits by inhibiting bone marrow ALAS2 activity, studies conducted to date have not investigated this.…”

“…Additionally, we explored whether cimetidine modulates ALAS2 activity in vitro and then in murine bone marrow cells, as cimetidine also has been proposed to be an effective treatment for erythropoietic protoporphyria (EPP) [36][37][38]. In EPP, the primary phenotype is skin photosensitivity due to decreased ferrochelatase activity that leads to accumulation of the photoreactive porphyrin protoporphyrin IX (PPIX) in bone marrow erythroid cells, where heme synthesis is mainly driven by the erythroid-specific ALAS2 isozyme (Supplemental Figure S1A).…”

Erythema and blistering after sun exposure in a 12‐year‐old boy

“…Erythropoietic protoporphyria (EPP) is a genetic porphyria caused by a deficiency of the enzyme ferrochelatase. The population prevalence ranges from 1 in 75 000‐200 000, and it is the most common porphyria in children . It is one of the two subtypes of protoporphyria, the other being delta‐aminolevulinic acid synthase 2 hyperactivity, also known as X‐linked protoporphyria (XLP).…”