Cutaneous phototoxicity is the hallmark feature of EPP & XLP1
Light exposure triggers acute phototoxic reactions characterized by severe pain, which may be accompanied by swelling, erythema, and systemic symptoms2
Symptoms of EPP and XLP usually begin in infancy or early childhood. Phototoxic skin reactions are associated with severe and prolonged pain, resulting in lifelong sunlight avoidance in patients with these conditions. Exposure to artificial or fluorescent light, as well as visible and long-wave UV light, can also trigger phototoxicity in some patients.1,3,4
Light tolerance varies significantly among patients, ranging from a few minutes to several hours. The severity of phototoxicity among patients may be associated in part with their PPIX levels, but is otherwise poorly understood. Symptoms may also fluctuate day-to-day depending on the season, time of day, cloud cover, and other factors. A "priming effect" is also widely reported among patients, in which light exposure on one day increases sensitivity and reduces tolerance to light on the following days.2,5,6
Variability in sun tolerance has been associated with5,7:
Erythrocyte PPIX levels
Season
Geographical location
Weather conditions
From early signs to full reaction—how phototoxicity erupts to the surface
Phototoxic pain is severe and not responsive to conventional analgesics, including narcotics.1
The clinical impact of EPP & XLP is more than skin deep1
In addition to phototoxicity, a significant number of patients may develop other complications and comorbidities due to EPP or XLP1
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Acute
liver failure10
Up to 5% of patients may develop acute cholestatic liver failure requiring transplantation.10
Liver
dysfunction11
Elevated liver enzymes may be seen in more than 50% of patients.11
Post-exposure illness12
Some patients report chills, fatigue, and other systemic symptoms following prolonged light exposure.12
Microcytic anemia1,7
Mild microcytic anemia may be found in approximately 30% to 60% of patients.1,7
Poor
bone health13
High rates of osteopenia (40%), osteoporosis (15%), and bone fractures (47%) are observed.13
Abnormal iron metabolism5
EPP & XLP are associated with disrupted iron metabolism due to unknown mechanisms.5
Vitamin D deficiency14
About 50% of patients develop vitamin D deficiency due to sun avoidance, leading to poor bone health.14
Gallstones10
PPIX-containing gallstones are reported in 23% to 26% of patients.10
Psychological conditions8
Depression, anxiety, and other psychosocial issues due to EPP & XLP are common.8
Reduced
quality of life3,8,15
EPP & XLP are associated with a significant reduction in quality of life.3,8,15
Cholestasis11,16
Insoluble PPIX crystals in bile may cause cholestasis, biliary obstruction, and inflammation.11,16
Chronic skin changes12
Chronic changes to sun-exposed skin may include lichenification, perioral grooving, and absent nail lunulae.12
Emerging insights: PPIX levels and clinical variability in EPP & XLP
In patients with EPP or XLP, those with liver dysfunction were found to have higher median PPIX levels compared with those with normal liver function. Additionally, higher PPIX levels may be associated with earlier age of symptom onset and more severe phototoxicity.6,7,11
However, determinants of disease severity remain poorly understood and there is currently no way to determine individual prognosis or risk of hepatobiliary complications. Further research is needed to generate new insights into prognostic indicators, as well as the natural history and individual risk of EPP- and XLP-related liver dysfunction.6,11,16
Higher PPIX levels are found in patients with liver dysfunction11
This longitudinal natural history study in the largest reported cohort of patients with EPP or XLP (N=322) confirmed previous findings that elevated PPIX levels are associated with abnormal liver enzymes. The study also found significantly higher PPIX levels in patients with more advanced EPP- or XLP-related liver disease.11
PPIX levels based on degree of liver enzyme elevation11
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Risk of significant liver complications remains highly individual and may occur in any patient, at any PPIX level, at any time.16
Higher PPIX levels are associated with more severe phototoxicity7
Higher PPIX levels were correlated with earlier age of symptom onset, decreased sun tolerance, and increased risk of liver dysfunction in this observational cohort study of patients with EPP or XLP (N=226).7
PPIX levels and time to first
phototoxic symptom7
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