The EPP LIGHT Study: A Survey Describing the Burden of Erythropoietic Protoporphyria and X-Linked Protoporphyria
Authors: Naik Hetanshi , Balwani Manisha , Colwell Hilary H , Mathias Susan D , Wheeden Kristen , Norregaard Chelsea , Chin Melanie , Savage William 
Published: December 2024

Background:
Erythropoietic protoporphyria and X-linked protoporphyria (collectively referred to as EPP) are rare, genetic disorders of the heme biosynthetic pathway, leading to accumulation of the photoactive metabolite protoporphyrin IX (PPIX). Clinically, these present with painful phototoxic reactions on sun exposure. In some patients, PPIX accumulation in the liver can lead to hepatobiliary disease, which can progress to liver failure and lead to liver and/or bone marrow transplantation. EPP can negatively impact health-related quality of life (HRQoL) and result in significant healthcare utilization (HCU). This study aimed to describe the full burden associated with EPP in all facets of life, including symptoms, HRQoL (eg, emotional functioning, physical functioning), work/school, and HCU.
Methods:
Participants, recruited by a patient advocacy group, were ≥12 years old; had a diagnosis of EPP; resided in North America; were able to speak, read, and write English; and completed a 1-time online survey. The survey included existing and original patient-reported outcome measures developed based on qualitative research with individuals with EPP. The study was approved by an institutional review board, and informed consent was obtained. Data collection is still underway for adolescents.
Results:
There were 164 adults who completed the survey. Mean age was 45; most participants were female (60%), white (96%), married (56%), working full time (54%), and had ≥college degree (64%). Mean age at diagnosis was 15 years. Most participants (77%) had their diagnosis confirmed by genetic testing, and for the majority (63%), it took ≥5 years to receive a diagnosis. Comorbid conditions included vitamin D deficiency (59%) and anemia (58%); 28% had their gallbladder removed. A majority (52%) regularly saw their physician; most (86%) saw their doctor ≥1 time per year. Most (83%) participants rated their health as “much worse” or “a little worse” than that of individuals without EPP.
Most (73%) “usually” or “always” worry about experiencing prodromal symptoms of a phototoxic reaction; 49% experience prodromal symptoms after spending ≤10 minutes in the sun, with most (73%) having prodromal symptoms ≥1 time in the past 3 months. Of the participants who experienced the prodromal symptoms of burning, stinging, sensitivity to hot or cold, sensitivity to touch, pain, feelings of warmth, swelling, redness/discoloration, and scabbing, ≥50% reported the severity as “moderate” or “severe.” About 80% have pain from indirect sun at least “sometimes.”
Most (67%) experienced ≥1 phototoxic reaction in the past 12 months, with 68% experiencing pain after &lt;30 minutes in sunlight. The last phototoxic reaction affected ability to do daily activities “very much” in 58% of participants. After a phototoxic reaction, it took on average 5.5±4.8 days for all symptoms to improve. On a scale from 0 (no pain) to 10 (worst pain imaginable), mean pain rating for the last phototoxic reaction was 7.6±1.6.
Adults with EPP experience much less satisfaction with social roles and activities and much greater social isolation than those in the general population. Over 70% of adults reported feeling depressed, anxious, isolated, frustrated, or lonely while coping with their EPP symptoms; 61% reported at least “sometimes” missing out doing activities they enjoy in the past 7 days due to EPP.
On average, those employed (n=108) missed 4.6±13.6 hours of work (range: 0-96) and those attending school (n=21) missed 3.3±6.5 hours of school (range: 0-20) in the past month due to EPP.
For individuals with ≥1 physician visit (n=134, 82%), the mean number of visits in the past 12 months was 8.0±13.3. Nine percent (n=14) had ≥1 emergency room (ER) visit (mean=5.4±10.2), and 6% (n=10) had been hospitalized ≥1 time (mean=2.2±1.5) in the past 12 months. Most ER visits and hospitalizations were due to pain from a phototoxic reaction or liver problems.
Conclusions:
Adults with EPP experience multiple symptoms that impact all facets of their lives, including the ability to be out in the sun for prolonged periods of time, ability to undertake daily activities, deficits in emotional functioning, and absenteeism at work and school. These lead to excess HCU and significant burden.