Light-Related Cutaneous Symptoms of Erythropoietic Protoporphyria and Associations With Light Sensitivity Measurements

Abstract

ImportanceErythropoietic protoporphyria (EPP) is a rare and underdiagnosed genetic disease characterized by painful sensitivity to light. A better understanding and characterization of its light-induced cutaneous symptoms may aid in the identification of EPP in patients.ObjectivesTo describe the cutaneous symptoms of erythropoietic protoporphyria (EPP) and to determine if these symptoms are associated with the degree of light sensitivity.Design, Setting, and ParticipantsThis was a cross-sectional study of adolescent and adult (≥15 years) patients with EPP across the US conducted by a single academic hospital via a remotely administered survey, measurements of light sensitivity by light dosimetry and by text message symptom assessments. Data analyses were conducted from November 2020 to April 2022.ExposuresSunlight exposure.Main Outcomes and MeasuresSelf-reported symptoms and association with measured light sensitivity.ResultsThe study sample consisted of 35 patients with EPP (mean [SD] age, 39.1 (15.5) years; 21 [60%] female; 14 [40%] male; 35 [100%] White individuals). The patients’ median [range] skin tone was 3.0 (1.0-8.0), based on self-reporting from 1 (lightest) to 12 (darkest). A total of 24 participants completed the light dosimeter measurements. Phototoxic reactions were characterized by pain (97%; 34 patients), burning (97%; 34), tingling (97%; 34), pruritus (83%; 29), allodynia (89%; 31), improvement of symptoms with cold (89%; 31), achiness (24%; 12), fatigue (46%; 16), mild swelling (83%; 29), severe swelling (63%; 22), erythema (51%; 18), petechiae (40%; 14), skin cracking (43%; 15), scabbing (46%; 16), scarring (66%; 23), and other chronic skin changes (40%; 14). Patients with EPP reported that their hands, feet, and face were most sensitive to light and that their shoulders and legs were least sensitive; 25.7% (9 patient) reported no chronic skin changes, and 5.7% (2 patients) reported never having had any visible symptoms. None of these findings varied with the degree of light sensitivity except that lower overall light sensitivity was associated with lower ranked sensitivity of the neck and arms.Conclusions and RelevanceThe findings of this cross-sectional study suggest that patients with EPP have distinctive cutaneous symptoms that may aid in identification of this underdiagnosed disease. Characteristic EPP symptoms include light-induced cutaneous burning pain and occasional swelling, particularly over the hands, with a prodrome of pruritus and paresthesias. Minimal skin changes or the absence of visible skin changes during reactions to light, including lack of erythema, do not exclude an EPP diagnosis nor suggest low EPP disease burden.

Development and Content Validation of Novel Patient-Reported Outcome Measures to Assess Disease Severity and Change in Patients with Erythropoietic Protoporphyria: The EPP Impact Questionnaire (EPIQ)

“…The most common symptoms reported were burning, pain, swelling, tingling, itching, sensitivity to touch, warmth/heat sensation, blisters, redness/discoloration, and sensitivity to hot/cold, which is consistent with previous studies. 1 , 3 Though burning and pain were reported as distinct symptoms by some participants, consistent with previous studies and case reports, 5 , 28 , 29 others reported “burning pain”. It is likely patients interpret these concepts on a continuum when describing their symptoms.…”

Afamelanotide in protoporphyria and other skin diseases: a review

“…Short-time exposure to light causes severe pain (neuropathic pain) in children, which usually occurs 1–20 min after direct exposure to the sun and may last several days and be unresponsive to analgesics. The skin may become erythematous and oedematous, with the presence of petechiae and erosions [ 16 , 18 , 19 ]. Quality of life in patients suffering from EPP is severely affected since early childhood due to their light-avoiding behaviour and limitations in social interactions [ 20 ].…”