Erythropoietic protoporphyria: time to prodrome, the warning signal to exit sun exposure without pain—a patient-reported outcome efficacy measure

Wensink, Debby; Langendonk, Janneke G.; Overbey, Jessica; Balwani, Manisha; Broekhoven, E. J. E. Van; Wagenmakers, M. A. E. M.; Wilson, J. H. P.; Wheeden, Kristen; Naik, Hetanshi; Desnick, Robert J.

doi:10.1038/s41436-021-01176-z

Cited by 12 publications

(9 citation statements)

References 26 publications

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“…The study confirms that afamelanotide treatment can improve tolerance to direct sunlight 9,11–13 . However, this is the first study that reports that treatment can possibly have a positive impact on employment rate.…”

Section: Discussionsupporting

confidence: 73%

“…The study confirms that afamelanotide treatment can improve tolerance to direct sunlight. 9,[11][12][13] However, this is the first study that reports that treatment can possibly have a positive impact on employment rate. Treatment resulted in more patients reporting a full-or part-time job, and requiring less adjustment at work (e.g.…”

Section: Discussionmentioning

confidence: 91%

“…8 From a young age patients develop light avoiding behavior due to the early onset and severity of the pain after sunlight exposure. They learn to recognize early symptoms, often referred to as prodromes, 9 as a warning signal to immediately go out of direct light. This is likely to result in impairment of social activities and career perspectives.…”

mentioning

confidence: 99%

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Erythropoietic protoporphyria in the Netherlands: Clinical features, psychosocial impact and the effect of afamelanotide

Wensink

Wagenmakers

Wilson

et al. 2022

The Journal of Dermatology

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Erythropoietic protoporphyria (EPP; OMIM 177000) is characterized by painful photosensitivity, starting from early childhood and lasting throughout life, which severely impairs quality of life. 1 Excessive light exposure triggers symptoms of intense pain, erythema, edema, and in severe cases petechiae and crusts. 2 The symptoms can last for days and the severe pain responds poorly to pain medication.Erythropoietic protoporphyria, a rare inherited disorder of heme biosynthesis, is caused by autosomal recessive mutations in the FECH

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 91%

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Erythropoietic protoporphyria in the Netherlands: Clinical features, psychosocial impact and the effect of afamelanotide

Wensink

Wagenmakers

Wilson

et al. 2022

The Journal of Dermatology

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“…However, this evidence of efficacy might be biased due to the reluctance of EPP patients to expose themselves to the sun. It was recently proposed that time to prodrome (TTP), i.e., the exposition time until the appearance of prodromal symptoms, could be a more reliable parameter to measure the pharmacological response as safer for patients [ 97 ]. Afamelanotide is an analog of the α melanocyte-stimulating hormone (α-MSH) and binds to the melanocortin 1 receptor (MC1R), stimulating the production of eumelanin [ 98 ], which provides photoprotection and antioxidant defence in melanocytes [ 99 ].…”

Section: Managementmentioning

confidence: 99%

Recognized and Emerging Features of Erythropoietic and X-Linked Protoporphyria

et al. 2022

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Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are inherited disorders resulting from defects in two different enzymes of the heme biosynthetic pathway, i.e., ferrochelatase (FECH) and delta-aminolevulinic acid synthase-2 (ALAS2), respectively. The ubiquitous FECH catalyzes the insertion of iron into the protoporphyrin ring to generate the final product, heme. After hemoglobinization, FECH can utilize other metals like zinc to bind the remainder of the protoporphyrin molecules, leading to the formation of zinc protoporphyrin. Therefore, FECH deficiency in EPP limits the formation of both heme and zinc protoporphyrin molecules. The erythroid-specific ALAS2 catalyses the synthesis of delta-aminolevulinic acid (ALA), from the union of glycine and succinyl-coenzyme A, in the first step of the pathway in the erythron. In XLP, ALAS2 activity increases, resulting in the amplified formation of ALA, and iron becomes the rate-limiting factor for heme synthesis in the erythroid tissue. Both EPP and XLP lead to the systemic accumulation of protoporphyrin IX (PPIX) in blood, erythrocytes, and tissues causing the major symptom of cutaneous photosensitivity and several other less recognized signs that need to be considered. Although significant advances have been made in our understanding of EPP and XLP in recent years, a complete understanding of the factors governing the variability in clinical expression and the severity (progression) of the disease remains elusive. The present review provides an overview of both well-established facts and the latest findings regarding these rare diseases.

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“…11,12 The degree of self-perceived skin photosensitivity depends, among other things, on geographical location, season, time of day, skin pigmentation, skin thickness and photopriming, producing uncertainties when evaluating treatment effect without a standardized test method. 2,8,13 Measurement of photosensitivity by phototesting has the advantage that the conditions can be kept constant while determining a defined reaction to a standardized illumination of the skin.…”

mentioning

confidence: 99%

Phototesting in erythropoietic protoporphyria trials: A systematic review

Heerfordt

Philipsen

Lerche

et al. 2023

Experimental Dermatology

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Severe skin pain when exposed to long wave ultraviolet radiation or visible light is the main symptom of erythropoietic protoporphyria (EPP). Treatment options for EPP are inadequate and new treatments are needed but hampered by the lack of valid efficacy outcomes. Phototesting with well‐defined illumination of the skin can be performed reliably. We aimed to provide an overview of phototest procedures used to evaluate EPP treatments. Systematic searches of Embase, MEDLINE and the Cochrane Library were performed. Searches identified 11 studies using photosensitivity as efficacy outcome. The studies used eight different phototest protocols. Illuminations were performed with a filtered high‐pressure mercury arc, or a xenon arc lamp equipped with monochromator or filters. Some used broadband, others narrowband illumination. In all protocols phototests were performed on the hands or the back. Endpoints were minimal dose required to induce either first symptom of discomfort, erythema, urticaria or intolerable pain. Other endpoints were change in erythema intensity or diameter of any type of flare after exposure compared to before. In conclusion, protocols displayed extensive variability in illumination set‐up and evaluation of phototest reactions. Implementation of a standardized phototest method will allow more consistent and reliable outcome evaluation in future therapeutic research of protoporphyric photosensitivity.

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Erythropoietic protoporphyria: time to prodrome, the warning signal to exit sun exposure without pain—a patient-reported outcome efficacy measure

Cited by 12 publications

References 26 publications

Erythropoietic protoporphyria in the Netherlands: Clinical features, psychosocial impact and the effect of afamelanotide

Erythropoietic protoporphyria in the Netherlands: Clinical features, psychosocial impact and the effect of afamelanotide

Recognized and Emerging Features of Erythropoietic and X-Linked Protoporphyria

Phototesting in erythropoietic protoporphyria trials: A systematic review

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