ABSTRACT
Erythropoietic protoporphyria (EPP) is an inherited metabolic disease that causes painful phototoxic reactions, starting in childhood. Studies have shown a reduced quality of life (QoL) in adults with EPP, however, data on children with the disease are lacking. Since treatment for EPP is currently not registered for children, knowledge about their QoL is of crucial importance. In this prospective, case-control study, we included children from the Netherlands and Belgium diagnosed with EPP and matched to healthy controls. Previously collected EPP quality of life (EPP-QoL) data from matched adults with EPP were used. QoL scores, utilizing the Pediatric Quality of Life Inventory (PedsQL) and the disease-specific EPP-QoL, were collected. Scores range from 0 to 100, with higher scores indicating a higher QoL. Non-parametric tests were used to compare groups. A total of 15 cases, 13 matched healthy control children, and 15 matched adults with EPP were included. Children with EPP exhibited lower median scores in the PedsQL in both physical (cases: 87.5 (interquartile range [IQR] 77.7-96.1), controls: 99.2 [IQR 94.9-100.0], p = 0.03) and social (cases: 77.5 [IQR 69.4-86.3], controls: 97.5 [IQR 78.8-100.0], p = 0.04) domains compared to healthy children, although these differences were not statistically significant after correcting for multiple testing. The overall median EPP-QoL score for children was similar to adults with EPP (children: 44.4 [IQR 25.0-54.2], adults: 45.8 [IQR 25.7-68.1], p = 0.68). However, within the EPP-QoL subdomain on QoL, children were found to have significantly lower median scores (children: 16.7 [IQR 0.0-33.3], adults: 33.3 [IQR 33.3-62.5], p < 0.01). In conclusion, children with EPP experience a reduced QoL compared to both healthy children and adults with EPP. Ensuring treatment availability for this patient group is crucial for improving their QoL. We advocate the inclusion of children in safety and efficacy studies, to ensure availability of treatment in the future.
ABSTRACT
BACKGROUND: Erythropoietic protoporphyria (EPP) patients experience lifelong painful photosensitivity resulting in a lack of sunlight exposure. Previous studies have shown that 47-63% of EPP patients suffer from vitamin D deficiency and a high prevalence of osteoporosis. As of 2016 an effective treatment for EPP is available: the alpha-MSH analogue afamelanotide. So far studies on vitamin D levels in EPP have only investigated patients who were not treated with afamelanotide. OBJECTIVES: To investigate the effects of afamelanotide treatment on vitamin D levels in EPP. METHODS: A multi-centre observational cohort study, in adult patients with EPP from the Erasmus Medical Centre, the Netherlands and the University Hospital Düsseldorf, Germany. Routinely-collected vitamin D levels between 2005 and 2021 were used for analysis. Patient exposure to cholecalciferol or afamelanotide was categorized into four treatment groups; untreated, cholecalciferol, afamelanotide, and combined treatment. A linear mixed model for longitudinal data was applied to measure the effect of the treatment groups, compared to the untreated, on vitamin D levels. RESULTS: A total of 230 patients and 1774 vitamin D measurements were included. Prevalence of vitamin D deficiency remained high despite afamelanotide treatment: <50 nmol/l in 71.8% of patients, and severe deficiency <30 nmol/l in 48.1%. Afamelanotide treatment alone did not lead to a significant average increase in vitamin D levels (ß:0.5, 95% Confidence Interval [CI]: -3.2 - 4.2). In contrast, cholecalciferol and combined therapy with afamelanotide, led to a significant increase in vitamin D levels (ß:11.6, CI: 7.2-15.9 and ß:15.2, CI: 12.3-18.1). CONCLUSION: Cholecalciferol remains essential for treatment of vitamin D deficiency in EPP, irrespective of new treatment options like afamelanotide. Afamelanotide treatment did not affect vitamin D levels. We suggest that future guidelines include continuous monitoring of vitamin D and prescription of cholecalciferol in all patients with EPP, including those treated with afamelanotide.
ABSTRACT
Toxic alcohol poisoning can be lethal if not identified early and treated appropriately. Toxic alcohol assays are often unavailable in low-resource setting, so clinicians have to infer a diagnosis based on suspicion, repeated evaluation and biochemical course. We report a case of toxic alcohol poisoning concealed by auto-intoxication with in-hospital hand sanitizer. The eventual appearance of a concurrent high anion gap prompted dialysis. In another case, a comatose patient presented with a high osmolal gap and a high anion gap. Incorrect a priori opinions caused us to defer dialysis and the patient died shortly afterwards. Clinicians should be aware that toxic alcohol poisoning can produce a confusing diagnostic picture with an insidious course, and that doctor delay can prove fatal. LEARNING POINTS: Toxic alcohol ingestion may be lethal and warrants early identification, but this is not always possible.Incorrect a priori opinions by clinicians, or the co-ingestion of other alcohols by a patient, may produce a confusing diagnostic picture.Physicians should not defer immediate treatment for patients suspected of toxic alcohol ingestion with a double gap or visual disturbances.
