F1000Research 2020, 9:9 Last updated: 16 JUL 2021 CASE REPORT Case Report: Pseudoxanthoma elasticum [version 1; peer review: 1 approved, 3 approved with reservations] Catarina Lucas 1, João Aranha2, Isabel da Rocha3, Domingos Sousa 4 1Family Health Unit, Baesuris Family Health Unit, Castro Marim, Faro, 8950-219, Portugal 2Dermatology Department, Hospital Distrital de Santarém, Santarém, Santarém, 2005-177, Portugal 3Personalized Health Care Unit, Personalized Health Care Unit of Penacova, Coimbra, Coimbra, 3360-205, Portugal 4Internal Medicine Department, Centro Hospitalar e Universitário do Algarve, Faro, Faro, 8000-386, Portugal v1 First published: 09 Jan 2020, 9:9 Open Peer Review https://doi.org/10.12688/f1000research.21431.1 Latest published: 09 Jan 2020, 9:9 https://doi.org/10.12688/f1000research.21431.1 Reviewer Status Invited Reviewers Abstract Pseudoxanthoma elasticum (PXE) is a rare inherited disorder, 1 2 3 4 characterised by a progressive mineralization and fragmentation of elastic fibres of the skin, retina and cardiovascular system. At an initial version 1 stage, the skin usually exhibits distinctive lesions and subsequently 09 Jan 2020 report report report report extra-dermal manifestations. The diagnosis is based on clinical manifestations, histological analysis of the lesions and genetic 1. Olivier M. Vanakker , Ghent University analysis. This is a case report of a 12-year-old child complaining of painless, Hospital, Ghent, Belgium mildly itchy yellow papules in the cervical region with 1 year of evolution. 2. Márta Medvecz , Semmelweis University, PXE is currently an incurable disease and has a favourable prognosis Budapest, Hungary when cardiovascular and retinal complications are prevented and monitored. 3. Annamaria Offidani, Polytechnic University of the Marche Region, Ancona, Italy Keywords Pseudoxanthoma elasticum, ABCC6 gene, retina angioid streaks, 4. Wilko Spiering , Utrecht University, hypertension Utrecht, The Netherlands Any reports and responses or comments on the article can be found at the end of the article. Page 1 of 12 F1000Research 2020, 9:9 Last updated: 16 JUL 2021 Corresponding author: Catarina Lucas ([email protected]) Author roles: Lucas C: Investigation; Aranha J: Investigation, Writing – Review & Editing; da Rocha I: Investigation; Sousa D: Investigation, Writing – Review & Editing Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2020 Lucas C et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite this article: Lucas C, Aranha J, da Rocha I and Sousa D. Case Report: Pseudoxanthoma elasticum [version 1; peer review: 1 approved, 3 approved with reservations] F1000Research 2020, 9:9 https://doi.org/10.12688/f1000research.21431.1 First published: 09 Jan 2020, 9:9 https://doi.org/10.12688/f1000research.21431.1 Page 2 of 12 F1000Research 2020, 9:9 Last updated: 16 JUL 2021 Introduction slightly itchy yellow papules in the cervical region with 1 year Pseudoxanthoma elasticum (PXE), also known as Grönblad- of evolution. These lesions remained stable throughout this Strandberg syndrome, is a rare inherited disorder presenting period with no medication or treatment. The child had no pain an autosomal recessive inheritance with a mutation in the complaints, or inflammatory signs on the lesions or around them, ABCC6 gene (ATP-binding cassette transporter C6), mapped in and did not have any associated symptoms. Previously she was the chromosome 16. It has an estimated prevalence of 1/25.000 a healthy child, was not taking any daily medication and had to 1/100.000 inhabitants and is 10 times more prevalent in no relevant personal or family medical history of dermatosis. women1,2. On examination, painless, uneven, rough and yellow plaques The disease is characterised by a progressive mineralization without inflammatory signs in the posterior cervical region that and fragmentation of elastic fibres of the skin, retina, merged bilaterally and symmetrically into the right and left side gastrointestinal and cardiovascular systems. cervical region was found (Figure 1). It was similar to a goose bump pattern, giving it a parchment-like skin appearance. The PXE results in a variety of signs and symptoms that vary in remaining integument had no changes. their number, type, and severity from person to person. Cer- tain effects of PXE can cause serious medical problems, while No other abnormalities were found on the rest of physical others have less impact. Effects may include: skin changes, examination. changes in the retina of the eye that may result in signifi- cant loss of central vision, changes in the cardiovascular In this appointment, the following exams were conducted: hemo- system that may involve calcification of arteries and decreased gram, general biochemistry with lipid profile and phosphorus- blood flow in the arms and legs, and/or changes in the gas- calcium balance and urinary sediment that were unremarkable. trointestinal system that may lead to bleeding in the stomach Moreover, a skin biopsy was promptly performed. or intestines. At present, there is no way to predict the exact progression of the disorder for an individual2. Some people have no skin lesions; others have no vision loss. Many people In the next appointment, still in November, the skin biopsy do not experience gastrointestinal complications or cardio- results revealed limited changes to the superficial/medium reticu- vascular difficulties. A few have no manifestations of PXE lar dermis with a long strip of elastic fibre fragmentation. They except for a positive skin biopsy or irregular streaks resembling were thick, granular, basophilic, with bizarre shapes between a blood vessel (angioid) in the retina of the eye1,2. the collagen fibres with a normal appearance. There was no evidence of mineralization or deposits of mucin. The diagnosis is based on major and minor criteria defined in 1994 taking into account the clinical manifestations described Following the investigation, further exams were conducted: above (Table 1), positive histological on Von Kossa stain electrocardiogram and echocardiogram, carotid and aortoiliac for reticular dermis, family history and genetic analysis of venous and arterial ultrasonography, retinogram with full oph- the ABCC6 gene1–3. thalmological examination (angioid streaks). The results were normal. There was the possibility of a genetic disorder, but PXE is currently an incurable disease but has a favourable the pathology specialist decided there was no need to perform prognosis with appropriate follow-up by multidisciplinary a study of the ABCC6 genes based on the clinical aspect of the teams. lesions, which were highly characteristic of PXE. Case description The child has been having annual follow-up with ophthalmo- A 12-year-old Caucasian girl presented for a dermatology logic, paediatric cardiology and dermatology appointments. Until appointment in November 2016 due to sporadically painless, February 2019 no systemic manifestations were reported. Table 1. Diagnostic criteria for Pseudoxanthoma elasticum (PXE) defined at the consensus conference in 19943. Major criteria • Characteristic skin signs – Yellow cobblestone lesions in flexural areas • Characteristic histological features of lesional skin – Elastic tissue and calcium or von Kossa stains • Characteristic ophthalmologic features – Angioid streaks, peau d’orange maculopathy – In adults > 20 years old Minor criteria • Characteristic histological features of non-lesional skin – Elastic tissue and calcium or von Kossa stains • Family history of PXE in first-degree relatives Page 3 of 12 F1000Research 2020, 9:9 Last updated: 16 JUL 2021 Figure 1. Photographs of the skin lesion taken from (a) behind, (b) the left and (c) right side of the patient’s neck. Uneven, rough and yellow plaques can be seen in the cervical region. Discussion scar formation on the retina. For the ocular complications, PXE is a rare inherited disorder, characterised by mineralization vascular endothelial growth factor antagonists have been used disturbances of the connective tissue with elastic fibre degenera- to prevent neovascularization, thus reducing the occurrence tion, mainly involving skin, eyeballs and cardiovascular system1–4. of the most severe complication: loss of vision4,6. At the consensus conference, in 1994, the PXE diagnosis Cardiovascular manifestations are a major cause of morbid- criteria were defined (Table 1)3. The patient presented two of ity in these patients: hypertension, angina pectoris and intermit- these major criteria: characteristic yellow cobblestone lesion tent claudication are some of the examples. Patients with PXE in the skin and positive von Kossa stain. may also develop early atherosclerosis due to the mineraliza- tion of the internal elastic lamina of the blood vessels and lipid Although the cutaneous manifestation is frequently flesh- alteration with high density lipoprotein (HDL) cholesterol colored to yellow macules or papules which progressively levels reduction in blood plasma and hypertriglyceridemia. agglutinate into bigger plaques, and the affected skin that This contributes to a higher incidence of acute myocardial becomes lax and wrinkled, the clinical manifestation is vari- infarction and