Pseudoxanthoma elasticum (PXE) is a rare autosomal recessive connective tissue disease that affects the skin, eyes, and the vasculature. The clinical presentation varies from one individual to another.
Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease characterized by progressive calcification, mineralization, and thus fragmentation of the elastic fibers present in the skin, arterial wall, and retina . This rare disorder affects the skin, eyes, cardiovascular system, and gastrointestinal (GI) system. It is a clinically heterogeneous disease that manifests in the second or third decade .
Skin features are the earliest sign. Lesions appear as small, yellow papules that coalesce to form a papule . It may be described as a rash with "cobblestone" pattern. The skin changes occur on the lateral neck with progression to other sites such as the axillae, inguinal folds, periumbilical region, and the antecubital and popliteal fossa . Hence, loose skin develops in these locations. The inner lower lip and mucosa of the vagina and rectum may be affected as well. Generally, these lesions do not resolve spontaneously .
Ocular signs include "peau d’orange" appearance on an ophthalmologic exam . This is followed later by angioid streaks, which reflect the mineralization of Bruch's membrane. As a result, neovascularization and subretinal hemorrhage may develop, which leads to loss of visual acuity . Blindness ensues if the macula is affected.
Although rare, patients are at risk for developing life-threatening sequelae such as myocardial infarction, cerebral aneurysm, ischemic strokes and other cardiovascular complications  . Also, GI bleeding is common, as it leads to hematemesis and melena .
Entire Body System
Sudden death may occur due to coronary atherosclerosis with acute myocardial ischemia, systemic hypertension, mitral valve prolapse, restrictive cardiomyopathy, gastrointestinal hemorrhage, and cerebral ischemia or hemorrhage. von Kossa stain [histopathology-india.net]
As anti-vascular endothelial growth factor agents are associated with increased risk of systemic effects, particularly arterial thromboembolic events, following intravenous administration, the absence of serious thromboembolic or cardiovascular adverse [ncbi.nlm.nih.gov]
bruising Once the ABCC6 mutations that cause PXE in a family are identified, unaffected relatives may be tested for the familial mutations to determine whether or not they are carriers.  Last updated: 8/16/2011 Testing Resources The Genetic Testing [rarediseases.info.nih.gov]
bruising, features that are frequent in thalassemic and SCD patients. [bloodjournal.org]
Also, GI bleeding is common, as it leads to hematemesis and melena. The clinical assessment consists of the patient's history, physical exam, and the appropriate studies. [symptoma.com]
[…] related to the heart and blood vessels include: Angina (chest pain) Myocardial infarction/heart attack Intermittent claudication: Leg pain during walking that resolves at rest Signs and symptoms related to the gastrointestinal (digestive) tract include: Hematemesis [dovemed.com]
Mitral Valve Prolapse
Mitral valve prolapse often occurs. This prolapse may not be significant unless there is also mitral regurgitation. GI haemorrhage is usually from the stomach and is the most significant vascular complication. [patient.info]
Cardiovascular manifestations include intermittent claudication, diminished or absent peripheral pulses, hypertension, mitral valve prolapse, and complications as described below. [symptoma.com]
Other areas that can be affected in PXE include the heart which can be affected by atherosclerosis and mitral valve prolapse. [medicinenet.com]
Angioid Streaks of the Retina
In the physical examination, typical skin lesions were present and also an angioid streak of the retina. The patient and a control group were evaluated by the CR-2000 Research Cardiovascular Profiling System. [ncbi.nlm.nih.gov]
The occurrence of angioid streaks in the retina was described by Grönblad (4) and Strandberg (5) in 1929, FULL TEXT [annals.org]
Angioid streaks in the retina, a tendency towards haemorrhage and arterial insufficiency are the most common complications. [dermis.net]
Elastic tissues become calcified and fragmented, leading to disruption of the involved organ systems: Ocular system: Angioid streaks of the retina, retinal hemorrhages, and gradual vision loss Cardiovascular system: Premature atherosclerosis with subsequent [msdmanuals.com]
• Other ocular findings: blue sclera Classification • Dominant type 1, which contains cutaneous changes and the skin becomes thin, delicate and bruises easily. [eyewiki.aao.org]
The clinical assessment consists of the patient's history, physical exam, and the appropriate studies. The diagnosis is achieved based on the clinical picture, histopathology, and identification of mutations in the gene responsible for this disease.
The gold standard for diagnosis is the detection of one or two ABCC6 mutations. Proposed diagnostic criteria include the presence of 1) at least one ophthalmic finding: peau d’orange and/or angioid streaks and 2) at least one skin feature: characteristic lesion (with or without cutaneous laxity) and/or a positive biopsy of the skin . It is imperative that both eye and skin manifestations are present for definitive diagnosis. If either is absent, then two pathogenic ABCC6 mutations must be identified .
Patients with GI bleeding are evaluated with a complete blood count (CBC) to screen for iron deficiency anemia as well as a fecal occult blood test (FOBT). Additionally, serum lipid levels are obtained since patients are at risk for atherosclerosis. Another component of the workup includes measurement of serum calcium and phosphate, which are usually normal but may be elevated. Also, a urinalysis should be done to test for hematuria.
Very importantly, echocardiography is performed in patients with cardiac manifestations and risk factors for cardiac disease. Also, GI endoscopy is indicated in individuals with clinical signs of bleeding while a computed tomography (CT) scan of the head is warranted for those with clinical signs suggestive of a cerebrovascular accident. Furthermore, an ankle-brachial index test is beneficial in the assessment of intermittent claudication.
A thorough ophthalmologic exam that includes fundoscopy should be performed. Moreover, biannual surveillance is recommended for patients greater than 40 years old and every 2 years for those less than 40 . Additionally, patients are encouraged to monitor their visual acuity with the use of the Amsler Grid.
Ranibizumab treatment was well tolerated with no adverse events reported. [ncbi.nlm.nih.gov]
In middle-aged or young adults with angioid streaks and no obvious systemic disease, the possibility of a hemoglobulinopathy or pseudoxanthoma elasticum (PXE) as etiologic entities should be investigated. [ncbi.nlm.nih.gov]
Etiology PXE is caused by homozygous or compound heterozygous mutations in the ABCC6 gene (16p13.1), which encodes a transmembrane protein from the ATP-binding cassette (ABC) transporter superfamily. [orpha.net]
THE low incidence of "essential" hypertension below the age of puberty has become more apparent as diagnostic methods have improved and new etiologic entities have been recognized. [nejm.org]
Washington University, College Of Arts and Sciences, 125 Michigan Avenue NE, Washington, DC 20017, USA 2 PXE International, 4301 Connecticut Avenue NW, Suite 404, Washington, DC 20008, USA 3 Laboratory of Translational Genomics, The Division of Cancer Epidemiology [mdpi.com]
[email protected] 12 PXE International, 4301 Connecticut Avenue NW, Suite 404, Washington, DC 20008, USA. [email protected] 13 Laboratory of Translational Genomics, The Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute, [ncbi.nlm.nih.gov]
Summary Epidemiology Prevalence is estimated at between 1/25,000 and 1/100,000. The female to male ratio is 2:1 but the cause of this female predominance remains poorly understood. [orpha.net]
Actually, no targeted therapies are available for the treatment; only prevention of complications is possible. Classically, pseudoxanthoma elasticum is a "benign" disease, without cancer association. [ncbi.nlm.nih.gov]
Medical Screening, Gray, Maine, USA 6 Division of Human Genetics, National Health Laboratory Service and the University of Witwatersrand, Johannesburg, South Africa 7 University of Cape Town, Cape Town, South Africa 8 Centers for Disease Control and Prevention [doi.org]
Alternatively, a lack of functioning MRP6 may impair the transport of a substance that would normally prevent mineralization, leading to the abnormal accumulation of calcium and other minerals characteristic of PXE. [ghr.nlm.nih.gov]
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