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8/9/2019 Pseudoxanthoma Elasticum, Dorsal Neck, Review
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Pseudoxanthoma elasticumPseudoxanthoma elasticum
Adam Mitchell, M4, CUMCAdam Mitchell, M4, CUMC
Deba P Sarma, MDDeba P Sarma, MD
OmahaOmaha
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15 y/o F at routine ophthalmology visit15 y/o F at routine ophthalmology visit
PMH: migraines, H. pylori, leg fxPMH: migraines, H. pylori, leg fx
Meds: noneMeds: none
Allergies: noneAllergies: none
FH: unremarkableFH: unremarkable
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Referred to dermatology afterReferred to dermatology after
ophthalmology noted angioid streaks onophthalmology noted angioid streaks onexamexam
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Unusual lesions on lateral aspect of her neckUnusual lesions on lateral aspect of her neck
bilaterallybilaterally plucked chicken skin appearanceplucked chicken skin appearance
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F 15,F 15,dorsaldorsalneckneck
H&E Elastic stain
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Papillary dermis, H&E Normal elastic fibers in papillary dermis(Elastic stain)
Skin biopsy, dorsal neck
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Mid-dermis: Fragmented, clumped,
swollen elastic tissue in between
collagen bundles, H&E.
Mid-dermis: Fragmented, clumped, swollen
elastic tissue in between collagen bundles.
Elastic stain.
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Pseudoxanthoma elasticumPseudoxanthoma elasticum
Rare autosomal recessive disorderRare autosomal recessive disorder
Progressive calcification and fragmentationProgressive calcification and fragmentation
of elastic fibersof elastic fibers Commonly involves mid to deep reticularCommonly involves mid to deep reticular
dermis, Bruch membrane of eye, and blooddermis, Bruch membrane of eye, and bloodvesselsvessels
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Pseudoxanthoma elasticumPseudoxanthoma elasticum
1 in 25,0001 in 25,000 100,000100,000
Male to female 2:1Male to female 2:1
Occurs in all racesOccurs in all races
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Clinical presentationClinical presentation
Average age of onset: 13 (10Average age of onset: 13 (10--15)15)
Usually present to dermatolology because ofUsually present to dermatolology because of
cutaneous lesionscutaneous lesions If mucosal involvement may present with GIIf mucosal involvement may present with GI
bleedingbleeding
Later with angina or HTNLater with angina or HTN
Occasionally hematuria or retinalOccasionally hematuria or retinalhemorrhagehemorrhage
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Ocular manifestationsOcular manifestations
Angioid streaks :breaks ofAngioid streaks :breaks ofcalcified,thickened Bruchscalcified,thickened Bruchsmembranemembrane
Peau dorange retinalPeau dorange retinalpigmentationpigmentation
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Cardiovascular manifestationsCardiovascular manifestations
Atherosclerosis/calcification of vessel wallsAtherosclerosis/calcification of vessel walls
Absent peripheral pulse (25%)Absent peripheral pulse (25%)
Hypertension (22%)Hypertension (22%)
Intermittent claudication (19%)Intermittent claudication (19%)
Angina pectoris (18%)Angina pectoris (18%)
GI hemorrhage (13%)GI hemorrhage (13%)
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Molecular geneticsMolecular genetics
Initial focus on genes involved in synthesis andInitial focus on genes involved in synthesis andassembly of elastin fiber networkassembly of elastin fiber network
Linkage analysisLinkage analysis chr16chr16 sequencingsequencing ATP bindingATP bindingcassette C6 gene (ABCC6)cassette C6 gene (ABCC6)
Expression:Expression:
liver >> kidneys >>> PXE involved tissuesliver >> kidneys >>> PXE involved tissues
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ABCC6 proteinABCC6 protein
Efflux transporter in liverEfflux transporter in liver
Substrate unknownSubstrate unknown
Explanation of diseaseExplanation of disease
Metabolic hypothesisMetabolic hypothesis
PXE cell hypothesisPXE cell hypothesis
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Pseudoxanthoma elasticum summaryPseudoxanthoma elasticum summary
Incidence: 1 in 25,000 to 100,000Incidence: 1 in 25,000 to 100,000
Autosomal recessive inheritance, occasional pseudoAutosomal recessive inheritance, occasional pseudo--dominant.dominant.
Mutations in multidrug resistance associated protein (MRP6),Mutations in multidrug resistance associated protein (MRP6),encoded by ( ABCC6) on chromosome 16q13.1.encoded by ( ABCC6) on chromosome 16q13.1.
Cutaneous features include yellow, flat,papules in the neck,Cutaneous features include yellow, flat,papules in the neck,flexures, and periumbilical areas. Less frequent skin,lesionsflexures, and periumbilical areas. Less frequent skin,lesionsinclude acneiform lesions, elastosis perforans serpiginosa, reticulateinclude acneiform lesions, elastosis perforans serpiginosa, reticulatepigmentation, and granulomatous nodules.pigmentation, and granulomatous nodules.
Extracutaneous manifestations include angioid streaks, visualExtracutaneous manifestations include angioid streaks, visualimpairment, peau dorange retinal hyperpigmentation, cardiovascularimpairment, peau dorange retinal hyperpigmentation, cardiovascular
disease, and bleeding.disease, and bleeding.
Histopathology shows swollen, clumped, fragmented elastic fibers andHistopathology shows swollen, clumped, fragmented elastic fibers andcalcium deposits in the mid and deep reticular dermis. Alterations easilycalcium deposits in the mid and deep reticular dermis. Alterations easilyvisualized with calcium ( i.e., von Kossa) and elastic (i.e., Verhoeffvisualized with calcium ( i.e., von Kossa) and elastic (i.e., Verhoeff--vanvanGieson or orcein) stains.Gieson or orcein) stains.
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