pseudoxanthoma elasticum, dorsal neck, review

8/9/2019 Pseudoxanthoma Elasticum, Dorsal Neck, Review

1/20

Pseudoxanthoma elasticumPseudoxanthoma elasticum

Adam Mitchell, M4, CUMCAdam Mitchell, M4, CUMC

Deba P Sarma, MDDeba P Sarma, MD

OmahaOmaha


2/20

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


3/20

Referred to dermatology afterReferred to dermatology after

ophthalmology noted angioid streaks onophthalmology noted angioid streaks onexamexam


4/20

Unusual lesions on lateral aspect of her neckUnusual lesions on lateral aspect of her neck

bilaterallybilaterally plucked chicken skin appearanceplucked chicken skin appearance


5/20


6/20

F 15,F 15,dorsaldorsalneckneck

H&E Elastic stain


7/20

Papillary dermis, H&E Normal elastic fibers in papillary dermis(Elastic stain)

Skin biopsy, dorsal neck


8/20

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.


9/20


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


10/20


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


11/20

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


12/20


13/20

Ocular manifestationsOcular manifestations

Angioid streaks :breaks ofAngioid streaks :breaks ofcalcified,thickened Bruchscalcified,thickened Bruchsmembranemembrane

Peau dorange retinalPeau dorange retinalpigmentationpigmentation


14/20

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%)


15/20

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


16/20

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


17/20


18/20


19/20

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.


20/20

pseudoxanthoma elasticum, dorsal neck, review

Documents