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Journal Name: Case Reports InternationalCase study of Grönblad ­ Strandberg syndromeAuthors: Blyta Y, Daka A, Pallaska K, Salihu Ndoi: To be assigned

Received: 24 November 2012Accepted: 04 February 2013Published Online (Early View Article): 14 June 2013Disclaimer: This manuscript has been accepted for publication in Case Reports International. Thisis a pdf file of the Early View Article. The Early View Article is an online published version of anaccepted article before final publication in Case Reports International. The proof of thismanuscript will be sent to the authors for corrections after which this manuscript will undergocontent check, copyediting/proofreading and content formatting to conform to journal'srequirements. Please note that during the above publication processes errors in content orpresentation may be discovered which will be rectified during manuscript processing. These errorsmay affect the contents of this manuscript and final published version of this manuscript may beextensively different in content and layout than this Early View Article.

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Case study of Grönblad ­ Strandberg syndromeBlyta Y1, Daka A1, Pallaska K2, Salihu N3

1Department of Dermatology, University Clinical Center of Kosovo2Department of Internal Disease, University Clinical Center of Kosovo3Department of Ophthalmology, University Clinical Center of Kosovo

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Corresponding Author: Ymran N Blyta, Department of Dermatology, University Clinical Centerof Kosovo; Email: ymranblyta@yahoo.com

ABSTRACTIntroduction: Grönblad–Strandberg syndrome, also known as Pseudoxanthoma elasticum (PXE)is a genetic disease that causes fragmentation and mineralization of elastic fibers in some tissues.The most common problems arise in the skin and eyes, and later in blood vessels in the form ofpremature atherosclerosis. PXE is caused by autosomal recessive mutations in the ABCC6 gene onthe short arm of chromosome 16. Case Report: It is a case presentation of 26­year­old female. Thefirst changes, were numerous yellow symmetric, asymptomatic papules, which began a year ago.The changes were noted on the lateral part of the neck and later involving axilar regions, cubitalfossa and posterior part of neck. Changes started after ceasing of 8 months diet, due to which shelost 15 kg. The diet consisted mostly on liquid foods. Skin in those areas become inelastic withsmall, soft yellow papules. Mucosal parts were not involved. Conclusion: It is a rare degenerativedisorder of elastic fibers with tiny areas of calcification involving all depth of skin, ocular fundus(retina), and blood vessels. It is important to recognize this disease in early to minimize theoccurrence of retinal or gastrointestinal hemorrhage, cardio and cerebrovascular complications.

KEYWORDSPseudoxanthoma elasticum (PXE), Grönblad­Strandberg syndrome, Elastic fibers

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INTRODUCTIONGrönblad­Strandberg syndrome or Psuedoxanthoma elasticum (PXE) is a rare, genetic disorder,

characterized by progressive calcification and fragmentation of elastic fibers in the skin, the retina,and the cardiovascular system, which is termed elastorrhexia [1]. Psuedoxanthoma elsaticum maybe autosomal dominant or autosomal recessive [2]. Mutations in the ABCC6 gene causepsuedoxanthoma elsaticum [3]. This disease is important to be recognized in early stages tominimize the occurrence of retinal or gastrointestinal hemorrhage and cardiovascularcomplications [4].

CASE REPORTThis is a case presentation of 26­year­old female. The reason of initial dermatologic

consultation was esthetic motivation. The first changes, small, yellowish papular lesions, 1–5 mmin diameter, elevated 1–2 mm above the skin, heterogenous distribution with excentricpredomination within lesion and with clear border margin with healthy skin, which began a yearago, were noted on the lateral part of the neck. After 6 months, changes involved axilar regions,cubital fossa and posterior part of neck. Skin in those areas become inelastic with small, soft yellowpapules, without local subjective complaints. Skin changes started after ceasing 8 months diet,which consisted mostly on liquid foods, after which she lost 15 kg. Mucosal parts were notinvolved. By the time, a year after the beginning of skin changes, just before the first consultationshe started to complain on visual impairment. Her father suffered double myocardial infarctionand latter he was surgically treated, ao­co by pass with reconstruction of fibrotic valves.Hematological and biochemical results were within referent values.

After complete investigation we found pathological changes in heart and eyes.Heart echo Doppler; slight thickening of aortal (V max AoV=1.3 m/s) and mitral valve as well,

mostly defined as fibrotic changes without significant hemodynamic repercussion and normalpattern of aortal and mitral flow. Parietal pericardium diffusely thickened due to the fibroticproliferation without transmitral blood flow.

Ophthalmologic examination, fundoscopy; showed pathognomonic, angiotic streaks in the botheyes.

Neurological status; without focal disturbances and neurological lateralization.Gastroenterological consultations; objective examination and examination on occult bleedingwithout pathological findings.

Biopsy was taken from the left axilla, approximately 1 cm in diameter, till subcutaneous tissue,showing features characterized for pseudoxanthoma. Pathohistological report; significant numberof short, waved, thickened, distorted, and irregulary shaped basophilic elastic fibers throughoutthe reticular dermis with significant calcium depositions. Immunohistochemistry was not done.No topical dermatological treatment was initiated.

Every six months regular fecal testing on occult blood and CBC count was performed, withyearly complete cardiological (ECG, Echo doppler) and ophtalmological investigation.

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DISCUSSIONPXE is hereditary degenerative dieasese, commonly involves the elastic fibers present in the

mid and deep reticular dermis of skin.PXE has an estimated prevalence of 1 case in 25,000–100,000 population. Females are affected

twice as often as males. PXE may occur at early age, usually it is diagnosed in the third to fourthdecades of life. The mortality and morbidity of PXE vary based on the extent of extra cutaneous,visceral involvement [5].

Physical findings of PXE can be divided into cutaneous, ocular, cardiovascular, gastrointestinal,neurological and peripheral arterial manifestations [6].

The cutaneous manifestations of PXE are of cosmetic concern.The characteristic skin changes in PXE consist of yellow plaques or xanthoma like papules in

the flexural areas of the body. Cardiovascular involvement in patients with PXE occurs at any earlyage but it is rarely presenting manifestation. It has been reported that 87% of patients with PXEhave associated angioid streaks in retina [7]. Histopathological changes studies from skin biopsyshow characteristic changes consisting of fragmented elastic fibers, which may be calcified in thedipper layers of the dermis [8]. In PXE, calcifications also occur in the internal elastic lamina ofthe vessels leading to atherosclerosis and eventually coronary and cerebrovascular diseases andrenovascular hypertension.

Possible life threatening complications of GSS are gastrointestinal or cerebral hemorrhagy,retinal hemorrhagy, progressive loss of central vision, hypertension, angina and myocardialinfarction which are due to the structural changes on blood vessels. It is important to establish thediagnosis as soon as possible, because of life threatening complications which may be aborted withcorrect multidisciplinary treatment [9, 10].

Many of the pathologic changes associated with GSS are irreversible, but prophylactic measurescan be undertaken to minimize the disease course [11]. Regular fecal testing on occult blood andCBC with yearly complete cardiological (ECG, Echo doppler) and ophtalmological investigationhave to be concidered to all cases with PXE.

Early detection of PXE is, therefore, of paramount importance. Prophylactic measures andlifestyle modifications can be used to minimize the risk of complications.

Preventive and prophylactic measures like regular cardiological, ophthalmological andgastroenterological investigations, may delay the systemic complications which may lead to finaloutcome. Healthy life style as physical activities, healthy organic food with a lot of fibers,vegetables, fruits and proteins and small amounts of fat may delay life­threatening vascularcomplications in heart and brain which are almost inevitable.

The prognosis of pseudoxanthoma elasticum (PXE) largely depends on the degree ofinvolvement of particularly heart and cerebral blood vesels. Patients may have a normal life span ifthere is no acute vascular complication in heart or brain or gastrointestinal system. Spontaneousresolution of skin changes has been reported, but is exceedingly rare [12].

CONCLUSIONThis presentation sustains that pseudoxanthoma elasticum is multisystem hereditary disease of

connective tissue, usually occurring in choroid vitreous lamina, visceral and extremity bloodvessels with non­curable evolution.

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REFERENCES1. Fitzpatrick, et al. Color atlas and synopsis of clinical dermatology, 3rd ed. McGraw­Hill

Professional; 1997. p.448–9.2. Dobreci, et al. Dermatologjia, 4rd ed. Pristina; 2009. p. 299–300.3. Albert DM, et al. Pseudoxanthoma elasticum [PXE]­angioid streaks/systemic associations.

In: Principles and Practice of Ophthalmology Clinical Practice. Philadelphia: WB Saunders1994.

4. Clarkson JG, Altman RD. Angioid streaks. Surv Ophthalmol 1982 Mar­Apr;26(5):235–46.5. CONNOR PJ Jr, JUERGENS JL, PERRY HO, HOLLENHORST RW, EDWARDS JE.

Pseudo­xanthoma elasticum and angioid streaks: a review of 106 cases. Am J Med1961;30:537–43.

6. Grand MG, Isserman MJ, Miller CW. Angioid streaks associated with pseudoxanthomaelasticum in a 13­year­old patient. Ophthalmology 1987 Feb;94(2):197–200.

7. Chung AK, Gauba V, Ghanchi FD. Photodynamic therapy (PDT) using verteporfin forjuxtafoveal choroidal neovascularisation (CNV) in angioid streaks (AS) associated withpseudoxanthoma elasticum: 40 months results. Eye (Lond) 2006 May;20(5):629–31.

8. Iqbal A, Alter M, Lee SH. Pseudoxanthoma elasticum: a review of neurologicalcomplications. Ann Neurol 1978 Jul;4(1):18–20.

9. Agarwal A, Patel P, Adkins T, Gass JD. Spectrum of pattern dystrophy in pseudoxanthomaelasticum. Arch Ophthalmol 2005 Jul;123(7):923–8.

10. GOODMAN RM, SMITH EW, PATON D, et al. Pseudoxanthoma elasticum: A clinical andhistopathological study. Medicine 1963;42:297–334.

11. Agarwal A, Patel P, Adkins T, Gass JD. Spectrum of pattern dystrophy in pseudoxanthomaelasticum. Arch Ophthalmol 2005 Jul;123(7):923–8.

12. Chassaing N, Martin L, Calvas P, Le Bert M, Hovnanian A. Pseudoxanthoma elasticum: aclinical, pathophysiological and genetic update including 11 novel ABCC6 mutations. J MedGenet 2005 Dec;42(12):881–92.

Figure 1: Inelastic small, soft, yellow papules.

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Figure 2: Inelastic small, soft, yellow papules.

Figure 3: Thickened aortal valve in lax.

Figure 4: Thickened aortal valve in M mode.

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Figure 5: Thickened of Pericardium and mitral valve in 2D and M mode.

Figure 6: Angioid streaks.

Figure 7: Fragmented elastic fibers deeper layers of the dermis.

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