Lax skin and blurring of vision- A case report of pseudoxanthoma elasticum

ABSTRACT

Increased laxity of the skin can be caused by aging, significant weight loss, or defects in the elastic tissue. A 38-year-old female presented with increased laxity of the skin over the neck, thighs, and abdomen for 6 years, associated with headache and blurring of vision for a week. On cutaneous examination, prominent skin folds, laxity, and wrinkles were noted over the neck, abdomen, thighs, and groin, with yellowish papules along the neck creases. Ocular examination revealed features suggestive of angioid streaks. Skin biopsy showed fragmented elastic fibers and intervening calcium deposits on Verhoeff Van Gieson and Von Kossa stains. Based on these findings, a diagnosis of pseudoxanthoma elasticum (PXE) was made. The patient was started on oral and topical sunscreens and eye protection and advised regular follow-up. Diagnosing the condition early based on skin findings can help prevent further multi-system manifestations by taking appropriate preventive measures as this condition is progressive and has no cure.

Introduction

Increased laxity of the skin can be caused by aging, significant weight loss, or defects in the elastic tissue. Localized lysis of elastic fibers occurs under conditions such as cutis laxa, blepharochalasis, and granulomatous slack skin. Pseudoxanthoma elasticum (PXE) is caused by a mutation of ATP-binding cassette (ABC) sub-family C member 6 (ABCC6). The mutation causes reduction or the absence of the said protein, resulting in fragmentation of the elastic fibers.[1] Skin biopsy can be performed to confirm the diagnosis, and routine multi-system screening can help us monitor the severity of the disease.[2] This condition can be associated with significant mortality and is presently intractable. Herein, we present a case of PXE for its rarity of occurrence.

Case Report

A 38-year-old female presented to the out-patient department with a 6 year history of increased laxity of the skin over the neck, thighs, and abdomen. The patient gave a history of blurring of vision, photophobia, and headache for the past 1 week. The patient gave no history of breathlessness, chest pain, palpitations, claudicating pain, or neurological deficits. On cutaneous examination, prominent skin folds, skin laxity, and wrinkles were noted over the right side of the neck, abdominal folds, thighs, and groin. A single, skin-colored papule of a size of 2 mm was present over the right lower lid, near the medial canthus, and similar skin-colored to yellowish papules of a size of 1.5–2 mm were noted over the neck and face [Figure 1]. Fundus examination of both eyes showed dark brownish-red, irregular streaks surrounding and extending radially from the optic disc, suggestive of angioid streaks [Figure 2]. 2D-echo and electrocardiogram were investigated to check for cardiac involvement but were normal. A skin biopsy was performed from the neck, which showed an unremarkable epidermis. Degenerate basophilic collagen bundles were noted in the mid-dermis and lower dermis with intervening sclerotic areas that were seen extending to the lower dermis. Certain areas in the dermis showed a pale interstitial material (mucin) [Figure 3]. Verhoeff Van Gieson staining showed elastic fibers with a short and curled appearance [Figure 4]. Von Kossa staining was performed, and it showed evidence of calcium deposition.

Figure 1.

Prominent skin folds, wrinkles, and laxity noted over the right side of the neck, along with a few skin-colored to yellowish papules, approximately of a size of 1 mm

Figure 2.

Fundus photo of both eyes, suggestive of angioid streaks

Figure 3.

Studied section shows the mid-dermis with aggregated, tortuous collagen bundles, extending into the lower dermis

Figure 4.

Verhoeff Van Gieson staining showing elastic fibers with a short and curled appearance

Based on the clinical and histopathological findings, a diagnosis of PXE was made. The patient was started on oral and topical sunscreens, advised rigid eye protection to prevent accidental blunt trauma, and regular follow-up.

Discussion

PXE is an autosomal, recessive disease charecterized by fragmentation of the elastic tissue, involving multiple systems such as the skin, eyes, and cardiovascular system. There is mutation of the ABCC6 gene, which causes a defect in the transmembrane transport ADP-dependent protein (MRP6), resulting in collection of extracellular content, leading to accumulation of minerals such as calcium in the elastic tissue. Although the precise prevalence of the condition is unknown, a variable involvement between 1:25,000 and 100,000 people worldwide is estimated, with prevalence being more in women.[3]

Clinical manifestation involves the skin, eyes, oral mucosa, gastro-intestinal tract, and arteries. Similar mucosal features can be observed in the oral, genital, and gastro-intestinal mucosae.[4]

Tiny waxy yellowish papules typically appear in early adolescence with “plucked chicken skin” appearance. The skin lesions have a predilection for flexural areas, neck, and axillae, but over a period of time, these become generalized. Gradually, the skin becomes lax and hangs in folds, clinically resembling cutis laxa.[5]

The primary ocular feature is the occurrence of angioid streaks, which is because of the deposition of calcium in the retinal Bruch’s membrane. This might lead to the disruption of vessels, along with retinal hemorrhages, leading to gradual loss of visual acuity. Other fundoscopic features, such as Peau De orange appearance, choroidal neo-vascularization, and disciform macular degeneration can occur in association with angioid streaks. Fundus examination must be routinely performed to evaluate for ocular involvement.[6] The walls of small- and medium-caliber arteries can get calcified causing early atheromatosis, which might present itself as hemorrhage of the gastro-intestinal tract, systemic hypertension, myocardial infarcts, or cerebro-vascular accident and peripheral arterial occlusion.[7,8] The diagnosis is mainly clinical and supported by the classic pathological picture of distorted and fragmented elastic fibers in the reticular dermis. Multiple, frayed, and short basophilic appearing elastin fibers may be noted in the mid-dermis, termed as ravelled wool appearance.[9] Stains performed in particular for the abnormal elastic fibers, such as Verhoeff Van Gieson and Calleja stains, make these changes easier to detect. Von Kossa stain can be used to identify the calcified fibers. There is no specific therapy as of present day. Early detection and management of complications associated with the disease can be performed by periodic tracking and surveillance. Baseline investigations such as a complete hemogram, fasting lipid profile, and echocardiogram, along with routine ophthalmologic monitoring, should be performed when required. A diet rich in magnesium and vitamin K could decrease chances of disease progression and enhance the patient’s life quality. Drugs such as aspirin, anti-platelet agents, and non-steroidal anti-inflammatory drugs should be avoided. Surgery for aesthetic correction of the skin lesions is not regularly preferred because of increased chances of adverse reactions such as keloidal scars and leakage of the calcium through the wound. Novel treatments under clinical trials include phosphate binders (aluminum hydroxide, sevelamer hydrochloride), VEGF antagonists (bevacizumab and ranibizumab), and sodium thiosulfate.[10]

Early clinical suspicion at the primary care level can lead to appropriate referral, early diagnosis, and prompt monitoring for systemic involvement. This case displayed classic clinical manifestations of PXE. The ocular involvement in the form of angioid streaks and skin biopsy helped clinch the diagnosis. However, serious involvement of the cardiovascular system was not noted at the time of presentation in the case.

Conclusion

Although the disease is rare, because of the multi-system nature of the disease, early detection is of paramount importance to watch for and prevent disabling complications. Awareness of the classical skin manifestations is important for general physicians and primary healthcare workers as this will prompt them to be more vigilant in following up the patient for routine ophthalmological and cardiovascular screening.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.