|   INTRODUCTION 
                            The use of biodegradable dermal fillers has become 
                            increasingly popular for facial rejuvenation, partly 
                            replacing the conventional surgical procedures with 
                            which long and painful recovery time is unavoidable.1,2 
                            Although numerous kinds of materials have been used 
                            as biodegradable dermal fillers in the last decade2-4, 
                            hyaluronic acid and collagen appear to be the materials 
                            of choice with convincing evidence of their safety 
                            and efficacy2,4-9.  
                            Most common adverse effects of injection of hyaluronic 
                            acid and collagen previously known are bruising and 
                            erythema5,8,10-13. These symptoms almost always resolve 
                            within a week, with no residual complications. The 
                            most serious side effect in the acute phase is localized 
                            tissue necrosis, which is induced by mechanical interruption 
                            of local vascularity and has been reported to occur 
                            very rarely (9 in 10,000 cases who underwent collagen 
                            implantation11). On the other hand, allergic changes, 
                            abscess formation, and granulomatous changes are known 
                            as adverse effects in the chronic phase11,13-15, though 
                            they are less frequent.  
                            Among the adverse effects of dermal fillers, the most 
                            serious one always leading to resultant scar formation 
                            is tissue necrosis. More than half of the reported 
                            cases involved the glabellar region, while only 4% 
                            of them involved the nose11. Only one case of arterial 
                            embolization following the injection of dermal fillers 
                            has been reported16. In this case, the patient underwent 
                            hyaluronic acid injection (RestylaneR) and suffered 
                            transient skin ulceration on the glabella; the ulceration 
                            cured within weeks leaving no cosmetic blemish. Here, 
                            we report a case who received injections of two kinds 
                            of fillers at one time, hyaluronic acid gel (RestylaneR, 
                            Q-Med, Sweden) and human-tissue-derived reconstituted 
                            collagen matrix (ShebaR, Hansbiomed, Korea), and suffered 
                            arterial embolization and distant skin necrosis of 
                            the nasal ala. This is the first detailed report of 
                            nasal alar necrosis associated with arterial embolization 
                            following injection of dermal fillers. 
                             
                            CASE REPORT 
                            A 50-year-old Japanese woman, who had no previous 
                            history of cosmetic surgery, underwent injection of 
                            RestylaneR for shaping the nasal tip contour, and 
                            of ShebaR for wrinkle correction of the upper white 
                            lip and the nasolabial fold and augmentation of the 
                            upper vermillion. Nothing was injected into the nasal 
                            ala. Immediately after the injection the patient had 
                            a striking pain on the left side of the face, and 
                            a few hours later noticed reddish discoloration from 
                            the left side of the nose and the upper lip to the 
                            glabellar region. By the third day from the onset, 
                            blisters appeared at the left nasal ala. When the 
                            patient consulted our hospital on the sixth day, a 
                            gangrenous skin necrosis measuring 1 cm by 1.5 cm 
                            was present on the left nasal ala. (Fig. 1). 
                            Three-dimensional computed tomographic angiography 
                            (3D-CTA) was performed on the 9th day, which suggested 
                            local occlusion of the left angular branch of the 
                            facial artery (Fig. 2). Intravenous administration 
                            of alprostadil (ProstandinR, 120 μg/day) was then 
                            started and the surrounding erythema decreased with 
                            time, but the necrosis extended to the surrounding 
                            skin and subcutaneous tissue, which was surgically 
                            removed on the 12th day (Fig. 3). Histopathological 
                            examination indicated intra-arterial and subdermal 
                            deposition of foreign bodies as well as reactive changes 
                            of the surrounding tissues (Fig. 4). The foreign bodies 
                            were likely the injected dermal fillers, although 
                            we could not identify whether it was Restylane or 
                            Sheba. A full-thickness skin taken from the postauricular 
                            area was grafted to the residual skin defect on the 
                            43rd day, which was successfully accepted. 
                            
                            DISCUSSION 
                            The blood supply of the nasal alar region depends 
                            mainly on the facial artery, of which the running 
                            course and branching are highly varied. Previous studies 
                            demonstrated that the alar region is perfused by two 
                            or three courses of blood supply17-22 (Fig. 5). The 
                            most predominant course is the alar branch of the 
                            facial artery, which branches directly from the angular 
                            branch of the facial artery or from the superior labial 
                            artery. The other courses are communicating arteries 
                            coming through either the nasal dorsum or through 
                            the columella. These arteries are anastomosed with 
                            each other through the subdermal plexus17,18,21.  
                            In the present case, the alar skin resulted in massive 
                            necrosis, despite the absence of filler injection 
                            into the ala. The histopathologic study of the biopsy 
                            specimen of the ala revealed intradermal and intraarterial 
                            foreign bodies (Fig. 4), which showed histopathologic 
                            features comparable to hyaluronic acid or collagen 
                            fillers as previously reported10,11,23,24. Arterial 
                            embolization was suggested also by 3D-CTA that demonstrated 
                            local occlusion of the angular branch of the facial 
                            artery and compensatory dilation of collateral vessels 
                            such as the infraorbital artery and its daughter branches 
                            (Fig. 2). Sharp pain and the erythema observed on 
                            the area nourished by the angular branch of the facial 
                            artery in the early phase also suggested acute and 
                            widespread embolization of the artery. Thus we diagnosed 
                            the patient as suffering from arterial embolizations 
                            of the angular branch and its daughter branches. Theoretically, 
                            accidental injection of filler material into subcutaneous 
                            small vessels caused arterial embolization, developing 
                            into skin necrosis of particular regions.  
                            The only reported case of arterial embolization induced 
                            by hyaluronic acid injection involved the glabellar 
                            region16. In addition, the glabella is the most common 
                            region for local necrosis after bovine collagen injection11. 
                            These cases, however, underwent dermal filler injection 
                            at the same region as subsequent skin necrosis. In 
                            the present case, massive skin necrosis occurred on 
                            the nasal ala, although the patient had no injection 
                            of dermal fillers in the area. Additionally, the patient 
                            had no history of rhinoplasty that would likely affect 
                            the condition of blood supply. Like the glabellar 
                            region, the nasal ala may be a particular region in 
                            which blood supply depends strongly on a single arterial 
                            branch. Otherwise, collateral blood supply through 
                            the nasal tip was blocked by the concurrent filler 
                            injection to the nasal tip, which may be a critical 
                            factor in this case. We could not distinguish whether 
                            the foreign bodies found in the biopsy specimen were 
                            RestylaneR or ShebaR. It also remains unknown whether 
                            physical or biological characteristics of particular 
                            products can influence the susceptibility toward vascular 
                            embolization.  
                            Although biodegradable dermal fillers have been proven 
                            to be sufficiently safe, physicians should recognize 
                            that they are still not devoid of serious side effects 
                            as shown in this case. We think arterial embolization 
                            is an adverse event not only of RestylaneR or ShebaR, 
                            but also of any other dermal filler. The potential 
                            risk of vascular embolization should be noted especially 
                            when treating the nasal alar and perioral regions 
                            as well as the glabellar region. Although accidental 
                            intra-arterial injection of dermal fillers is apparently 
                            rare, fillers should be injected into the dermis, 
                            great care should be taken when injecting into the 
                            subcutis to prevent intra-arterial injection, and 
                            the anatomical feature of the facial artery and its 
                            network should be correctly kept in mind. 
                            
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                            1. de Maio, M. The minimal approach: An innovation 
                            in facial cosmetic procedures. Aesthetic Plast Surg. 
                            28: 295, 2004. 
                            2. Narins, R. S., and Bowman, P. H. Injectable skin 
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                            3. Sclafani, A. P., and Romo, T., 3rd. Injectable 
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                            4. Homicz, M. R., and Watson, D. Review of injectable 
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                            5. Bauman, L. Cosmoderm/Cosmoplast (human bioengineered 
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                            6. Narins, R. S., Brandt, F., Leyden, J. et al. A 
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                            8. Friedman, P. M., Mafong, E. A., Kauvar, A. N. et 
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                            9. Bowman, P. H., and Narins, R. S. Hylans and soft 
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                            1997 to 2001. J Eur Acad Dermatol Venereol. 18: 422, 
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                            13. Lowe, N. J., Maxwell, C. A., Lowe, P. et al. Hyaluronic 
                            acid skin fillers: Adverse reactions and skin testing. 
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                            FIGURE LEGENDS 
                          Fig. 1. Views at the 
                            first visit (6 days after injection). Gangrenous skin 
                            necrosis was seen on the left nasal ala. Erythema 
                            was seen on the whole area nourished by the angular 
                            branch of the facial artery; the glabellar region, 
                            the left side of the nose, and the left upper lip. 
                             
                            
                            Fig. 2. Three-dimensional computed tomographic angiography 
                            (3D-CTA) on the 9th day. 3D-CTA presented the local 
                            occlusion of the left angular branch of the facial 
                            artery. Compensatory dilation of collateral vessels 
                            from the infraorbital artery was noted (arrowhead). 
                            Contralateral angular branch of the facial artery 
                            was patent and not dilated (arrow). 
                          Fig. 3. Views before 
                            (left), just after (center), and 4 weeks after (right) 
                            debridement of the necrotic skin. Debridement was 
                            performed on the 12th day and skin graft was performed 
                            on 43rd day. 
                            
                            Fig. 4. Histology of debridement sample. Upper left: 
                            low-power photomicrograph of the necrotic skin on 
                            the nasolabial fold shows epidermal necrosis and intradermal 
                            deposition of filler material (arrow). Lower left: 
                            higher magnification of the upper left photograph 
                            shows intradermal foreign bodies (?) accompanied by 
                            infiltration of inflammatory cells. Upper right: low-power 
                            photograph of subcutaneous tissue shows multiple intraarterial 
                            embolizations (arrow). Lower right: higher magnification 
                            ofupper right photograph shows intraarterial foreign 
                            bodies (?) and thickening of the intima. Haematoxylin 
                            and eosin stain. Bar = 800 μm for above and 200 μm 
                            for below. 
                            
                            Fig. 5. Schematic view of the blood supply of the 
                            nasal ala. The angular branch (A) of the facial artery 
                            (F) runs along the nasolabial fold, branching off 
                            the superior labial artery (SL). The alar branch is 
                            a terminal branch of the angular branch, which is 
                            the main feeding artery for the nasal ala. The superior 
                            labial artery and the dorsal branch (D) of the superior 
                            trochlear artery (ST) communicate with the alar branch 
                            around the nasal tip. 
                          
                             
                           
                            
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