Cosmetic in Japan 美容医学への扉-東京大学美容外科-アンチエイジング
Japanese page
Web Master -Kotaro Yoshimura, M.D.-

Arterial Embolization and Skin Necrosis of the Nasal Ala Following Injection of Dermal Fillers 

Keita Inoue, Katsujiro Sato, Daisuke Matsumoto, Koichi Gonda, Kotaro Yoshimura. (2006年1月)

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.

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.

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.

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 fillers. Clin Plast Surg. 32: 151, 2005.
3. Sclafani, A. P., and Romo, T., 3rd. Injectable fillers for facial soft tissue enhancement. Facial Plast Surg. 16: 29, 2000.
4. Homicz, M. R., and Watson, D. Review of injectable materials for soft tissue augmentation. Facial Plast Surg. 20: 21, 2004.
5. Bauman, L. Cosmoderm/Cosmoplast (human bioengineered collagen) for the aging face. Facial Plast Surg. 20: 125, 2004.
6. Narins, R. S., Brandt, F., Leyden, J. et al. A randomized, double-blind, multicenter comparison of the efficacy and tolerability of Restylane versus Zyplast for the correction of nasolabial folds. Dermatol Surg. 29: 588, 2003.
7. Douglas, R. S., Donsoff, I., Cook, T. et al. Collagen fillers in facial aesthetic surgery. Facial Plast Surg. 20: 117, 2004.
8. Friedman, P. M., Mafong, E. A., Kauvar, A. N. et al. Safety data of injectable nonanimal stabilized hyaluronic acid gel for soft tissue augmentation. Dermatol Surg. 28: 491, 2002.
9. Bowman, P. H., and Narins, R. S. Hylans and soft tissue augmentation. In J. Carruther, A. Carruther, Procedures in Cosmetic Dermatology Series: Soft Tissue Augmentation, 1st Ed. Philadelphia: WB Saunders, 2005. Pp 33-54.
10. Duranti, F., Salti, G., Bovani, B. et al. Injectable hyaluronic acid gel for soft tissue augmentation. A clinical and histological study. Dermatol Surg. 24: 1317, 1998.
11. Hanke, C. W., Higley, H. R., Jolivette, D. M. et al. Abscess formation and local necrosis after treatment with Zyderm or Zyplast collagen implant. J Am Acad Dermatol. 25: 319, 1991.
12. Andre, P. Evaluation of the safety of a non-animal stabilized hyaluronic acid (NASHA -- Q-medical, Sweden) in european countries: A retrospective study from 1997 to 2001. J Eur Acad Dermatol Venereol. 18: 422, 2004.
13. Lowe, N. J., Maxwell, C. A., Lowe, P. et al. Hyaluronic acid skin fillers: Adverse reactions and skin testing. J Am Acad Dermatol. 45: 930, 2001.
14. Lupton, J. R., and Alster, T. S. Cutaneous hypersensitivity reaction to injectable hyaluronic acid gel. Dermatol Surg. 26: 135, 2000.
15. Shafir, R., Amir, A., and Gur, E. Long-term complications of facial injections with Restylane (injectable hyaluronic acid). Plast Reconstr Surg. 106: 1215, 2000.
16. Schanz, S., Schippert, W., Ulmer, A. et al. Arterial embolization caused by injection of hyaluronic acid (Restylane). Br J Dermatol. 146: 928, 2002.
17. Pinar, Y. A., Bilge, O., and Govsa, F. Anatomic study of the blood supply of perioral region. Clin Anat. 18: 330, 2005.
18. Jung, D. H., Kim, H. J., Koh, K. S. et al. Arterial supply of the nasal tip in Asians. Laryngoscope. 110: 308, 2000.
19. Nakajima, H., Imanishi, N., and Aiso, S. Facial artery in the upper lip and nose: Anatomy and a clinical application. Plast Reconstr Surg. 109: 855, 2002.
20. Toriumi, D. M., Mueller, R. A., Grosch, T. et al. Vascular anatomy of the nose and the external rhinoplasty approach. Arch Otolaryngol Head Neck Surg. 122: 24, 1996.
21. Magden, O., Edizer, M., Atabey, A. et al. Cadaveric study of the arterial anatomy of the upper lip. Plast Reconstr Surg. 114: 355, 2004.
22. Rohrich, R. J., Muzaffar, A. R., and Gunter, J. P. Nasal tip blood supply: Confirming the safety of the transcolumellar incision in rhinoplasty. Plast Reconstr Surg. 106: 1640, 2000.


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.


Copyright -Cosmetic Medicine in Japan- 東大病院美容外科、トレチノイン(レチノイン酸)療法、アンチエイジング(若返り)