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Calcium hydroxylapatite associated soft tissue necrosis: a case report and treatment guideline

Calcium hydroxylapatite associated softtissue necrosis: A case report and treatmentguideline Lauren Tracy , James Ridgway , J. Stuart Nelson Nelson Lowe , Brian Wong a Department of Otolaryngology e Head and Neck Surgery, University of California Irvine, 101 The CityDrive, Bldg. 56, Suite 500, Orange, CA 92868, USAb Larrabee Center for Plastic Surgery, 600 Broadway, Suite 280, Seattle, WA 98122, USAc Beckman Laser Institute and Medical Clinic, University of California Irvine, 1002 Health Sciences RoadEast, Irvine, CA 92612, USAd 999 North Tustin Avenue, Suite 117, Santa Ana, CA 92705, USA Received 28 May 2013; accepted 6 August 2013 We present an uncommon case of nasal alar and facial necrosis following calcium Injectable filler; hydroxylapatite filler injection performed elsewhere without direct physician supervision. The patient developed severe full-thickness necrosis of cheek and nasal alar skin 24 h after injec- tions into the melolabial folds. Management prior to referral included oral antibiotics, predni- sone taper, and referral to a dermatologist (day 3) who prescribed valacyclovir for a presumptive herpes zoster reactivation induced by the injection. Referral to our institution Nasal alar necrosis was made on day 11, and after herpetic outbreak was ruled out by a negative Tzanck smear,debridement with aggressive local wound care was initiated. After re-epithelialization and thefashioning of a custom intranasal stent to prevent vestibular stenosis, pulsed dye laser therapywas performed for wound modification. The patient healed with an acceptable cosmeticoutcome. This report underscores the importance of facial vasculature anatomy, injectiontechniques, and identification of adverse events when using fillers. A current treatment para-digm for such events is also presented.
ª 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published byElsevier Ltd. All rights reserved.
* Corresponding author. Tel.: þ1 (949) 824 6996; fax: þ1 (949) 824 8413.
E-mail addresses: (L. Tracy).
1748-6815/$ - see front matter ª 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Calcium hydroxylapatite associated soft tissue necrosis Injectable fillers are a common, minimally invasiveapproach in the early treatment of facial aging due tovolume depletion. Use of calcium hydroxylapatite (CHA)has grown in popularity following FDA approval in 2006 toimprove moderate to severe wrinkles. Radiesse (Merz Aes-thetics, San Mateo, CA) is the CHA approved for aestheticapplications in the United States, and is composed of25e45 mm spheres suspended in a carboxymethylcellulosecarrier. Therapeutic results can be expected to last a yearor more, depending on injection location. CHA must beinjected at the dermal-subcutaneous border. If injectedsuperficially CHA can lead to nodule formation and indu-ration. Use of CHA filler in areas with a thinner dermis, suchas the nasal dorsum and tear troughs, increases the risk of Appearance of the infarcted area after complete inadvertent product show through the skin. Many practi- healing and treatment with pulsed dye laser. Photograph was tioners have noted that CHA seems to expand during the taken 4 months after the offending injection.
first 5 min following an injection, resulting in a transientdiscomfort noted by some patients. Other common adverseevents related to filler injection include tenderness, local erythema, and bruising. In a recent 5-year review assessingsoft tissue fillers, CHA was associated with the greatest risk The patient was a 41-year-old woman with a past medical of complications (2.6%), which include cellulitis, tissue history of rhinoplasty surgery, septal perforation, and necrosis, and nodule More severe, but less multiple prior dermal filler injections to the melolabial common complications include herpes zoster reactivation, folds, who received CHA injections to both melolabial folds arterial embolization leading to infarction, temporary with extension to the alar-facial creases. A nurse at a local blindness and oculomotor palsyThe most feared "med spa" performed the injection without direct physi- complication is vascular compromise and tissue necrosis.
cian supervision. Approximately 24 h following the injec- Although adequate data is not available to quantify the risk tion, the patient noted swelling and skin changes to her left of necrosis with CHA fillers, smaller studies estimate this alar crease. She initially sought treatment at the spa and incidence to correlate with the known 0.001% incidence of was treated for presumptive infection with ciprofloxacin collagen or hyaluronic acid fillers.eThe glabellar region is and prednisone taper. On post-injection day 3, the patient most notoriously at risk for tissue necrosis following fillerinjection due to its reliance on the supratrochlear bloodsupply. Similarly, there have been recently reported casesof nasal alar necrosis following both CHA and hyaluronicacid injection.We present a recent case of soft tissuenecrosis of the melolabial and nasal ala region that was notaccurately identified, leading to delay in therapeuticintervention and increase in patient morbidity.
Native vascular anatomy to the nasal ala. Although Necrosis, diffuse inflammation, and fibrinous the infraorbital and dorsal nasal arteries provide some redun- exudate were apparent upon presentation to our institute on dancy, the nasal alar region receives most of its blood supply day 11 following the filler injection.
from the angular artery.

L. Tracy et al.
developed soft tissue necrosis and was seen by a derma- intranasal acrylic resin stent was fashioned to reduce the tologist who prescribed valacyclovir for a presumptive risk of cicatricial vestibular stenosis. Finally, on post- herpes zoster reactivation induced by the injection. On injection day 74, pulsed dye laser therapy was utilized to post-injection day 11, the patient was referred to our reduce scarring and hyperpigmentation. The patient healed institution. On presentation, frank tissue necrosis, diffuse with an acceptable result and declined additional scar inflammation, and fibrinous exudate were observed. Gentle revision surgery ).
debridement was performed revealing a partial thicknesstissue loss (An aggressive daily local wound careregimen was implemented and daily wound debridement was performed. During this time herpes zoster reactivationwas ruled out with a Tzanck smear. The wound was then Although rarely reported, nasal alar tissue necrosis is a allowed to heal by secondary intention and a custom known complication of injectable filler use. Tissue necrosis Management strategy for impending tissue necrosis associated with injection of CHA dermal filler.
Calcium hydroxylapatite associated soft tissue necrosis can result from direct embolization of vasculature with complete vascular occlusion and worsening necrosis. If filler filler material or from compression of local vasculature by embolization is suspected, low molecular weight heparin or the filler product. The complication described in this case enoxaparin may be useful to reduce further thrombus for- represents an insult to the distribution of the angular mation and minimize the extent of necrosis.
branch of the facial artery (The patient had un-dergone prior nasal surgery and it is likely that her native vascular anatomy had been altered, leaving her nasal alarregion dependent on arcades from the superior labial and To prevent injectable associated tissue necrosis a complete infraorbital arteries. Given the delayed onset of symptoms understanding of vascular anatomy, filler properties and (approximately 24 h), arterial embolization is less likely indications for use, as well as knowledge of the patient's versus vascular compression. While excluded in this case, it complete medical history is mandatory. In the circumstance is important to consider an acute herpetic reactivation of impending necrosis, early identification and the use of which can mimic impending tissue Given the appropriate vasodilatory, anti-inflammatory, and antimi- significant morbidity and deformities associated with soft crobial therapies is paramount to improve tissue survival tissue necrosis, we advocate the consideration of this and optimal wound healing. Consideration of an infectious worst-case scenario to prevent any delay in therapeutic or herpetic presentation should be made, but not at the sacrifice of addressing vascular compromise. Finally, To prevent filler associated tissue injury, a complete custom prosthetics, such as an intranasal stent, are useful understanding of facial vascular anatomy is necessary. In in reducing soft tissue retraction and stenosis.
our practice, we inject only with a moving needle in aretrograde fashion and avoid large bolus injections in areasnear known vascular landmarks. We also use microcannulas Conflict of interest for product placement to reduce the incidence of common,transitory adverse events as well as vascular cannulization or injuryMicrocannulas are highly flexible, have a roundblunted tip, and employ a side port for the actual injection of filler material. Their flexibility and lack of the sharpbevel tip inherent in traditional needles make the risk of arterial puncture with microcannulas much less likely.
Further, we feel that product placement is more accurateas a cutting needle tip creates a plane of injection while a Appendix A. Supplementary data microcannula follows the natural anatomic tissue planes.
If impending necrosis is suspected, or even considered, Supplementary data related to this article can be found at prompt treatment is absolutely mandatory (The downside for taking action in a circumstance withoutvasculature injury is minimal in comparison to the case example given. Current recommendations include imme-diate cessation of filler injection, prompt massage with the intent to mechanically distribute the filler away from local vasculature, application of a warm compress, and prompt use of topical nitroglycerin paste to encourage vasodila- 2. Sires B, Laukaitis S, Whitehouse P. Radiesse-induced herpes tion.The minimal amount of nitroglycerin paste needed to zoster. Ophthal Plast and Reconstr Surg;24:218e9.
cover the affected area should be reapplied daily, 12 h on 3. Sung MS, Kim HG, Woo KI, Kim Y-D. Ocular ischemia and and 12 h off, until local capillary refill times improve. We ischemic oculomotor nerve palsy after vascular embolization of recommend the use of 10e30 units hyaluronidase (Vitrase, injectable calcium hydroxylapatite filler. Ophthal Plast and ISTA Pharmaceuticals, Irvine, CA) diluted 1:1 in saline, regardless of the type of filler Hyaluronan is a known mediator of early inflammation, and hyaluronidase has been shown to reduce edema and tissue necrosis in the setting of myocardial infarction.Anecdotally, hyaluroni- dase has been used successfully via the same presumptive mechanism to mitigate inflammation and edema in cases of necrosis related to dermal filler injection, even those using CHA. Daily aspirin and a corticosteroid taper are used to decrease the inflammatory component of the vascular injury. If available, hyperbaric oxygen can also be utilized to promote tissue oxygenation. If vascular compression rather than filler embolus is suspected, consider the addi- tional use of oral vasodilators such as sildenafil or tadalafil.
There is some concern that the use of vasodilatory agents in the case of known arterial cannulization may further push filler material into the tissue capillary bed, leading to L. Tracy et al.


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Amplification of the Angiogenic Signal through theActivation of the TSC/mTOR/HIF Axis by the KSHV vGPCRin Kaposi's Sarcoma Bruno C. Jham1, Tao Ma1, Jiadi Hu1, Risa Chaisuparat1, Eitan R. Friedman1, Pier Paolo Pandolfi4, Abraham Schneider1,3, Akrit Sodhi5, Silvia Montaner1,2,3* 1 Department of Oncology and Diagnostic Sciences, School of Dentistry, University of Maryland, Baltimore, Maryland, United States of America, 2 Department of