Percutaneous Intra-arterial Hyaluronidase Injection for Hyaluronic Acid Filler Embolism Threatening Skin Barrier Integrity: Implementation of a Stepwise Treatment Protocol.

BACKGROUND: Hyaluronic acid (HA) filler-induced vascular embolism that threatens skin integrity is an urgent situation. There is increasing evidence that percutaneous intra-arterial hyaluronidase injection is an effective therapeutic technique for it. However, until now, there is a lack of a unifying protocol about the technique. OBJECTIVES: This study aims to provide a conclusion of percutaneous intra-arterial hyaluronidase injection along with adjunctive measures on the treatment of occlusions precipitated by HA-based filler and develop a stepwise treatment protocol. METHODS: We searched PubMed for peer-reviewed studies, consensus statements, case series, and case reports using a variety of keywords. RESULTS: High-dose, pulsed hyaluronidase is the mainstay for the treatment of HA filler-induced embolism, but percutaneous intra-arterial hyaluronidase injection is a more effective technique. Until now, hyaluronidase is injected into three arteries percutaneously, including facial artery, supratrochlear artery, and superficial temporal artery. Furthermore, the adjunctive measures that may optimize clearance of an occlusion and/or skin barrier repair such as the use of image guidance and CGF should be considered. CONCLUSION: Vascular occlusions that threaten skin integrity are an urgent matter which requires accurate diagnosis and effective intervention. Percutaneous intra-arterial hyaluronidase injection along with adjunctive measures performed in a stepwise manner is key to an optimal outcome. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Efficacy of Percutaneous Superficial Temporal Arterial Hyaluronidase Injection for Hyaluronic Acid Filler-Induced Necrosis of Frontotemporal Skin and/or the Ipsilateral Scalp With Subsequent Alopecia.

BACKGROUND: Necrosis of frontotemporal skin and/or the ipsilateral scalp with subsequent alopecia after hyaluronic acid (HA) filler injection into the temple is rare complications with superficial temporal artery embolization are suspected as the major pathological mechanism. The main treatment currently is intralesional hyaluronidase (HAase) injection, but the effectiveness of percutaneous superficial temporal arterial HAase injection still lacks consensus. OBJECTIVES: To investigate the effectiveness of superficial temporal arterial HAase injection in dissolving HA filler-induced necrosis of frontotemporal skin and/or the ipsilateral scalp with subsequent alopecia. METHODS: Five recent clinical cases with necrosis of frontotemporal skin and/or the ipsilateral scalp with subsequent alopecia after HA filler injection into the temple were analyzed retrospectively. The patients underwent HAase injection via superficial temporal artery combined with adjunctive treatments, and the clinical progress was observed. RESULTS: Significant improvement was observed in terms of necrosis of frontotemporal skin and the ipsilateral scalp after treatment, and the patients were relieved of their clinical symptoms. Alopecia occurred approximately 1 to 2 weeks after HA filler injection, and the well-defined alopecia areas were formed 15 to 20 days after HAase injection. Patients were followed for 3 to 6 months. During follow-up, the skin lesions of all patients were restored to near normal appearance. Hair regrowth was observed 2 to 3 months after HAase treatment, and hair density nearly reached the normal level 3 to 4 months later. CONCLUSIONS: Percutaneous superficial temporal arterial HAase injection is an effective treatment option for HA filler-induced necrosis of frontotemporal skin and/or the ipsilateral scalp with subsequent alopecia.

Efficacy of Percutaneous Intraarterial Facial/Supratrochlear Arterial Hyaluronidase Injection for Treatment of Vascular Embolism Resulting From Hyaluronic Acid Filler Cosmetic Injection.

BACKGROUND: Vascular embolism is a serious complication of hyaluronic acid (HA) filler cosmetic injection, and hyaluronidase injection has been proposed as the treatment. Until now, there has been a lack of adequate clinical evidence regarding the benefits of treatment for HA filler-induced vascular embolism by percutaneous facial or supratrochlear arterial hyaluronidase injection. OBJECTIVES: The authors sough to evaluate the efficacy of percutaneous facial or supratrochlear arterial hyaluronidase injection as a rescue treatment for HA filler-induced vascular embolism. METHODS: We included 17 patients with vascular embolism after facial HA filler injection. Intraarterial injection of 1500 units hyaluronidase was performed via facial artery for 13 cases with skin necrosis and via supratrochlear arterial for 4 cases with severe ptosis and skin necrosis but no visual impairment. Simultaneously, general symptomatic treatment and nutritional therapy were performed. RESULTS: After hyaluronidase injection, facial skin necrosis in all cases was restored and ptosis in the 4 cases was also significantly relieved. Patients were subsequently followed-up for 1 month to 1 year. The skin necrosis in 16 patients completely healed, and only 1 patient had small superficial scars. CONCLUSIONS: It is effective to alleviate skin necrosis and ptosis resulting from HA filler embolism via percutaneous facial or supratrochlear arterial hyaluronidase injection.

The role of altered fatty acid in pathological scars and their dermal fibroblasts.

PURPOSE: The proposed pathological mechanism for scar formation is controversial, and increased attention has been paid to the fatty acids (FAs) in the formation of pathological scars. Notably, FAs are known to be important in inflammation and mechanotransduction, which is closely related to scar formation. Therefore, it is necessary to clarify the roles of FA in scar formation. METHODS: Hypertrophic scar and keloid formed for more than a year and without other treatment, as well as normal skin samples were obtained from patients who underwent plastic surgery. Finally, keloids (n = 10), hypertrophic scars (n = 10), and normal skin samples (n = 10) were collected under informed consent. Primary dermal fibroblasts were isolated and cultured. The amount and variety of FAs were detected by lipid chromatography-mass spectrometry. Immunohistochemistry, real-time PCR, and western blotting were used to verify the expression of sterol regulatory element-binding protein-1 (SREBP1) and fatty acid synthase (FASN) in the samples and their fibroblasts. Student's t-test, ANOVA, and orthogonal partial least square discriminant analysis were performed for statistical analysis (∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001). RESULTS: Compared with full-thickness normal skin, there were 27 differential FAs in keloids and 15 differential FAs in hypertrophic scars (∗p < 0.05 and variable influence on projection >1.0). The expression of SREBP1 and FASN was lower in pathological scars both at mRNA and protein levels (all ∗p < 0.05). However, the mRNA levels of SREBP1 (∗∗∗p = 0.0002) and FASN (∗∗∗p = 0.0021) in keloid-derived fibroblasts were higher than that in normal skin fibroblasts (NFBs), while the expression in hypertrophic scar-derived fibroblasts was lower than that in NFBs (both ∗p < 0.05). Whereas there was no significant difference in FASN protein expression between keloid-derived fibroblasts and NFBs (p > 0.05). CONCLUSION: FAs involved in pathological scars are abnormally changed in scar formation. Thus, fatty acid-derived inflammation and de novo synthesis pathway of FA may play a key role in the formation of pathological scars.

Evaluation of Intraarterial Thrombolysis in Treatment of Cosmetic Facial Filler-Related Ophthalmic Artery Occlusion.

BACKGROUND: With an increase in recent years in the number of people receiving cosmetic facial injection treatments of hyaluronic acid, the incidence of hyaluronic acid embolism has also increased commensurately. Hyaluronic acid embolism leads to serious complications, including blindness, eye and eyelid movement disorders, skin necrosis, and cerebral embolism. However, there is a lack of robust clinical evidence regarding the benefits of treatment for hyaluronic acid embolism by intraarterial thrombolysis therapy. METHODS: This study included 24 patients with a decrease in visual acuity and other complications induced by facial hyaluronic acid injection. Patients underwent emergency intraarterial thrombolysis therapy by injection of hyaluronidase (500 to 1500 units) alone or hyaluronidase (750 to 1500 units) combined with urokinase (100,000 to 250,000 units), followed in both cases by a general symptomatic treatment and nutritional therapy. RESULTS: Ten (42 percent) of 24 patients ultimately had improvements to visual acuity, even when the clinical application of the thrombolytic treatments had passed the recommended window for optimal treatment. In all cases, patients' facial skin necrosis was restored to nearly normal appearance. In addition, the authors found that hyaluronidase combined with urokinase was a more effective therapy than hyaluronidase alone. CONCLUSIONS: The authors' results indicate that intraarterial thrombolysis therapy is beneficial to patients suffering from blindness induced by hyaluronic acid embolism. The therapy was shown to be worthy of clinical application because it alleviated the impairment to patients' vision and was also beneficial in the recovery from other serious complications, including eye movement disorder, eye edema, headaches, and skin necrosis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

[The treatment of deformity of axillary scar contracture after burns].

OBJECTIVE: To explore the best methods to repair the deformity of axillary scar contracture after burns. METHODS: Ninety cases in 78 patients with axillary scar contracture after burns from January 1998 to January 2002 were analyzed. According to the severity of the deformity and its influence on the function of the shoulder joint. 46 cases suffered from mild degree axillary scar contracture, 26 cases with moderate and 18 with severe degree. The deformities of axillary scar contracture were repaired by Z plasty (18 cases), five-flap plasty (14 cases), skin graft (23 cases), Z plasty and skin graft (14 cases), transfer of scapular skin flaps (5 cases), lateral throatic skin flaps (4 cases) and scar flaps (12 cases), respectively. Exopexy, anti-scar drug and functional exercises were applied postoperationally. RESULTS: All the flaps were survived with first intention, except for necrosis of the split skin graft occurring in 4 cases. The function and configuration in all the cases were satisfactory after 6 months to 4 years follow-up. CONCLUSION: Appropriate methods should be chosen to restore the function and configuration of the shoulder joint and improve patients' living condition according to the size, degree of the deformity of axillary scar contracture after burns.

[Expression of hyaluronic acid and its receptor in the process of wound healing in different skin tissues and its significance].

OBJECTIVE: To explore the expression of hyaluronic acid (HA) and its receptor, Cluster of differentiation 44 (CD44) in proliferative scar and in the process of wound healing of normal human adult skin and fetal skin, and the effect of HA and its receptor on the process of human fetal skin scarless healing. METHODS: An incision and then a hypodermic cavity were made on each side of the dorsal median line of 32 female adult BALB/c rats. Skin grafts from 8 human fetuses delivered by natural abortion, full-thickness skin grafts from 8 normal adults undergoing plastic operation, skin wound sample from the donor sites in legs of 8 patients undergoing dermatoplasty with intermediate split thickness skin graft, and proliferative scar from 8 patients of plastic surgery, non-adult and adult, were grafted into the hypodermic cavities. The levels of HA and its receptor were examined by radioimmunoassay, immunohistochemistry and flow cytometry. RESULTS: The level of HA in normal fetal skin was 143 micro g/g +/- 10 micro g/g, 283 micro g/g +/- 12 micro g/g 12 hours after injury, 315 micro g/g +/- 12 micro g/g one days after injury, reached the peak (321 micro g/g +/- 12 micro g/g) 3 days after injury, and then decrease, became 319 micro g/g +/- 11 micro g/g one week after injury (P > 0.05 in comparison with that 3 days after injury). The level of HA in normal fetal skin was 143 micro g/g +/- 10 micro g/g, significantly higher than that in normal adult skin (51 micro g/g +/- 4 micro g/g), skin wound of normal adult (92 micro g/g +/- 6 micro g/g), and proliferative scar (72 micro g/g +/- 5 micro g/g, all P < 0.01). The level of HA in wounded adult skin was significantly higher than that in the proliferative scar, and even much higher than that in normal skin (P < 0.01). The level of CD44 in normal fetal skin was significantly higher than that in proliferative scar and adult skin (all P < 0.01). The level of CD44 in wounded fetal skin 24 hours after injury decreased, significantly lower than that in normal fetal skin. There was no statistically significant difference between the level of CD44 in fetal skin one week after injury and that 24 hours after injury (P > 0.05). The level of CD44 in wounded adult skin was significantly higher than that in the normal adult skin (P < 0.01). The level of CD44 in the proliferative scar was between the level of CD44 in normal adult skin and that in wounded adult one. In normal fetal skin, CD44, positively stained at a moderate level, was distributed in keratinized cells, basic cells of hair follicle, and fibroblast of dermis. After injury, staining of CD44 became milder, especially by the incision. Immunohistochemistry showed that in normal adult skin, CD44 was distributed mainly in fibroblast of dermis and basic cells of hair follicle, weakly positively stained. After injury, the staning became stronger. CONCLUSION: The expression of HA and its receptor during the process of wound healing in human fetal skin is different from that in proliferative scars and adult skin, which might be one of the important causes of scarless healing of wounded fatal skin.

[Repairing of lower eyelid ectropion with expanded flap].

OBJECTIVE: To investigate the effect of reconstruction of lower eyelid ectropion with expanded flap. METHODS: Fourty patients with lower eyelid ectropion were reconstructed using tissue expander. The volume of the smallest expander was 30 ml, and that of the biggest one was 150 ml. The expand time was from 2-months to 3-months, then advancement or transposition flaps were created and employed in the defected lesion where the scar was removed just in one operation. RESULTS: All patients have been followed up for 2-year with satisfactory results and no recurrences was appearance. CONCLUSIONS: Application of expander reasonable may get satisfactory result in reconstruction of lower eyelid ectropion. The incision in donor site is hidden and the symptom seldom recurs.

[Laparoscopic small intestinal flap colpopoiesis].

OBJECTIVE: To investigate the possibility of Laparoscopic reconstruction of vagina using pedicled ileal autograft and provide a new procedure of colpopoiesis. METHODS: The abdominal and perineal approaches were performed simultaneously under a sufficiently deep general anaesthesia. Laparoscopically, a 15-18 cm segment of the ileum on its vascular pedicle, ileal branches of the superior mesenteric artery and its concomitant veins, was selected and isolated for transplantation using ultrasonically-powered instruments. The distal of the transferred ileal segment was 15cm apart from the ileocecal junction. The ileum continuity was restored immediately by end-to-end anastomosis and the distal oral of the transplant was closed using a curved intraluminal stapler. Meanwhile, a neovaginal tract was completed to dissect from the perineum into the peritoneum and the tract widened laterally. Then the ileum transplant was reversed to reach the perineum through the peritoneal incision at the top of the neovaginal tract without subjecting the mesenteric neurovascular pedicle to undue tension and subsequent necrosis. The oral edge of the ileum transplant was sutured to the perineal skin. RESULTS: Followed up for over 1-53 months postoperatively, 36 patients who received laparoscopic vaginoplasty by transferring ileal segment flaps got satisfactory neovaginal function similar to a normal vagina with mucus and moistness. CONCLUSIONS: The advantages of using a laparoscopic ileum colpopoiesis are that (1) satisfactory neovaginal function similar to a normal vagina with mucus and moistness, (2) no disturbance of bowel function, (minimal scarring in abdominal wall and less secondary deformity in perineum and (3) no need for frequent dilation or stent wearing to the reconstructed vagina. And so laparoscopic vaginoplasty was a preferable alternative of vaginoplasty.

[Differential display of homeobox gene expressions in the normal, wounded human fetal and adult skins by DNA microarray].

OBJECTIVE: To explore the differential expression of homeobox genes in the normal, wounded human fetal and adult skins and its significance in fetal scarless healing. METHODS: Gene chips containing 14 000 human genes were used to investigate homeobox gene expressions of the normal, wounded human fetal and adult skins. RESULTS: There were significant differences between the expression of homeobox genes, especially for PRX-2, HOXB13, HOXB6 and HOXB7. CONCLUSIONS: The homeobox gene is in close relation to developmental biology. The different expressions and changes of homeobox genes in the normal, wounded human fetal and adult skin may be a primary cause of different wound healing between fetal and adult skin.

[The role of tyrosine phosphorylation proteins in procollagen gene expression of fibroblasts in wound healing].

OBJECTIVE: To investigate the role of adhesion between fibronectin and fibroblasts in wound healing as well as tyrosine phosphorylation proteins in procollagen mRNA expression. METHODS: The level of proalpha1 (I) mRNA and tyrosine phosphorylation protein were detected employing the techniques of RT-PCR and immunoblotting. After inhibition of tyrosine kinases, herbimycin A was added to the medium to block the pathway of tyrosine phosphorylation, the changes of procollagen mRNA and tyrosine phosphorylation proteins were further investigated. RESULTS: The adhesion between fibroblasts and fibronectin in wound healing not only induced the production of 98kd and 65kd tyrosine phosphorylation protein, but also enhanced obviously the expression of procollagen alpha1 (I) mRNA. When the pathway of tyrosine phosphorylation was blocked, the level of procollagen alpha1 (I) mRNA lowered remarkably, accompanied by the decrease of 98kd, 65kd tyrosine phosphorylation proteins. CONCLUSION: The adhesion between fibronectin and fibroblasts plays an important role in expression increase of procollagen mRNA during wound healing, in the process of which tyrosine phosphorylation is a key step.

[A comparative study of PDGF and EGF expression in skin wound healing between human fetal and adult].

OBJECTIVE: To explore the differences of PDGF and EGF expression in the wound healing between fatal and adult. METHODS: With the established animal model of fetal scarless healing and the adult samples, an immunohistochemical technique was used to evaluate the expression of PDGF and EGF in the normal adult skin, normal fetal skin, and the process of their wound healing. RESULTS: 1. The expression of the PDGF was not found in the fetal skin, but a mild amount of the PDGF was shown in the epidermis and the upper dermal layer 12 hours and 1 day after the wounding process. In the normal adult skin, expression of PDGF was shown in the dermal fibroblasts, macrophagocytes and blood capillaries, and a strong expression was presented during its wound healing process. 2. In the fetal skin, the expression of the EGF was seen in the epidermis, hair follicles, sebaceous glands and sweat glands, but there were no markedly changes during the wound healing. In the adult skin, a positive stain of the EGF was shown in the basal layer of the epidermis while the mild stain in hair follicles and sweat glands. The level of the expression became gradually decreasing with the time going in the wounded adult skin. CONCLUSION: The different expression of growth factors between fetal and adult skin in wound healing may be one of the important reasons that the fetal wound could produce scarless healing.

[The significance and the expression of homeobox genes during human burn wound healing].

OBJECTIVE: To investigate the expression of several homeobox genes during the wound healing in fetal and adult skin and their roles in fetal scarless wound healing. METHODS: The expressions of PRX-2, HOXB13, HOX2.2 and HOX2.3 during wound healing in fetal and adult skin were determined with in situ hybridization. RESULTS: (1) PRX-2 positive expression could be identified in normal fetal and adult skin, especially in the fetus. But there was difference in location sites of the genes. The positive expression in normal fetal skin was mainly found in the peripheral cells at the hair shafts within dermal papilla layers and was also found in the epithelium. Nevertheless, weak positive expression of PRX-2 was found in the epithelial basal layer cells in normal adult skin but not in dermal tissue. There was strong positive expression of the PRX-2 in the tissue around the wound in fetus but not of that in adults except the epithelial basal layers. (2) Positive expression of HOXB13 could be identified in both normal fetal and adult skins. And the expression was concentrated mainly in hair follicle cells in the dermis and in the basal layer cells in the epithelium. Furthermore, the expression became weak after trauma, especially in fetal skin. (3) The positive expression of HOX2.2 and HOX2.3 in normal fetal skin was observed mainly in the whole layer of the epithelium and especially in the epithelial basal layers. Weak positive expression could be found in the dermis and strong expression found in the tissue near the wound. But there was no positive expression of the HOX genes in normal adult skin and wounds. CONCLUSION: The difference in the HOX expression in fetal and adult skin wound healing might be the key factor leading to different wound healing. Homeobox genes might be closely related with the developmental biology.