Alopecia Secondary to Hyaluronic Acid Injection: A Case Report and Literature Review

Introduction

Over the past two decades, hyaluronic acid (HA) filler injections have become a widely used procedure in aesthetic medicine, employed for facial volume restoration, wrinkle correction, skin rejuvenation, and non-surgical facelifting.^1,2 HA is a naturally occurring, high-molecular-weight glycosaminoglycan composed of repeating disaccharide units of D-glucuronic acid and N-acetyl-D-glucosamine.³ It is abundantly present in the extracellular matrix of connective tissues, particularly in the skin, eyes, synovial fluid, and soft connective tissues, underscoring its crucial physiological roles.⁴ One of its most notable properties is its ability to bind and retain water—up to 1000 times its own weight—thereby contributing to tissue hydration, structural integrity, and volumizing effects.² Although HA occurs naturally in the body and plays a key role in maintaining skin health and moisture, it is commonly modified or synthesized for use in cosmetic and dermatological applications.⁵ These formulations are designed for various routes of administration, including intradermal, subcutaneous, intra-articular, topical, and ocular delivery. When used as a dermal filler, HA provides immediate volume and helps reduce the appearance of wrinkles by restoring lost structural support.² As the material gradually degrades over time, water replaces the gel matrix, allowing for prolonged volumetric effect through a process known as isovolumetric degradation. The duration of action generally ranges from 4 to 6 months, although this may vary depending on the specific product, injection site, and technique used.⁵

Despite its widespread use and general safety profile, HA injections are associated with both cutaneous and systemic adverse effects.⁶ Complications such as allergic reactions, hypersensitivity, edema, infections, and even vascular occlusion leading to vision loss have been reported.^7,8 Among these, secondary alopecia following HA filler injection is a rare but increasingly recognized complication, yet its exact pathophysiological mechanisms remain poorly understood.

In this case report and literature review, we present a case of a patient with HA-induced alopecia on the left temporal scalp who achieved complete hair regrowth after four months of treatment with Concentrated Growth Factor (CGF) combined with microneedling (MN) and minoxidil, and we provide a comprehensive analysis of alopecia secondary to HA, including detailed data on filler type, injection site, complication location, onset of alopecia, associated symptoms, diagnostic evaluations, potential pathophysiological mechanisms, treatment approaches, and outcomes. Our primary aim is to broaden the therapeutic options for such patients and highlight that alopecia following HA injections is an underreported complication. Clinicians should remain vigilant, recognize its clinical manifestations, and be prepared with effective prevention and management strategies.

Case Report

A 23-year-old woman underwent facial augmentation performed by a registered nurse, during which 5 mL of HA filler (Restylane, Medicis, Scottsdale, AZ, USA) was injected into the left frontal region. The procedure was uneventful at the time of injection; however, 4 days later, she developed localized erythema and pain in the same area. The patient visited a clinic after experiencing persistent pain for three days and received three sessions of hyaluronidase (HAase) treatment (total 1500 units), which alleviated the symptoms. On day 15 post-HA injection, she noticed an area of alopecia with superficial crusts on the left frontal scalp, which progressively worsened. She was subsequently referred to our hospital for further management. On initial examination, the affected region measured approximately 4×5 cm, with well-defined borders and complete absence of hair shafts. Dermoscopic examination revealed characteristic signs of active alopecia, including black dots, broken hairs, reduced hair density, scaling, and erythematous patches (Figure 1a and b). There were no signs of pustules or significant exudate. A provisional diagnosis of HA-induced alopecia was made based on the clinical presentation and temporal correlation with the injection. Treatment was initiated with topical application of recombinant bovine basic fibroblast growth factor (bFGF) gel to the affected area, aiming to promote tissue regeneration. By day 21, the condition had progressed to a well-demarcated alopecia patch measuring 5×6.5 cm (Figure 1c), with no spontaneous regrowth observed. The hair pull test yielded negative results, suggesting that the disease activity might be resolving or entering a quiescent phase.

Figure 1 A 23-year old female showing alopecia secondary to hyaluronic acid injection. (a and b) Dermoscopic pictures at baseline: black dots, broken hairs, reduced hair density, scaling and erythematous patches. (c) A well-demarcated alopecia patch measuring 5×6.5 cm after the hair loss had stabilized. (d) CGF. Three blood fractions were obtained after centrifugation with anticoagulant: the upper layer represented by PPP; the middle layer or buffy coat represented by CGF; and the lower red blood cell (RBC) layer. (e) Dermoscopic picture at 3-month follow-up after the last session: absence of signs indicative of HA-related alopecia, and complete hair regrowth. (f) Follow- up for 3 months after the last session.

Treatment Protocol for Alopecia

Given the lack of response to initial conservative therapy and the desire to explore regenerative options, a multimodal therapeutic strategy combining Concentrated Growth Factor (CGF), microneedling (MN), and 5% minoxidil was implemented. This approach was selected based on its potential to stimulate hair follicle regeneration through multiple mechanisms, including growth factor delivery, dermal remodeling, and enhanced drug penetration. CGF was prepared using differential centrifugation. Briefly, 9 mL of fresh blood was collected in vacutainer tubes containing EDTA-K2 as an anticoagulant (K.S MEDICAL; Zhejiang, China) under aseptic conditions. The blood sample was centrifuged using a specific protocol:⁹ 30 seconds of acceleration, followed by 2 minutes at 2700 rpm, 4 minutes at 2400 rpm, 4 minutes at 2700 rpm, 3 minutes at 3000 rpm, and 36 seconds of deceleration and stop. This process separated the blood into three distinct layers (Figure 1d). The upper platelet-poor plasma (PPP) and the lower red blood cell layer were discarded, while the middle buffy coat layer, totaling 2–3 mL, was collected as CGF.

Before the therapeutic intervention, the alopecia area was meticulously prepared aseptically using normal saline and iodophor solution, followed by local anesthetic injections administered circumferentially. CGF was then injected into the alopecia-affected scalp at a dosage of 0.1–0.2 mL/cm² and a depth of 2 mm. Subsequently, MN was performed using a dermaroller device equipped with 540 needles of 1.5 mm length. The device was rolled diagonally, vertically, and horizontally across the treated area, repeating the process four to five times along each axis to ensure thorough coverage. Pinpoint bleeding, indicative of adequate dermal stimulation, was observed as the endpoint. Immediately following MN, 5% minoxidil (Mandi, Zhejiang Wansheng Mandi Pharmaceutical Co., Ltd., China) was applied topically to the scalp and gently massaged into the micro-punctures created by the MN procedure. This step aimed to enhance transdermal absorption of minoxidil, thereby potentiating its vasodilatory and hair growth-promoting effects. The patient underwent a total of three treatment sessions, spaced 1 to 2 weeks apart, to ensure cumulative therapeutic exposure and optimize follicular stimulation. No adverse events or complications were observed throughout the treatment course. At the four-month follow-up, complete hair regrowth was evident both clinically and photographically (Figure 1e and f), with full restoration of hair density and texture. The progression and treatment timeline of the case are summarized in Figure 2.

Figure 2 Therapeutic timeline showing: Day 0: 5 mL HA injection; Day 4: Erythema & pain; Day 7: HAase 1500U; Day 15: Alopecia onset, bFGF; Weeks 3–7: CGF+MN sessions; 4 Months: Complete regrowth.

Literature Review

A comprehensive literature search spanning the years 2000 to 2024 was conducted across PubMed, Web of Science, and Embase to identify cases of alopecia secondary to HA injection. The search utilized relevant keywords, including “hyaluronic acid”, “injectable dermal fillers”, “fillers”, and “cosmetic procedures”, combined with “alopecia”, “hair loss”, and “filler-induced alopecia” using the Boolean operator “AND”. Duplicates, non-English articles, and studies unrelated to the topic were excluded. Prospective and retrospective studies, clinical trials, case reports, and case series involving human subjects were included if they provided detailed information on the types of products used, injection sites, and locations of hair loss. Studies lacking sufficient detail were excluded from the review. Flowchart describing the systematic study selection process is shown in Figure 3.

Figure 3 Flowchart describing the systematic study selection process.

Results

A total of 13 reports involving 19 patients (18 females, 1 male) with alopecia following HA injections were identified. Data extracted from these cases included the type of products used, injection sites, complication locations, onset of alopecia, associated symptoms, diagnostic imaging findings, proposed mechanisms of alopecia, treatment approaches, and outcomes, as summarized in Table 1. Alopecia typically developed 1 week to 4 weeks following cosmetic injection procedures. The majority of injections were administered in the temple region (11/19 cases), followed by posterior temple (5/19). Alopecia consistently occurred adjacent to the injection site, with the temporoparietal scalp (6/19), temple scalp (3/19) and parietal scalp (2/19) most frequently affected. Diagnostic tools such as trichoscopy,^10,11 dermatoscopy,¹² ultrasound,^13,14 and histopathology^{10,12,15–18} played a critical role in confirming the diagnosis. Proposed mechanisms for alopecia included extravascular compression, intravascular HA embolism, and inflammatory injury.

Table 1 Cases of Hyaluronic Acid Injections Leading to Alopecia

Therapeutic interventions for HA-induced alopecia were multifaceted, with HAase serving as the cornerstone of acute management. HAase was administered in 16 cases (84.2%),^{10–14,16,17,19–22} with doses ranging from 50 to 69,000 units to mitigate ischemic damage. Adjunctive therapies included: topical minoxidil,^{10,11,16,17,20,21} intralesional triamcinolone acetonide,^{10,11,15,17,18} platelet-rich plasma (PRP),^19,21 basic fibroblast growth factor (bFGF),^16,19 hyperbaric oxygen therapy¹⁹ and botulinum toxin A (BTXA).¹⁹ In our case, Concentrated Growth Factor (CGF) with microneedling (MN) and minoxidil achieved complete regrowth by synergistically targeting ischemia, upregulating hair-growth genes, and enhancing drug delivery. Most cases reported partial or complete resolution of alopecia following treatment.

Discussion

HA is widely employed as a dermal filler to address age-related wrinkles and folds. Its natural biodegradability and rapid degradation via exogenous HAase make it a safer option compared to other fillers.¹⁸ Paradoxically, while HA or compounds containing HA are increasingly utilized in hair growth formulations due to its ability to modulate dermal papilla cells, promote angiogenesis, and exert antioxidant and anti-inflammatory effects.^23,24 This study highlights its potential to induce alopecia when injected inappropriately. An increasing number of cases have reported alopecia following HA administration, particularly associated with temporal area volumization (Table 1). Although less common than transient edema, cutaneous erythema, immunologic responses, infections, or granulomatous inflammation, HA-induced alopecia remains a clinically significant complication.

The dual role of HA in hair biology warrants attention: topical or low-dose intradermal HA may promote hair growth by improving perifollicular vascularization and reducing oxidative stress,²⁴ whereas high-volume injections—especially in vascular-rich areas—can trigger ischemia and follicle damage. The mechanisms underlying HA-induced alopecia include vascular occlusion due to excessive filler volume (type 2 pressure-induced alopecia), intravascular obstruction from HA emboli,²⁵ and inflammatory or foreign body reactions.¹⁸ The injection volume is a critical risk factor, with site-specific variations influencing the likelihood of complications.¹⁸ HA’s hygroscopic nature can also lead to increased hydrostatic pressure in the interstitial space²⁶ causing ischemia and hypoxia. These conditions disrupt hair follicle metabolism, prematurely terminating the anagen phase and resulting in hair loss.

Currently, no standardized protocols exist for managing HA-induced alopecia; however, early intervention is critical to restore blood perfusion, reduce tissue ischemia and hypoxia, and reverse localized hair loss. Clinical evidence indicates that timely administration of HAase is an effective emergency measure to address compromised blood perfusion caused by HA fillers. The optimal window for HAase administration is within the first 48 hours post-HA treatment, as this period is crucial for preventing ischemic damage to skin tissues.^26,27 While some patients may be reluctant to reverse the aesthetic effects of the filler prematurely,²⁸ even delayed HAase injection can alleviate pain and improve skin ischemia, underscoring its therapeutic value. Although direct injection of HAase at the site of vascular occlusion is challenging due to its low probability, the broad diffusion properties of HAase enable its therapeutic effects even when administered into the ischemic area rather than directly into the occluded vessel. Ultrasound-guided HAase injection is recommended for its precision in localizing the filler.^14,29 Beyond HAase,^{10–14,16,17,19–22} adjunctive therapies such as intradermal triamcinolone acetonide,^{10,11,15,17,18} hyperbaric oxygen therapy,¹⁹ minoxidil,^{10,11,16,17,20} platelet-rich plasma (PRP),^19,21 and botulinum toxin A (BTXA)¹⁹ can further support reperfusion efforts.

In our case, the patient received a high-volume injection of 5 mL HA in the left frontal region. The combination of the substantial filler volume and HA’s hygroscopic nature likely exerted pressure on local blood vessels, leading to type 2 pressure-induced alopecia. Early application of hyaluronidase effectively alleviated skin ischemia by degrading the HA filler. To address HA-induced alopecia, a multimodal approach incorporating CGF, MN, and minoxidil was implemented. CGF represents the latest generation of platelet products, containing a high concentration of growth factors and CD34-positive stem cells, which play key roles in wound healing and tissue regeneration. CGF has been shown to promote hair growth in androgenic alopecia.³⁰ Additionally, CGF is a potent anti-inflammatory agent that can suppress cytokine release, thus limiting local tissue inflammation. Given that alopecia induced by HA may be accompanied by skin necrosis and inflammatory response, the anti-inflammatory effects of CGF are likely to be highly beneficial in managing this condition. MN has been observed to induce the expression of several hair growth pathway mediators, such as Vascular Endothelial Growth Factor (VEGF), β-catenin, Wnt3a, and Wnt10b,³¹ which play essential roles in regulating the hair cycle, hair shaft production, and follicle development. When minoxidil is delivered through MN-assisted transdermal pathways, it experiences enhanced permeation and absorption into the skin. This not only ensures a deeper and more efficient delivery to the targeted hair follicular units but also potentially increases the drug’s bioavailability at the site of action, thereby amplifying its therapeutic effect on hair growth stimulation. This comprehensive strategy not only addresses the ischemic and inflammatory mechanisms underlying HA-induced alopecia but also facilitates effective hair regrowth and scalp recovery.

Dermoscopy serves as a valuable tool not only for distinguishing HA-induced alopecia from other hair loss conditions but also as a noninvasive method for comprehensive monitoring and longitudinal assessment of therapeutic responses in patients with HA injection-related alopecia. Dermoscopic evaluation in such cases typically reveals characteristic features of non-cicatricial alopecia, including yellow and black dots, fractured hair shafts, and abnormal vascular patterns such as vessel dilation, cutaneous erythema, and pigment accumulation.¹⁰ In our case, initial dermoscopic findings included black dots, broken hairs, and irregular vascular proliferation. By the 4-month follow-up, these features had completely resolved, aligning with the patient’s clinical improvement and validating the efficacy of the combined therapy. These dermoscopic changes highlight their potential as favorable prognostic indicators for treatment outcomes in HA-induced alopecia. Furthermore, histopathological analysis often shows reduced anagen hair follicle density, vascular ectasia, perifollicular lymphocytic infiltration, and basophilic foreign material within vascular structures, consistent with HA deposition. These findings underscore the diagnostic and therapeutic utility of dermoscopy and histopathological analysis in managing HA-induced alopecia.

Although various treatment options exist for HA-induced alopecia, prevention remains the most effective strategy. To minimize the risk of alopecia following cosmetic injections, a thorough assessment of the patient’s scalp health and hair loss history is essential. This preliminary evaluation helps identify potential risk factors prior to the procedure. Practitioners must possess a deep understanding of the anatomical structures and vascular systems in the treatment area,³² recognize specific “high-risk zones”, and be proficient in managing complications. These principles are fundamental to ensuring safety and achieving optimal outcomes in aesthetic injections.^33–35 To reduce the risk of intravascular injection, pre-injection aspiration is recommended to verify that the needle is not positioned within a blood vessel. However, the reliability of aspiration varies between 33% and 63%, influenced by factors such as needle gauge, retraction time, and needle length.^36–38 Adjusting aspiration techniques based on filler rheology can enhance reliability. The use of blunt-tipped cannulas (25G or larger) is advisable, as they are less likely to penetrate vessels.^32,39 The force applied during injection and the patient’s age can also impact the likelihood of vessel penetration. Caution is warranted when using products containing local anesthetics or epinephrine, as these agents may mask signs of vascular occlusion.³³

A low-pressure, slow injection technique is recommended to ensure precise filler placement at the correct depth and tissue plane.^8,39,40 Using the minimal volume required to achieve the desired outcome helps prevent overfilling and vessel compression.³⁹ If additional product is necessary, repeating the treatment within 7–14 days is a safer approach.^32,40,41 The choice of injectable materials significantly influences treatment outcomes. Higher-density fillers, characterized by greater G’ values, pose an increased risk of vascular occlusion due to elevated external pressure on vessels.⁴² For less experienced practitioners, reversible HA fillers are preferable, as they can be managed with HAase in cases of vascular occlusion.³⁹

Conclusion

HA injection procedures are now widely utilized not only by physicians but also by nonmedical personnel. Although adverse reactions are relatively rare, secondary alopecia must be acknowledged as a potential complication, particularly in anatomically sensitive areas such as the scalp, forehead, and temporal regions. Clinicians should maintain a high level of vigilance regarding this complication following aesthetic dermal injections, promptly recognize its clinical manifestations, and have appropriate preventive and therapeutic strategies in place. The case presented in this study suggests that a combination of CGF, MN, and topical minoxidil may be an effective treatment option for HA-induced alopecia, warranting further investigation in larger studies.