Non-Insulated Microneedle Radiofrequency for the Treatment of Hydroquinone-Induced Exogenous Ochronosis: A Case Report and Literature Review

Introduction

Exogenous ochronosis (EO) is an acquired hyperpigmented disorder characterized by bluish-grey skin discoloration on the face, neck, back, or extensor surfaces of the extremities. EO demonstrates histopathological characteristics of ochre-colored banana-shaped deposits in the dermis with collagen and elastic fiber degeneration. While hydroquinone is the most common cause of EO, resorcinol, phenol, and mercury can also contribute to this condition. The pathophysiology of hydroquinone-induced exogenous ochronosis remains unclear and has been proposed by numerous theories. However, the most widely accepted explanation is that topically applied hydroquinone inhibits the local action of the enzyme homogentisic acid oxidase within the dermis, resulting in the accumulation of homogentisic acid, which has the propensity to form ochronotic pigment.¹

EO requires a multimodal treatment approach and is usually refractory and unresponsive to standard treatments. This includes ceasing the offending agent, avoiding sun exposure, oral medication, and topical medication.¹ Recent reports have been integrating lasers and light therapies to manage EO. Previous light-based treatments, such as ablative lasers including CO2 lasers and Erbium lasers, Q-switched lasers, fractional lasers, and intense pulsed light (IPL), have been reported to be efficacious. Nevertheless, these treatments are sometimes associated with post-inflammatory hyperpigmentation (PIH).¹ Consequently, energy-based devices as radiofrequency (RF) has garnered attention as an alternative treatment for hyperpigmented disease owing to their safety profile, characterized by minimal scattering effects and absence of chromophore absorption, resulting in fewer complications compared to traditional laser-based approaches. However, none of the previous literature documents the usage of the energy-based device for treating EO. Hence, we present the first case of EO successfully treated with bipolar non-insulated microneedle radiofrequency (MNRF).

Case Report

A 63-year-old Thai female with Fitzpatrick’s skin type IV presented with multiple greyish macules and papules on the face for 10 years. She was diagnosed with melasma and had been treated with a regimen comprising a combination of whitening agents containing hydroquinone, chemical peels, and unspecified laser treatments. Over the past decade, she developed slight erythema in the malar regions, gradually progressing to multiple tiny black dots on the preexisting melasma. Dermatological examination revealed multiple tiny pinpoint dark brown macules and papules mixed with reticulate brown to grey patches with some telangiectasia on the forehead, bilateral cheeks, nose, and chin (Figure 1A). Dermatoscopy showed brownish to greyish caviar-like macules and papules with an ill-defined brown reticular network with telangiectasia (Figure 1B). A 3-mm punch biopsy performed on the left nasolabial fold revealed multiple brownish banana-shaped materials deposited in the upper dermis, which were compatible with exogenous ochronosis (Figure 2).

Figure 1 Digital photograph (A) by digital camera (D5100 model, Nikon Corporation, Japan) revealed exogenous ochronosis as multiple tiny black dots at bilateral malar, nose, forehead, and chin on top of preexisting melasma. The black box labeled the area of dermatoscopic examination. Dermatoscopic examination (B) showed tiny pinpoint carvial dark brown papules (arrows) throughout the lesion and the overlying melasma before treatment. (C) Dermatoscopic image at 12-week follow-up after three sessions of non-insulated microneedle radiofrequency, showing marked reduction in papular pigmentation (arrows) and background hyperpigmentation.

Figure 2 H&E stain from punch biopsy at left nasolabial fold at 100x magnification (A) and 400x magnification (B) revealed superficial perivascular infiltration with lymphocytes and ochronotic materials in brown banana-shaped deposits at the upper dermis. The measured depth of ochronotic material is 0.5 mm below the epidermis. Solar elastosis and telangiectasia were also noted.

The patient was treated with three sessions of bipolar non-insulated MNRF (Sylfirm X plus, Viol, Gyeonggi, South Korea) with a disposable tip composed of 25 non-insulated microneedles in 5×5 arrays. She was instructed to apply topical anesthetic cream containing 5% lidocaine and 5% prilocaine cream (Racser^®, Galentic Pharma, Navi Mumbai, India) 30 minutes before the procedure. She was given a treatment in pulsed-wave mode at the forehead, malar areas, nose, and chin for treating EO and melasma; meanwhile, continuous-wave mode was performed at infraorbital, malar, and jawline areas for skin tightening. The specific parameters for each area are described in Table 1. The same setting of the MNRF device was performed for all three sessions with a 4-week interval. She was also instructed to apply sunscreen, moisturizer, and avoid sun exposure after each treatment.

Table 1 Summarized Protocol of Treatment with Bipolar Non-Insulated MNRF Throughout All Sessions

Results

At the 4-week follow-up after a single treatment, clinical improvement of the lightening of the lesion was observed compared to baseline (Figure 3A and B). The noticeable reduction of ochronotic pigments, telangiectasia, and preexisting melasma was significantly observed at 8 weeks follow-up (Figure 3C). After three sessions, the lesion clearance continued, and overall skin texture improved (Figure 3D). Facial analysis machine (Trica3D, Qingdao Xiaoyou Intelligent Technology, China) revealed lesion lightening from baseline to 12 weeks (Figure 3E–H). Brown field mode was also utilized to enhance brown pigment, indicating a notable improvement of hyperpigmented lesions, especially at the nose and bilateral malar regions (Figure 3I–L). The red area mode also noted the significant improvement of telangiectasia (Figure 3M–P). In each session, the patient reported mild pain. Side effects, including transient redness and mild swelling, were self-limited and resolved within 4–5 days. Post-inflammatory hyper- or hypopigmentation or prolonged erythema were not observed. The patient expressed high satisfaction with the treatment outcome.

Figure 3 Clinical photographs and facial analysis reveal significant improvement of exogenous ochronosis and overall skin quality from baseline to week 12 post-treatment (A–D). The improvement of pigmented lesions is observed in facial analysis in cross-polarized light (E–H) and brown spots mode (I–L). Significant improvement of telangiectasia is noted in the red area mode (M–P).

Discussion

EO is a challenging dermatological condition that causes significant physical and psychological burdens for affected individuals. Exogenous ochronosis (EO) may mimic melasma in its early stages, but differs by showing gray-blue to blue-black macules with “caviar-like” papules and pathognomonic banana-shaped fibers on histology. In contrast, melasma presents with brown reticular macules and epidermal pigmentation.² Dermoscopy may assist, but a biopsy remains the definitive method. Importantly, early recognition or suspicion of EO is critical, as misdiagnosis as melasma often leads to continued hydroquinone use, which can aggravate EO and worsen outcomes. Various treatment modalities, including topical and oral medications, light-based treatments, and laser interventions, have been explored to manage the disease. While avoiding exposure to the causative agents alone results in minimal disease improvement. Topical therapies, such as retinoic acid, have shown different responses and lead to transient hyperpigmentation in some cases. A combination of retinoic acid with chemical peels has also shown no significant benefit. The efficacy of topical low-potency corticosteroids (1 to 2.5 percentage of hydrocortisone) appears to be minimal in terms of lightening effects.¹

The first report of laser treatment in EO was introduced in 1990, with a combination of dermabrasion and CO₂ laser revealed to be effective and provided a satisfying result.³ Ablative lasers such as CO₂ laser⁴ and Erbium-doped yttrium aluminium garnet (Er:YAG) ablative laser (2,940 nm)⁵ has been reported to effectively lighten lesions by removing the damaged tissue through vaporization process. This process, while effective, typically results in a longer recovery time and may cause discomfort or pain for the patient during treatment. Subsequently, studies have explored the efficacy of pigment-specific lasers as a monotherapy, including Q-switch Ruby, Alexandrite, and Nd:YAG lasers. These lasers are effective, but multiple treatment sessions were often required to obtain optimal results.^6–10 The combination of Q-switch laser, especially 1,064-nm Nd:YAG, with other treatments has also shown significant improvement. However, PIH usually occurs in cases with dark skin type.^11–13 More recently, Picosecond lasers (755 nm and 1,064 nm) were also reported to be useful in EO without any side effects.^14,15 The mechanism of action of the laser therapies involves the laser’s ability to deliver high-energy light to target ochronotic pigments, causing them to shatter and subsequently be eliminated through the lymphatic system or via trans-epidermal elimination.¹⁵ IPL devices also reported to be effective for treating EO by causing melanosomes elimination together with necrotic keratinocytes induced by thermal heating.^16,17

The summarized data of light-based and laser devices for EO treatment is reported in Table 2.

Table 2 Efficacy of Lasers and Light-Based Therapy as Treatment for Ochronosis

Following advances in the laser and light-based therapies, RF devices have emerged as a promising alternative modality for treating pigmentary disorders. Microneedle radiofrequency (MNRF) delivers RF energy via insulated or non-insulated microneedles in monopolar, bipolar, or fractional modes, inducing dermal remodeling through bulk heating. By directly targeting dermal pathological structures while sparing the epidermis, minimizing surface disruption.¹⁸ Beyond its physical effects, RF-induced thermal effects have been shown to reduce senescent fibroblasts and restore basement membrane integrity.¹⁹ In vitro studies further demonstrated that RF irradiation enhances the expression of genes that inhibit tyrosinase activity and promote lymphangiogenesis, addressing histopathological features commonly observed in melasma, including increased senescent fibroblasts, basement membrane disruption, pendulous melanocytes, and neovascularization.^20,21 Clinically, MNRF has demonstrated superior efficacy in recalcitrant melasma when combined with Q-switched Nd:YAG lasers, as shown in split-face trials compared with QS-Nd:YAG alone.^22–24 The combination group showed greater clinical improvement with minimal adverse effects. These outcomes are thought to result from a combination of dermal remodeling and pigment clearance mediated through transepidermal elimination and lymphatic drainage.

In non-insulated bipolar systems, RF energy is emitted between two adjacent active electrodes, generating localized thermal reactions that propagate upward from the distal part of each needle tip. This results in a teardrop- or cocoon-shaped coagulation zone within the dermis with minimal epidermal reaction, known as the “Na effect”. The selective extension of RF energy based on tissue impedance ensures that low-impedance structures, such as the epidermis, are relatively preserved, thereby reducing the risk of post-inflammatory complications.^18,25 Beyond solely thermal effects, non-insulated electrodes in bipolar systems can also induce electromagnetic-selective tissue reactions, leading to vascular modulation and remodeling of dermal structures.²⁶ These combined thermo-selective and electromagnetic effects enable broader dermal engagement compared to insulated electrodes, which confine energy only to the needle tips and predominantly generate localized coagulation. As a result, this pattern is particularly beneficial for EO, where ochronotic pigment deposits and dermal pathology are located throughout the upper to mid-dermis. As melasma and EO share key pathological features such as dermal pigment deposition, basement membrane disruption, and superficial telangiectasia, the therapeutic benefits of MNRF demonstrated in melasma may extend to EO through similar mechanisms.

We selected non-insulated bipolar MNRF (Sylfirm X plus, Viol, Gyeonggi, South Korea) for treating EO with underlying melasma. This machine allows precise needle depth adjustment from 0.3 to 4.0 mm, facilitating targeted delivery of RF energy directly into the dermis, corresponding to the typical depth of ochronotic pigment. PW mode was used to restore basement membrane disruption, enhance dermal microenvironment, and target pathological pigment deposits at histopathologically identified depths, promoting the elimination of scattered pigment via the transepidermal and lymphatic system. Meanwhile, CW mode, characterized by a longer duration RF energy delivery, was utilized to promote neocollagenesis, addressing the patient’s additional concerns related to skin texture and laxity. Furthermore, since MNRF does not interfere with chromophore absorption, it poses a lower risk of complications such as post-inflammatory hyper or hypopigmentation, which is common among patients with dark skin tones like EO patients. The treatment session is brief, well-tolerated, and requires minimal downtime.

This case highlights the MNRF’s potential in targeting hyperpigmented diseases by addressing key pathological factors within the upper dermis and basement membrane, including the basement membrane disruption, neovascularization, and senescent fibroblasts. The patient remained free of recurrence during the 12-week follow-up; however, the relatively short duration is a limitation. This case report only represents one patient, and longer observation is necessary to establish the durability of treatment outcomes. A repeat biopsy was not performed due to ethical and patient comfort considerations. Further research should investigate the association between exogenous ochronosis and dermal pathology while validating MNRF as a treatment option for this condition.

Conclusion

This is the first report using MNRF for exogenous ochronosis. After three sessions of dual-wave bipolar non-insulated MNRF, a noticeable reduction of ochronotic pigments and improvement in overall skin quality with no serious side effects were observed. Non-insulated MNRF may be valuable for patients with darker skin types at higher risk of laser complications.