The case of Botulinum toxin type A and depressed skin lesion: Case presentation, review of the literature, and definition proposal

INTRODUCTION

The injection of botulinum toxin A for the treatment of rhytidosis and upper face rejuvenation is a safe and reliable procedure, without major diverse effects.

The authors describe a variant of the already referred^1,2 development of “morphea-like” lesions as a side effect of its injection and suggest a definition.

CASE REPORT

A 51-year-old woman with a history of cosmetic injections with Abo-botulinum toxin Type A presented with a depressed skin area located in her right temple and underlying zygomatic area.

Her medical history listed an episode of encephalitis 3 years before, successfully treated; no other pathologies were referred.

She referred the onset 3 weeks after her last injection, in late October 2020, when she received 50 Speywood units to treat the glabella and 30 US for crow’s feet on each side, diluted on label.

An objective examination performed in late December 2020 revealed an oval, depressed skin lesion located in the para-canthal area, extending down to the zygoma, measuring 2 cm × 1 cm, with a regular border, well-defined limits, a smooth surface, and a pearly color [Figure 1].

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Figure 1:

Ovalar depressed skin lesion, located in the para-canthal area down to the zygoma, showing regular border, net limits, smooth surface, and pearly colour.

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An ultrasound evaluation performed in January 2021 did not reveal any pathological findings, while blood analysis detected no autoantibodies. Histological samples were therefore collected with any correlation to the one of linear scleroderma “en Coup de Sabre” (LSCS) [Figures 2-5].

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Figure 2:

Ex vivo sample of the lesion; Hematoxylin-Eosin stain, magnification ×2.5.

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Figure 3:

Ex vivo sample of the lesion; Hematoxylin-Eosin stain, magnification ×4.

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Figure 4:

Ex vivo sample of the lesion; Hematoxylin-Eosin stain, magnification ×10.

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Figure 5:

Ex vivo sample of the lesion; Perls stain, magnification ×4.

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The course of the lesion appeared to worsen, as its central part progressively enlarged over the following months [Figure 6].

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Figure 6:

Ovalar depressed skin lesion worsened with its central part looked progressively enlarged.

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In February 2021, she was sent for consultation to a dermatologist who excluded LSCS and suggested strict follow-up. In March 2021, she underwent magnetic resonance imaging (MRI) without specific findings.

The authors noticed progressive healing starting from May up to July, eventually ending up in some asymmetry of the temporal and zygomatic area with respect to the contralateral side [Figure 7].

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Figure 7:

Progressive healing of the ovalar depressed skin lesion.

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In November 2021, after the regression of the residual skin depression, the patient received additional botulinum toxin injection again, and surprisingly, she developed a lesion located contralaterally [Figure 8], smaller than the previous one but again in the temporal area.

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Figure 8:

Lesion located contralaterally, in the left temporal area.

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DISCUSSION

Atrophic lesions in patients who have received botulinum toxin injections have been reported with Ona-botulinum Toxin type A,¹ while Landau et al.,² did not point out the toxin injected in the three cases they even so referred.

It must be pointed out that a case of bilateral corrugator supercilii muscle atrophy is reported,¹ therefore related to any skin disease and confirmed as the same effect on procerus muscle too by the MRI case–control study³ and on temporalis muscle.⁴

The capability of the botulinum toxin type A to induce muscle atrophy and volume reduction for cosmetic purposes has been extensively examined,^5,6 with any structural change or induced pathological condition of the skin in the treated areas ever reported.

Landau et al.,² did not find a sound correlation with the development of the atrophic skin lesion and the action of the injected toxin, nothing more than a coincidence in time of its injection and lesion onset: Therefore, they brilliantly claim that the syringe lubricant could be responsible for the transient lesions.

LSCS is a descriptive term to denote atrophy and furrowing of the skin in the frontoparietal region of the face and scalp.

LSCS presents as a single, paramedian, band-like skin lesion associated with hypoplasia of the underlying structures and even hemiatrophy of the face, which has a slowly progressive course.⁷

The most common pattern often starts with contraction and stiffness of the affected area, forming a depressed groove as a single line near to the midline of the forehead, with a second line laterally terminating at the eyebrow and possibly a third one over the lateral forehead following Blaschko lines, possibly extending beyond the hairline in the scalp, eventually ending up in an area of linear alopecia.¹

Nevertheless, except for the traumatism caused by needle at the injection, none of the LSCS diagnostic conditions or findings could be identified in the presented patient; therefore, the statement of Landau et al.,² related to the uncertain pathophysiology of the reported condition must be confirmed even though it is authors’ opinion that the related role of botulinum toxin has rather to be clarified with respect to the available evidence of its efficacy in the treatment of morphea like lesions since 2016, both when located on the face^8-10 and even in case of body area,¹¹ that definitely point out a therapeutic role rather than causative.

The precipitating factor, also for the contralateral recurrence, appeared, in the authors’ opinion, to be the trauma induced by the injection, presumably both the puncture trauma and the stretching of the tissue caused by the injected solution.

It is therefore conceivable, given that the patient was not naive, that the skin of the temporal and periocular regions, thinner and with a less represented subcutaneous layer due to aging and multiple previous therapies, may have suffered more from the mechanical stress induced by the secondary dilation from the injection of the diluted solution. However, the histological and instrumental picture of the lesion only allows for the hypothesis of a possible causal link underlying its onset, as suggested by other cited authors.^2,4

The case herein described may represent an instance of a depressed cutaneous lesion secondary to botulinum toxin injection, occurring, however, outside the typical perimedial area most commonly documented in the literature. Furthermore, skin lesions relapsed contralaterally in the same patient.

As with every drug, pharmacovigilance is essential to ensure safety for both physicians and patients.

In the Authors’ opinion, considering the total number of botulinum toxin vials administered annually, it is appropriate to reconsider the terminology currently in use. Although the term “morphea-like” has been employed to clinically describe the lesions --without any accompanying systemic or histopathological findings --it may no longer be adequate.

Given that five cases have now been reported, including the one presented herein, all occurring after botulinum toxin type A injection (either Onabotulinum or Abobotulinum), the time has come to propose a more specific and standardized designation.

The Authors suggest naming these events simply as “Botulinum-Induced Skin Lesions (BotIS lesions)”, similar to the classification approach adopted for cutaneous reactions following COVID-19 vaccination. Notably, this proposal is made despite the current absence of a clearly defined pathogenic mechanism underlying these reactions, as previously noted in literature concerning both botulinum toxin type A and vaccine-related dermal events.^[12]

CONCLUSION

Skin lesions secondary to Botulinum toxin A injection are nowadays seldom reported but considering the large number of vials injected per year they number could raise as growing evidence.

Even if spontaneous healing is reported for some, it could take time therefore with some social impairment.

It is Auhtors’ opinion that awareness of the problem must be spread among practitioners as it will allow more attentive vigilance to rapidly diagnose the condition whilst further research will allow to define the role played by the drug and the host.