Botulinum Toxin Injections as a Treatment of Refractory Vulvodynia in Adolescents: A Case Series.

We describe 3 adolescents who presented to our pediatric tertiary care center between 2018 and 2021 with vulvodynia refractory to multimodal management who were treated with transvaginal injections of BT into the pelvic floor. IRB approval was not required.

An 18-year-old girl presented with vulvar discomfort for “as long as [she] can remember.” She initially reported pain only when provoked. At age 14 years, she was evaluated for severe pain with attempt at tampon insertion, and Q-tip touch of her external genitalia elicited pain. She underwent a hymenotomy and reported unprovoked severe vulvodynia thereafter, which she described as constant, burning soreness with occasional “stab” sensations. This was exacerbated by prolonged sitting and tight clothing (including underwear), and pain caused missed school. Menstruation was associated with dyschezia, dysuria, and exacerbation of vulvodynia and chronic abdominal pain. Her past medical history was significant for major depressive disorder, generalized anxiety disorder, and pelvic floor dysfunction. Family history was significant for surgically-diagnosed endometriosis in her mother. A trial of continuous oral contraceptive pills for menstrual suppression was discontinued due to persistent breakthrough bleeding and no improvement of pain. Oral gabapentin initially decreased pain but subsequently was ineffective despite dosage increase and addition of tizanidine. Duloxetine, rectal diazepam suppositories (due to intolerance of vaginal insertion), and topical estrogen/testosterone gel did not improve pain. Pain improved immediately after physical therapy (PT) sessions but recurred the following day. Given chronic abdominal pain exacerbated by menstruation and a family history of endometriosis, the possibility of endometriosis was discussed, and she began continuous contraceptive patches for menstrual suppression. Two months later, she reported improvement in abdominal pain but not in vulvar pain. Oral amitriptyline was added. Four months later, the patient underwent pudendal nerve block and injection of BT in the pelvic floor musculature and perineum under anesthesia. She returned 2 months later reporting an initial significant decrease in pain, particularly in her clitoris. At 9-month follow-up, the patient reported significant improvement in her vulvar pain (with some pain-free days and severe pain reduced to once weekly) and resolution of menstrual pain ( Table 1 ). She opted to continue treatment with the contraceptive patch, pelvic floor PT, and amitriptyline. A 15-year-old girl presented at age 11 years with a 13-month history of chronic pelvic, vulvar, and clitoral pain. A month after her onset of pain at age 10 years, imaging showed abnormality of spine and lipoma, and she underwent laminectomy and debulking of lipoma. Following the surgery, she reported no change in pain, which she described as constant sharp stabbing pain inside her vagina with intermittent worsening, cramping, pressure, or the feeling of rocks in her pelvis. Due to extreme pain to vulvar touch, she was unable to wear pants for 6 months and underwear for 1 year and had stopped showering for 6 months and bathing for 1 year before presentation. She was unable to walk, used a wheelchair, and did not participate in any activity due to increased pain with movement. She did not yet have regular menses, reporting a day of spotting 6 months prior. Her past medical history was significant for urinary hesitancy with intermittent overflow incontinence since laminectomy and debulking of lipoma. Pelvic floor PT was discontinued after 8 months due to discomfort and no improvement of pain. External pudendal nerve block did not improve pain. A trial of gabapentin, quetiapine, and duloxetine initially resulted in improvement until symptoms began to worsen after 6 months. She was prescribed a TENS unit that did not decrease symptoms. Given no improvement in symptoms and the concern for exacerbation of pain with menstruation, she underwent injection of BT in the urethral sphincter and pelvic floor, pudendal nerve block with bupivacaine, and insertion of a 52 mg levonorgestrel-releasing IUD under anesthesia. For approximately 24 hours after the procedure, she reported complete resolution of vulvodynia. She was able to bathe for the first time in over 1 year, wear pants, and sleep well. The sensitivity returned the following day but remained improved ( Table 1 ). She has been able to shower daily, wear underwear and pants, and go to school. When discussing symptoms, thinking of traveling, or getting ready for an appointment, she reports that her pain returns and is unbearable, likely due to anxiety. She had 3 additional injections of botulinum toxin to the pelvic floor over the next 3 years with good response. She no longer requires a wheelchair and can exercise on a treadmill. She has opted to continue treatment with BT injections, which she now typically requires every 12 months. A 12-year-old girl presented with a 2-year history of vulvodynia, which she described as itchy and like “sitting on a ball.” The pain started one month before menarche and was exacerbated by heat, walking, and prolonged sitting. She had to wear loose bottoms and reduce participation in dance class. She was otherwise healthy and has no significant past medical history. She was initially treated for yeast vaginitis by her primary care provider. Due to persistent symptoms, she subsequently trialed gabapentin, fluconazole, lidocaine cream, hydrocortisone, compound cream of gabapentin/amitriptyline/ketamine, and doxepin with no improvement in her pain. She was also referred for pelvic floor PT. Given that the persistence of pain was affecting her quality of life (i.e., decreased sleep and participation in dance class, difficulty concentrating at school), she underwent examination under anesthesia with pudendal nerve block and injection of BT into pelvic floor musculature. Although her pain completely resolved immediately post-procedure, the soreness and pain recurred after 2 days ( Table 1 ). Two weeks later, she started experiencing a different type of “shock”-like pain originating in the lower abdomen/pelvis and radiating to the external genital area. The pain was triggered by prolonged sitting, occurred throughout the day, and sometimes woke her at night, lasting 30 minutes. She currently is not taking any medications, continues with pelvic PT, and has resumed a regular dance class schedule.

While there is increasing awareness of vulvar pain disorders in children and adolescents, optimal management remains poorly defined, and recommended treatments, including topical anesthetics, neuromodulators, and pelvic floor PT, mirror those of adults. 2 BT has been used for the treatment of vulvodynia in adults with satisfactory results, albeit at varying sites and doses which precludes generalizability. Yoon et al. reported a resolution of pain in 7 adults after single or repeated injections of 20 to 40 U BT in the vestibule, levator ani muscle, or perineal body, with mean follow-up of 11.6 months. 5 Pelletier et al. reported a significant reduction of pain 3 and 6 months after 20 adult patients with provoked vestibulodynia received 50 U BT injections bilaterally in the bulbospongiosus muscle. 6 However, in a randomized controlled trial of 64 adults who received injection of 20 U BT or saline in the bulbospongiosus, both groups reported significant pain reduction with no difference between the groups, calling into question the efficacy of BT in the treatment of vulvodynia. 7 While BT injections have been used to successfully treat neuropathic pain in areas of hypersensitivity or allodynia in chronic pain conditions including occipital neuralgia and complex regional pain syndrome, there remains a lack of consensus as to optimal injection sites for the treatment of vulvodynia. 8 The analgesic effects of BT are not instantaneous and the immediate decrease in symptoms in our patients was likely due to the use of bupivacaine or ropivaciane for the pudental nerve block. Historically, the analgesic effect of BT was thought to be due to muscle relaxation. More recent studies demonstrate that BT inhibits the release of neurotransmitters that regulate pain and inflammation. 8 BT injections into the pelvic floor musculature affect pelvic somatic and visceral nerves that may participate in pain signaling. The variable response to BT injections in this case series may reflect non-standardized injection sites resulting in differential interference with signal transmission of nociceptive neurons and anti-neuroinflammatory effect within pain signaling pathways ( Table 1 , Figure 1 ). A more targeted approach towards involved nociceptive fields as could be elicited by palpation of the pelvic floor musculature to identify trigger points immediately prior to the administration of general anesthesia followed by BT injections within these defined areas may yield better results in the treatment of vulvodynia. The management of vulvodynia in children and adolescents can be difficult. In select adolescent patients with vulvodynia, transvaginal BT injection into the pelvic floor may be a useful adjunct to other therapies. However, care must be taken given the lack of available data regarding patient selection, optimal dosing, frequency, and sites of BT injections. Although quality of life was not assessed with validated questionnaires, the patients in this series reported increased participation in school and activities after the procedure. Further studies are needed to assess the safety and efficacy of BT injections in the treatment of vulvodynia in pediatric and adolescent patients.

Vulvodynia includes varied manifestations of vulvar discomfort that occur in the absence of an identifiable cause. It presents in girls and women of all ages and is most often described as burning pain that may be generalized (i.e., throughout vulva) or localized (e.g., clitoral) and may spontaneously occur or be provoked (e.g., tight clothes, touch). 1 Premenarchal girls with vulvodynia are more likely to present with abnormal vaginal sensations such as nocturnal stabbing pain or bubbling sensations, whereas postmenarchal girls are more likely to present with dyspareunia or pain inserting tampons. 2 Although vulvodynia can severely diminish quality of life, there is currently a paucity of literature on the optimal treatment of vulvodynia in adolescents, and recommendations are based largely on a multimodal approach to treatment in adults. 3 Approximately 15% of patients have no improvement of symptoms with therapy including neuromodulators and PT. 2 Transvaginal botulinum toxin (BT) injection into the pelvic floor ( Figure 1 ) has been proposed as a possible treatment because vulvodynia is often accompanied by myofascial pain and pelvic floor tension. By reducing muscle tone and preventing further muscle spasm, BT injections have successfully been used to treat myofascial pain in other locations of the body, including cervical and shoulder muscles and the lower back. 4 BT injections have been found to be a safe, effective treatment for provoked vulvodynia in adult patients, reducing pain and improving quality of life and sexual function. 5 , 6 Data on the safety and efficacy of BT injections for the treatment of vulvodynia in adolescents is limited.