Treatment of cutaneous leiomyomas with botulinum toxin. Case report and review of literature.

Abstract

A 36-year-old male with clinical and genetic diagnose of hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) also known as Reed syndrome (p.Arg233Cys pathogenic variant in FH gen, associated with HLRCC), consulted for a 6 years' history of multiple painful lesions in his back. In physical examination multiple skin-color papules arranged in plaques in scapular area and lumbar region were observed (Figure 1B–D). Screening for associated neoplasm showed no malignancy, including an abdominal MRI for RCC screening with subsequently annual MRI. Skin biopsy was performed showing a non-encapsulated tumor composed of bundles of smooth muscle arranged in an interlacing pattern, compatible with cutaneous leiomyoma (Figure 1A). Treatment with oral analgesics was not effective. Due to persistence of intense pain, we performed an intralesional botulinum toxin A (BTA) injection, 2 IU per lesion (12 lesions were treated from 0.4 to 1.2 cm) after reconstitution of 100 BTA IU vial in 5 ml of saline serum 0.9% (20 IU/ml). We performed an intradermal injection with a 30G needle. The technique was well tolerated, with only mild pain reported, and immediate pain relief was achieved, with very little episodes in the following 2 months, with progressive loss of efficacy. Treatment has been repeated every 3 months for 1.5 years maintaining an excellent response. Leiomyomas are the most common smooth muscle tumors. Cutaneous leiomyomas (CLM) are divided into three categories: piloleiomyomas (arising from the arrector pili muscle), genital leiomyomas, and angioleiomyomas.1 CLM may occur sporadically or in association with renal cell cancer in an autosomal dominant with incomplete penetrance disorder called HLRCC. It is characterized by multiple CLM, uterine leiomyomas and increase risk of renal cell carcinoma. Clinically, CLM are characterized by solitary or multiple flesh-color, erythematous or hyperpigmented firm papules, generally smaller than 1.5 cm that may be clustered in plaques. Around 90% of CLM are reported to be painful.2 Pain may be triggered spontaneously or in response to cold, trauma, emotional stress or mild touch and may affect severely the quality of life.3 Pain mechanism associated with CLM is unclear. It may be related to augmented neuropeptide release (such as calcitonine gene-related peptide, involved in pain conduction), pressure on nerve fibers within the lesions4 or for the contraction of the arrector pili muscle.5 Surgery is the gold standard treatment (even its high rate of recurrence after excision). However, multiple lesions or poor aesthetic results may be a limitation to a surgical approach. In these cases CO2 ablation laser, cryotherapy, or intralesional BTA injection has shown some efficacy in pain relief. BTA has been used in the management of several chronic pain syndromes.6 It is a neuropeptide which blocks the release of acetylcholine at the neuromuscular junction resulting in decreased muscle tone, even in smooth muscle, reducing muscle spasms. BTA may also inhibits the release of pain related neuropeptides including substance P, CGRP, and glutamate, resulting in the inhibition of peripheral sensibilization.7 BTA has been reported to be effective in two case reports of treatment of CLM in HLRCC,8, 9 with injection of 5–20 units per lesion with a decrease of pain intensity and frequency of attacks between 1 month8 and 3 months9 after injection, with progressive relapse and need of repeated treatments. Naik et al.5 presents the only randomized trial in CLM management including 18 patients, half of them received placebo and the other half received intralesional BTA intralesional (5 units per cm2). They reported statistical improvement in the skin related quality of life and in the specific skin-pain related question on DLQI as well as a non-statistically significant improvement in pain at rest and pain severity. In conclusion, treatment of CLM, especially when they are painful, may be challenging. If surgery is not an option due to its extension or poor aesthetic results, intralesional BTA is a safe and effective treatment for associated pain, maintaining its efficacy over repeated treatments. The authors declare no conflicts of interest. David Vega Díez has made significant contribution to literature search, data acquisition, manuscript preparation, and manuscript editing. Ana Rodríguez-Villa Lario has made significant contribution to concept, design, manuscript review, and guarantor. Marta González Cañete has made significant contribution to data acquisition, manuscript preparation, and manuscript review. María Dolores Vélez-Velazquez has made significant contribution to concepts, histological examination, definition of intellectual content, and manuscript review. Isabel Polo Rodríguez has made significant contribution to concepts, definition of intellectual content, design, and manuscript preparation and review. Susana Medina has made significant contribution to concepts, definition of intellectual content, design, and manuscript preparation and review. Written informed consent from the patients for the use of image and publication of their case details has been obtained by the authors. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.