Published on 19/03/2015 by admin
Filed under Dermatology
Last modified 22/04/2025
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Waseem Bakkour, Loma S. Gardner and Ian Coulson
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Cutaneous leiomyomas are rare benign neoplasms originating from smooth muscle. Three types exist: (1) piloleiomyoma, the most common type, arising from the arrectores pilorum muscle; (2) dartoic myoma or genital leiomyoma, arising from scrotal/labial dartos muscle or smooth muscle of the nipple; and (3) angioleiomyoma, arising from vascular wall muscle. Piloleiomyoma frequently occur as multiple lesions (80%). Multiple leiomyomas can be inherited in an autosomal dominant fashion in association with uterine leiomyoma (Reed syndrome, multiple cutaneous and uterine leiomyomata [MCUL1; OMIM 150800]). Familial multiple leiomyomata can rarely be associated with renal cell cancer (hereditary leiomyomatosis and renal cell cancer [HLRCC; OMIM 605839]). Both familial forms are caused by mutations in the fumarate hydratase gene (coding for an enzyme in the tricarboxylic acid cycle) on 1q42.1, which is hypothesized to act as a tumor suppressor gene through an unknown mechanism. Clinically, cutaneous leiomyomas present as flesh-colored or brownish-red dermal papules or nodules up to 2 cm in diameter, typically distributed on the trunk and extensor surfaces of extremities. They often appear from the second to fourth decade and gradually increase in number and size. Paroxysmal pain, described as stabbing, burning, or pinching, may be triggered by cold or mechanical stimulation and is possibly due to muscle contraction or compression of entrapped nerves. Angioleiomyomas are less frequently symptomatic, whilst genital leiomyomas are asymptomatic.
Symptomatic solitary lesions are best excised. Symptomatic multiple leiomyomas are therapeutically challenging because they involve a large area and recur after excision in 50% of cases. Selective excision of larger painful lesions may be considered, but patients warned of the relatively high chance or recurrence. CO2 laser ablation of symptomatic lesions may be successful. Other therapeutic methods aim to inhibit smooth muscle contraction, and thus pain, by interfering with local tissue mediators, e.g., norepinephrine, epinephrine, and acetylcholine. There are reports of success with oral doxazosin (a selective α1-blocker) 1–4 mg daily, oral nifedipine (calcium channel blocker) 10 mg three times daily, phenoxybenzamine (non-selective α-blocker) 10 mg twice daily, topical 9% hyoscine hydrobromide (anticholinergic), and oral glyceryl trinitrate (nitroglycerin) 0.8–1.6 mg as needed. Analgesics that target neuropathic pain, e.g., oral gabapentin 300 mg three times daily, have been beneficial. Potential triggers should be avoided.
Women, particularly those with a family history, should undergo gynecologic review to exclude possible uterine involvement (‘fibroids’). Menorrhagia may necessitate hysterectomy, and leiomyosarcoma, although rare, should be excluded. Potential familial forms require referral to a clinical geneticist with informed consent for mutational analysis of the fumarate hydratase gene. Individuals felt to have HLRCC will require renal ultrasound surveillance to detect the development of renal tumors.
Biopsy
Biochemical assay of fumarate hydratase – for low/absent activity
Genetic analysis – for fumarate hydratase gene mutations
Holst VA, Junkins-Hopkins JM, Elenitas R. J Am Acad Dermatol 2002; 46: 477–90.
A well-referenced review covering leiomyoma and angioleiomyoma. On histologic examination, leiomyomas stained with special stains such as Masson trichrome reveal brick-red smooth muscle fibers. Immunohistochemical techniques demonstrating desmin, smooth-muscle actin, or muscle-specific actin confirm tumor origin.
Tomlinson IP, Alam NA, Rowan AJ, Barclay E, Jaeger EE, Kelsell D, et al. Multiple Leiomyoma Consortium. Nature Genet 2002; 30: 406–10.
The authors demonstrate that the gene predisposing to uterine fibroids, cutaneous leiomyoma, and renal cell carcinoma encodes fumarate hydratase. This enzyme acts as a tumor suppressor in familial leiomyomas, and its measured activity in the tumor is very low or absent. Mutations of the fumarate hydratase gene are found in individuals with dominantly inherited susceptibilities to multiple cutaneous and uterine leiomyomatosis and renal cancer.
Parmentier L, Tomlinson I, Happle R, Borradori L. Dermatology 2010; 221: 149–53.
A novel mutation c.695delG, leading to a truncated protein p.Gly232AspfsX24, was found.
Fisher WC, Helwig EB. Arch Dermatol 1963; 88: 510–20.
The clinical findings and natural course of 54 cutaneous leiomyomas from 38 patients are described. Surgically excised leiomyomas were found to have a high recurrence rate of 50%.
The rarity of the condition means that most publications on therapy are case reports. The therapeutic agents are not consistently effective.
Batchelor RJ, Lyon CC, Highet AS. Br J Dermatol 2004; 150: 775–6.
Two women with symptomatic cutaneous leiomyoma, were treated with oral doxazosin 1–4 mg daily, a reversible α1-blocker which, unlike phenoxybenzamine, is selective. Doxazosin was well tolerated and patients experienced ‘dramatic improvement’/complete relief of symptoms that was sustained for 6 months in one patient.
Archer CB, Whittaker S, Greaves MW. Br J Dermatol 1988; 118: 255–60.
Two cases of cutaneous leiomyoma. One patient responded only to phenoxybenzamine 10 mg twice daily and the other responded to hyoscine hydrobromide (the response lasted only 6 hours). The latter patient also improved with cryotherapy.
Venencie PY, Puissant A, Boffa GA, Sohier J, Duperrat B. Br J Dermatol 1982; 107: 483–6.
A 41-year-old woman with leiomyomas who had complete pain relief 10 days after commencing phenoxybenzamine 10 mg twice daily, sustained throughout 7 months of follow-up.
Thompson JA. J Am Acad Dermatol 1985; 13: 865–7.
A 24-year-old man with multiple painful leiomyomas treated successfully with nifedipine 10 mg three times daily for 8 months. The dosage was increased to 10 mg four times daily following the onset of cool weather and increased pain.
Abraham Z, Cohen A, Haim S. Dermatologica 1983; 166: 255–6.
A 21-year-old man with multiple cutaneous leiomyomas who had complete pain relief and partial involution of the lesions with nifedipine 10 mg three times daily, during 5 months of follow-up.
Engelke H, Christophers E. Acta Derm Venereol 1979; 59: 51–4.
A woman with cutaneous leiomyoma that responded to oral glyceryl trinitrate 0.8–1.6 mg for acute attacks, with maintenance nifedipine 20 mg and phenoxybenzamine 60 mg administered during 2 years of follow-up.
Alam M, Rabinowitz AD, Engler DE. J Am Acad Dermatol 2002; 46: S27–9.
A 54-year-old woman with numerous cutaneous leiomyomas who experienced near complete pain relief with gabapentin 300 mg three times daily introduced gradually.
Kostopanagiotou G, Arvaniti C, Kitsiou MC, Apostolaki S, Chatzimichael K, Matsota P. J Pain Symptom Manage 2009; 38: e3–e5.
A combination of pregabalin 600 mg daily and duloxetine 60 mg daily was used successfully to treat a 34-year-old woman with multiple leiomyomas. This produced complete pain relief that was maintained over 12 months follow-up period.
Onder M, Adısxen E. J Am Acad Dermatol 2009; 60: 325–8.
A 35-year-old female with multiple leiomyomas was treated with intralesional botulinum toxin A. This reduced the severity and frequency of pain over a 3-month period.
Sifaki MK, Krueger-Krasagakis S, Koutsopoulos A, Evangelou GI, Tosca AD. Dermatology 2009; 218: 44–7.
A patient with multiple cutaneous piloleiomyomas was treated with botulinum toxin A injections 3-monthly for 2 years. There was a rapid and sustained decrease in pain.
Christenson LJ, Smith K, Arpey CJ. Dermatol Surg 2000; 26: 319–22.
A 73-year-old woman not eligible for pharmacologic therapy who had multiple cutaneous leiomyomas. CO2 laser ablation of six symptomatic cutaneous leiomyomas induced complete pain relief that was sustained during 9 months of follow-up.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
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Surgical excision
Doxazosin
Phenoxybenzamine
Topical hyoscine hydrobromide
Nifedipine
Oral glyceryl trinitrate
Cryotherapy
Simple analgesics
Gabapentin
Duloxetine
Botulinum toxin A
CO2 laser
