CASE
REPORT
Treatment of cutaneous leiomyomas with 5% lidocaine patches in a patient with hereditary leiomyomatosis and renal cell cancer (Reed syndrome) Tina Hsu, BA,a Lynn A. Cornelius, MD,b Ilana S. Rosman, MD,b,c and Kathleen M. Nemer, MDb St. Louis, Missouri Key words: cutaneous leiomyomas; hereditary leiomyomatosis and renal cell cancer; lidocaine patches; Reed syndrome.
INTRODUCTION Hereditary leiomyomatosis and renal cell cancer (HLRCC) (formerly known as Reed syndrome, multiple cutaneous and uterine leiomyomatosis, leiomyomatosis cutis et uteri, and multiple leiomyomatosis) is an autosomal dominant syndrome comprising cutaneous leiomyomas, uterine leiomyomas, or renal tumors. The cutaneous leiomyomas of HLRCC are classically painful and difficult to treat. We report the first case, to our knowledge, of cutaneous leiomyomas symptomatically treated with 5% lidocaine patches.
Abbreviation used: HLRCC:
hereditary leiomyomatosis and renal cell cancer
REPORT OF A CASE A 37-year-old white woman presented with painful lesions on the trunk and extremities of 3 years’ duration. These lesions intermittently ached and itched, especially when bumped, scratched, or exposed to cold. Symptoms worsened with fatigue and stress. Her father suffered from similar lesions. Physical examination found numerous smooth, firm, pink dermal papules and nodules. These were grouped in tight clusters on the upper back, right shoulder, and left thigh (Fig 1). A skin biopsy was performed from the upper back. Histopathology found a well-circumscribed proliferation of fascicles of spindle cells that stained positive with smooth muscle actin immunohistochemistry (Fig 2, A and B) compatible with cutaneous leiomyoma. Before presentation, the patient struggled with menorrhagia and infertility secondary to From the Division of Dermatologyb and Department of Pathology and Immunology,c Washington University School of Medicine.a Funding sources: None. Conflicts of interest: None declared. Correspondence to: Kathleen M. Nemer, MD, Division of Dermatology, Washington University School of Medicine, 660 S Euclid Ave, Campus Box 8123, St Louis, MO 63110. E-mail: [email protected].
Fig 1. Clinical image of cutaneous leiomyomas. Numerous smooth, firm, pink dermal papules and nodules coalescing into plaques on the left upper back.
uterine fibroids, necessitating myomectomy. Uterine pathology found a large smooth muscle neoplasm with focal atypia, compatible with atypical uterine leiomyoma (Fig 2, C and D). Images of the kidneys were normal. The patient was referred for genetic testing, and analysis of the fumarate hydratase gene found a pathogenic FH mutation. Her clinical, genetic, and histopathologic findings were consistent with a diagnosis of HLRCC. JAAD Case Reports 2017;3:407-9. 2352-5126 Ó 2017 by the American Academy of Dermatology, Inc. Published by Elsevier, Inc. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/). http://dx.doi.org/10.1016/j.jdcr.2017.06.007
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408 Hsu et al
JAAD CASE REPORTS
SEPTEMBER 2017
Fig 2. Histopathology A and B, Cutaneous leiomyoma: there is a well-circumscribed dermal proliferation composed of fascicles of spindle cells that stain diffusely with smooth muscle actin immunohistochemistry. (A, Hematoxylin-eosin stain; B, smooth muscle actin; original magnifications: A and B, 3100.) C and D, Atypical leiomyoma: in the uterus, there is a wellcircumscribed somewhat fascicular neoplasm composed of smooth muscle cells with mild pleomorphism. (C and D, Hematoxylin-eosin stain; original magnifications: C, 316; D, 3100.)
DISCUSSION HLRCC is characterized by cutaneous leiomyomas, early-onset uterine leiomyomas, and an increased risk of renal cell carcinoma. Renal cell carcinoma is a serious complication of HLRCC but present in only 10% to 15% of individuals.1 In contrast, cutaneous leiomyomas are present in all patients. Eighty-nine percent of patients report lesion-associated pain, characteristically precipitated by heat/cold, trauma, or light touch.2 Cutaneous leiomyomas do not resolve spontaneously; thus, symptoms should guide treatment. In mild cases, avoidance of painful triggers may be sufficient. Painful lesions can be treated with excision; however, this treatment has a high rate of recurrence, may necessitate skin grafting with an undesired cosmetic outcome, and may be impractical, as leiomyomas tend to group together in larger ‘‘school-of-fish’’ arrays. Destructive techniques such as electrodessication, cryotherapy, and radiotherapy have been used with varying results and are complicated by scarring, hypopigmentation, and incomplete removal.2-4 Medications such as nitroglycerin, nifedipine, phenoxybenzamine, doxazosin, and gabapentin have been used with limited-to-moderate
success in providing periodic pain relief by decreasing smooth muscle contraction and nerve stimulation.2-4 However, some of these medications can provoke systemic side effects. Newer therapeutic options include botulinum toxin injection and carbon dioxide laser ablation,3,4 but these procedures are often expensive and, in the case of botulinum toxin injection, have not found a significant decrease in average lesional pain or pain after ice provocation.5 Our patient’s main concern was pain relief, which she was unable to achieve with daily nonsteroidal anti-inflammatory medications. She preferred a noninvasive, nondisfiguring approach and was started on 5% lidocaine patches. She easily cut the patches to size and applied them topically for pain relief. Each patch is 10 3 14 cm with an adhesive layer of 5% lidocaine (700 mg per patch). Up to 3 patches can be applied for 12 hours within a 24-hour period.6 On a pain scale of 0 to 10 (0 = no pain, 10 = the worst pain possible), a single patch reduced her pain from 5 to 0. After using the patches for several months, the patient’s pain frequency significantly decreased from a patch application of 1 to 3 times per week to once every 1 to 2 months.
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Hsu et al 409
VOLUME 3, NUMBER 5
Topical lidocaine treats localized pain by decreasing the transmission of excitatory pain and itch impulses to the dorsal horn of the spinal cord.7 Lidocaine patches are inexpensive and easily transportable and can be customized to size. Systemic adverse reactions are rare because of the small dose absorbed.6 Our patient reported a significant decrease in severity and frequency of pain and has found lidocaine patches to be a preferable treatment to oral medications. Lidocaine patches provide an alternate noninvasive, safe, and effective treatment for painful cutaneous leiomyomas. The authors thank the patient for granting permission to publish this article. REFERENCES 1. Toro JR, Nickerson ML, Wei M-H, et al. Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis
2.
3.
4.
5.
6. 7.
and renal cell cancer in families in North America. Am J Hum Genet. 2003;73(1):95-106. Alam NA, Barclay E, Rowan AJ, et al. Clinical features of multiple cutaneous and uterine leiomyomatosis: an underdiagnosed tumor syndrome. Arch Dermatol. 2005;141(2): 199-206. Basendwh MA, Fatani M, Baltow B. Reed’s Syndrome: A Case of multiple cutaneous leiomyomas treated with liquid nitrogen cryotherapy. Case Rep Dermatol. 2016;8(1):65-70. Emer JJ, Solomon S, Mercer SE. Reed’s syndrome: A case of multiple cutaneous and uterine leiomyomas. J Clin Aesthet Dermatol. 2011;4(12):37-42. Naik HB, Steinberg SM, Middelton LA, et al. Efficacy of intralesional botulinum toxin A for treatment of painful cutaneous leiomyomas. JAMA Dermatol. 2015;151(10):1096. Lidoderm (lidocaine patch 5%). Malvern (PA): Endo Pharmaceuticals, Inc; 2015 Jan. Package insert. NDC 63481-687-06. Inan S, Dun NJ, Cowan A. Inhibitory effect of lidocaine on pain and itch using formalin-induced nociception and 5???-guanidinonaltrindole-induced scratching models in mice: Behavioral and neuroanatomical evidence. Eur J Pharmacol. 2009; 616(1-3):141-146.
REPORT
Treatment of cutaneous leiomyomas with 5% lidocaine patches in a patient with hereditary leiomyomatosis and renal cell cancer (Reed syndrome) Tina Hsu, BA,a Lynn A. Cornelius, MD,b Ilana S. Rosman, MD,b,c and Kathleen M. Nemer, MDb St. Louis, Missouri Key words: cutaneous leiomyomas; hereditary leiomyomatosis and renal cell cancer; lidocaine patches; Reed syndrome.
INTRODUCTION Hereditary leiomyomatosis and renal cell cancer (HLRCC) (formerly known as Reed syndrome, multiple cutaneous and uterine leiomyomatosis, leiomyomatosis cutis et uteri, and multiple leiomyomatosis) is an autosomal dominant syndrome comprising cutaneous leiomyomas, uterine leiomyomas, or renal tumors. The cutaneous leiomyomas of HLRCC are classically painful and difficult to treat. We report the first case, to our knowledge, of cutaneous leiomyomas symptomatically treated with 5% lidocaine patches.
Abbreviation used: HLRCC:
hereditary leiomyomatosis and renal cell cancer
REPORT OF A CASE A 37-year-old white woman presented with painful lesions on the trunk and extremities of 3 years’ duration. These lesions intermittently ached and itched, especially when bumped, scratched, or exposed to cold. Symptoms worsened with fatigue and stress. Her father suffered from similar lesions. Physical examination found numerous smooth, firm, pink dermal papules and nodules. These were grouped in tight clusters on the upper back, right shoulder, and left thigh (Fig 1). A skin biopsy was performed from the upper back. Histopathology found a well-circumscribed proliferation of fascicles of spindle cells that stained positive with smooth muscle actin immunohistochemistry (Fig 2, A and B) compatible with cutaneous leiomyoma. Before presentation, the patient struggled with menorrhagia and infertility secondary to From the Division of Dermatologyb and Department of Pathology and Immunology,c Washington University School of Medicine.a Funding sources: None. Conflicts of interest: None declared. Correspondence to: Kathleen M. Nemer, MD, Division of Dermatology, Washington University School of Medicine, 660 S Euclid Ave, Campus Box 8123, St Louis, MO 63110. E-mail: [email protected].
Fig 1. Clinical image of cutaneous leiomyomas. Numerous smooth, firm, pink dermal papules and nodules coalescing into plaques on the left upper back.
uterine fibroids, necessitating myomectomy. Uterine pathology found a large smooth muscle neoplasm with focal atypia, compatible with atypical uterine leiomyoma (Fig 2, C and D). Images of the kidneys were normal. The patient was referred for genetic testing, and analysis of the fumarate hydratase gene found a pathogenic FH mutation. Her clinical, genetic, and histopathologic findings were consistent with a diagnosis of HLRCC. JAAD Case Reports 2017;3:407-9. 2352-5126 Ó 2017 by the American Academy of Dermatology, Inc. Published by Elsevier, Inc. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/). http://dx.doi.org/10.1016/j.jdcr.2017.06.007
407
408 Hsu et al
JAAD CASE REPORTS
SEPTEMBER 2017
Fig 2. Histopathology A and B, Cutaneous leiomyoma: there is a well-circumscribed dermal proliferation composed of fascicles of spindle cells that stain diffusely with smooth muscle actin immunohistochemistry. (A, Hematoxylin-eosin stain; B, smooth muscle actin; original magnifications: A and B, 3100.) C and D, Atypical leiomyoma: in the uterus, there is a wellcircumscribed somewhat fascicular neoplasm composed of smooth muscle cells with mild pleomorphism. (C and D, Hematoxylin-eosin stain; original magnifications: C, 316; D, 3100.)
DISCUSSION HLRCC is characterized by cutaneous leiomyomas, early-onset uterine leiomyomas, and an increased risk of renal cell carcinoma. Renal cell carcinoma is a serious complication of HLRCC but present in only 10% to 15% of individuals.1 In contrast, cutaneous leiomyomas are present in all patients. Eighty-nine percent of patients report lesion-associated pain, characteristically precipitated by heat/cold, trauma, or light touch.2 Cutaneous leiomyomas do not resolve spontaneously; thus, symptoms should guide treatment. In mild cases, avoidance of painful triggers may be sufficient. Painful lesions can be treated with excision; however, this treatment has a high rate of recurrence, may necessitate skin grafting with an undesired cosmetic outcome, and may be impractical, as leiomyomas tend to group together in larger ‘‘school-of-fish’’ arrays. Destructive techniques such as electrodessication, cryotherapy, and radiotherapy have been used with varying results and are complicated by scarring, hypopigmentation, and incomplete removal.2-4 Medications such as nitroglycerin, nifedipine, phenoxybenzamine, doxazosin, and gabapentin have been used with limited-to-moderate
success in providing periodic pain relief by decreasing smooth muscle contraction and nerve stimulation.2-4 However, some of these medications can provoke systemic side effects. Newer therapeutic options include botulinum toxin injection and carbon dioxide laser ablation,3,4 but these procedures are often expensive and, in the case of botulinum toxin injection, have not found a significant decrease in average lesional pain or pain after ice provocation.5 Our patient’s main concern was pain relief, which she was unable to achieve with daily nonsteroidal anti-inflammatory medications. She preferred a noninvasive, nondisfiguring approach and was started on 5% lidocaine patches. She easily cut the patches to size and applied them topically for pain relief. Each patch is 10 3 14 cm with an adhesive layer of 5% lidocaine (700 mg per patch). Up to 3 patches can be applied for 12 hours within a 24-hour period.6 On a pain scale of 0 to 10 (0 = no pain, 10 = the worst pain possible), a single patch reduced her pain from 5 to 0. After using the patches for several months, the patient’s pain frequency significantly decreased from a patch application of 1 to 3 times per week to once every 1 to 2 months.
JAAD CASE REPORTS
Hsu et al 409
VOLUME 3, NUMBER 5
Topical lidocaine treats localized pain by decreasing the transmission of excitatory pain and itch impulses to the dorsal horn of the spinal cord.7 Lidocaine patches are inexpensive and easily transportable and can be customized to size. Systemic adverse reactions are rare because of the small dose absorbed.6 Our patient reported a significant decrease in severity and frequency of pain and has found lidocaine patches to be a preferable treatment to oral medications. Lidocaine patches provide an alternate noninvasive, safe, and effective treatment for painful cutaneous leiomyomas. The authors thank the patient for granting permission to publish this article. REFERENCES 1. Toro JR, Nickerson ML, Wei M-H, et al. Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis
2.
3.
4.
5.
6. 7.
and renal cell cancer in families in North America. Am J Hum Genet. 2003;73(1):95-106. Alam NA, Barclay E, Rowan AJ, et al. Clinical features of multiple cutaneous and uterine leiomyomatosis: an underdiagnosed tumor syndrome. Arch Dermatol. 2005;141(2): 199-206. Basendwh MA, Fatani M, Baltow B. Reed’s Syndrome: A Case of multiple cutaneous leiomyomas treated with liquid nitrogen cryotherapy. Case Rep Dermatol. 2016;8(1):65-70. Emer JJ, Solomon S, Mercer SE. Reed’s syndrome: A case of multiple cutaneous and uterine leiomyomas. J Clin Aesthet Dermatol. 2011;4(12):37-42. Naik HB, Steinberg SM, Middelton LA, et al. Efficacy of intralesional botulinum toxin A for treatment of painful cutaneous leiomyomas. JAMA Dermatol. 2015;151(10):1096. Lidoderm (lidocaine patch 5%). Malvern (PA): Endo Pharmaceuticals, Inc; 2015 Jan. Package insert. NDC 63481-687-06. Inan S, Dun NJ, Cowan A. Inhibitory effect of lidocaine on pain and itch using formalin-induced nociception and 5???-guanidinonaltrindole-induced scratching models in mice: Behavioral and neuroanatomical evidence. Eur J Pharmacol. 2009; 616(1-3):141-146.
