Published on 19/03/2015 by admin
Filed under Dermatology
Last modified 22/04/2025
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Jessica A. Kaffenberger and Joslyn S. Kirby
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Lichen myxedematosus (LM) is a rare, chronic disease characterized by infiltration of the skin with mucin-producing fibroblasts. Typical examination findings include shiny, flesh-colored to erythematous papules, nodules, and plaques. More extensive cutaneous disease can cause widespread thickening and hardening of the skin with large, raised folds. The disease favors the face and extremities. Localized and systemic subtypes of the disease are now recognized. The systemic form, scleromyxedema, is associated with a monoclonal IgG lambda gammopathy. Localized forms of the disease are limited to the skin, have a better prognosis and are not associated with paraproteinemia. Localized forms include acral persistent papular mucinosis, self-healing papular mucinosis, discrete LM, nodular LM, and cutaneous mucinosis of infancy. The cause of the disease is unknown.
The treatment of LM remains a challenge. The absence of any controlled studies makes comparison of different drugs or drug regimens difficult.
Localized forms may be observed or treated with topical medications such as topical calcineurin inhibitors or destructive therapies such as cryotherapy, dermabrasion, or hyaluronidase.
The systemic form, scleromyxedema, is treated more aggressively and patients may require treatment with multiple medications either serially or in combination before a successful therapy is found. Given the association between scleromyxedema and monoclonal gammopathy, some of the therapies for systemic LM are taken from the treatment of multiple myeloma. Melphalan is an alkylating agent generally prescribed as a pulse regimen of four times daily for 4 days every 4 to 6 weeks, or four times daily until symptoms resolve; however, its use is limited by secondary adverse effects including malignancy, sepsis, and death. Melphalan has also shown beneficial results when used in combination with other therapies including plasmapheresis, oral prednisone, or autologous stem cell transplant. Several other agents, including bortezomib, 2-chlorodeoxyadenosine (cladribine), cyclophosphamide, cyclosporine, methotrexate, and thalidomide, have demonstrated some efficacy.
Other alternatives to immunosuppressive agents include intravenous immunoglobulin (IVIG), isotretinoin, interferon-α2b, intralesional triamcinolone acetonide, psoralen with UVA (PUVA), and extracorporeal photochemotherapy.
Serum protein electrophoresis
Tests for HIV infection
Thyroid function testing
Tests for hepatitis C infection
Rongioletti F. Semin Cutan Med Surg 2006; 25: 100–4.
An abnormal paraprotein, most commonly a monoclonal IgG lambda is found in most patients (>80%) with scleromyxedema. Myeloma develops in fewer than 10%. It does not appear to represent a primary plasma cell dyscrasia, nor is there a consistent association with multiple myeloma. Fourteen cases of localized LM in HIV-positive patients have been reported. Thyroid disease-associated mucinoses must be distinguished.
Banno H, Takama H, Nitta Y, Ikeya T, Hirooka Y. Int J Dermatol 2000; 39: 212–14.
Eight of 16 Japanese patients displayed liver dysfunction with anti-HCV antibodies in association with LM. Only two cases outside Japan have been reported.
Dinneen AM, Dicken CH. J Am Acad Dermatol 1995; 33: 37–43.
A review of 17 patients treated with melphalan. Twelve of the patients revealed improvement in their cutaneous symptoms; however, eight of the patients had only temporary improvement. Ten of the treated patients died from complications of the disease or treatment.
Lin YC, Wang HC, Shen JL. J Dermatol 2006; 33: 207–10.
A case report of successful treatment with prednisolone 0.3 mg/kg/day divided four times daily for 1 week then tapered for 3 more weeks. Other studies have successfully used prednisone 60 mg four times daily for 4 to 6 weeks with gradual taper or pulse dexamethasone.
Nieves DS, Bondi EE, Wallmark J, Raps EC, Seykora JT. Cutis 2000; 65: 89–92.
A man with cutaneous and central nervous system disease had a very good response after treatment with plasmapheresis and melphalan. There is a mixed success rate in other case reports.
Blum M, Wigley FM, Hummers LK. Medicine 2008; 87: 10–20.
Eight patients had dramatic improvement of their cutaneous and visceral disease and were subsequently maintained with IVIG. Numerous other case reports, including a report of a patient with dermatoneuro syndrome, also demonstrate remarkable skin and systemic symptom improvement with IVIG (0.5–2 g/kg).
Serdar ZA, Altunay IK, Yasar SP, Erfan GT, Gunes P. Indian J Dermatol Venereol Leprol 2010; 76: 592.
A report of scleromyxedema improving with isotretinoin 60 mg daily for 6 months. Previous case reports of scleromyxedema treated with isotretinoin demonstrate mixed results.
Sansbury J, Cocuroccia B, Jorizzo J, Gubinelli E, Gisondi P, Girolomoni G. J Am Acad Dermatol 2004; 51: 126–31.
Within 2 months of starting thalidomide treatment, three patients with recalcitrant scleromyxedema displayed marked improvement of cutaneous lesions, joint mobility, and reduction of paraprotein levels. Several case reports have demonstrated the successful use of thalidomide in doses of 50–400 mg/day for several months. Case reports have also reported the efficacy and safety of thalidomide in combination with other therapies such as IVIG, dexamethasone, and chemotherapeutic agents.
Reynolds NJ, Collins CM, Burton JL. Arch Dermatol 1992; 128: 857–8.
A case report of a complete response to intralesional triamcinolone acetonide and Haelan, an adhesive polyethylene tape impregnated with flurandrenolide. Multiple other case reports show mixed results with the use of topical or intralesional steroids.
Rongioletti F, Zaccaria E, Cozzani E, Parodi A. J Am Acad Dermatol 2008; 58: 530–52.
Two patients with near complete resolution of lichen myxedematosus with twice-daily application for 8 weeks. One patient previously did not respond to topical steroids. Another case report also documents rapid, almost complete clearance of plaques within 3 weeks.
In another report, pimecrolimus resulted in symptomatic relief.
Donato ML, Feasel AM, Weber DM, Prieto VG, Giralt SA, Champlin RE, et al. Blood 2006; 107: 463–6.
Seven patients were treated. All of the patients survived, and five had complete remission of the skin disease. Visceral disease also greatly improved.
Migkou M, Gkotzamanidou M, Terpos E, Dimopoulos MA, Kastritis E. Leuk Res 2011; 35: e209–11.
A case report of a patient, with a history of numerous unsuccessful treatments, treated with 21-day cycles of bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 and dexamethasone 40 mg on days 1–4. The patient experienced sensory peripheral neuropathy after the second cycle so the bortezomib dose was reduced to 1 mg/m2. Eight cycles of bortezomib with dexamethasone were completed with near resolution at 24 months.
Prasad PV, Joseph JM, Kaviarasan PK, Viswanathan P. Indian J Dermatol Venereol Leprol 2004; 70: 36–8.
A case report of a patient with scleromyxedema and myositis treated with cyclophosphamide 50 mg twice a day and prednisolone 40 mg/day. The patient had a 75% improvement at 1 month and did not relapse.
Saigoh S, Tashiro A, Fujita S, Matsui M, Shibata S, Takeshita H, et al. Dermatol 2003; 207: 410–11.
After failing PUVA, oral prednisone, and plasmapheresis, a patient’s condition improved with cyclosporine A at doses of 50–100 mg/day. There was a 50% improvement at 4 months and near resolution at 18 months.
Mehta V, Balachandran C, Rao R. Indian J Dermatol 2009; 54: 193–5.
A single report of a patient who had over 75% improvement in cutaneous induration after treatment with minipulses of betamethasone 3 mg twice weekly and methotrexate 10 mg weekly.
Wieder JM, Barton KL, Baron JM, Soltani K. J Dermatol Surg Oncol 1993; 19: 475–6.
One patient was treated with chlorambucil 4–6 mg daily for 18 months with improvement of her cutaneous symptoms. Her paraproteinemia was unchanged. The authors believe that this medication is less immunosuppressive and causes fewer secondary malignancies than melphalan or cyclophosphamide.
Tschen JA, Chang JR. J Am Acad Dermatol 1999; 40: 303–7.
One patient who failed to respond to chlorambucil and isotretinoin improved with interferon-α2b 6–10 mU three times weekly over more than 3 months. Her visceral symptoms did not improve. A couple of reports have remarked on exacerbation of scleromyxedema during interferon treatment for hepatitis C or multiple sclerosis.
D’Incan M, Franck F, Kanold J, Bacin F, Achin R, Beyvin AJ, et al. Ann Dermatol Venereol 2001; 128: 38–41.
A complete cutaneous therapeutic response was obtained in one patient after 12 extracorporeal photopheresis courses and four pulse treatments of prednisolone.
Adachi Y, Iba S, Horio T. Photodermatol Photoimmunol Photomed 2000; 16: 229–31.
A patient received PUVA treatments three times a week and showed improvement after only seven treatments. He had near resolution after 35 treatments and only a minor recurrence after 2 years.
Rampino M, Garibaldi E, Ragona R, Ricardi U. Int J Dermatol 2007; 46: 864–7.
The report of one patient successfully treated with radiation therapy and a review of previous reports.
Laimer M, Namberger K, Massone C, Koller J, Emberger M, Pleyer L, et al. Acta Derm Venereol 2009; 89: 631–5.
A case report of a patient treated with the chemotherapeutic regimen of vincristine, idarubicin, and dexamethasone (VID regimen) in addition to daily oral thalidomide which led to clinical and laboratory remission in 12 weeks.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
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Melphalan
Systemic corticosteroids
Plasmapheresis
Intravenous immunoglobulin
Isotretinoin/etretinate
Thalidomide
Topical or intralesional corticosteroids
Topical calcineurin inhibitors
Autologous stem cell transplantation
Bortezomib
Cyclophosphamide
Cyclosporine
Methotrexate
Chlorambucil
Interferon-α2b
Extracorporeal photopheresis
PUVA
Radiation
Vincristine
