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• W2894895498 abstract "Pretibial myxedema (PTM) is a rare form of diffuse dermal mucinosis caused by glycosaminoglycan deposition in pretibial skin. It generally occurs in association with autoimmune thyroid disorders and affects 0.5% to 4.3% of patients with Graves disease (GD).1Kriss J.P. Pathogenesis and treatment of pretibial myxedema.Endocrinol Metab Clin North Am. 1987; 16: 409-415Abstract Full Text PDF PubMed Google Scholar PTM rarely improves with correction of the hyperthyroid state and may lead to pain, pruritus, or cosmetic concerns.2Burman K.D. McKinley-Grant L. Dermatologic aspects of thyroid disease.Clin Dermatol. 2006; 24: 247-255Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar Therefore, treatment is usually desired. Topical and intralesional corticosteroids, octreotide, and systemic immunomodulating agents have been used with largely unsatisfactory results.3Fatourechi V. Pretibial myxedema: pathophysiology and treatment options.Am J Clin Dermatol. 2005; 6: 295-309Crossref PubMed Scopus (144) Google Scholar Hyaluronidase is a naturally occurring enzyme that degrades hyaluronic acid (HA), a primary constituent of dermal mucin. Its current US Food and Drug Administration–approved indications include hypodermoclysis, enhancement of subcutaneous absorption of injected drugs, and improving resorption of radiopaque agents during subcutaneous urography.4Bailey S.H. Fagien S. Rohrich R.J. Changing role of hyaluronidase in plastic surgery.Plast Reconstr Surg. 2014; 133: 127e-132eCrossref Scopus (30) Google Scholar, 5Pirrello R.D. Ting C. Thomas S.H. Initial experiences with subcutaneous recombinant hyaluronidase.J Palliat Med. 2007; 10: 861-864Crossref PubMed Scopus (41) Google Scholar Given its efficacy and safety in the degradation of HA, intralesional hyaluronidase (ILH) should be considered in the treatment of cutaneous mucinoses. Here we describe 2 patients with severe PTM successfully treated with ILH. A woman in her 60s with a history of GD treated with thyroid ablation 7 years previously presented with a 5-year history of pruritic lesions on her shins and feet. She had a prior diagnosis of PTM, which was refractory to clobetasol cream twice daily under occlusion for the last several months. Intralesional corticosteroids and oral pentoxifylline had also failed. Physical examination found confluent, indurated, peau d'orange plaques involving the shins and feet (Fig 1, A). After negative intradermal allergy testing, plaques on the left foot were treated with ILH (150 U/mL). The regimen was week 0, 75 U in 5 equal aliquots; week 6, 105 U, 7 aliquots; week 12, 150 U, 10 aliquots; and week 18, 105 U, 7 aliquots. Clobetasol cream twice daily under occlusion was continued for both feet. The left foot gradually improved throughout the treatment course, with substantial plaque regression observed after 24 weeks (Fig 1, B). The right foot did not improve. No adverse events occurred. A woman in her 60s with a history of GD presented with a 7-year history of progressive painful induration involving the lower extremities and feet. She denied prior topical treatments. Her GD was treated 2 years prior with total thyroidectomy and levothyroxine. Physical examination found multiple indurated skin-colored plaques involving the ankles and feet, consistent with PTM (Fig 2, A). After negative intradermal allergy testing, a 5- × 5-cm plaque on the left dorsal foot was treated with ILH (150 U/mL; 1.0 mL) injected in 10 equal aliquots. Treatment was repeated at weeks 6, 12, and 18, with progressive flattening of the targeted plaque and resolution of pain (Fig 2, B). The patient reported mild discomfort during injections and no other complications. There was no improvement in the untreated, right foot. PTM is a chronic form of dermal mucinosis that occurs in association with GD or less commonly Hashimoto thyroiditis.2Burman K.D. McKinley-Grant L. Dermatologic aspects of thyroid disease.Clin Dermatol. 2006; 24: 247-255Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar Although recognizing and correcting the underlying abnormal thyroid state is critical, it rarely improves the mucinosis. Pretibial plaques are most commonly treated with immunomodulating agents including topical, intralesional, and systemic corticosteroids, oral octreotide, intravenous immunoglobulin, and plasmapheresis.1Kriss J.P. Pathogenesis and treatment of pretibial myxedema.Endocrinol Metab Clin North Am. 1987; 16: 409-415Abstract Full Text PDF PubMed Google Scholar, 3Fatourechi V. Pretibial myxedema: pathophysiology and treatment options.Am J Clin Dermatol. 2005; 6: 295-309Crossref PubMed Scopus (144) Google Scholar Although these therapies may have some benefit in early or mild disease, results are generally disappointing. The indurated plaques in PTM arise as a result of excessive mucin production by dermal fibroblasts.1Kriss J.P. Pathogenesis and treatment of pretibial myxedema.Endocrinol Metab Clin North Am. 1987; 16: 409-415Abstract Full Text PDF PubMed Google Scholar Mucin comprises various glycosaminoglycans, with HA being most abundant. Therefore, HA represents a potential therapeutic target in patients affected by PTM. Hyaluronidase is a commercially available hexosaminidase that functions in HA degradation through hydrolysis. Its current approved uses are in the enhanced dispersion or absorption of subcutaneous drugs. Off-label uses include the dissolution of misplaced hyaluronic acid filler during facial rejuvenation.4Bailey S.H. Fagien S. Rohrich R.J. Changing role of hyaluronidase in plastic surgery.Plast Reconstr Surg. 2014; 133: 127e-132eCrossref Scopus (30) Google Scholar Although hyaluronidase did effectively treat 2 cases of PTM in 1949 and 1950,6Rosman D. The treatment of localized (pretibial) myxedema with hyaluronidase.N Y State J Med. 1950; 50: 1939-1942Google Scholar, 7Grais M.L. Local injections of a preparation of hyaluronidase in the treatment of localized (pretibial) myxedema.J Invest Dermatol. 1949; 12: 345-348Abstract Full Text PDF Scopus (4) Google Scholar subsequent reports of its use in the treatment of PTM are rare.8Menzinger S. Kaya A. Saurat J.H. Kaya G. Injected hyaluronidase reduces the volume of exogenous hyaluronate fillers in mice and results in clinical improvement in a patient with pretibial myxedema.Dermatopathology (Basel). 2016; 3: 61-67Crossref PubMed Google Scholar In the current cases, 2 patients with severe PTM showed notable improvement after 4 ILH treatments. Case 1 showed a response even after not responding to prolonged courses of conventional therapies. The anticipated treatment protocol in each case was 1.0 mL (150 U) injected at 6-week intervals. In case 1, doses were decreased because of mild discomfort during injections. Still, this patient showed considerable response to therapy, and it is unclear whether higher doses would have resulted in greater improvement. Continued treatments at regular intervals are anticipated for both patients, as hyaluronidase is not expected to alter fibroblast mucin production. The most common adverse effects of hyaluronidase are transient erythema and pruritus at the injection site, occurring in up to 25% of patients.9Vartanian A.J. Frankel A.S. Rubin M.G. Injected hyaluronidase reduces restylane-mediated cutaneous augmentation.Arch Facial Plast Surg. 2005; 7: 231-237Crossref PubMed Scopus (55) Google Scholar Although severe hypersensitivity reactions such as angioedema and anaphylaxis have been reported, the incidence is estimated to be less than 0.1%.10Dunn A.L. Heavner J.E. Racz G. Day M. Hyaluronidase: a review of approved formulations, indications and off-label use in chronic pain management.Expert Opin Biol Ther. 2010; 10: 127-131Crossref Scopus (65) Google Scholar Anaphylaxis risk appears to be especially low if human recombinant hyaluronidase, rather than product derived from bovine or ovine tissues, is used.9Vartanian A.J. Frankel A.S. Rubin M.G. Injected hyaluronidase reduces restylane-mediated cutaneous augmentation.Arch Facial Plast Surg. 2005; 7: 231-237Crossref PubMed Scopus (55) Google Scholar, 10Dunn A.L. Heavner J.E. Racz G. Day M. Hyaluronidase: a review of approved formulations, indications and off-label use in chronic pain management.Expert Opin Biol Ther. 2010; 10: 127-131Crossref Scopus (65) Google Scholar Pretreatment skin allergy testing to hyaluronidase is still often advocated even for the human recombinant formulation despite its low risk of adverse immunogenic responses.11Brody H.J. Use of hyaluronidase in the treatment of granulomatous hyaluronic acid reactions or unwanted hyaluronic acid misplacement.Dermatol Surg. 2005; 31: 893-897Crossref PubMed Scopus (179) Google Scholar ILH may be an effective, well-tolerated, and underutilized treatment for PTM and should be considered in cases refractory to conventional therapies. Prospective studies are needed to determine dosing schedules that maximize efficacy and durability of response. Pretibial myxedema treated with intralesional hyaluronidase and triamcinoloneJAAD Case ReportsVol. 6Issue 9PreviewTo the Editor: Pretibial myxedema (PTM) is a cutaneous manifestation of Graves disease that is often refractory to treatment even with control of underlying thyroid disease. We read with great interest the case series by Hoesly et al1 describing PTM successfully treated with hyaluronidase. Here we report a case of recalcitrant pretibial myxedema that improved significantly with intralesional hyaluronidase and triamcinolone. Full-Text PDF Open Access" @default.
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• W2894895498 title "Pretibial myxedema successfully treated with intralesional hyaluronidase" @default.
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