Localized insulin-dependent amyloidosis with scar-tissue formation
Authors: Friederike Damm, Sergij Goerdt, Astrid Schmieder
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: The incidence and prevalence of diabetes mellitus has increased dramatically in the last few years as a result of increasing prevalence of obesity, physical inactivity, and aging. In the course of the disease nearly all patients develop skin complications caused by the long-term effects of diabetes mellitus.1Van Hattem S. Bootsma A.H. Thio H.B. Skin manifestations of diabetes.Cleve Clin J Med. 2008; 75 (772, 4, 6-7 passim)Crossref PubMed Scopus (61) Google Scholar Sequelae can, however, also be caused by the treatment regimen. Here we describe the case of a 26-year-old male patient with a 24-year history of type 1 diabetes mellitus, who presented with 2 relocatable, indurated subcutaneous lumps below his navel (Fig 1, A). His treatment regimen included regular subcutaneous administration of insulin detemir and insulin lispro, which he had habitually injected into these nodules for 2 to 3 years. His diabetic control was moderate (hemoglobin A1c 8.0%) and he had no diabetic long-term complications. For diagnostic purposes, 1 nodule was excised. Histologic examination showed a highly homogenized connective tissue with a depletion of cells and vessels in the tumor area accompanied by foci of necrobiosis and calcification (Fig 1, B). Congo-red staining revealed the brick-red coloration of amyloid within the subcutaneous nodule (Fig 1, C). Immunohistochemical staining for insulin demonstrated that the amyloid fibrils originated from insulin deposits (Fig 1, D). Insulin-induced localized amyloidosis combined with scar tissue is an underdiagnosed complication of regular insulin injections in patients with insulin-dependent diabetes. Only a few cases of localized insulin-derived amyloidosis have been described in the literature2Albert S.G. Obadiah J. Parseghian S.A. Yadira Hurley M. Mooradian A.D. Severe insulin resistance associated with subcutaneous amyloid deposition.Diabetes Res Clin Pract. 2007; 75: 374-376Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar and even fewer cases of insulin-induced amyloid deposits were associated with scar-tissue formation.3Swift B. Examination of insulin injection sites: an unexpected finding of localized amyloidosis.Diabet Med. 2002; 19: 881-882Crossref PubMed Scopus (76) Google Scholar In 1 case, insulin injections caused scar-tissue formation without amyloid depositions. Here, the authors suggested that the scar tissue might be caused traumatically by the repeated subcutaneous injections.4Wallymahmed M.E. Littler P. Clegg C. Haqqani M.T. Macfarlane I.A. Nodules of fibrocollagenous scar tissue induced by subcutaneous insulin injections: a cause of poor diabetic control.Postgrad Med J. 2004; 80: 732-733Crossref PubMed Scopus (35) Google Scholar The mechanism underlying insulin-derived amyloid formation is not entirely clear. It has been shown that insulin in the absence of its C-peptide can assemble into fibrils and that an acidic environment frequently found in scar tissue in combination with high insulin concentrations can accelerate this process.5D'Souza A. Theis J.D. Vrana J.A. Dogan A. Pharmaceutical amyloidosis associated with subcutaneous insulin and enfuvirtide administration.Amyloid. 2014; 21: 71-75Crossref PubMed Scopus (52) Google Scholar Compared with the well-known insulin-induced lipohypertrophy, the nodules form more solid and firm lesions, which do not resolve quickly after rotation of the insulin injection site.3Swift B. Examination of insulin injection sites: an unexpected finding of localized amyloidosis.Diabet Med. 2002; 19: 881-882Crossref PubMed Scopus (76) Google Scholar Dermatologists should think of this differential diagnosis when diabetic patients present with firm nodes at the injection site, as regular insulin injections in these subcutaneous nodules can be associated with poor diabetic control. In addition, the presence of scar tissue in localized insulin-induced amyloidosis is worth mentioning as the low pH present in this environment might trigger insulin-derived amyloid formation.