A Case of Insulin-induced Localized Lobular Panniculitis with Evidence for the Phagocytosis of Insulin by Histiocytes

Abstract

Insulin-induced localized lipoatrophy is a well-known localized side effect. Although an immune process has been suggested as its etiology, no definitive evidence has been reported to show that insulin is involved. Here, we report the first evidence for the phagocytosis of insulin by histiocytes as a very early stage of lipoatrophy, which was reproducible in two different lobular panniculitis tissues from a 71 year-old male patient. He had taken a subcutaneous insulin injection in his arms because of a sight disturbance. Since these subcutaneous tumors were likely due to inflammation by insulin, a biopsy sample was taken from the subcutaneous tumor of his right arm with his consent. The primary antibodies for insulin (1 : 200) and CD68 (1 : 50) were obtained from DAKO (guinea pig anti-insulin and mouse anti-human CD68). HE staining revealed the infiltration of mononuclear cells and histiocytes into the subcutaneous fat tissue, and some parts of this tissue had fibrosis with rich collagen fibers. These findings are consistent with a lobular panniculitis. Some histiocytes contained intracellular substances with a positive immunoreactivity to insulin. This activity was reduced when the anti-insulin antibody was preincubated with an excess amount of insulin antigen. The same substances were also positive to CD68. Thus, the phagocytosis of insulin by histiocytes appears to occur in this region. Therefore, the activation of subcutaneous macrophages by the complex of insulin and insulin antibodies may account for the initial autoimmune process.