Insulin resistance and acanthosis nigricans: evidence for a postbinding defect in vivo.

Acanthosis nigricans (AN) with insulin resistance has been traditionally attributed to insulin receptor abnormalities. To further clarify the postbinding defects of in vivo insulin action in this state, we applied the euglycemic insulin clamp technique, combined with the glucose trace infusion method, to 26 subjects: 12 AN patients (eight normoglycemic and four hyperglycemic), eight obese, and eight lean control subjects. The normoglycemic AN group exhibited fasting hyperinsulinemia (666% of control), 160% elevated hepatic glucose production (HGP), 425% increased posthepatic insulin delivery rate, and only slightly reduced (19%) insulin clearance rates, compared with controls. Except for the latter, all these abnormalities were statistically significant (P less than .05), and could not be accounted for by body overweight. AN patients with diabetes mellitus (AN + DM) exhibited a further decreased insulin responsiveness (30%) and clearance (38%), together with a major increase in HGP (320%). All AN patients showed a significant right-shift in the insulin dose-response curve, indicating a decrease in insulin sensitivity. In conclusion, AN is characterized by increased basal rates of HGP, and peripheral insulin resistance, which can be partially attributed to postbinding defects. In AN + DM, a worsening of these abnormalities may be responsible for unmasking the existence of diabetes.

Localized granuloma annulare. Histopathological and direct immunofluorescence study of early lesions, and the adjacent normal-looking skin of actively spreading lesions.

We studied 10 biopsies of early (< 1 week) localized granuloma annulare (LGA) lesions and 10 specimens of the normal-looking skin adjacent to actively spreading LGA lesions for signs of vasculitis, using histological and direct immunofluorescent (DIF) techniques. In the early LGA lesions, the collagen fibers showed various forms of alterations, with hyalinization and fragmentation being the most common; in half of these lesions, neutrophils and nuclear fragments in various numbers and densities were found among the altered collagen fibers. Some of the small blood vessels in the areas of granulomatous inflammation showed endothelial cell hypertrophy in four cases, and in one case also endothelial cell proliferation and luminal occlusion. In only one case, a single small blood vessel, which was situated in the center of a palisading granuloma, showed fibrinoid necrosis of its walls. The DIF study of all 20 specimens and the histological study of the 10 specimens of normal-looking adjacent skin did not reveal immune deposits in the vessels' walls, or histological evidence of vasculitis, respectively. We believe that these findings do not support a role of vasculitis in the formation of LGA lesions, but suggest that neutrophils might play a primary or secondary role in their pathogenesis.

A study of keratin expression in benign familial chronic pemphigus.

We studied keratin expression in the involved and uninvolved skin of six benign familial chronic pemphigus (BFCP) patients, using monoclonal antibodies specific for various keratin polypeptides and immunohistopathologic techniques. Normal and psoriatic (i.e., hyperproliferative) skin specimens served as controls. The uninvolved BFCP epidermis showed keratin profiles identical to that of normal epidermis. In the acantholytic epidermal segments of the involved BFCP skin, some of the lower suprabasal acantholytic cells failed to express keratin polypeptides 10 and 11 (Moll's catalog). This delay in expression of suprabasal keratins was not accompanied by an expression of hyperproliferative keratin polypeptide 16. Also, some of the lower suprabasal acantholytic cells of the involved BFCP epidermis retained staining by the antikeratin KS-1A3 antibody, which in the normal, psoriatic, and uninvolved epidermis was limited to the basal cell layer. Staining for keratin polypeptide 18 was negative in the epidermis of all four types of specimens. We believe that the delay in suprabasal keratin expression in the involved BFCP epidermis was more likely secondary to the acantholysis (i.e., "arrest of differentiation" due to acantholysis) rather than due to a primary defect in keratin expression.