Neutrophil mobility in granuloma annulare and necrobiosis lipoidica

Neutrophil mobility was investigated in thirteen cases of granuloma annulare and in twelve cases of necrobiosis lipoidica and found to be normal. Plasma from these patients did not inhibit the random or directed migration of neutrophils obtained from normal donors. The nature of the ‘in vivo’ defect of neutrophil migration previously reported in these conditions is at present unclear.     

Anti-collagen antibodies in granuloma annulare and necrobiosis lipoidica

Antibodies to native collagens I-V were measured by enzyme-linked immunosorbent assay (ELISA) in sera from 32 patients with granuloma annulare (GA), 32 patients with necrobiosis lipoidica (NL) and 31 healthy controls. Antibodies to all collagen types were detected in all patient groups and in normal controls. No difference in antibody levels between patient and control groups was found except for a significant reduction in collagen type III antibodies in patients with GA compared with normal control subjects.     

Glycosylated haemoglobin in patients with necrobiosis lipoidica and granuloma annulare

Glycosylated haemoglobin (HbA₁) content in the blood of twenty-two cases of necrobiosis lipoidica and fourteen cases of granuloma annulare were measured to see if it was elevated. Only eleven patients, all with known diabetes, had elevated HbA₁. These data support the concept that the microangiopathic changes in these two conditions occur independently of elevated blood glucose concentrations.     

Serum alpha 2 globulin levels in granuloma annulare and necrobiosis lipoidica

Alpha 2-macroglobulin, caeruloplasmin and haptoglobin were measured in the sera of patients with necrobiosis lipoidica, granuloma annulare and diabetes. Alpha 2 Macroglobulin and caeruloplasmin were significantly raised in diabetes, and caeruloplasmin was raised in necrobiosis lipoidica without diabetes. The ratio of alpha 2-globulin to serum albumin was significantly high for all three proteins in diabetes, and for haptoglobin and caeruloplasmin in necrobiosis lipoidica. None of these proteins was abnormally raised in non-diabetic patients with granuloma annulare. There is good evidence that the plasma protein changes in diabetes contribute to the development of microangiopathy by their influence on blood viscosity. The altered plasma protein profile in necrobiosis lipoidica may therefore be of relevance to the development of the vascular lesions in this disorder.     

Maturity-onset diabetes of the young with necrobiosis lipoidica and granuloma annulare

We describe a 12-year-old white girl with granuloma annulare localized to both ankles since she was five, necrobiosis lipoidica in the left pretibial region since she was ten, and a recent history of weakness, migraine, and weight loss. After initial evaluation, high fasting blood glucose levels and high hemoglobin A1c were found. The family history for non-insulin-dependent diabetes was suggestive of maturity-onset diabetes of the young. Coexistence of necrobiosis lipoidica and granuloma annulare, together with a family history of non-insulin-dependent diabetes, the age of onset, and the absence of ketosis, are specific features making possible, a clinical diagnosis. Genetic confirmation may not be so easily accessible or necessary.     

Epidermal dendritic S100 positive cells in necrobiosis lipoidica and granuloma annulare

Using an antibody to S100 protein, the number of dendritic cells above the basal layer in the epidermis was assessed in necrobiosis lipoidica and granuloma annulare. A statistically significantly higher number of these cells was found within the epidermis in necrobiosis lipoidica compared with granuloma annulare and normal skin. The numbers were similar to those seen in sarcoidosis and tuberculous reactions in the skin, which raises the possibility of an immune pathogenesis for necrobiosis lipoidica.     

Defective neutrophil migration in granuloma annulare, necrobiosis lipoidica, and sarcoidosis.

The neutrophil mobility in patients with granuloma annulare, necrobiosis lipoidica, and sarcoidosis was tested using both in vivo and in vitro techniques. Use of a skin window chamber for measurement of chemotaxis in vivo demonstrated defective neutrophil migration in each group. This contrasted with the finding that, in vitro, chemotaxis toward casein and endotoxin-activated sera was normal. The importance of this dissociation is discussed. Abnormal neutrophil accumulation at sites of inflammation may be of importance in the pathogenesis of these granulomatous disorders.     

Increased plasma fibronectin in diabetes mellitus, necrobiosis lipoidica and widespread granuloma annulare

The plasma level of fibronectin was measured in patients with granuloma annulare, necrobiosis lipoidica and diabetes mellitus and compared with levels in healthy controls. A significant increase was observed in necrobiosis lipoidica, generalised granuloma annulare and diabetes but not in patients with solitary lesions of granuloma annulare. The possible role of fibronectin in the development of micro-angiopathy is discussed.     

Serum beta-glucuronidase activity in human diabetes mellitus, granuloma annulare and necrobiosis lipoidica

Serum levels of β-glucuronidase, lysozyme and lactate dehydrogenase were measured in patients with granuloma annulare, necrobiosis lipoidica and diabetes mellitus and compared with levels in healthy controls. Significant elevation of serum levels of β-glucuronidase were observed in diabetes mellitus and granuloma annulare. β-Glucuronidase in necrobiosis lipoidica was not significantly different from the control group, although six out of twenty patients did show elevated enzyme levels. Serum lysozyme was not raised in any of the test groups, although a few sera from patients with severe lesions were found to be high. No difference in lactate dehydrogenase levels was observed between patient and control sera. The significance of these findings is discussed.     

Increased factor VIII-related antigen in necrobiosis lipoidica and widespread granuloma annulare without associated diabetes

Factor VIII-related antigen was found to be raised in diabetics, and in patients with necrobiosis lipoidica and widespread granuloma annulare who were not diabetic. It was not increased in patients with solitary lesions of granuloma annulare. The relationship of factor VIII-related antigen to the development of micro-angiopathy in these conditions is discussed.     

Direct immunofluorescence studies in granuloma annulare, necrobiosis lipoidica and granulomatosis disciformis Miescher.

Direct immunofluorescence studies in granuloma annulare, necrobiosis lipoidica and granulomatosis disciformis Miescher are reported. In all 29 cases fibrillar deposits of fibrin in the necrobiotic areas have been found. Complement, mainly C3, was present in the region of the dermo-epidermal junction in 83% of the cases. Although the walls of the vessels in the superficial layers of the dermis showed a positive staining with antifibrinogen and complement, those around the necrobiotic areas were negative in most of the cases. The possible significance of these findings for the pathogenesis has been discussed.     

Increased activity of serum amine oxidases in granuloma annulare, necrobiosis lipoidica and diabetes

Serum monoamine oxidase, diamine oxidase and lysyl oxidase-like activity were measured in patients with granuloma annulare (GA), necrobiosis lipoidica (NL) and diabetes mellitus. In diabetes, all enzyme measurements were raised by a factor of about 2 X 2, and in NL by a factor of about 1 X 5. The rise in patients with GA was small and only significant in the case of benzylamine monoamine oxidase. "Stiff' collagen would seem to link these three disorders and the present results suggest that these amine oxidases could be useful in monitoring collagen abnormality in diabetes and diabetes-associated disorders, particularly in the absence of chronic liver disease. A negative correlation was found between enzyme activity and blood glucose levels, thus collagen changes in these conditions may occur independently of elevated blood glucose levels. Possible involvement of these enzymes in angiopathy remains to be elucidated.