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16 patients with clinically and histologically verified necrobiosis lipoidica lesions were treated with either 40 mg acetylsalicylic acid or placebo daily for 24 weeks in a double-blind controlled study. The lesions became statistically significantly larger in both groups in spite of inhibition of the aggregation of the platelets in the acetylsalicylic group.
Elimination of necrotic material through the hair follicle as a means of excretion has been observed in three cases of necrobiosis lipoidica. Clinically this process presents as comedo-like plugs localized mainly in the periphery of the lesions.
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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.
The aim of our study was to evaluate the long-term results of topical psoralen ultraviolet A (PUVA) in patients with necrobiosis lipoidica (NL), in whom conventional methods (pentoxifylline, vitamin E, tretinoin, and topical or intralesional corticosteroids) had failed. The study comprised 10 women (age range 17-44 years), six of whom were insulin-dependent diabetics and four were diabetes-free. Duration of NL ranged from 3 to 10 years. The patients were treated with a 0.005% aqueous solution of 8-methoxypsoralen, applied topically for 30 min, and subsequently irradiated with UVA three times weekly. All the patients experienced almost complete remission (softening of skin lesions, no hyperpigmentation, lack of lesion progression) after a mean of 47 sessions (mean UVA cumulative dose 69.5 J/cm2). They were followed up for 12-24 months, during which time two recurrences, both in diabetic patients, were observed after 8 and 12 months of treatment cessation, which further resolved after another course of topical PUVA. We conclude that topical PUVA is well tolerated by NL patients and may serve as an alternative therapeutic regimen.
Two young insulin-dependent diabetic patients suffering from chronic nonhealing leg ulcers of necrobiosis lipoidica diabeticorum were treated by applying topically recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) on the ulcer repetitively during 10 weeks. Evaluation of ulcer size was assessed with clinical examinations at 1-week or 2-week intervals. Topical GM-CSF healed the ulcers of both patients in 10 weeks. Decrease in the size of the ulcers was already evident after the first topical applications. During follow-up, the ulcers have remained healed for more than 3 years. This excellent treatment result suggests that topically applied GM-CSF may be a valuable drug for chronic, nonhealing ulcers in patients with diabetes.
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A patient who had had pulmonary sarcoidosis for 11 years developed multiple symmetrical lesions with ulcerations on the lower legs. The lesions showed the typical clinical picture of necrobiosis lipoidica and could not be differentiated histologically with certainty. Three years later persistent reddish plaques appeared on both arms, which allowed clinical and histological diagnosis of cutaneous sarcoidosis.
A 63-year-old diabetic woman presented with new-onset intermittent claudication of the right calf accompanied by ipsilateral necrobiosis lipoidica (NL). The latter presented the typical appearance of oval, indurated plaques, with brownish-red margins and central atrophy, scattered over the right thigh and calf. Arteriography demonstrated severe obstructive lesions on the right femoral artery. NL and claudication spared the left leg. A possible ischemic pathogenesis of NL emerges from this observation and is supported by recent studies in the literature.
A 39-year old nondiabetic female had severely ulcerated necrobiosis lipoidica of the legs which was refractory to medical management for 2 1/2 years. Surgical management with porcine grafting followed by autologous split-thickness skin grafts successfully healed these ulcerations. With the use of custom-fitted contoured pads and pressure gradient stockings, the grafts have remained intact for 2 1/2 years, and there has been significant improvement of the nonulcerated plaques.
A 43-year-old woman had asymptomatic eruptions on the anterior sides of both legs for 5 years. Biopsy specimens revealed the typical findings of necrobiosis lipoidica. An immunofluorescence study demonstrated no deposits of immunoglobulins, complement, or fibrinogen in vessel walls. Immunohistochemical staining revealed CD4 positive lymphocytes dominating in the lesion and strong expression of ICAM-1 on the endothelial cells, giant cells, lymphocytes and dermal fibroblasts in the lesion. The eruptions resolved remarkably with oral corticosteroid therapy.
A 48-year-old woman with generalized scleroderma of the acrosclerosis type developed several lesions clinically, histologically and ultrastructurally, which were characteristic of necrobiosis lipoidica. The lesions were located to scar tissue. An increased collagen synthesis is suggested as a possible explanation.
The goal of the present study was to follow the clinical behaviour of 6 non diabetic patients (5 females and 1 male, aged 23-68) suffering from necrobiosis lipoidica. Thickening of the basalmembrane of capillaries could be confirmed by electron microscopy, although the histological structure of skin alterations are not different from those observed in diabetes mellitus. Three patients (2 females and one male) showed impaired glucose tolerance, 2 other patients had increased levels of total cholesterol, whereas one patient suffered from both metabolic disturbances. After treatment with ASA (acetylsalicylic acid, 1.0 g/day) and dipyridamole (200 mg/day) for six weeks, the decrease of platelet in vitro aggregation in platelet rich plasma could be observed by stimulation with arachidonic acid, epinephrine, ADP and collagen, respectively. Healing of the exulceration of skin lesion could be detected by the use of the combined treatment of ASA and dipyridamole in 4 cases.
We report the case of a 33-year-old patient who had had insulin-dependent diabetes mellitus (IDDM) since he was 11 months old, and who presented with major perforating necrobiosis lipoidica (PNL) complicated by a well-differentiated epidermoid carcinoma. PNL is a rare clinical form of NL, always associated with diabetes. Only seven cases have been reported to date in the literature, and to the best of our knowledge, an association of epidermoid carcinoma and PNL has never been described. The development of a tumoral transformation on a classical NL plaque has only been described 12 times. The presence of an epidermoid carcinoma on a weakened background with permanent ulceration suggests that early surgical excision of the tumour and of the NL followed by a skin graft might be the treatment of choice. Radiotherapy seems to be a poor therapeutic option.
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Type 2 diabetes mellitus and associated long-term complications have become a significant health problem in adolescents. We report a 16-year-old girl with poorly controlled type 2 diabetes mellitus who had recurrent necrobiosis lipoidica diabeticorum associated with venous insufficiency.
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The prevalence of persistent microalbuminuria, retinopathy, and peripheral and autonomic neuropathy was assessed in 18 children and adolescents with type 1 (insulin-dependent) diabetes mellitus (IDDM) who suffered from necrobiosis lipoidica diabeticorum (NLD) and in 40 diabetics without NLD, matched for sex, age, duration of disease, and metabolic control. The mean +/- SD age of the patients was 15.1 +/- 8.6 years (range 7.9-23.9 yrs) and their duration of IDDM was 10.9 +/- 8.1 years (range 7.1-21.0 yrs). Their mean glycosylated hemoglobin level was 9.9 +/- 5.0% (7.3-16.6%) and their fructosamine level was 274 +/- 180 mumol/L (199-466 mumol/L). Patients with NLD had a higher frequency of persistent microalbuminuria (p < 0.001) and retinopathy (p < 0.001) than those without NLD. Our study suggests that children as well as adult diabetics with NLD can be at high risk for nephropathy and retinopathy; NLD can be a clue for diabetic nephropathy and retinopathy.