it is more common in female with female - to - male ratio of 3:1 .
not all the cases of necrobiosis are associated with diabetes ; hence the terminology necrobiosis lipoidica diabeticorum has been abandoned .
the ulcers in nl are quite painful leading to impaired quality of life of these patients .
we present a case of ulcerative nl , which failed to respond to traditional treatment modalities but responded quickly to thalidomide .
a 58-year - old woman with 15 years history of insulin - dependent diabetes presented with nonhealing ulcers on her shin since 5 years .
four months later , she noticed a pinhead sized lesion over the red area , which enlarged and ulcerated .
three similar ulcers [ figure 1a and b ] appeared on the shin over the next one month .
the ulcers were non healing and extremely painful but not associated with any constitutional symptoms .
local wound care , topical corticosteroids , topical calcineurin inhibitors were tried along with oral antibiotics , dapsone , pentoxyphylline , and analgesics , without much relief .
she had multiple discrete tender ulcers over a waxy , erythematous , atrophic plaque on the anterior aspect of her left leg , variying in size from 3  2 cm to 1  1 cm .
the borders of ulcer were undermined , base was indurated , and floor was covered with necrotic debris .
her hemogram , renal and liver function tests , and venous doppler test results were normal .
pus culture grew staphylococcus aureus sensitive to linezolid , amoxycillin and clavulanic acid , and tazobactam  piperacillin .
skin biopsy from the edge of the ulcer revealed a hyperplastic , sclerotic epidermis and a dense superficial and deep dermal infiltrate of lymphocyte and plasma cells concentrated around the blood vessels and sweat glands [ figure 2a - c ] .
we started the patient on oral linezolid 600 mg twice daily for 7 days and chloroquine 250 mg once daily for 4 weeks along with local dressings .
topical human recombinant epidermal growth factor , oral clopidrogel and aspirin were added to the above regime and continued for another 2 months , with no improvement .
pain reduced dramatically within 2 weeks and the ulcers healed completely after 4 weeks [ figures 3a and b ] .
( a and b ) multiple non healing ulcers over the shin ( a - c ) hyperplastic , sclerotic epidermis and a dense superficial and deep dermal infiltrate of lymphocyte and plasma cells concentrated around the blood vessels and sweat glands with several granulomas arranged in a horizontal manner in mid and lower dermis .
( h and e , 10 , 40 , 40 ) ( a and b ) complete healing and softening of skin after treatment with thalidomide
there is no consistently effective therapy , and lack of uniform guidelines make treatment more challenging .
many theories were put forward to explain the pathogenesis of nl : diabetic microangiopathy due to deposition of glycoprotein in the blood vessel wall could lead to impaired blood supply to the skin ; greater cross - linking of the collagen fibres in nl could lead to thickening of the basement membrane zone ; immune complex deposition in the dermal blood vessel walls could lead to vasculitis ; recently a role of disturbance in glucose transport by fibroblasts has been postulated .
glut-1 is the human erythrocyte glucose transporter , which mediates facilitative transport of glucose across epithelial and endothelial barrier tissues .
this protein was expressed in the sclerotic collagen of nl patients , indicating insulin resistance in these tissues .
these include cutaneous blood flow enhancers , such as dypyridamol , clopidrogel , aspirin , pentoxyphylline ; topical and intralesional steroids , and topical calcineurin inhibitors ; wound healing enhancers such as epidermal growth factors , platelet - derived growth factors , collagen gel , hyperbaric oxygen ; surgery and pulse dye laser ; and immune modulators such as antimalarials , cyclosporine , and biologics .
our patient was treated with various drugs but failed to respond . in several case studies ,
tnf - alpha inhibitors such as etanercept , adalimumab , and infliximab were shown to improve ulcerated nld .
tnf - alpha has been found in high concentrations in the sera and skin of patients with nl thalidomide acts as an anti - inflammatory agent by suppressing tnf - alpha via degradation of its messenger rna and by decreasing the ratio of helper t cells to suppressor t cells .
the ulcer healed rapidly and thalidomide was withdrawn over 12 weeks , with no relapse till date .
 ulcerative necrobiosis lipoidica ( nl ) in diabetic patients is a rare , painful condition . 
 it is a difficult - to - treat condition , impairing quality of life of patients . 
 although various drugs have been tried , none of them is consistently effective . 
 biologics in the form of tnf - alpha inhibitors show promising results in the treatment . 
 but because of their high cost we chose thalidomide , which also has tnf - alpha inhibiting properties to successfully treat a long - standing case of ulcerative nl , which was refractory to various treatment modalities . 
INTRODUCTION
CASE REPORT
DISCUSSION
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