necrobiosis lipoidica ( nl ) is a disease with clinical features that are seldom misinterpreted .
a 67-year - old woman was admitted to our department with a well - defined , persistent plaque on her right shin ( fig
the old lesion , which was located on the anterior surface of the shin , was characterized by sharply defined , slightly elevated , red - bluish borders and a yellow - orange , atrophic , porcelain - like center .
both lesions were not painful , but slightly pruritic and there was no history of recent trauma or infection .
the patient had a history of type 2 diabetes mellitus ( dm ) since 2000 .
blood glucose levels had been poorly controlled ever since , with hba1c reaching 7.3% , but with no apparent complications of dm .
although clinically the shin lesion was compatible with nl , the arm lesion was not typical of any dermatosis .
therefore , both lesions were biopsied to identify their nature and rule out sarcoidosis or granuloma annulare .
histology revealed identical features despite the dissimilar clinical presentation . a granulomatous dermatitis with foci of degenerated collagen surrounded by histiocytes , some of them multinucleated ( fig .
3 ) , as well as thickened collagen bundles arranged horizontally in the dermis are all typical findings of nl . the patient was treated with 0.1% topical tacrolimus ointment twice daily for 8 weeks and once daily for 8 weeks .
a significant improvement and no further lesions were observed after 1 year of follow - up .
it more commonly occurs in women than in men with a ratio of 3:1 [ 1 , 2 , 3 ] .
the average age of onset is 3040 years [ 1 , 2 , 3 ] , although it has been frequently reported in older age groups and seldom in children .
the lesions are distributed on the anterior and lateral surfaces of the lower legs . however , there are other sites that can rarely be affected , such as upper extremities [ 1 , 2 ] , trunk [ 1 , 3 ] , face ( even periorbitally ) , scalp [ 1 , 3 ] and penis [ 3 , 4 ] .
however , diabetic microangiopathy , immune - complex vasculitis , and collagen abnormalities are some potential underlying causes .
nakajima et al .   assert that both hyperlipidemia and venous reflux , in addition to other pathogenic factors , can trigger tissue damage in the lower legs and lead to the onset of nl . in constrast ,
refute the hypothesis that nl is a manifestation of microvascular ischemic disease of the skin and conclude that the increased blood flow seen in nl lesions suggests an ongoing inflammatory process . despite the debates on pathogenesis ,
7590% of patients with nl have or will develop dm [ 2 , 3 ] .
in contrast , nl is present only in 0.33% of the diabetic population [ 1 , 2 , 3 ] .
it is most commonly seen in patients with type 1 dm , but may also occur in type 2 dm . whether glucose control and treatment of dm improve or
have no effect on nl lesions is still a controversy [ 1 , 2 ] .
nl has also been associated with other diseases such as sarcoidosis , rheumatoid arthritis , autoimmune thyroid disease and inflammatory bowel disease .
ulceration is the most frequent and hard to treat complication of nl in 2533% of patients [ 1 , 2 , 3 ] .
additionally , squamous cell carcinoma developing in areas of nl has also been reported [ 1 , 2 , 3 ] .
although there are plenty therapeutic options for nl , its treatment is still challenging and sometimes ineffective [ 1 , 2 ] .
first - line treatment includes corticosteroids , either topically or intralesionally , and sometimes systemically [ 1 , 2 , 3 , 8 ] . according to some reports ,
other therapeutic options are antiplatelet agents , cyclosporine [ 1 , 2 , 3 , 8 ] , thalidomide [ 3 , 8 ] , clofazimine , anti - tnf agents [ 3 , 8 ] , fumaric acid esters [ 2 , 8 ] , puva [ 2 , 3 , 8 ] , photodynamic therapy [ 8 , 9 ] , hydroxychloroquine   and tacrolimus [ 3 , 11 , 12 , 13 ] .
we report a case of non - ulcerated , recent lesions of nl well managed with topical tacrolimus 0.1% ointment twice daily for 8 weeks and once daily for 8 weeks . despite the limited experience with topical tacrolimus treatment in nl
tacrolimus induces anti - inflammatory and immunomodulatory effects with suppression of the granulomatous infiltrate in granuloma annulare and nl , including the reduction of chemotactic activity of fibroblasts and the inhibition of collagen synthesis [ 11 , 12 , 13 ] .
subsequently , tacrolimus is thought to be effective at the early inflammatory stages of nl .
making a diagnosis of nl of the lower legs is not difficult ; however , a high index of suspicion regarding nl lesions with atypical clinical presentation on different body sites is advised in order to avoid misdiagnosis , wrong treatment decisions and ulceration .
additionally , it appears that topical tacrolimus treatment is an effective therapeutic option in patients with recent , non - ulcerated nl lesions .
 we present a case of necrobiosis lipoidica ( nl ) with atypical early lesions and good response to topical tacrolimus . 
 nl is a disease with clinical features that are seldom misinterpreted . 
 often histology just confirms the clinician 's diagnosis . only in rare cases , the clinical presentation and 
 the involved body sites may be misleading . 
 a 67-year - old diabetic woman was admitted to our department with a well - defined , persistent plaque on her left arm and on her right shin . 
 histologic examination of both lesions revealed features of nl despite the dissimilar clinical presentation . 
 the patient was treated with 0.1% topical tacrolimus ointment twice daily for 8 weeks and once daily for 8 weeks . 
 a significant improvement and no further lesions were observed after 1 year of follow - up . 
 a high index of suspicion regarding nl lesions with atypical clinical presentation on different body sites is advised in order to avoid misdiagnosis , wrong treatment decisions and ulceration . 
 additionally , it appears that topical tacrolimus treatment is an effective therapeutic option in patients with recent , non - ulcerated nl lesions . 
Introduction
Case Report
Discussion
Disclosure Statement