The use of these drugs is off\label, because they are only approved for the treatment of rheumatoid diseases and therapy\refractory psoriasis. a conclusion that ulcerating necrobiosis lipoidica can be seen as part of a generalised inflammatory reaction similar to the inflammatory reaction already known in the pathophysiology of rheumatoid diseases or psoriasis. LAMNB2 In patients with clinical atypical painful ulcerations, necrobiosis lipoidica should be considered as a possible differential diagnosis. Therapists should be aware of associated aspects in patients with ulcerated necrobiosis lipoidica who besides diabetes often suffer from other aspects of a metabolic syndrome with increased cardiovascular risk factors. Therefore, Ezatiostat hydrochloride these related comorbidities should also be diagnosed and treated. in which 7 of the 13 patients with ulcerated necrobiosis lipoidica were male and 6 female 12. Even though reported quantity of patients with ulcerated necrobiosis lipoidica in their study is usually bigger than ours, our study is the first one focussing on cofactors and comorbidities. As gender\related differences in ulcerations of patients with necrobiosis lipoidica have not been assessed so far in other studies, further investigations and a large number of patients are necessary. Necrobiosis lipoidica and comorbidities There have been controversial discussions about the association of diabetes mellitus and necrobiosis lipoidica. Muller and Winkelmann found diabetes mellitus in 65% of 171 patients with necrobiosis lipoidica and an association with abnormal glucose tolerance in 42% of the non\diabetic cases. In their study, 35% of the diabetic patients and 33% of the non\diabetic patients with necrobiosis lipoidica experienced ulcerations within plaques 3. The group of patients with ulcerated necrobiosis lipoidica however had not been analysed separately as in our study. O’Toole found that in a retrospective review of 65 patients in Dublin with necrobiosis lipoidica only 11% experienced diabetes mellitus and only 5% showed impaired glucose tolerance. Another 11% were diagnosed with diabetes mellitus or impaired glucose tolerance within the 15\12 months follow\up period. Of these 65 patients, 6 experienced ulcerating necrobiosis lipoidica. Four of these patients experienced impaired glucose tolerance or diabetes mellitus 2. This group of patients with ulcerated necrobiosis lipoidica has not been described further by O’Toole The recent multicentre study by Erfurt\Berge showed that of the 52 patients with necrobiosis lipoidica Ezatiostat hydrochloride collected over a period of 5?years, 24 patients (46%) had diabetes mellitus 12. In our group of patients with ulcerated necrobiosis lipoidica, 70% showed an association with diabetes mellitus. Altogether, 60% of our patients with ulcerated necrobiosis lipoidica were suffering from arterial hypertension, were obese, smokers and showed Ezatiostat hydrochloride hypercholesterolaemia. This is significantly higher than in the study of Erfurt\Berge in which different comorbidities of patients with necrobiosis lipoidica were evaluated, but not distinguished for patients with ulcerations 12. An association of necrobiosis lipoidica with diabetes mellitus as well as with elevated serum lipids has been described in literature before 15. This association can be explained by the fact that even therapeutically well\controlled forms of diabetes mellitus cannot accomplish an optimal excess fat and carbohydrate metabolism. This also prospects to diabetic microangiopathy and arteriosclerosis, which gives way to arterial hypertension. Lack of exercise and malnutrition can lead to obesity and diabetes mellitus, too. A close association of necrobiosis lipoidica with other diseases of the metabolic syndrome in our cohort is usually therefore explicable. Treatment Treatment of the ulcerations in patients with necrobiosis lipoidica is very hard and relapses occur frequently. No known standardised effective treatment for ulcerated necrobiosis lipoidica is usually available until today. There are a number of treatment options explained in literature that are not evidence\based. The main reason is the low number of cases, especially of ulcerating necrobiosis lipoidica, and the amazing quantity of side effects of most therapies that a lot of patients are not willing to tolerate, considering thatin many casesjust the non\ulcerated patches do not cause strain. Recorded treatment options are intralesional and topical steroids or tacrolimus 16, topical PUVA 17, 18 or UVA1 19, 20, systemic steroids, doxycycline 21, antimalarial drugs 22, fumaric acid esters (FAEs) 23, pentoxifylline 24, cyclosporine A 25, biological brokers 26, 27 and surgery with excision followed by skin grafting (Furniture ?(Furniture22 and ?and33). Table 2 Topical therapies of ulcerated necrobiosis lipoidica CO2 laserPhotodynamic therapy (PDT)Phototherapy (PUVA and UVA1)Surgical excision (with or without skin grafting)Topical calcineurin inhibitorsTopical steroids Open in a separate window.