Comorbidity and Therapeutic Approaches in Patients with Necrobiosis Lipoidica.

BACKGROUND: Necrobiosis lipoidica (NL) is a rare granulomatous disorder of unknown aetiology. Randomized controlled studies are not available due to it being an orphan disease. OBJECTIVES: We evaluated patients in 2 dermatological centres to cluster data about epidemiology, the therapeutic approaches for NL, and their efficacy. MATERIALS AND METHODS: Comorbidity and the efficacy of the applied treatment was assessed for 98 patients. RESULTS: We identified 54% of patients with concomitant diabetes and 19% with thyroidal disorders. Topical steroids (85.7%) were predominantly used followed by calcineurin inhibitors (31%) and phototherapy (41.8%). Systemically, fumaric acid esters were more frequently applied (26.8%) than steroids (24.4%) and dapsone (24.4%). Steroids, compression therapy, calcineurin inhibitors, phototherapy, fumaric acid esters, and dapsone showed remarkable efficacy. CONCLUSION: Therapeutic options were chosen individually in accordance with the severity of NL and presence of ulceration. Topical calcineurin inhibitors, systemic application of fumaric acid esters, and dapsone represent effective alternatives to the use of steroids.

Treatment-resistant ulcerative necrobiosis lipoidica in a diabetic patient responsive to ustekinumab.

Necrobiosis lipoidica is a chronic granulomatous disease of unknown etiopathogenesis, which is often difficult to treat. While data from randomized controlled trials for the treatment of necrobiosis lipoidica is lacking, several treatments of varying efficacy for necrobiosis lipoidica have been reported in the scientific literature. We present a case of a 29-year-old female with uncontrolled diabetes and treatment-resistant necrobiosis lipoidica which was responsive to ustekinumab.

Clinical Features and Comorbidities of Patients With Necrobiosis Lipoidica With or Without Diabetes.

Importance: Necrobiosis lipoidica (NL) is a rare granulomatous condition. Current knowledge of its key features is based on a limited number of studies and case reports, leading to wide variability in the characterization of its defining features, with limited comparison of patients with or without diabetes. Objective: To evaluate the epidemiologic characteristics, clinical features, and disease associations of NL in patients with or without type 1 or 2 diabetes. Design, Setting, and Participants: This multicenter retrospective review included 236 patients aged 15 to 84 years who were evaluated and received a diagnosis of NL at the University of Pennsylvania Health System between January 1, 2008, and July 15, 2018; University of Iowa Hospitals and Clinics between January 1, 2000, and June 15, 2018; and Brigham and Women's Hospital and Massachusetts General Hospital between January 1, 2000, and February 15, 2018. Main Outcomes and Measures: Patient demographics, clinical features, medical comorbidities, and biopsy status. Results: Of the 236 patients with NL, 200 were women and 36 were men, and 182 were white, with a median age at presentation of 50.0 years (interquartile range, 33.0-59.0 years). The diagnosis was biopsy proven in 156 patients (66.1%). Of the 230 patients with location specified, 225 (97.8%) had NL on the lower legs. A total of 138 patients with NL (58.5%; 95% CI, 52.7%-65.3%) had diabetes. The median hemoglobin A1c for patients with diabetes was 8.00% (interquartile range, 6.68%-9.50%) (to convert hemoglobin A1c to proportion of total hemoglobin, multiply by 0.01). Patients with diabetes were significantly younger than patients without diabetes (median age, 45.0 vs 52.0 years; P = .005), and slightly less likely to be female (112 of 138 [81.2%] vs 87 of 96 [90.6%]; P = .046), but lesion characteristics were otherwise comparable. Other notable comorbidities included obesity in 95 of 184 patients (51.6%; 95% CI, 44.4%-58.9%), hypertension in 104 of 230 patients (45.2%), dyslipidemia in 98 of 225 patients (43.6%), and thyroid disease in 56 of 229 patients (24.5%). Conclusions and Relevance: This study of NL supports its associations with diabetes as well as obesity, hypertension, dyslipidemia, and thyroid disease. Younger age and female sex were observed more frequently in patients with diabetes. Otherwise, NL lesions in patients with or without diabetes shared many clinical features, suggesting that risk factors outside of elevated blood glucose may play an important role in the disease. Future studies should evaluate these associations with the goal of further elucidating NL's underlying pathophysiologic characteristics.

Advances in Inflammatory Granulomatous Skin Diseases.

Inflammatory granulomatous dermatitides include cutaneous sarcoidosis, necrobiosis lipoidica, granuloma annulare, and reactive granulomatous dermatitis. The etiopathogenesis of these disorders is not well understood; but the T helper 1 response mediated by interferon-gamma, tumor necrosis factor-alpha, and interleukin (IL) 1, 2, and 6 and the T helper 17 response mediated by IL-17 play a role. These inflammatory granulomatous disorders often have cutaneous manifestations in addition to extracutaneous manifestations or associations with systemic diseases. The authors review these disorders, propose diagnostic and evaluative approaches to these diseases, and explore recent literature with regard to the etiopathogenesis and treatment of these entities.

[First manifestation of leg ulcers : Analysis of data from 1000 patients]. / Erstmanifestation eines Ulcus cruris : Analyse der Daten von 1000 Patienten.

BACKGROUND: More than 1 million people in Germany suffer from leg ulcers. The diagnosis leg ulcer summarizes many different etiologies. The therapy of leg ulcers is an interdisciplinary and interprofessional challenge. Early identification of the cause of the leg ulcer and initiation of a causal therapy are essential for healing. OBJECTIVES: The aim of this study was to investigate the initial manifestation age of patients with causally associated leg ulcers. Afterwards we calculated the most common etiologies according to decade. PATIENTS AND METHODS: A prospective database at the University Hospital Essen, dermatological wound care center, was used to identify patients with chronic leg ulcers between 2002 and 2014. Clinical data of 1000 patients with chronic leg ulcers were analyzed in this monocentric study. RESULTS: A total of 29 different etiologies were differentiated. Approximately 70% of etiologies were of vascular origin, while 30% were rare causes. The count of different etiologies showed significant differences related to the onset and the occurrence in individual decades of life. In particular, nonvascular etiologies such as pyoderma gangrenosum or necrobiosis lipoidica are relatively more common in younger patients than in the aged. CONCLUSION: Based on the findings of our study, it is possible to limit the underlying etiology on the basis of the age of first manifestation of the leg ulcer in order to make targeted diagnostics more effective. Thus, this information can help to optimize scarce time resources in daily practice and improve the prediction probability of leg ulcers.

Risk factors for necrobiosis lipoidica in Type 1 diabetes mellitus.

AIMS: To compare the clinical and metabolic characteristics of patients with Type 1 diabetes and necrobiosis lipoidica with those of patients with Type 1 diabetes who do not have necrobiosis lipoidica. A multicentre analysis was performed. METHODS: Clinical and laboratory data were obtained from 64 133 patients (aged 0-25 years) with Type 1 diabetes with and without necrobiosis lipoidica who were registered in the German/Austrian Diabetes Prospective Documentation Initiative registry. Data were analysed using multivariable regression modelling. Age, diabetes duration, treatment year and sex were considered as confounding factors. RESULTS: Results adjusted for demographic variables are presented. In patients with necrobiosis lipoidica, metabolic control was worse (HbA1c 72 vs. 67 mmol/mol, 8.7% vs. 8.3%; P = 0.0065) and the duration of diabetes was longer [6.24 (3.28-9.97) vs. 5.11 (2.08-8.83) years; P = 0.014; not adjusted]. Patients with necrobiosis lipoidica required higher insulin doses than those without (1.02 vs. 0.92 U/kg/day; P < 0.0001). There was no significant difference in the frequency of microvascular complications (microalbuminuria and retinopathy) between the groups. Furthermore, 24.8% and 17.5% of patients with Type 1 diabetes with and without necrobiosis lipoidica, respectively, had elevated thyroid antibodies (P = 0.051). Necrobiosis lipoidica was correlated with coeliac disease in patients with Type 1 diabetes (3.4% vs. 1.0%; P = 0.0035). CONCLUSIONS: Our data indicate a strong correlation between hyperglycaemia and the development of necrobiosis lipoidica. We postulate that the underlying pathogenic processes differ from those leading to microalbuminuria and retinopathy, and additional immunological mechanisms may play a role.

Cofactors and comorbidities of necrobiosis lipoidica: analysis of the German DRG data from 2012.

BACKGROUND: Necrobiosis lipoidica (NL) is a rare granulomatous inflammatory skin disease of unknown pathophysiology. Its potential association with diabetes mellitus is well known. Other relevant cofactors and comorbidities are subject to controversial debate. PATIENTS AND METHODS: DRG (diagnosis-related groups) data of all inpatients with a coded primary or secondary diagnosis of NL treated at German hospitals in 2012 were evaluated. RESULTS: Data of 262 inpatient cases with the primary or secondary diagnosis of NL were analyzed. Women (63.4%; n = 166) were nearly twice as frequently affected as men (36.2%; n = 96). Most NL patients (14.8%) were in the age group between 50 and 55 years. Among comorbidities included in the metabolic syndrome complex, diabetes mellitus was the most common (34.4%; IDDM 20.6%, NIDDM 13.8%), while essential hypertension was observed in 9.2%, obesity in 4.6%, chronic heart failure in 4.1%, and dyslipidemias in 2.3% of cases. Leg ulcers were diagnosed in 7.3% of individuals; other venous disorders, in 5.7%. CONCLUSIONS: Our data analysis describes one of the largest compilations of patient cases with the diagnosis of NL worldwide. Besides the well-known association with diabetes mellitus, there are numerous other potentially relevant cofactors and comorbidities that should be considered in the diagnosis and management of NL patients.

Updated results of 100 patients on clinical features and therapeutic options in necrobiosis lipoidica in a retrospective multicentre study.

BACKGROUND: Necrobiosis lipoidica (NL) is a rare granulomatous disorder of unknown aetiology which can manifest in ulcerative skin lesions and is widely recognised in association with diabetes. We evaluated in total 100 patients to improve knowledge about the epidemiology and clinical course of NL. Additionally we focused on treatment options according to evidence level and expert opinion. OBJECTIVE: To examine the clinical features of patients with necrobiosis lipoidica and to give recommendations for topical and systemic treatment. MATERIALS & METHODS: This multicentre retrospective study covers data from 100 patients with the diagnosis of NL of the lower leg, treated during the period between 01/2006 and 06/2014. Data from 5 German dermatological centres with 23 men and 77 women with a median age of 52 years were evaluated. We also asked 15 dermatological experts for their opinions about ulceration, associated diseases and their preferences for treatment modalities of NL. RESULTS: Patients' ages ranged from 15 to 95 years (median age 52 years, mean age 49.8 years). NL was significantly more common in women (77%). Ulceration of the NL was observed in 33% of cases, in particular in male patients and in patients with concomitant diabetes mellitus. Thyroidal disorders were found in 15% of all cases. CONCLUSION: Our data confirm that female sex, middle age and endocrine disorders like diabetes mellitus or thyroid dysfunction are characteristics of patients suffering from NL. Existing therapeutic options were very variable and - according to the opinion of our experts - only a few highly effective.

Necrobiosis lipoidica: a descriptive study of 35 cases.

INTRODUCTION AND OBJECTIVES: Necrobiosis lipoidica (NL) is a chronic idiopathic granulomatous disease considered to occur in association with diabetes mellitus. Data on the frequency of this association, however, are inconsistent. Our aim was to retrospectively analyze the clinical characteristics of patients diagnosed with NL at our hospital and to investigate the association with diabetes mellitus and other diseases. MATERIAL AND METHODS: We performed a chart review of all patients with a clinical and histologic diagnosis of NL treated and followed in the dermatology department of Hospital de Bellvitge in Barcelona, Spain between 1987 and 2013. RESULTS: Thirty-five patients (6 men and 29 women with a mean age of 47.20 years) were diagnosed with NL in the study period. At the time of diagnosis, 31 patients had pretibial lesions. Thirteen patients (37%) had a single lesion at diagnosis, and the mean number of lesions was 3.37. Twenty-three patients (65.71%) had diabetes mellitus (type 1 in 10 cases and type 2 in 13). In 20 patients, onset of diabetes preceded that of NL by a mean of 135.70 months. The 2 conditions were diagnosed simultaneously in 3 patients. None of the 35 patients developed diabetes mellitus during follow-up. Six patients had hypothyroidism, and 4 of these also had type 1 diabetes. CONCLUSIONS: NL is frequently associated with type 1 and 2 diabetes. Although diabetes tends to develop before NL, it can occur simultaneously.