A Breakthrough in the Treatment of Necrobiosis Lipoidica? Update on Treatment, Etiopathogenesis, Diagnosis, and Clinical Presentation.

Necrobiosis lipoidica (NL) is a rare granulomatous disease of a not fully understood etiopathogenesis. Classically, NL is associated with insulin-dependent diabetes mellitus. The disease often fails to respond to conventional treatments and adversely affects patients' quality of life. First-line medications are usually topical corticosteroids, but patients respond to them with varying degrees of success. Other options include tacrolimus, phototherapy, cyclosporine, fumaric acid esters, and biologics (adalimumab, etanercept, and infliximab). Our review aims to present new therapeutic approaches potentially effective in patients with refractory lesions, describe the presumed etiopathogenesis, and provide diagnostic guidance for clinicians. The review concludes that Janus kinase inhibitors and biologics such as ustekinumab and secukinumab can be used effectively in patients with recalcitrant NL. Another promising treatment option is tapinarof (an aryl hydrocarbon receptor agonist). However, studies on larger groups of patients are still needed to evaluate the effectiveness of different therapeutic options and to define consistent treatment regimens for NL. It is advisable to improve the awareness of physicians of various specialties regarding necrobiosis lipoidica as lesions diagnosed earlier usually have a better response to treatment.

Don't Go Breaking My Heart: Not Your Ordinary Tattoo Reaction.

ABSTRACT: Necrobiosis lipoidica (NL) is a rare, chronic idiopathic granulomatous dermatitis with a somewhat controversial association with diabetes and other systemic diseases. We report a case of NL developing within a polychromic tattoo on the lower leg of a 53-year-old woman. Characteristic histopathologic findings of both active and chronic "burnt-out" NL appeared to originate from the tattoo where red ink was used 13 years prior. To the best of our knowledge, only 3 other cases of tattoo-associated NL have been reported.

Characteristics of ulcerated and non-ulcerated necrobiosis lipoidica.

BACKGROUND: Necrobiosis lipoidica (NL) is complicated by ulceration in up to 35% of cases. METHODS: Retrospective study of patients with NL seen at our institution between January 1, 1992, and May 25, 2021, was conducted. Ulcerated NL (UNL, n = 83) and non-ulcerated NL (NUNL, n = 233) groups were compared. RESULTS: Twenty-six percent (83/316) of patients with NL experienced ulceration. UNL was significantly more likely to be painful (52% vs. 36%, P = 0.01), was more likely to have a lesion-associated cutaneous malignancy (7% vs. 0%, P < 0.001), and had a larger median size (7 vs. 5 cm, P = 0.004) compared to NUNL. Vascular studies were performed on a subset of patients and revealed transcutaneous oxygen pressure (TcPO2) < 40 mm Hg in 53% and venous insufficiency in 62% with no significant differences between UNL and NUNL groups. In patients with unilateral ulceration, mean TcPO2 values (39.7 vs. 46.6 mm Hg), regional perfusion index <0.6 (29% vs. 14%), and TcPO2 < 40 mm Hg (43% vs. 14%) were worse in the ulcerated leg compared to the non-ulcerated leg, but these differences were not statistically significant. CONCLUSIONS: UNL was more likely to be painful, develop lesion-associated malignancy, and be larger in size compared to NUNL. There were no statistically significant differences in venous insufficiency, arterial Doppler/ankle brachial index, or TcPO2 values between UNL and NUNL patients, however, a significant portion of the cohort demonstrated abnormal vascular studies, particularly on TcPO2 and venous insufficiency testing.

Pediatric necrobiosis lipoidica: case report and review of the literature.

Necrobiosis lipoidica (NL) is a rare, granulomatous disease considered to be associated with diabetes. It is frequently seen in female and middle-aged patients and is rarely observed in children. We present a 14-year-old boy with poorly controlled type 1 diabetes who developed biopsy-proven NL. He had improvement, but not resolution of the plaque with improved glycemic control. Pediatric NL may be associated with diabetes and could be related to poor glycemic control. However, further investigation is warranted in this young population.

Cutaneous Manifestations of Diabetes.

Diabetes mellitus is a significant worldwide health concern and cutaneous manifestations are common. This review describes characteristic skin findings of diabetes, general skin findings related to diabetes, and findings related to diabetes treatment with a focus on clinical presentation, diagnosis, pathophysiology, epidemiology, and treatment. As the prevalence of diabetes continues to rise, cutaneous manifestations of diabetes mellitus likely will be encountered more frequently by physicians in all disciplines including dermatologists and primary care physicians. Accordingly, knowledge regarding the prevention, diagnosis, and management of cutaneous manifestations is an important aspect in the care of patients with diabetes.

[Rare skin condition in a child with diabetes mellitus]. / Zeldzame huidaandoening bij een kind met diabetes mellitus.

BACKGROUND: Necrobiosis lipoidica is a painless but disfiguring skin condition regularly complicated by ulceration and that is related to diabetes mellitus. CASE DESCRIPTION: We present the case of a 17-year-old girl with type 1 diabetes mellitus in whom necrobiosis lipoidica was diagnosed. After falling with a bicycle, a traumatic ulcer developed. The patient underwent several different treatments (local and systemic glucocorticoids, antibiotics, hydroxychloroquine, calcineurin inhibitor, laser therapy and surgery), but these ultimately resulted in no more than minimal improvement of the skin condition. CONCLUSION: Necrobiosis lipoidica is difficult to treat. Treatment recommendations are based on patient descriptions and results of small clinical trials.

Cutaneous Manifestations of Diabetes Mellitus and Prediabetes.

Diabetes is a serious, chronic disease with a rising prevalence worldwide. Its complications are a major cause of morbidity and mortality and contribute substantially to health care costs. In this article the authors review the most common and sensitive skin manifestations that can be present on patients with diabetes and prediabetes. The prompt recognition of these frequently underestimated entities is extremely important as it may trigger not only an adequate metabolic evaluation but also a timely referral and appropriate treatment, minimizing the secondary effects of long-term diabetes and improving the prognosis of diabetic patients.

A diabetes mellitus é uma doença crónica, com uma prevalência crescente a nível mundial. As complicações da diabetes são uma causa major de morbilidade e mortalidade, condicionando custos importantes na área da saúde. Neste artigo é efetuada uma revisão das manifestações cutâneas mais frequentes presentes em doentes com diabetes e pré-diabetes. O reconhecimento atempado destas entidades é fulcral, levando não só a uma avaliação atempada do perfil metabólico como a uma referenciação e tratamento precoces. Desta forma, é possível minimizar os efeitos secundários da diabetes a longo prazo, melhorando significativamente o prognóstico dos doentes.

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.

La nécrobiose lipoïdique: à propos d'un cas: Necrobiosis lipoidica: about a case.

Necrobiosis lipoidica is a rare granulomatous dermatosis. It occurs in 0.3-1.2% of diabetic patients mainly at the level of the leg. The lesions appear as erythematous plaques with central depressions. We here report the case of a 21-year old female patient with a 6-year history of type 1 diabetes presenting with a 1-year history of well circumscribed, symmetrical and asymptomatic erythematous plaques with atrophic yellowish center at the level of the anterior compartments of the legs (A, B). The diagnosis of necrobiosis lipoidica was suspected, a biopsy was performed which confirmed the diagnosis. The patient had a granulomatous inflammatory reaction with palisade-like border disposed around poorly delimited foci of altered connective tissue on the entire dermis layer. The inflammatory reaction was also characterized by multinucleate giant cells, dendrocytes and lipid deposits. Local corticosteroid therapy was prescribed. Patient's evolution was marked by the persistence of the lesions.

A systematic review of the relationship between glycemic control and necrobiosis lipoidica diabeticorum in patients with diabetes mellitus.

The association of specific skin disorders with diabetes mellitus (DM) has been well established. Current literature suggests that approximately 30-91% of patients with diabetes will experience at least one cutaneous manifestation of this systemic disease in their lifetime. To date, there are limited articles summarizing the link between necrobiosis lipoidica diabeticorum (NLD) prognosis and glycemic control in patients with diabetes. The objective of the study is to summarize and appraise the available evidence assessing the relationship between glycemic control and NLD. A literature search was conducted based on MEDLINE (1946-2015), EMBASE (1980-2015), Google Scholar, and PubMed for publications that described the results of diabetes control and NLD. Further studies were identified from bibliographies of all relevant studies, gray literature, and annual scientific assemblies. All studies investigating the relationship between DM (type 1 and type 2) management and NLD were included. Two reviewers independently extracted data including demographics, type of diabetes management measures (glucose, HbA1c, insulin), comorbidities, and outcome. A total of 622 studies were identified, and 10 studies met the inclusion and exclusion criteria: two case series and eight case reports. Of the 24 patients with NLD, 13 patients reported resolution of NLD after implementing various methods of glycemic control (diabetic diet consisting of 1600 kcal/day [1 patient], insulin regimen [3 patients], and pancreatic transplantation [9 patients]). Glycemic control may have a role in influencing the prognosis of necrobiosis lipoidica in patients with diabetes; however, there is currently insufficient evidence to support or refute this claim.

Diabetes mellitus and the skin.

Several dermatoses are routinely associated with diabetes mellitus, especially in patients with chronic disease. This relationship can be easily proven in some skin disorders, but it is not so clear in others. Dermatoses such necrobiosis lipoidica, granuloma annulare, acanthosis nigricans and others are discussed in this text, with an emphasis on proven link with the diabetes or not, disease identification and treatment strategy used to control those dermatoses and diabetes.

Diabetes mellitus and the skin

Abstract: Several dermatoses are routinely associated with diabetes mellitus, especially in patients with chronic disease. This relationship can be easily proven in some skin disorders, but it is not so clear in others. Dermatoses such necrobiosis lipoidica, granuloma annulare, acanthosis nigricans and others are discussed in this text, with an emphasis on proven link with the diabetes or not, disease identification and treatment strategy used to control those dermatoses and diabetes.

Anti-TNFα treatment for recalcitrant ulcerative necrobiosis lipoidica diabeticorum: A case report and review of the literature.

INTRODUCTION: Necrobiosis lipoidica diabeticorum (NLD) is a rare degenerative connective tissue disorder associated with diabetes mellitus, which usually presents with red papules or plaques with raised edges and occasional ulceration. Ulcerating NLD is notoriously difficult to treat. We present a young patient with ulcerative NLD who was successfully treated with the anti-TNFα agent infliximab. Case presentation is followed by a review of therapeutic TNFα blockade in NLD. CASE PRESENTATION: A 17-year old woman with type 1 diabetes since the age of 8, presented with a long-standing and extensively ulcerated and infected NLD lesion on her left shin. After achieving better glycemic control and treating her for infection of the wound, several NLD treatments failed to help, including corticosteroids and hyperbaric oxygen. She was treated successfully with 4 monthly sessions of 5mg/kg body weight intravenous infliximab, achieving complete resolution of ulceration. DISCUSSION: A multitude of available treatments have been suggested for NLD over the past decades, based on two axes, one through wound healing and the other through immunosuppression. Anti-TNFα agents are relatively new drugs that brought a revolution in chronic inflammatory diseases and have been on the rise as novel potential treatments for NLD. Three out of the five available anti-TNFα agents have been safely tested so far, both topically and systematically, with mostly favorable results. CONCLUSION: Intravenous infliximab was successful in the treatment of recalcitrant ulcerating NLD in our patient. Taken together with an increasing number of similar reports revealing a pathogenetic role of TNFα in NLD, we suggest that anti-TNFα agents are promising drugs in the management of this condition.

Ulcerative necrobiosis lipoidica successfully treated with photodynamic therapy: case report and literature review.

Ulcerative necrobiosis lipoidica (NL) is a rare skin condition refractory to conventional therapies. We treated a forty-four year old woman affected by widespread ulcerative NL with 6 sessions of topical ALA-PDT at two weeks intervals. At the end of the treatment a dramatic improvement of the clinical features was observed, with complete healing of cutaneous ulcers and marked reduction of erythema in all the treated areas. The mechanism of action of PDT in ulcer healing is still unknown; however, it is possible to hypothesize a combination of anti-inflammatory effect, immunomodulatory activity and keratinocytes photoactivation.

Ulcerated necrobiosis lipoidica to a teenager with diabetes mellitus and obesity.

Many skin lesions are associated with diabetes mellitus (DM) type 1 or 2, due to the use of antidiabetics or to metabolic and endocrine disorders caused by this disease. Necrobiosis lipoidica (NL) occurs more frequently in patients with DM. Painful ulcerations may occur on NL areas in about 20-25% of the cases and usually they are related to trauma. We present the case of a teenager, male, 17-year-old, having NL with multiple plaques, some of them spontaneously ulcerated after about 33 months of onset. He is known with type 1 DM from 2.5 years and the NL preceding the diagnosis of diabetes mellitus with about six months, presented erythematous-infiltrative skin plaques, some ulcerated for about three months, interesting both shins. Based on clinical, histopathological and paraclinical examinations, we established the following diagnoses: ulcerated NL, type 1 DM, moderate mixed dyslipidemia, class I obesity; commissural candidiasis, juvenile acne. Under treatment with Pentoxifyllinum, Sulodexidum, Ketotifenum and topical therapy with 0.2% Hyaluronic acid two months later, we have managed to heal two of the three ulcerated plaques and of the third has become superficial. We applied 0.5% Fluocortolonum on non-ulcerated plaques recording an improvement after two weeks of treatment. NL is a skin disease with a predilection for the shins, more frequent in patients with diabetes and is a part of palisading granulomatous dermatitis, which leads to skin atrophy. NL is found in the 0.3-1.2% of diabetic patients and is rare in children with diabetes (0.006%). It is more common in the patients with type 1 DM. The onset is in the third decade in diabetic patients and in the fourth decade in non-diabetics. There is no consensus concerning the treatment of NL, and the results are often modest. Antiplatelet agents, corticosteroids (local and general), immunomodulatory drugs, cyclins, wide synthetic antipaludics, heparin, Thalidomide are used. NL treatment is very difficult, especially in the ulcerated forms. Many of the drugs listed have proven efficacy only in isolated cases. Studies are necessary on large series of patients to determine the optimal therapy of NL.

Selective case study describing the use of Apligraf on necrobiosis lipoidica associated with diabetes.

Necrobiosis lipoidica is a rare skin disease characterised by large, well-demarcated, symmetrical plaques with overlying telangiectasias and atrophic, fibrotic features. The disease is associated with diabetes mellitus (1 in 300 cases), but can also be linked to other diseases such as rheumatoid arthritis. Women are three times more likely to develop necrobiosis lipoidica compared to men. Ulcerations are the most serious type of complications in necrobiosis lipoidica, and they occur most frequently on the legs of patients. However, the aetiology of necrobiosis lipoidica still remains unclear. Although many studies have been conducted in order to determine necrobiosis lipoidica's pathophysiology, a clear and definite path to disease has not been recorded. In this case study, a patient with necrobiosis lipoidica that had been refractory to conventional therapy received treatment with Apligraf® bioengineered wound dressings. Apligraf was shown to be effective in managing the patient's multiple hard-to-heal wounds. It was more successful than previous therapies in achieving granulation tissue formation and wound volume reduction, in addition to being a more rapid form of treatment.

Necrobiotic granulomatous tattoo reaction: report of an unusual case showing features of both necrobiosis lipoidica and granuloma annulare patterns.

The application of decorative tattoos to the skin is an ancient practice, which continues to be popular in the present day. Increasingly, a number of complications of tattoo application are recognized, including a diverse variety of cutaneous hypersensitivity reactions to tattoo pigments. Herein we describe an unusual case of a necrobiotic granulomatous tattoo reaction showing combined features of necrobiosis lipoidica and early granuloma annulare. The relevant literature is reviewed, and the practical significance of such unusual histological features as a part of the tattoo reaction is discussed.