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.

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.

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.

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.

Update on necrobiosis lipoidica: a review of etiology, diagnosis, and treatment options.

Necrobiosis lipoidica (NL) is a rare chronic granulomatous disease that has historically been associated with diabetes mellitus. Debate exists regarding the etiology and pathogenesis of NL with a widely accepted theory that microangiopathy plays a significant role. NL typically presents clinically as erythematous papules on the front of the lower extremities that can coalesce to form atrophic telangiectatic plaques. NL is usually a clinical diagnosis, but if the clinical suspicion is uncertain, skin biopsy specimen can help differentiate it from sarcoidosis, necrobiotic xanthogranuloma, and granuloma annulare. NL is a difficult disease to manage despite a large armamentarium of treatment options that include topical and intralesional corticosteroids, immunomodulators, biologics, platelet inhibitors, phototherapy, and surgery. Randomized control trials are lacking to evaluate the many treatment methods and establish a standard regimen of care. Disease complications such as ulceration are common, and lesions should also be monitored for transition to squamous cell carcinoma, a less common sequelae.

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.

[Breast repaired by silicone implant. Case report of necrobiosis lipoidica]. / Nécrobiose lipoïdique sur sein reconstruit par implant en silicone : à propos d'un cas.

The authors report a very rare case of necrobiosis lipoidica, histopathologically confirmed, which happened in the breast a few months following the insertion of a silicone implant (post-mastectomy reconstruction). This case raises two problems: the physiopathology (role of the silicone implant) and the treatment of this accident, resistant to current therapy.

Necrobiosis lipoidica.

A 58-year-old woman presented with a seven-year history of an eruption on her lower legs that was associated with edema, weeping, pruritus, and a burning sensation. Past medical history included Hashimoto thyroiditis, which was diagnosed eight years prior to presentation. Histopathologic examination was consistent with necrobiosis lipoidica (NL). To our knowledge, NL that is associated with Hashimoto thyroiditis has been described in only one prior report. NL is a chronic, cutaneous, granulomatous condition with degenerative connective-tissue changes of unknown etiology. Our patient responded well to a potent topical glucocorticoid and topical tretinoin. Although our patient did not have diabetes mellitus, 75 percent of patients with NL have diabetes mellitus at the time of diagnosis or will subsequently develop diabetes mellitus. This association with diabetes mellitus mandates screening for glucose intolerance in all patients with NL.

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.

Necrobiosis lipoidica therapy with biologicals: an ulcerated case responding to etanercept and a review of the literature.

Necrobiosis lipoidica (NL) is an idiopathic chronic granulomatous skin condition. There is currently no standardized effective treatment of NL. Ulceration occurs in up to 35% of cases. Treatment of ulcerative lesions is challenging and often unsuccessful. On the basis of the implication of the tumor necrosis factor alpha (TNF-alpha) on the formation of granulomas, since 2003 anti-TNF-alpha agents have been employed in cases of NL refractory to other therapeutic agents. We report a 50-year-old white woman with treatment-resistant chronic ulcerative NL of both shins successfully treated with subcutaneous etanercept. A review of the published literature suggests that biological agents (etanercept and infliximab) should be considered as a therapeutic alternative mainly in ulcerative NL unresponsive to prior conventional regimens. The dose and duration of treatment with these agents is not defined, therefore it is required to report management of these patients in order to develop an optimal therapeutic strategy.

Links between granuloma annulare, necrobiosis lipoidica diabeticorum and childhood diabetes: a matter of time?

Diabetes mellitus is associated with a range of dermatologic presentations, including granuloma annulare and necrobiosis lipoidica diabeticorum. Granuloma annulare occurs earlier than necrobiosis lipoidica diabeticorum and the association with diabetes mellitus is much weaker. We describe two children with diabetes who both developed granuloma annulare and later, necrobiosis lipoidica diabeticorum. We postulate that the early onset and transient nature of granuloma annulare, compared with the later onset and persistence of necrobiosis lipoidica diabeticorum, might account for the different apparent rates of association with diabetes mellitus.

[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.

A case of perforating necrobiosis lipoidica in an African American female.

An African American female with type II diabetes of 4 years duration presents with a 3-year history of smooth firm, dark brown plaques focally studded with comedone-like papules. Clinically and histologically her lesions were consistent with the rare entity perforating necrobiosis lipoidica.

Perforating necrobiosis lipoidica in a girl with type 1 diabetes mellitus: a new case reported.

Necrobiosis lipoidica is an idiopathic dermatological condition that is strongly associated with diabetes mellitus. It is more commonly seen in women than men. The average age of onset is 30-40 years. Necrobiosis Lipoidica diabeticorum is an extremely rare finding in childhood diabetes. We describe the case of a 13-year-old girl who has had type 1 diabetes mellitus since she was 8 years old. The patient presented with 2 well-defined, persistent plaques with a depressed central area and elevated purple peripheral ring, one on the right thigh and the other over the lateral left leg. Histopathologic evaluation of the patient's biopsy confirmed the diagnosis of necrobiosis lipoidica with transfollicular elimination. Our patient is the second pediatric case described with perforating necrobiosis lipoidica. We review the literature and discuss clinical features, several complications, and the most recent treatment options for necrobiosis lipoidica in diabetic children.