Treatment options for necrobiosis lipoidica: a systematic review.

BACKGROUND: Necrobiosis lipoidica (NL) is a rare, idiopathic, and recalcitrant disease of collagen degeneration for which treatment options have been poorly studied. Due to its recurring nature, risk for ulceration, and high morbidity, there is a need to understand existing treatment modalities to better inform clinical care. OBJECTIVE: This review aims to describe the therapeutic modalities reported in the literature for the treatment of NL. METHODS: A literature search of treatments was performed by searching for publications between January 2016 and May 2022 on PubMed and Scopus. Given the limited high-quality evidence, case reports and series were included. Only publications presenting information on both attempted treatments and outcomes were included. RESULTS: A total of 60 novel articles were identified (54 case reports, two case series, and four retrospective cohort studies). These studies cumulatively reported on 274 patients and covered treatments including phototherapy, topical corticosteroids, topical calcineurin inhibitors, biologics, immunosuppressants, JAK inhibitors, combination therapies, and several others. The greatest amount of evidence was found for photodynamic therapy (improvement in 72 of 80 patients), UVA-based phototherapy (12 of 33), topical corticosteroids (21 of 46), compression therapy (15 of 20), and topical calcineurin inhibitors (11 of 17). Several newer treatments were also described, including ustekinumab and JAK inhibitors. CONCLUSIONS: This systematic review provides a comprehensive summary of recently published treatments for NL. As the existing data comes predominantly from case reports and series, statistical conclusions are not assessed. A greater number of randomized controlled trials with standardized endpoints are necessary to compare treatment efficacy.

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.

Laser and light therapies for the treatment of necrobiosis lipoidica.

Necrobiosis lipoidica (NL) is a rare, inflammatory granulomatous skin disorder involving collagen degeneration. In recent years, several light and laser therapies have been proposed and used in the treatment of NL with variable outcomes. The aim of the study was to investigate the efficacy and safety of lasers and light therapies for the treatment of NL. A review of PubMed was conducted to search for studies using laser and light therapies for the treatment of NL. Articles that employed a combination of treatment modalities were excluded. Twenty-four studies were reviewed. Light and laser therapies used in these studies included CO2 laser, pulsed dye laser, methyl aminolevulinate (MAL)-photodynamic therapy (PDT), aminolevulinic acid (ALA)-PDT, ultraviolet A1 (UVA1) phototherapy, and psoralen plus ultraviolet-A (PUVA). PUVA was identified as the modality with the most available evidence (7 studies), followed by MAL-PDT and ALA-PDT (5 studies each), pulsed dye laser and UVA1 (3 studies each), and lastly CO2 laser (2 studies). Most modalities demonstrated variable efficacies and side effects with the exception of PDL, which consistently showed successful outcomes. Multiple dermatologic light and laser therapies have been investigated for the treatment of NL, including PUVA, ALA-PDT, MAL-PDT, pulsed dye laser, UVA1, and CO2 laser. However, a clear consensus on the preferred treatment is yet to be addressed. Each treatment option demonstrates both advantages and disadvantages that should be discussed with patients when selecting the treatment modality.

Necrobiosis lipoidica with superimposed pyoderma vegetans.

Necrobiosis lipoidica (NL) is a granulomatous inflammatory skin disease strongly associated with diabetes mellitus (DM). Red-brown papules expanding into plaques with erythematous indurated borders on the lower extremities are characteristic of NL. Diagnosis is made clinically; however, biopsy of lesions confirms the diagnosis. Untreated NL may ulcerate and lead to further complications, but progression to superimposed pyoderma vegetans (PV) is not a known occurrence.

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.

Update: Treatment of necrobiosis lipoidica.

Necrobiosis lipoidica (NL) is a rare granulomatous disease of hitherto unclear etiology frequently seen in patients with diabetes. Characterized by its potential for ulcerations, it often presents a serious burden for those affected. There are currently neither German nor European guidelines for the treatment of NL. At the same time, standard treatment with topical or intralesional corticosteroids does not always show satisfactory results. We therefore set out to evaluate whether the various treatment regimens published since 2000 have actually expanded the therapeutic armamentarium in a relevant manner. Included were all publications that described more than one patient being treated with any given therapeutic modality. Overall, we analyzed data for 16 different treatment regimens reported in 49 publications. The largest amount of data exists for topical PUVA therapy, photodynamic therapy (PDT), and systemic treatment with fumaric acid esters. Remarkably, our analysis showed that with an increase in the number of documented patients treated with a given therapeutic modality, the proportion of those achieving a complete or partial response actually decreased. This was interpreted as publication bias. Thus, no clear recommendation can be given for second-line therapy in case topical or intralesional corticosteroids fail.

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.

Ulcerated necrobiosis lipoidica as a rare cause for chronic leg ulcers: case report series of ten patients.

Necrobiosis lipoidica is a rare granulomatous disorder of the skin. In up to 30% of the affected patients it can lead to ulcerations, which can impair the quality of life and are also very difficult to treat. Its pathogenesis is not fully understood. Only few studies focussing on necrobiosis lipoidica can be found, but none of them focus on ulcerated necrobiosis lipoidica. Therefore, we collected demographic data and comorbidities and assessed treatment options for patients with ulcerated necrobiosis lipoidica. Data of patients who were treated in the wound care centre of the University Hospital of Essen for ulcerated necrobiosis lipoidica over the past 10 years were retrospectively analysed. Hence, data of altogether ten patients (nine women and one man) with ulcerated necrobiosis lipoidica were collected. Of these, 70% of the patients had diabetes mellitus of which 30% had type I diabetes and 40% had type II diabetes; 60% of the patients suffered from arterial hypertension, obesity and hypercholesterolaemia; 40% of the patients suffered from psychiatric disorders such as depression and borderline disorder. Our clinical data demonstrate an association of ulcerated necrobiosis lipoidica and aspects of metabolic syndrome. This leads to 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. 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, these related comorbidities should also be diagnosed and treated.

Effectiveness of platelet-rich plasma in healing necrobiosis lipoidica diabeticorum ulcers.

Necrobiosis lipoidica diabeticorum (NLD) is a chronic condition, which is characterized by single or multiple lesions on the legs, and occurs in 0.3% of patients with diabetes. Recently, platelet-rich plasma (PRP) has been used in several clinical settings to promote sustained healing and better outcome. We propose the use of PRP for the treatment of NLD-associated recalcitrant wounds. In this study, 15 patients were treated with homologous PRP; all showed marked enhancement in wound healing without any adverse effects. After PRP application, advanced dressings were used until closure of the lesion was obtained, which was complete for all our patients. We therefore propose the use of PRP for recalcitrant wounds in patients with NLD.

Necrobiosis lipoídica en paciente diabético tipo 1: reporte de un caso / Necrobiosis lipodica in a type 1 diabetic patient: case report

La necrobiosis lipoídica es una enfermedad crónica granulomatosa de la piel de origen desconocido, que se caracteriza por placas inflamatorias amarronadas con bordes indurados y centro atrófico. Dos tercios de los casos se reportan en pacientes diabéticos, con predominio en el sexo femenino. Se describe el caso de una mujer de 18 años de edad con diagnóstico de diabetes tipo 1 de más de 15 años de evolución, en tratamiento con insulina detemir 88 U/día, con inadecuada adherencia al tratamiento y mal control metabólico. Presentó lesiones hipotróficas en cara anterior de ambas piernas (región pretibial derecha y antepié izquierdo), de centro ulcerado, no dolorosas, con bordes indurados, de meses de evolución. Se realizó diagnóstico de necrobiosis lipoídica mediante biopsia de piel. La paciente mejoró con tratamiento local de las lesiones (corticoides intralesionales y antibióticos tópicos) y adecuado control de la glucemia. En la literatura se discuten numerosas opciones de tratamiento, pero no existen recomendaciones terapéuticas firmes basadas en estudios controlados.

Necrobiosis lipoidica is a chronic granulomatous skin disease of unknown origin characterized by inflammatory plaques with indurated edges and brownish atrophic center. Two thirds of cases are reported in diabetic patients, with a predominance in females. The case of a 18-year-old woman with type 1 diabetes for 15 years is described; she was on insulin detemir 88 U/day, with inadequate adherence to treatment and poor metabolic control. She presented painless hypotrophic dermic lesions in the anterior aspect of both legs and in the left forefoot; they had ulcerated center and indurated edges; the evolution was chronic (several months). Diagnosis of necrobiosis lipoidica was made by skin biopsy. The patient improved with local treatment of lesions (intradermic steroids and topical antibiotics) and adequate glycemic control. In the literature many treatment options are discussed, but there are no firm therapeutic recommendations based on controlled studies.

Necrobiosis lipoídica en paciente diabético tipo 1: reporte de un caso / Necrobiosis lipodica in a type 1 diabetic patient: case report

La necrobiosis lipoídica es una enfermedad crónica granulomatosa de la piel de origen desconocido, que se caracteriza por placas inflamatorias amarronadas con bordes indurados y centro atrófico. Dos tercios de los casos se reportan en pacientes diabéticos, con predominio en el sexo femenino. Se describe el caso de una mujer de 18 años de edad con diagnóstico de diabetes tipo 1 de más de 15 años de evolución, en tratamiento con insulina detemir 88 U/día, con inadecuada adherencia al tratamiento y mal control metabólico. Presentó lesiones hipotróficas en cara anterior de ambas piernas (región pretibial derecha y antepié izquierdo), de centro ulcerado, no dolorosas, con bordes indurados, de meses de evolución. Se realizó diagnóstico de necrobiosis lipoídica mediante biopsia de piel. La paciente mejoró con tratamiento local de las lesiones (corticoides intralesionales y antibióticos tópicos) y adecuado control de la glucemia. En la literatura se discuten numerosas opciones de tratamiento, pero no existen recomendaciones terapéuticas firmes basadas en estudios controlados. (AU)

Necrobiosis lipoidica is a chronic granulomatous skin disease of unknown origin characterized by inflammatory plaques with indurated edges and brownish atrophic center. Two thirds of cases are reported in diabetic patients, with a predominance in females. The case of a 18-year-old woman with type 1 diabetes for 15 years is described; she was on insulin detemir 88 U/day, with inadequate adherence to treatment and poor metabolic control. She presented painless hypotrophic dermic lesions in the anterior aspect of both legs and in the left forefoot; they had ulcerated center and indurated edges; the evolution was chronic (several months). Diagnosis of necrobiosis lipoidica was made by skin biopsy. The patient improved with local treatment of lesions (intradermic steroids and topical antibiotics) and adequate glycemic control. In the literature many treatment options are discussed, but there are no firm therapeutic recommendations based on controlled studies. (AU)

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.

Necrobiosis lipoidica diabeticorum: necrobiosis lipoidica diabeticorum in a Nigerian from the north. A case report.

BACKGROUND: Necrobiosis lipoidica is a rare complication of diabetes mellitus.It is said to occur more often in people with diabetes,a family history of diabetes,tendency to develop diabetes mellitus and those with insulin dependent diabetes. METHOD: We report an evaluated case of necrobiosis lipoidica diabeticorum residing in the northern part of Nigeria. RESULT: The patient was treated for 3 weeks in the hospital on admission and was followed up in the general-out-patient department (GOPD) and has been in good health. AIM AND OBJECTIVE: To bring to the fore of clinicians this dermal complication of diabetes mellitus, the different medical treatments available and the medical treatment employed in our index patient. CONCLUSION: That necrobiosis lipoidica diabeticorum does exist in our environment and requires a high index of suspicion and scrupplelousness in making the diagnosis and treating the patient.

Treatment of ulcerated necrobiosis lipoidica with ovine forestomach matrix.

Necrobiosis lipoidica (NL) results from degradation of the collagen extracellular matrix; these recurring ulcerated lesions are an especially challenging condition to treat. Ovine forestomach matrix (OFM) is a decellularised extracellular matrix and was used to successfully close a pretibial ulcer resulting from NL. Complete closure of the wound was achieved in 22 weeks, after four applications of OFM. This suggests OFM may be considered for the treatment of these challenging wounds.

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.

[Lipoid necrobiosis in the practical work of a therapist and dermatologist].

This paper deals with the main aspects of etiology and pathogensis, clinical picture and therapy of lipoid necrobiosis. A case of successful treatment of the disease that developed long before clinical and laboratory manifestations of disturbed carbohydrate metabolism is reported.

Atypical ulcers.

Atypical ulcers of the skin challenge the dermatologist with respect to recognition, diagnosis, management, and treatment. The entire gamut of pathogenic categories including vascular, inflammatory, neoplastic, genetic, medication-related, and infectious processes may give rise to atypical ulcers. By definition, these ulcers are unusual, and accurate diagnosis may ultimately require the clinician to violate the dictum that "common things are common." Atypical ulcers may present with features that the clinician has not previously encountered, or may present with seemingly typical features that actually mislead due to phenotypic mimicry. Because skin ulcers are inherently tissue-destructive, and may reflect an underlying systemic disease process, there is heightened urgency to achieving an accurate diagnosis and initiating appropriate therapy.

Necrobiosis lipoidica de localizacion atipica / Necrobiosis lipoidica in unusual location

La necrobiosis lipoidica constituye una dermatosis de origen desconocido incluida dentro de los procesos con granulomas necrobi¢ticos. La necrobiosis lipoidicase presenta en la mayor¡a de los casos con una morfolog¡a e histolog¡a caracter¡sticas y diagn¢sticas y son muy poco frecuentes las formas at¡picas. Se presenta el caso de una paciente mujer de 75 a¤os de edad con un tiempo de enfermedad de cuatro meses, que acude a la consulta por una lesi¢n papuloeritematosa de 0,5 cm, en la regi¢n proximal posterior del brazo izquierdo, con leve prurito espor dico. Esta lesi¢n fue aumentando de tama¤o, hasta alcanzar aproximadamente 4 cm, y presenta un cambio de coloraci¢n (viol cea) y dolor a la fricci¢n o roce.

The necrobiosis lipoidica is a dermatosis of unknown origin included within the processes with necrobiotic granuloma, necrobiosis lipoidica. The presents in most cases with a morphology and histology and diagnostic features are rare and atypical. We report the case al a female patient aged 75 with a time of 4 months disease presents with a lesion 010,5 cm erythematous papulo in posterior proximal region o] the left arm, with occasional mild pruritus. The lesion was increasing in size (up to about 4 cm) and features color change (purple) and pain to friction.