RARE DISEASE
Necrobiosis lipoidica
Necrobiosis lipoidica
Necrobiosis lipoidica
Synonyms: Oppenheim-Urbach disease
Synonyms: Oppenheim-Urbach disease
Synonyms: Oppenheim-Urbach disease
Drug discovery
1
drug
With orphan designation
Overview
Necrobiosis Lipoidica (NL) is a rare, chronic granulomatous disorder characterized by collagen degeneration, granuloma formation, and dermal vascular changes. It classically presents as asymptomatic, yellow-brown atrophic plaques on the pretibial regions, with potential ulceration. Though strongly associated with diabetes (11–65% of cases), it also occurs in non-diabetic individuals. Pathogenesis involves immune dysregulation, microangiopathy, and metabolic factors. Treatment remains challenging, with no universal standard of care [1][6][10].
Population
Predominantly affects females (3:1 female-to-male ratio) and individuals aged 30–50 years [7][10].
Diabetes linkage: 65–71% of cases occur in those with diabetes (both type 1 and type 2), though prevalence in diabetic populations is only 0.3–1.2% [1][7][16].
Associated comorbidities: obesity, hypertension, thyroid disease (19–24%), and dyslipidemia [2][10][12].
Burden
Chronicity: 50–75% of lesions persist indefinitely; spontaneous remission occurs in <20% [1][6][9].
Morbidity: Ulceration in 12–35% of cases, risk of secondary infection, and scarring [3][6][9].
Psychosocial impact: Cosmetic disfigurement and reduced quality of life due to recalcitrant lesions [10][12].
Therapies
First-line: Topical/intralesional corticosteroids (improvement in 45% of cases) [3][6][9].
Advanced options: Photodynamic therapy (72/80 cases improved), UV phototherapy, systemic immunomodulators (e.g., cyclosporine, JAK inhibitors), and biologics (e.g., ustekinumab) [3][8][14].
Adjunctive measures: Aspirin, pentoxifylline, hyperbaric oxygen, and compression therapy for ulcer management [4][6][8].
Categories: rare skin diseases
Research Papers
220 drug discovery papers about Necrobiosis lipoidica, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
220 drug discovery papers about Necrobiosis lipoidica, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-10 | Necrobiosis Lipoidica Mimicking Chronic Infectious Ulceration: A Case Report and Literature Review
Necrobiosis lipoidica (NL) is a rare, granulating autoimmune disease that can be quite difficult to diagnose. It has a higher incidence in diabetic patients than in the general population. Diagnosis often depends upon both clinical and histopathologic examinations. It has a frequent association with diabetes, metabolic syndrome (obesity, hypertension, high cholesterol), and thyroid diseases. This is the case of a 50-year-old male patient who developed ulcerative skin lesions that were refractory to antibiotic therapy. He underwent antibiotic treatments for about two years, as well as multiple surgical debridement with skin grafting. However, the lesions continued to recur. Finally, after two years, a diagnosis of NL was made. He was subsequently prescribed steroids and immunologics, which improved his symptoms significantly. NL treatment is determined by whether the lesions are ulcerative or not. Typically, management will begin with topical corticosteroids and advance to systemic treatments as indicated. Surgical interventions are generally not recommended, as this disease is known to have pathergy. NL is a rare disease that is difficult to diagnose. It can be mistaken for an infectious etiology, like in our case. Due to the difficulty in diagnosing the disease, treatment can be delayed and, in turn, result in unintended harm to the patient with unnecessary procedures. In the future, there should be further investigation into the pathogenesis of this disease and advancement of diagnostic tools for earlier, accurate diagnosis.
2026-07-02 | Orthopaedic Implant Surgery or Trauma as a Trigger for Necrobiosis Lipoidica: A Manifestation of an Immunocompromised Cutaneous District?
Necrobiosis lipoidica (NL) is a rare chronic granulomatous skin disorder most commonly associated with diabetes mellitus, typically presenting in middle-aged women. We report an unusual case of NL in a young, non-diabetic male following orthopedic surgery involving a metallic implant. The patient developed characteristic well demarcated, atrophic, violaceous-brown plaques with violaceous borders localized over shin area of his left lower leg. Histopathological examination confirmed the diagnosis of NL, showing palisading granulomas with necrobiosis and lipid-laden macrophages. Notably, there was no history of diabetes, hypothyroidism, glucose intolerance, or autoimmune disease. This case highlights a rare presentation of NL potentially triggered by local immune dysregulation by trauma, surgery and the presence of a metallic implant. The report underscores the importance of considering NL in the differential diagnosis of persistent postsurgical cutaneous lesions, even in non-diabetic individuals, and raises questions about trauma, implant-related immune dysregulation, or microvascular changes as possible pathophysiological mechanisms.
2026-05-25 | Pediatric necrobiosis lipoidica: Adults and kids are not the same
N ecrobiosis lipoidica (NL) is a rare cutaneous granulomatous disorder of unknown etiology.1 In adults, it has been variably associated with diabetes mellitus (DM). 1 NL is less well described in pediatric patients due to its rarity.2 We conducted a descriptive retrospective chart review of NL pediatric cases from 1980 to 2025 at CHU Sainte-Justine, Montreal, Canada.Patients were included who were younger than 18 years of age at the time NL was diagnosed clinically or by histology and supported by photography.Descriptive analyses were used.In our cohort of 10 children with NL (Table I), 8 were girls, and 90% of patients had type 1 diabetes (T1DM).The mean age at diagnosis of DM was 4.5 years old, and 12.7 years for NL.Eight had a poor control of their DM with a mean HbA1c at 10.3%.Seven patients had classic pretibial plaques (Fig 1).All our patients received a variety of topical treatments as first line therapy (high-potency corticosteroids, calcineurin inhibitors, lactic acid, retinoid, or JAKinhibitors).Topicals conferred improved control of symptoms with limited improvement in appearance.Four patients agreed to intralesional corticosteroid injections (triamcinolone acetonide 3-10 mg/mL) that provided partial improvement on disease activity, meaning a slight decrease in reported symptoms and the absence of enlargement of the skin lesions or
2026-04-29 | Deuterated Pentoxifylline Analog in the Treatment of Necrobiosis Lipoidica: A Nonrandomized Clinical Trial.
Necrobiosis lipoidica (NL) is a rare, chronic granulomatous skin disease for which no US Food and Drug Administration (FDA)-approved treatments exist. PCS499, an oral deuterated pentoxifylline analog, may offer therapeutic benefit. To evaluate the safety and exploratory efficacy of PCS499 in adults with biopsy-confirmed NL. A phase 2, open-label nonrandomized clinical trial (from January 2019-February 2020) with a 6-month treatment period with an optional 6-month extension was conducted at the University of Pennsylvania and University of Pittsburgh dermatology research centers. Adults aged 18 to 80 years with biopsy-confirmed NL were eligible. Inclusion required a reference lesion of 10 cm2 or larger and Investigator Global Assessment (IGA) of NL activity score of 2 or greater (scale 0-5). Key exclusions were recent corticosteroid, immunosuppressant, biologic, phototherapy, or pentoxifylline-class use; significant comorbidities; and pregnancy or lactation. Data were analyzed in May 2025. PCS499, 900 mg, orally twice daily for 6 months, with optional 6-month extension. Safety was assessed through adverse event (AE) monitoring, laboratory testing, and electrocardiograms. Exploratory efficacy end points included changes from baseline in IGA, Physician Global Assessments and Patient Global Assessments (PGA, PtGA), NL Color and Ulcer Scale (NLCUS), Dermatology Life Quality Index (DLQI), and Skindex-29 scores. Twelve participants were enrolled (median [range] age, 41 [19-66] years; all female individuals; 10 [83%] with diabetes; mean [SD] disease duration, 12.7 [9.3] years), and 10 completed treatment. The most common AE was mild gastrointestinal symptoms (33%). No serious AEs or clinically significant laboratory abnormalities occurred. Participants with ulcerated NL (n = 2 [17%]) achieved complete ulcer closure by day 85 and day 351 without recurrence. Six participants (50%) achieved clear or almost clear IGA status (median [range] time, 111 [54-166] days). Significant improvements were observed in IGA activity (median [IQR] change, -1.5 [-2.0 to 0.0]; P = .03), PGA (median [IQR] change, -1.3 [-2.8 to -0.9]; P = .04), NLCUS inflammation/color (median [IQR] change, -1.0 [-1.8 to 0.0]; P = .02), and induration (median [IQR] change, -1.0 [-2.0 to 0.0]; P = .04), and Skindex-29 function scores (median [IQR] change, -14.6 [-27.1 to 3.1]; P = .05). This nonrandomized clinical trial found that PCS499 was safe and well tolerated, with evidence of clinical and quality-of-life improvement, particularly in ulcerated NL; however, larger trials are warranted. ClinicalTrials.gov Identifier: NCT03698864.
2026-01-12 | Ulcerative Necrobiosis Lipoidica in the Setting of Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma and Glucose-6-Phosphate Dehydrogenase Deficiency.
Necrobiosis lipoidica (NL) is a chronic granulomatous disease most commonly manifesting as yellow, atrophic plaques and ulcerations on the lower extremities. We present an exacerbation of NL in a patient with a known history of glucose-6-phosphate dehydrogenase deficiency, who, following a clinical and histopathologic diagnosis of NL, was found to have oropharyngeal Epstein-Barr virus-positive diffuse large B-cell lymphoma. After implementation of therapies for lymphoma, chemotherapeutic complications, and NL, the patient reported improvement in both pain and ulcerations. Though noninfectious granulomatous reactions are common in lymphoproliferative disorders, the skin is rarely involved. This case presentation provides evidence for an association between NL and underlying lymphoma development and encourages clinicians to rule out lymphomatous processes in the setting of reoccurring or recalcitrant noninfectious cutaneous granulomas.
cell therapies
2022-08-26 | Lower leg reconstruction after resection of a squamous cell carcinoma on necrobiosis lipoidica with a pedicled fibula and an extended anterolateral thigh flap – A case report
Abstract Background : Extensive loss of soft tissue and bone due to neoplasia, trauma or infection in extremities often lead to amputation. Case presentation: We present the case of a 72 year old female patient presenting with an extended cutaneous scquamous cell carcinoma of the lower leg, developed on top of necrobiosis lipoidica. After achieving the R0 resection, a 26X20 cm soft tissue and 15 cm tibial bone defect resulted. The contralateral leg had been lost due to the same disease 18 years before. We achieved a successfull reconstruction of the leg using a pedicled fibula transplantation, an extended anterolateral thigh perforator flap and an internal fixation with plate and screws. Two years after the original surgery the patient is relaps-free and mobile, with adequate function of the reconstructed foot. Conclusions: Our case presented a unique combination of pedicled fibula transplantation and free extended ALT perforator flap to reconstruct an extensive defect after resection of a rare cSCC on top of NL. In selected cases, the boundaries of limb salvage can be pushed far beyond the current standards of treatment.
2013-07-01 | 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.
2012-07-23 | Treatment of intractable skin ulcers caused by vascular insufficiency with allogeneic cultured dermal substitute: a report of eight cases.
Chronic leg ulcers have various causes and can be difficult to treat, although topical treatments, including basic fibroblast growth factor and PGE1, have been used. We applied an allogeneic cultured dermal substitute (CDS) to eight patients with intractable ulcers. The patients had various underlying diseases, including diabetes mellitus, systemic lupus erythematosus, antiphospholipid syndrome, necrobiosis lipoidica, stasis dermatitis, livedo vasculopathy, and rheumatoid arthritis. The CDS was prepared by seeding cultured human fibroblasts on a spongy matrix consisting of hyaluronic acid and atelocollagen. Good clinical results were achieved, as demonstrated by reepithelization, healthy granulation tissue formation, and a subsequent decrease in wound size. Daily dressing changes became unnecessary when the allogeneic CDS was used. Based on these results, we suggest that CDS may be useful for the treatment of intractable skin ulcers.
2011-11-01 | Resolution of Long-Standing Necrobiosis Lipoidica Diabeticorum (NLD) Lesion After Restoration of Euglycemia Following Successful Pancreas After Kidney (PAK) Transplantation: A Case Report
Necrobiosis lipoidica diabeticorum (NLD) is an inflammatory skin disorder of unknown cause which can be seen in patients with diabetes mellitus. Various treatments, including immunosuppressive agents have been tried, without consistent efficacy. NLD is generally thought not to correlate well with tight diabetic control. Pancreas transplantation is the only widely and clinically used treatment that restores euglycemia in type I diabetic recipients. We report a case of resolution of NLD that had been unchanged for decades before pancreas after kidney transplantation. Another unique aspect of our case was that immunosuppression was discounted as a confounding factor, because the patient had been exposed to the same antirejection regimen for 3 years preceding the pancreas transplantation.
2009-08-18 | Does pancreas transplant in diabetic patients affect the evolution of necrobiosis lipoidica?
Abstract Background Necrobiosis lipoidica (NL) is a non‐infectious granulomatous skin disorder, with average age of onset is between 30 to 41 years, and female : male ratio of 3 : 1. The strongest systemic disease associated is diabetes mellitus (DM). Many treatment options are used for NL with variable success. To verify if reversal of the diabetic state is related to improvement of NL, we compared the evolution of NL lesions in patients who received a pancreas transplant with those who received a kidney. Methods Retrospective chart review of diabetic patients with NL who underwent transplant. Results A total of fifteen patients were identified and divided into two groups: group I ( n = 11) consisted of patients who underwent pancreas only or pancreas plus kidney transplant, group II ( n = 4) underwent kidney only transplant. Of the eleven patients in Group I, five had NL lesions at the time of transplant and all achieved resolution of these lesions. One patient experienced recurrence of NL associated with transplant rejection. In group II, one patient who had NL lesions at the time of transplant had persistent lesions after the transplant. Resolution of NL was observed in 45% (five/eleven) of the cases in the pancreas +/− kidney transplant group, whereas the one patient who had active NL and kidney transplant failed to demonstrate improvement of the lesion after the procedure, despite the concomitant use of immunosuppressant therapy. Conclusions Patients experienced improvement of NL within 2–8 weeks following pancreas transplantation. Metabolic changes, improvement of the microcirculation and normalization of blood glucose levels may be playing a role in the resolution of NL.
antibodies
2025-04-25 | Psoriasis in Obese Adolescents with Diabetes-From Common Molecular Background to Vicious Circle of Metabolic Syndrome-Case Report and Review of Literature.
Psoriasis and type 1 diabetes mellitus (T1DM) are chronic autoimmune diseases sharing common immunological pathways, particularly the involvement of interleukin 17 (IL-17), driving Th17-mediated inflammation. This review explores the overlap between psoriasis, obesity, T1DM, and necrobiosis lipoidica (NL), a skin condition associated with diabetes. Obesity exacerbates inflammation through immune cell activation in adipose tissue and the release of proinflammatory adipokines, such as leptin, resistin, and IL-18, which enhance autoimmune responses and insulin resistance. Leptin promotes the differentiation of Th1 and Th17 cells, which are central to autoimmune responses in both psoriasis and T1DM. The coexistence of psoriasis, T1DM, and insulin resistance further complicates metabolic control, increasing the risk of complications like diabetic nephropathy and cardiovascular disease. Biologic treatments targeting IL-17A and IL-17F offer promising therapeutic options for managing both skin and metabolic symptoms. The early identification and management of metabolic risk factors, along with personalized interventions, are essential to improve clinical outcomes in patients with psoriasis and T1DM, particularly in obese individuals. This case report and review highlight the complex interplay of these conditions and emphasize the need for integrated treatment strategies.
2025-03-10 | Treatment of Refractory Extensive Ulcerative Necrobiosis Lipoidica With Infliximab
The authors declare no conflicts of interest.
2023-09-25 | Post-traumatic ulcerated and chronic necrobiosis lipoidica of the elbow: A new entity?
Necrobiosis lipoidica (NL) is a chronic granulomatous dermatosis usually affecting the lower limbs, although less common sites have been described. Herein we report a series of cases of NL located on the elbow, with an unusual presentation and occurring after trauma or surgery. Our series includes three men and one woman, with a mean age of 64 years. Three had undergone surgery for elbow bursitis and one had had trauma after a fall from a horse, with exposure of subcutaneous tissue prior to healing. Within 5 years, they had all developed an atrophic erythematous annular plaque with papular and telangiectatic edges, with recurrent episodes of ulceration and scarring. Repeated tests for infectious agents were negative. Histological examinations showed granulomas and necrobiosis with palisading or early-stage palisading. Partial healing was achieved in two patients after 6 months of doxycycline. Treatment with adalimumab resulted in disappearance of the ulcers at 6 months in one patient. Unusual sites of NL impose consideration of other types of palisading granuloma or mycobacterial infections, which we were able to rule out. Two other cases of NL of the elbow similar to ours are reported in the literature. These cases, involving multiple ulcerations over a very long period of time, probably constitute a distinct entity because of the very distinct character of these 6 cases. Tetracyclines are partially active and tumour necrosis factor alpha (TNF)-alpha inhibitors may offer an option.
2023-08-10 | Successful treatment of necrobiosis lipoidica and associated retinal vasculitis with tumor necrosis factor (TNF)-alpha inhibitor.
To report the clinical and histopathologic features of necrobiosis lipoidica and associated retinal vasculitis and describe successful treatment of both skin and eye manifestations with adalimumab, a tumor necrosis factor (TNF)-alpha inhibitor. A 35-year-old patient with bipolar disorder and ocular hypertension was referred for evaluation of bilateral retinal vasculitis. Fluorescein angiography revealed bilateral occlusive retinal vasculitis. Physical exam was notable for multiple annular and round erythematous hyperpigmented and atrophic patches and plaques on both lower extremities. Skin biopsy revealed a diagnosis of necrobiosis lipoidica, a rare granulomatous skin disease. Both the patient's retinal vasculitis and skin patches responded favorably to treatment with adalimumab, a TNF-alpha inhibitor. This case highlights the importance of obtaining a complete history and physical exam in patients who present with ocular inflammation, as extraocular manifestations of disease may be present. It also demonstrates the effectiveness of a multidisciplinary approach to evaluation and management of these patients, as both skin and eye involvement were successfully treated with adalimumab, a TNF-alpha inhibitor.
2023-08-10 | Molecularly Targeted Therapies for Inflammatory Cutaneous Granulomatous Disorders: A Review of the Evidence and Implications for Understanding Disease Pathogenesis
Inflammatory cutaneous granulomatous diseases, including granuloma annulare, cutaneous sarcoidosis, and necrobiosis lipoidica, are distinct diseases unified by the hallmark of macrophage accumulation and activation in the skin. There are currently no Food and Drug Administration–approved therapies for these conditions except prednisone and repository corticotropin injection for pulmonary sarcoidosis. Treatment of these diseases has generally been guided by low-quality evidence and may involve broadly immunomodulatory medications. Development of new treatments has in part been limited by an incomplete understanding of disease pathogenesis. Recently, there has been substantial progress in better understanding the molecular pathogenesis of these disorders, opening the door for therapeutic innovation. Likewise, reported outcomes of treatment with immunologically targeted therapies may offer insights into disease pathogenesis. In this systematic review, we summarize progress in deciphering the pathomechanisms of these disorders and discuss this in the context of emerging evidence on the use of molecularly targeted therapies in treatment of these diseases. Inflammatory cutaneous granulomatous diseases, including granuloma annulare, cutaneous sarcoidosis, and necrobiosis lipoidica, are distinct diseases unified by the hallmark of macrophage accumulation and activation in the skin. There are currently no Food and Drug Administration–approved therapies for these conditions except prednisone and repository corticotropin injection for pulmonary sarcoidosis. Treatment of these diseases has generally been guided by low-quality evidence and may involve broadly immunomodulatory medications. Development of new treatments has in part been limited by an incomplete understanding of disease pathogenesis. Recently, there has been substantial progress in better understanding the molecular pathogenesis of these disorders, opening the door for therapeutic innovation. Likewise, reported outcomes of treatment with immunologically targeted therapies may offer insights into disease pathogenesis. In this systematic review, we summarize progress in deciphering the pathomechanisms of these disorders and discuss this in the context of emerging evidence on the use of molecularly targeted therapies in treatment of these diseases.
proteins
2025-10-01 | MON-631 Double Diabetes Case Series: A Hybrid Pathology Requiring Hybrid Therapy
Abstract Disclosure: J.S. Martins Torrontegui: None. L.L. Ponce Rosas: None. A. Al-Thunaibat: None. P.S. Sidhu: None. A. Abualnil: None. C. Penaherrera: None. From the time when the Ebers Papyrus first described symptoms resembling diabetes to the recent classification of its various forms, one central concept has remained: the link between hyperglycemia and its characteristic symptoms. While the core pathology (hyperglycemia) has always unified these disorders, the depth of our understanding has allowed for increasingly precise descriptions and classifications of what we now recognize as a diverse group of metabolic diseases. As our knowledge has advanced, it may now be time to formally recognize a new category within this group: Type 1.5 diabetes, or double diabetes. This hybrid condition is more common than previously thought, with approximately 1 in 4 individuals with Type 1 diabetes mellitus (T1DM) presenting features of Type 2 diabetes mellitus (T2DM), such as metabolic syndrome, adding insulin resistance to the autoimmune basis of T1DM. This reflects a complex overlap of genetic, metabolic, and environmental factors, and may warrant distinct recognition in both diagnosis and management. We present a case series of four patients with double diabetes. The first case is a 24-year-old woman with T1DM who developed polycystic ovary syndrome (PCOS), progressively increasing insulin requirements, and significant weight gain despite no changes in dietary habits. The second case is a 68-year-old woman diagnosed with T1DM at age 19 and treated with an insulin pump for 10 years, who presented with acanthosis nigricans, and rising insulin needs following chemotherapy and corticosteroid treatment for uterine cancer. The third case involves a 38-year-old woman with childhood-onset T1DM who reported difficulty losing weight and developed morbid obesity, hyperlipidemia, acanthosis nigricans, and elevated insulin requirements. The final case is a 26-year-old woman with a medical history including necrobiosis lipoidica diabeticorum, PCOS, obesity, hypothyroidism, and T1DM, who required over 120 units of insulin daily to achieve glycemic control, features consistent with T2DM pathophysiology. Notably, all patients in this series demonstrated significant improvement in glycemic control after the initiation of GLP-1 receptor agonist therapy. These cases raise an important question: Since patients with double diabetes exhibit both insulin resistance and autoimmune-driven β-cell destruction, shouldn’t we also address the insulin resistance directly with the therapy? Given that intensive insulin therapy is often associated with weight gain and subsequent insulin resistance, glucose-lowering drugs seem to be a reasonable option to be added to patients already treated with insulin. Additionally, could GLP-1a help manage this dual pathology by addressing insulin resistance, weight gain and glucose control? Further investigation is needed to identify and develop appropriate recommendations for the effective management of double diabetes. Presentation: Monday, July 14, 2025
small molecules
2026-08-10 | Necrobiosis Lipoidica Mimicking Chronic Infectious Ulceration: A Case Report and Literature Review
Necrobiosis lipoidica (NL) is a rare, granulating autoimmune disease that can be quite difficult to diagnose. It has a higher incidence in diabetic patients than in the general population. Diagnosis often depends upon both clinical and histopathologic examinations. It has a frequent association with diabetes, metabolic syndrome (obesity, hypertension, high cholesterol), and thyroid diseases. This is the case of a 50-year-old male patient who developed ulcerative skin lesions that were refractory to antibiotic therapy. He underwent antibiotic treatments for about two years, as well as multiple surgical debridement with skin grafting. However, the lesions continued to recur. Finally, after two years, a diagnosis of NL was made. He was subsequently prescribed steroids and immunologics, which improved his symptoms significantly. NL treatment is determined by whether the lesions are ulcerative or not. Typically, management will begin with topical corticosteroids and advance to systemic treatments as indicated. Surgical interventions are generally not recommended, as this disease is known to have pathergy. NL is a rare disease that is difficult to diagnose. It can be mistaken for an infectious etiology, like in our case. Due to the difficulty in diagnosing the disease, treatment can be delayed and, in turn, result in unintended harm to the patient with unnecessary procedures. In the future, there should be further investigation into the pathogenesis of this disease and advancement of diagnostic tools for earlier, accurate diagnosis.
2026-07-02 | Orthopaedic Implant Surgery or Trauma as a Trigger for Necrobiosis Lipoidica: A Manifestation of an Immunocompromised Cutaneous District?
Necrobiosis lipoidica (NL) is a rare chronic granulomatous skin disorder most commonly associated with diabetes mellitus, typically presenting in middle-aged women. We report an unusual case of NL in a young, non-diabetic male following orthopedic surgery involving a metallic implant. The patient developed characteristic well demarcated, atrophic, violaceous-brown plaques with violaceous borders localized over shin area of his left lower leg. Histopathological examination confirmed the diagnosis of NL, showing palisading granulomas with necrobiosis and lipid-laden macrophages. Notably, there was no history of diabetes, hypothyroidism, glucose intolerance, or autoimmune disease. This case highlights a rare presentation of NL potentially triggered by local immune dysregulation by trauma, surgery and the presence of a metallic implant. The report underscores the importance of considering NL in the differential diagnosis of persistent postsurgical cutaneous lesions, even in non-diabetic individuals, and raises questions about trauma, implant-related immune dysregulation, or microvascular changes as possible pathophysiological mechanisms.
2026-05-25 | Pediatric necrobiosis lipoidica: Adults and kids are not the same
N ecrobiosis lipoidica (NL) is a rare cutaneous granulomatous disorder of unknown etiology.1 In adults, it has been variably associated with diabetes mellitus (DM). 1 NL is less well described in pediatric patients due to its rarity.2 We conducted a descriptive retrospective chart review of NL pediatric cases from 1980 to 2025 at CHU Sainte-Justine, Montreal, Canada.Patients were included who were younger than 18 years of age at the time NL was diagnosed clinically or by histology and supported by photography.Descriptive analyses were used.In our cohort of 10 children with NL (Table I), 8 were girls, and 90% of patients had type 1 diabetes (T1DM).The mean age at diagnosis of DM was 4.5 years old, and 12.7 years for NL.Eight had a poor control of their DM with a mean HbA1c at 10.3%.Seven patients had classic pretibial plaques (Fig 1).All our patients received a variety of topical treatments as first line therapy (high-potency corticosteroids, calcineurin inhibitors, lactic acid, retinoid, or JAKinhibitors).Topicals conferred improved control of symptoms with limited improvement in appearance.Four patients agreed to intralesional corticosteroid injections (triamcinolone acetonide 3-10 mg/mL) that provided partial improvement on disease activity, meaning a slight decrease in reported symptoms and the absence of enlargement of the skin lesions or
2026-04-29 | Deuterated Pentoxifylline Analog in the Treatment of Necrobiosis Lipoidica: A Nonrandomized Clinical Trial.
Necrobiosis lipoidica (NL) is a rare, chronic granulomatous skin disease for which no US Food and Drug Administration (FDA)-approved treatments exist. PCS499, an oral deuterated pentoxifylline analog, may offer therapeutic benefit. To evaluate the safety and exploratory efficacy of PCS499 in adults with biopsy-confirmed NL. A phase 2, open-label nonrandomized clinical trial (from January 2019-February 2020) with a 6-month treatment period with an optional 6-month extension was conducted at the University of Pennsylvania and University of Pittsburgh dermatology research centers. Adults aged 18 to 80 years with biopsy-confirmed NL were eligible. Inclusion required a reference lesion of 10 cm2 or larger and Investigator Global Assessment (IGA) of NL activity score of 2 or greater (scale 0-5). Key exclusions were recent corticosteroid, immunosuppressant, biologic, phototherapy, or pentoxifylline-class use; significant comorbidities; and pregnancy or lactation. Data were analyzed in May 2025. PCS499, 900 mg, orally twice daily for 6 months, with optional 6-month extension. Safety was assessed through adverse event (AE) monitoring, laboratory testing, and electrocardiograms. Exploratory efficacy end points included changes from baseline in IGA, Physician Global Assessments and Patient Global Assessments (PGA, PtGA), NL Color and Ulcer Scale (NLCUS), Dermatology Life Quality Index (DLQI), and Skindex-29 scores. Twelve participants were enrolled (median [range] age, 41 [19-66] years; all female individuals; 10 [83%] with diabetes; mean [SD] disease duration, 12.7 [9.3] years), and 10 completed treatment. The most common AE was mild gastrointestinal symptoms (33%). No serious AEs or clinically significant laboratory abnormalities occurred. Participants with ulcerated NL (n = 2 [17%]) achieved complete ulcer closure by day 85 and day 351 without recurrence. Six participants (50%) achieved clear or almost clear IGA status (median [range] time, 111 [54-166] days). Significant improvements were observed in IGA activity (median [IQR] change, -1.5 [-2.0 to 0.0]; P = .03), PGA (median [IQR] change, -1.3 [-2.8 to -0.9]; P = .04), NLCUS inflammation/color (median [IQR] change, -1.0 [-1.8 to 0.0]; P = .02), and induration (median [IQR] change, -1.0 [-2.0 to 0.0]; P = .04), and Skindex-29 function scores (median [IQR] change, -14.6 [-27.1 to 3.1]; P = .05). This nonrandomized clinical trial found that PCS499 was safe and well tolerated, with evidence of clinical and quality-of-life improvement, particularly in ulcerated NL; however, larger trials are warranted. ClinicalTrials.gov Identifier: NCT03698864.
2026-01-12 | Ulcerative Necrobiosis Lipoidica in the Setting of Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma and Glucose-6-Phosphate Dehydrogenase Deficiency.
Necrobiosis lipoidica (NL) is a chronic granulomatous disease most commonly manifesting as yellow, atrophic plaques and ulcerations on the lower extremities. We present an exacerbation of NL in a patient with a known history of glucose-6-phosphate dehydrogenase deficiency, who, following a clinical and histopathologic diagnosis of NL, was found to have oropharyngeal Epstein-Barr virus-positive diffuse large B-cell lymphoma. After implementation of therapies for lymphoma, chemotherapeutic complications, and NL, the patient reported improvement in both pain and ulcerations. Though noninfectious granulomatous reactions are common in lymphoproliferative disorders, the skin is rarely involved. This case presentation provides evidence for an association between NL and underlying lymphoma development and encourages clinicians to rule out lymphomatous processes in the setting of reoccurring or recalcitrant noninfectious cutaneous granulomas.
cell therapies
2022-08-26 | Lower leg reconstruction after resection of a squamous cell carcinoma on necrobiosis lipoidica with a pedicled fibula and an extended anterolateral thigh flap – A case report
Abstract Background : Extensive loss of soft tissue and bone due to neoplasia, trauma or infection in extremities often lead to amputation. Case presentation: We present the case of a 72 year old female patient presenting with an extended cutaneous scquamous cell carcinoma of the lower leg, developed on top of necrobiosis lipoidica. After achieving the R0 resection, a 26X20 cm soft tissue and 15 cm tibial bone defect resulted. The contralateral leg had been lost due to the same disease 18 years before. We achieved a successfull reconstruction of the leg using a pedicled fibula transplantation, an extended anterolateral thigh perforator flap and an internal fixation with plate and screws. Two years after the original surgery the patient is relaps-free and mobile, with adequate function of the reconstructed foot. Conclusions: Our case presented a unique combination of pedicled fibula transplantation and free extended ALT perforator flap to reconstruct an extensive defect after resection of a rare cSCC on top of NL. In selected cases, the boundaries of limb salvage can be pushed far beyond the current standards of treatment.
2013-07-01 | 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.
2012-07-23 | Treatment of intractable skin ulcers caused by vascular insufficiency with allogeneic cultured dermal substitute: a report of eight cases.
Chronic leg ulcers have various causes and can be difficult to treat, although topical treatments, including basic fibroblast growth factor and PGE1, have been used. We applied an allogeneic cultured dermal substitute (CDS) to eight patients with intractable ulcers. The patients had various underlying diseases, including diabetes mellitus, systemic lupus erythematosus, antiphospholipid syndrome, necrobiosis lipoidica, stasis dermatitis, livedo vasculopathy, and rheumatoid arthritis. The CDS was prepared by seeding cultured human fibroblasts on a spongy matrix consisting of hyaluronic acid and atelocollagen. Good clinical results were achieved, as demonstrated by reepithelization, healthy granulation tissue formation, and a subsequent decrease in wound size. Daily dressing changes became unnecessary when the allogeneic CDS was used. Based on these results, we suggest that CDS may be useful for the treatment of intractable skin ulcers.
2011-11-01 | Resolution of Long-Standing Necrobiosis Lipoidica Diabeticorum (NLD) Lesion After Restoration of Euglycemia Following Successful Pancreas After Kidney (PAK) Transplantation: A Case Report
Necrobiosis lipoidica diabeticorum (NLD) is an inflammatory skin disorder of unknown cause which can be seen in patients with diabetes mellitus. Various treatments, including immunosuppressive agents have been tried, without consistent efficacy. NLD is generally thought not to correlate well with tight diabetic control. Pancreas transplantation is the only widely and clinically used treatment that restores euglycemia in type I diabetic recipients. We report a case of resolution of NLD that had been unchanged for decades before pancreas after kidney transplantation. Another unique aspect of our case was that immunosuppression was discounted as a confounding factor, because the patient had been exposed to the same antirejection regimen for 3 years preceding the pancreas transplantation.
2009-08-18 | Does pancreas transplant in diabetic patients affect the evolution of necrobiosis lipoidica?
Abstract Background Necrobiosis lipoidica (NL) is a non‐infectious granulomatous skin disorder, with average age of onset is between 30 to 41 years, and female : male ratio of 3 : 1. The strongest systemic disease associated is diabetes mellitus (DM). Many treatment options are used for NL with variable success. To verify if reversal of the diabetic state is related to improvement of NL, we compared the evolution of NL lesions in patients who received a pancreas transplant with those who received a kidney. Methods Retrospective chart review of diabetic patients with NL who underwent transplant. Results A total of fifteen patients were identified and divided into two groups: group I ( n = 11) consisted of patients who underwent pancreas only or pancreas plus kidney transplant, group II ( n = 4) underwent kidney only transplant. Of the eleven patients in Group I, five had NL lesions at the time of transplant and all achieved resolution of these lesions. One patient experienced recurrence of NL associated with transplant rejection. In group II, one patient who had NL lesions at the time of transplant had persistent lesions after the transplant. Resolution of NL was observed in 45% (five/eleven) of the cases in the pancreas +/− kidney transplant group, whereas the one patient who had active NL and kidney transplant failed to demonstrate improvement of the lesion after the procedure, despite the concomitant use of immunosuppressant therapy. Conclusions Patients experienced improvement of NL within 2–8 weeks following pancreas transplantation. Metabolic changes, improvement of the microcirculation and normalization of blood glucose levels may be playing a role in the resolution of NL.
antibodies
2025-04-25 | Psoriasis in Obese Adolescents with Diabetes-From Common Molecular Background to Vicious Circle of Metabolic Syndrome-Case Report and Review of Literature.
Psoriasis and type 1 diabetes mellitus (T1DM) are chronic autoimmune diseases sharing common immunological pathways, particularly the involvement of interleukin 17 (IL-17), driving Th17-mediated inflammation. This review explores the overlap between psoriasis, obesity, T1DM, and necrobiosis lipoidica (NL), a skin condition associated with diabetes. Obesity exacerbates inflammation through immune cell activation in adipose tissue and the release of proinflammatory adipokines, such as leptin, resistin, and IL-18, which enhance autoimmune responses and insulin resistance. Leptin promotes the differentiation of Th1 and Th17 cells, which are central to autoimmune responses in both psoriasis and T1DM. The coexistence of psoriasis, T1DM, and insulin resistance further complicates metabolic control, increasing the risk of complications like diabetic nephropathy and cardiovascular disease. Biologic treatments targeting IL-17A and IL-17F offer promising therapeutic options for managing both skin and metabolic symptoms. The early identification and management of metabolic risk factors, along with personalized interventions, are essential to improve clinical outcomes in patients with psoriasis and T1DM, particularly in obese individuals. This case report and review highlight the complex interplay of these conditions and emphasize the need for integrated treatment strategies.
2025-03-10 | Treatment of Refractory Extensive Ulcerative Necrobiosis Lipoidica With Infliximab
The authors declare no conflicts of interest.
2023-09-25 | Post-traumatic ulcerated and chronic necrobiosis lipoidica of the elbow: A new entity?
Necrobiosis lipoidica (NL) is a chronic granulomatous dermatosis usually affecting the lower limbs, although less common sites have been described. Herein we report a series of cases of NL located on the elbow, with an unusual presentation and occurring after trauma or surgery. Our series includes three men and one woman, with a mean age of 64 years. Three had undergone surgery for elbow bursitis and one had had trauma after a fall from a horse, with exposure of subcutaneous tissue prior to healing. Within 5 years, they had all developed an atrophic erythematous annular plaque with papular and telangiectatic edges, with recurrent episodes of ulceration and scarring. Repeated tests for infectious agents were negative. Histological examinations showed granulomas and necrobiosis with palisading or early-stage palisading. Partial healing was achieved in two patients after 6 months of doxycycline. Treatment with adalimumab resulted in disappearance of the ulcers at 6 months in one patient. Unusual sites of NL impose consideration of other types of palisading granuloma or mycobacterial infections, which we were able to rule out. Two other cases of NL of the elbow similar to ours are reported in the literature. These cases, involving multiple ulcerations over a very long period of time, probably constitute a distinct entity because of the very distinct character of these 6 cases. Tetracyclines are partially active and tumour necrosis factor alpha (TNF)-alpha inhibitors may offer an option.
2023-08-10 | Successful treatment of necrobiosis lipoidica and associated retinal vasculitis with tumor necrosis factor (TNF)-alpha inhibitor.
To report the clinical and histopathologic features of necrobiosis lipoidica and associated retinal vasculitis and describe successful treatment of both skin and eye manifestations with adalimumab, a tumor necrosis factor (TNF)-alpha inhibitor. A 35-year-old patient with bipolar disorder and ocular hypertension was referred for evaluation of bilateral retinal vasculitis. Fluorescein angiography revealed bilateral occlusive retinal vasculitis. Physical exam was notable for multiple annular and round erythematous hyperpigmented and atrophic patches and plaques on both lower extremities. Skin biopsy revealed a diagnosis of necrobiosis lipoidica, a rare granulomatous skin disease. Both the patient's retinal vasculitis and skin patches responded favorably to treatment with adalimumab, a TNF-alpha inhibitor. This case highlights the importance of obtaining a complete history and physical exam in patients who present with ocular inflammation, as extraocular manifestations of disease may be present. It also demonstrates the effectiveness of a multidisciplinary approach to evaluation and management of these patients, as both skin and eye involvement were successfully treated with adalimumab, a TNF-alpha inhibitor.
2023-08-10 | Molecularly Targeted Therapies for Inflammatory Cutaneous Granulomatous Disorders: A Review of the Evidence and Implications for Understanding Disease Pathogenesis
Inflammatory cutaneous granulomatous diseases, including granuloma annulare, cutaneous sarcoidosis, and necrobiosis lipoidica, are distinct diseases unified by the hallmark of macrophage accumulation and activation in the skin. There are currently no Food and Drug Administration–approved therapies for these conditions except prednisone and repository corticotropin injection for pulmonary sarcoidosis. Treatment of these diseases has generally been guided by low-quality evidence and may involve broadly immunomodulatory medications. Development of new treatments has in part been limited by an incomplete understanding of disease pathogenesis. Recently, there has been substantial progress in better understanding the molecular pathogenesis of these disorders, opening the door for therapeutic innovation. Likewise, reported outcomes of treatment with immunologically targeted therapies may offer insights into disease pathogenesis. In this systematic review, we summarize progress in deciphering the pathomechanisms of these disorders and discuss this in the context of emerging evidence on the use of molecularly targeted therapies in treatment of these diseases. Inflammatory cutaneous granulomatous diseases, including granuloma annulare, cutaneous sarcoidosis, and necrobiosis lipoidica, are distinct diseases unified by the hallmark of macrophage accumulation and activation in the skin. There are currently no Food and Drug Administration–approved therapies for these conditions except prednisone and repository corticotropin injection for pulmonary sarcoidosis. Treatment of these diseases has generally been guided by low-quality evidence and may involve broadly immunomodulatory medications. Development of new treatments has in part been limited by an incomplete understanding of disease pathogenesis. Recently, there has been substantial progress in better understanding the molecular pathogenesis of these disorders, opening the door for therapeutic innovation. Likewise, reported outcomes of treatment with immunologically targeted therapies may offer insights into disease pathogenesis. In this systematic review, we summarize progress in deciphering the pathomechanisms of these disorders and discuss this in the context of emerging evidence on the use of molecularly targeted therapies in treatment of these diseases.
proteins
2025-10-01 | MON-631 Double Diabetes Case Series: A Hybrid Pathology Requiring Hybrid Therapy
Abstract Disclosure: J.S. Martins Torrontegui: None. L.L. Ponce Rosas: None. A. Al-Thunaibat: None. P.S. Sidhu: None. A. Abualnil: None. C. Penaherrera: None. From the time when the Ebers Papyrus first described symptoms resembling diabetes to the recent classification of its various forms, one central concept has remained: the link between hyperglycemia and its characteristic symptoms. While the core pathology (hyperglycemia) has always unified these disorders, the depth of our understanding has allowed for increasingly precise descriptions and classifications of what we now recognize as a diverse group of metabolic diseases. As our knowledge has advanced, it may now be time to formally recognize a new category within this group: Type 1.5 diabetes, or double diabetes. This hybrid condition is more common than previously thought, with approximately 1 in 4 individuals with Type 1 diabetes mellitus (T1DM) presenting features of Type 2 diabetes mellitus (T2DM), such as metabolic syndrome, adding insulin resistance to the autoimmune basis of T1DM. This reflects a complex overlap of genetic, metabolic, and environmental factors, and may warrant distinct recognition in both diagnosis and management. We present a case series of four patients with double diabetes. The first case is a 24-year-old woman with T1DM who developed polycystic ovary syndrome (PCOS), progressively increasing insulin requirements, and significant weight gain despite no changes in dietary habits. The second case is a 68-year-old woman diagnosed with T1DM at age 19 and treated with an insulin pump for 10 years, who presented with acanthosis nigricans, and rising insulin needs following chemotherapy and corticosteroid treatment for uterine cancer. The third case involves a 38-year-old woman with childhood-onset T1DM who reported difficulty losing weight and developed morbid obesity, hyperlipidemia, acanthosis nigricans, and elevated insulin requirements. The final case is a 26-year-old woman with a medical history including necrobiosis lipoidica diabeticorum, PCOS, obesity, hypothyroidism, and T1DM, who required over 120 units of insulin daily to achieve glycemic control, features consistent with T2DM pathophysiology. Notably, all patients in this series demonstrated significant improvement in glycemic control after the initiation of GLP-1 receptor agonist therapy. These cases raise an important question: Since patients with double diabetes exhibit both insulin resistance and autoimmune-driven β-cell destruction, shouldn’t we also address the insulin resistance directly with the therapy? Given that intensive insulin therapy is often associated with weight gain and subsequent insulin resistance, glucose-lowering drugs seem to be a reasonable option to be added to patients already treated with insulin. Additionally, could GLP-1a help manage this dual pathology by addressing insulin resistance, weight gain and glucose control? Further investigation is needed to identify and develop appropriate recommendations for the effective management of double diabetes. Presentation: Monday, July 14, 2025
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Drug Discovery Landscape
1 orphan drug designation for Necrobiosis lipoidica.
1 orphan drug designation for Necrobiosis lipoidica.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
deuterated S-lisofylline | small molecules | FDA | 2018-06-18 | — | Processa Pharmaceuticals Inc |
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