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This disease is also referred to as necrobiosis lipoidica diabeticorum. There is still a close association with diabetes mellitus. The lesions present as red papules which enlarge to become shiny yellow-brown plaques with an atrophic center and raised red to purple edges. Ulceration may occur. The lesions most commonly occur on the legs (shins) as well as the forearms, hands, and trunk. They are frequently bilateral and multiple. Women are favored 3:1 with an average age of 34 years.

Diabetes mellitus is associated in 10-65% of cases. Conversely, only about 3 in 1000 cases of diabetics develop the disease. It is hypothesized that in early cases, a necrotizing vasculitis may be present.


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SYNONYMS Necrobiosis lipoidica diabeticorum



Granuloma annulare and necrobiosis lipoidica tissue reactions as a manifestation of systemic disease.

Magro CM, Crowson AN, Regauer S.

Department of Pathology, Beth Israel Hospital, Harvard Medical School, Boston, MA, USA

Hum Pathol 1996 Jan;27(1):50-6 Abstract quote

Granuloma annulare (GA) and necrobiosis lipoidica (NL) are generally considered to be idiopathic cutaneous palisading granulomatous dermatitides. There are sporadic reports of such lesions occurring in patients with coexistent systemic diseases other than diabetes mellitus.

Having encountered 49 patients whose skin biopsies showed GA or NL lesions in the setting of extracutaneous disease, the authors set out to assess their clinical and histopathological findings to determine if any parameters were predictive of underlying systemic disease.

Fifty-two skin biopsies from 49 patients having either GA or NL in whom there was a clinical history of an associated systemic disease were analyzed by light microscopy. The main systemic disease associations were rheumatologic, endocrine, hematologic, infectious, and inflammatory bowel diseases, ANCA positive vasculitic syndromes, and sarcoidosis. The clinical and histomorphological features were compared with those of a control group of patients whose skin biopsies showed GA or NL and in whom there was no history of extracutaneous disease. For the systemic disease group, patients were selected either retrospectively or prospectively from 160,000 cases accessioned in a 24-month period in the dermatopathology databases of Pathology Services, Inc (Cambridge, MA) and Central Medical Laboratories (Winnipeg, Canada). All systemic disease cases from the former service were analyzed blindly by the second author and from the latter service were analyzed blindly by the first author. Patients in the control group were obtained retrospectively from the Pathology Services Inc. database by the authors.

The location of the lesions was atypical in 30 of 34 biopsies from systemic disease patients with a GA tissue reaction versus 10 of 22 biopsies of GA in the control group (P = .001). Six of 18 biopsies from patients with NL tissue reactions in the systemic disease group showed an atypical location, versus only 1 of 9 biopsies of NL from the control group (P = .19). The clinical diagnostic considerations were much broader in the systemic disease group versus the control group and included vasculitis, panniculitis, and connective tissue diseases including morphea in the former.

In 22 of 34 GA biopsies and 16 of 18 NL biopsies from the systemic disease group, an active vasculopathy of leukocytoclastic, granulomatous, or thrombogenic subtypes was demonstrable. None of the GA or NL biopsies from the control group showed a similar active vasculopathy. An active vasculopathy was predictive of systemic disease in patients having either a GA-like or an NL-like tissue reaction (P < .001). Fifteen of 34 GA and 7 of 18 NL biopsies in the systemic diseases group showed extravascular neutrophilia in contrast to 3 of 22 GA (P = .02) biopsies and 2 of 9 NL (P = .33) biopsies in the control group.

The finding of an active vasculopathy in a skin biopsy specimen showing a GA- or NL-like tissue reaction, particularly in the setting of an atypical clinical presentation both with respect to the location and appearance of lesions, should prompt consideration of an underlying systemic disease, as should extravascular neutrophilia in a skin biopsy showing a GA-like tissue reaction.


Necrobiosis lipoidica: only a minority of patients have diabetes mellitus.

O'Toole EA, Kennedy U, Nolan JJ, Young MM, Rogers S, Barnes L.

Department of Dermatology, St James's Hospital and Trinity College Dublin, Ireland.

Br J Dermatol 1999 Feb;140(2):283-6 Abstract quote

Although it is commonly accepted that necrobiosis lipoidica (NL) is associated with diabetes mellitus (DM), there is some controversy regarding the degree of this association. In a retrospective review of 65 patients with NL attending our dermatology out-patient clinics we found that just seven (11%) were known to have DM at the time of presentation.

Seven further patients (11%) were diagnosed as having impaired glucose tolerance/DM at presentation and over a 15-year follow-up period. Thus, only a minority of our patients with NL had DM.

Light-chain-restricted plasmacellular infiltrates in necrobiosis lipoidica - a clue to an underlying monoclonal gammopathy.

Cioc AM, Frambach GE, Magro CM.

Department of Pathology, The Ohio State University, OH, USA.
J Cutan Pathol. 2005 Apr;32(4):263-7. Abstract quote  

Background: Necrobiosis lipoidica (NL) is a member of the palisading granulomatous dermatitides that is associated, in most cases, with diabetes mellitus. However, there are an increasing number of cases of NL associated with other forms of systemic disease. We describe a novel case of NL associated with a light-chain-restricted plasmacellular infiltrate; subsequent investigations established an underlying monoclonal gammopathy.

Methods: Skin biopsy material was obtained and was processed in the usual fashion for hematoxylin and eosin (H&E) examination. Immunohistochemical staining was performed by utilizing kappa and lambda monoclonal antibodies (Dako Corporation, Carpentiera, CA, USA). Kappa and lambda in situ hybridization was also performed (Ventana Medical Systems, Tucson, AZ, USA).

Results: A 55-year-old woman with a 5-year history of bilateral thigh subcutaneous nodules underwent a skin biopsy, showing typical changes of NL; there was a concomitant prominent perivascular plasmacellular infiltrate. Kappa light chain restriction was observed amid the plasmacellular infiltrate. Bone marrow biopsy and immunophenotyping studies revealed a clonal plasmacytosis with kappa light chain restriction.

Conclusions: Granulomatous inflammation, including NL, may be a cutaneous paraneoplastic expression of low-grade B-cell lymphoproliferative disease in the context of an underlying plasma cell dyscrasia.

Necrobiosis lipoidica diabeticorum: association with background retinopathy, smoking, and proteinuria. A case controlled study.

Kelly WF, Nicholas J, Adams J, Mahmood R.

Diabetes Care Centre, Middlesborough General Hospital, UK.

Diabet Med 1993 Oct;10(8):725-8 Abstract quote

In order to evaluate patients with necrobiosis lipoidica diabeticorum and to compare them with age, sex, and duration of diabetes matched controls, 15 patients with necrobiosis were each matched with 5 control subjects with diabetes mellitus.

Complications of diabetes, glycaemic control, and proteinuria were measured. Patients with necrobiosis (mean age 40, range 18-74 years) had a mean duration of diabetes of 14 (range 3-36) years; 8 patients were male, and 7 were female. For necrobiosis versus controls, background retinopathy (67% vs 27%, p = 0.009), proteinuria (53% vs 17%, p = 0.006), and smoking (60% vs 20%, p = 0.003) were all more common with necrobiosis. There were no significant differences between patients with necrobiosis and control patients in the prevalence of vascular disease and neuropathy. Glycosylated haemoglobin concentrations were higher in patients with necrobiosis (p = 0.02). Blood pressure measurements were similar in both groups.

We conclude that smoking, proteinuria, and retinopathy were more prevalent in diabetic patients with necrobiosis; the skin lesion may therefore share common aetiological factors which affect the microvascular circulation, leading to damage to basement membranes and vascular endothelial cells.

Necrobiosis lipoidica diabeticorum in children and adolescents: a clue for underlying renal and retinal disease.

Verrotti A, Chiarelli F, Amerio P, Morgese G.

Department of Pediatrics, University of Chieti, Italy.

Pediatr Dermatol 1995 Sep;12(3):220-3 Abstract quote

The prevalence of persistent microalbuminuria, retinopathy, and peripheral and autonomic neuropathy was assessed in 18 children and adolescents with type 1 (insulin-dependent) diabetes mellitus (IDDM) who suffered from necrobiosis lipoidica diabeticorum (NLD) and in 40 diabetics without NLD, matched for sex, age, duration of disease, and metabolic control.

The mean +/- SD age of the patients was 15.1 +/- 8.6 years (range 7.9-23.9 yrs) and their duration of IDDM was 10.9 +/- 8.1 years (range 7.1-21.0 yrs). Their mean glycosylated hemoglobin level was 9.9 +/- 5.0% (7.3-16.6%) and their fructosamine level was 274 +/- 180 mumol/L (199-466 mumol/L). Patients with NLD had a higher frequency of persistent microalbuminuria (p < 0.001) and retinopathy (p < 0.001) than those without NLD.

Our study suggests that children as well as adult diabetics with NLD can be at high risk for nephropathy and retinopathy; NLD can be a clue for diabetic nephropathy and retinopathy.



Expression of interstitial collagenase, 92-kDa gelatinase, and tissue inhibitor of metalloproteinases-1 in granuloma annulare and necrobiosis lipoidica diabeticorum.

Saarialho-Kere UK, Chang ES, Welgus HG, Parks WC.

Division of Dermatology, Jewish Hospital, Washington University Medical Center, St. Louis, MO 63110.

J Invest Dermatol 1993 Mar;100(3):335-42 Abstract quote

Granuloma annular (GA) and necrobiosis lipoidica diabeticorum (NLD) are disorders characterized by granulomatous inflammation and degenerative changes in collagen and elastic fibers. Because these disorders have often been described as being associated with altered extracellular matrix deposition, we studied the in situ expression of interstitial collagenase, 92-kDa gelatinase, and tissue inhibitor of metalloproteinases (TIMP)-1.

Twelve lesions each of GA and NLD of different histopathologic types and durations were examined. Interstitial collagenase mRNA was seen in histiocyte-like cells in one-third of the cases of both diseases, typically in younger lesions. In GA, collagenase mRNA was only detected in lesions of the palisading type. Signal for 92-kDa gelatinase mRNA was observed in eosinophils, which were present in low numbers in five of 12 GA and three of 12 NLD samples. The signal for this enzyme and the presence of eosinophils did not correlate with the age of lesion. TIMP-1 mRNA was consistently expressed by histiocyte-like cells in both disorders. In GA, TIMP-1 mRNA was detected at the outer edge of the palisading granulomas, but in NLD, inhibitor expression was seen in the perivascular and periadnexal accumulation of inflammatory cells.

Our data indicate that collagenase and TIMP are expressed early in these disorders and that these proteins may contribute to stromal remodeling associated with necrobiotic lesions.

Our results further indicate that the localization of TIMP-1 production may provide a distinction between the two disorders, whereas metalloproteinase expression is not sufficiently specific to aid in the differential diagnosis of GA and NLD.


Expression of the human erythrocyte glucose transporter glut-1 in areas of sclerotic collagen in necrobiosis lipoidica

Cheryl Holland, etal.

Journal of Cutaneous Pathology 2001;28 (6):287-290

Background: Glut-1 is the human erythrocyte glucose transporter which mediates facilitative transport of glucose across epithelial and endothelial barrier tissues. A primary abnormality in glucose transport and Glut-1 cell-surface content has been observed in fibroblasts from NIDDM and obese individuals. With the strong correlation between necrobiosis lipoidica and diabetes mellitus, we investigated the expression of Glut-1 in diabetic individuals with necrobiosis lipoidica (NL).

Methods: A polyclonal anti-Glut-1 antibody was used with a standard immunoperoxidase technique to determine Glut-1 expression by fibroblasts in areas of sclerotic collagen from specimens taken from diabetic individuals with necrobiosis lipoidica,and non-diabetic individuals with scars and granuloma annulare (GA).

Results: Our results showed Glut-1 expression in the areas of sclerotic collagen in patients with NL, possibly contributing to insulin resistance in these tissues.

Conclusions: Our findings raises the question as to whether abnormalities in glucose transport by fibroblasts in individuals with necrobiosis lipoidica contribute to the histopathologic changes.




HLA antigens and necrobiosis lipoidica diabeticorum--a comparison between insulin-dependent diabetics with and without necrobiosis.

Soler NG, McConnachie PR.

Postgrad Med J 1983 Dec;59(698):759-62 Abstract quote

To investigate whether HLA-A, -B, -C, and -DR alloantigen frequencies are different in diabetic patients with and without necrobiosis lipoidica diabeticorum we studied 37 insulin-dependent (Type I) diabetics, 15 with and 22 without necrobiosis, and 96 normal control subjects.

Compared to controls Type I diabetics had increased frequencies of B8, CW3, and DR4 and decreased frequencies of DR5 and DR7. Diabetics with necrobiosis differed from diabetics without necrobiosis only in that HLA-A2 was significantly less frequent in patients with necrobiosis.

It is suggested that the lack of major differences between patients with and without necrobiosis argues in favour of the role of metabolic and/or vascular rather than genetic factors in the aetiology of necrobiosis.



Necrobiosis lipoidica in a 9-year-old girl with new-onset type II diabetes mellitus.

Szabo RM, Harris GD, Burke WA.

University Health Systems of Eastern North Carolina-Pitt County Memorial Hospital, Greenville, North Carolina 27858-4354, USA.

Pediatr Dermatol 2001 Jul-Aug;18(4):316-9 Abstract quote

Necrobiosis lipoidica (NL) is an idiopathic dermatologic condition that is strongly associated with, but not pathognomonic for, diabetes mellitus. It is more commonly seen in women than men and in adults than children.

We present the youngest child, to our knowledge, diagnosed with NL at initial presentation with type II diabetes mellitus. We review the literature and discuss pathogenesis, clinical features, and treatment options for NL.

Recurrent necrobiosis lipoidica diabeticorum associated with venous insufficiency in an adolescent with poorly controlled type 2 diabetes mellitus.

Yigit S, Estrada E.

Pediatric Endocrinology and Diabetes, Connecticut Children's Medical Center, University of Connecticut, Hartford, CT 06106, USA.

J Pediatr 2002 Aug;141(2):280-2 Abstract quote

Type 2 diabetes mellitus and associated long-term complications have become a significant health problem in adolescents.

We report a 16-year-old girl with poorly controlled type 2 diabetes mellitus who had recurrent necrobiosis lipoidica diabeticorum associated with venous insufficiency.


General Superficial and deep perivascular and interstitial mixed inflammatory cell infiltrate. There are areas of necrobiosis with surrounding histiocytes and giant cells. The deeper dermis has lymphoid cell infiltrates. In older atrophic lesions, there is less necrobiosis and more dermal fibrosis. Fat may be present in the necrobiotic areas as well as mucin. Vessels show endothelial swelling to areas of a lymphocytic vasculitis.

Focal endothelial cell degeneration and proliferative endarteritis in trauma-induced early lesions of necrobiosis lipoidica diabeticorum.

Heng MC, Allen SG, Song MK, Heng MK.

Division of Dermatology, Veterans Administration Medical Center, Sepulveda, CA 91343.

Am J Dermatopathol 1991 Apr;13(2):108-14 Abstract quote

Microangiopathy is an essential component in diabetic vascular pathology. We report ultrastructural observations of ballooning degeneration involving isolated endothelial cells of cutaneous capillaries, while leaving adjacent endothelial cells relatively intact in six diabetic patients with early lesions of necrobiosis lipoidica induced by trauma. Focal proliferation of endothelial cells encroaching upon the vascular lumina (obliterative endarteritis) was also observed. Lectin studies on biopsy specimens of older lesions of necrobiosis lipoidica revealed paucity of dermal blood vessels.

These observations enable us to gain further insight into the pathophysiological mechanisms that underlie diabetic microvascular disease.


A new histopathologic feature of necrobiosis lipoidica diabeticorum: lymphoid nodules.

Alegre VA, Winkelmann RK.

Department of Dermatology, Mayo Clinic, Rochester, Minnesota 55905.

J Cutan Pathol 1988 Apr;15(2):75-7 Abstract quote

We have found a previously undescribed histopathologic feature of necrobiosis lipoidica diabeticorum among 310 biopsied cases: lymphoid nodules. This feature does not correlate with unique clinical lesions or forms of the disease.

The lymphoid nodules are similar in appearance to those in other chronic dermal inflammations.


Necrobiosis lipoidica: a case with prominent cholesterol clefting and transepithelial elimination.

De la Torre C, Losada A, Cruces MJ.

Service of Dermatology, Hospital Provincial, Pontevedra, Spain.

Am J Dermatopathol 1999 Dec;21(6):575-7 Abstract quote

Transepithelial elimination of degenerated collagen through the hair follicle in necrobiosis lipoidica is rare, clinically manifesting as comedo-like plugs. Also unusual in necrobiosis lipoidica is the finding of cholesterol cleft formation.

We report a case of necrobiosis lipoidica with transepithelial elimination of cholesterol crystals through hair follicles. This has been described in necrobiotic xanthogranuloma, demonstrating some overlap in the histopathologic findings in both necrobiotic granulomas. Additional criteria should be used to establish the diagnosis.



Epidermal dendritic S100 positive cells in necrobiosis lipoidica and granuloma annulare.

Chambers B, Milligan A, Fletcher A.

Department of Histopathology, Leicester Royal Infirmary, U.K.

Br J Dermatol 1990 Dec;123(6):765-8 Abstract quote

Using an antibody to S100 protein, the number of dendritic cells above the basal layer in the epidermis was assessed in necrobiosis lipoidica and granuloma annulare. A statistically significantly higher number of these cells was found within the epidermis in necrobiosis lipoidica compared with granuloma annulare and normal skin.

The numbers were similar to those seen in sarcoidosis and tuberculous reactions in the skin, which raises the possibility of an immune pathogenesis for necrobiosis lipoidica.

Direct immunofluorescence (DIF) Fibrin in the necrobiotic areas associated with IgM and C3 within the blood vessel walls. C3 and fibrinogen may be present at the dermoepidermal junction.

The cutaneous immunopathology of necrobiosis lipoidica diabeticorum.

Quimby SR, Muller SA, Schroeter AL.

Department of Dermatology, Mayo Clinic, Rochester, MN 55905.

Arch Dermatol 1988 Sep;124(9):1364-71 Abstract quote

Twelve female patients with necrobiosis lipoidica diabeticorum (six with diabetes and six without) had a 5-mm punch biopsy of the skin lesion performed. The tissue was processed for dermatopathologic examination in 12 cases and for direct immunofluorescence in 11. V

asculopathy with inflammation and thickening of vessel walls, at times leading to occlusion, was found in lesional skin in all 12 cases. Vessels contained deposits of immunoreactants in the involved skin in 11 cases. This included IgM in six, C3 in nine, fibrin in ten, IgG in one, and IgA in two.

Vessels contained deposits of immunoreactants in uninvolved skin in seven patients (C3 in four, IgM in three, fibrin in three, C4 in one, and IgA in one), three of whom had type I diabetes.


Necrobiosis lipoidica: ultrastructural and biochemical demonstration of a collagen defect.

Oikarinen A, Mortenhumer M, Kallioinen M, Savolainen ER.

J Invest Dermatol 1987 Feb;88(2):227-32 Abstract quote

Ten patients with necrobiosis lipoidica lesions were studied. Five patients had diabetes mellitus. The age of the patients varied from 15 to 73 years and the duration of the skin lesions was from 2 to 20 years.

Histologically, the lesions were characterized by degeneration of collagen and elastin. In some lesions elastin fibers could be seen in areas devoid of normal-looking collagen. Electron microscopy revealed loss of cross-striation of collagen fibrils and a marked variation in the diameter of individual collagen fibrils. The concentration of collagen, measured by assay of hydroxy-proline, a collagen-specific amino acid, was markedly decreased in the lesional skin, but the ratio of type I/III collagen was unchanged in the affected skin. Fibroblasts established from affected skin synthesized less collagen than cells derived from healthy-looking skin. The decreased collagen synthesis was due to a decreased amount of messenger RNA for type I procollagen, measured by hybridization with a specific human cDNA clone. The production of collagenase by these fibroblasts was not increased.

Our results thus indicate that in necrobiosis lipoidica lesions, collagen fibrils are defective and the amount of collagen is reduced, probably due to decreased synthesis of collagen by affected fibroblasts.



Necrobiosis lipoidica diabeticorum with cholesterol clefts in the differential diagnosis of necrobiotic xanthogranuloma.

Gibson LE, Reizner GT, Winkelmann RK.

Department of Dermatology, Mayo Clinic, Rochester, MN 55905.

J Cutan Pathol 1988 Feb;15(1):18-21 Abstract quote

The histopathologic findings in 331 cases of necrobiosis lipoidica diabeticorum seen during a 50-year period were reviewed.

Three cases showing cholesterol cleft formation were found. All 3 cases were associated with severe diabetes mellitus. The differential diagnosis of importance is necrobiotic xanthogranuloma. Common features included extensive hyaline necrobiosis and foreign-body giant cells. Atypical and Touton-type giant cells are more common in necrobiotic xanthogranuloma. Vascular changes in necrobiotic xanthogranuloma may include granulomatous involvement of muscular walls with thrombosis. Explanations for cholesterol cleft formation are offered.

When cholesterol clefts are seen in biopsy specimens of necrobiosis, necrobiotic xanthogranuloma must be ruled out. In addition, when found in necrobiosis lipoidica diabeticorum, these clefts may imply diabetes mellitus with complications.


Squamous cell carcinoma arising in an area of long-standing necrobiosis lipoidica.

Davies Campbell de Lambert, Rhodes, NSW, Australia.


J Cutan Pathol. 2006 Aug;33(8):581-3. Abstract quote

Squamous cell carcinoma in an area of chronic ulceration is a well-documented phenomenon. However, its occurrence arising de novo in an area of necrobiosis lipoidica is rare. We report a case in a 53-year-old female who presented with a 2 month history of an erythematous nodule occurring in a plaque of necrobiosis lipoidica on the medical aspect of the right lower leg. She had a background of poorly controlled Type 1 diabetes.

Histopathological findings revealed a well-differentiated squamous cell carcinoma overlying an area of necrobiosis lipoidica. Treatment was by excision and split-thickness skin graft.

Clinicians should be aware of malignant transformation within a plaque of necrobiosis lipoidica. Early detection will allow conservative treatment.

Squamous cell carcinoma in an area of necrobiosis lipoidica diabeticorum: a case report.

Gudi VS, Campbell S, Gould DJ, Marshall R.

Department of Dermatology, Treliske Hospital, Truro, UK

Clin Exp Dermatol 2000 Nov;25(8):597-9 Abstract quote

Ulceration in an area of necrobiosis lipoidica diabeticorum is a frequent complication but malignant transformation is rare.

One such case is reported in a diabetic patient and the literature is reviewed.

Squamous cell carcinoma developing in necrobiosis lipoidica.

Imtiaz KE, Khaleeli AA.

Halton General Hospital, Runcorn, UK.

Diabet Med 2001 Apr;18(4):325-8 Abstract quote

We describe a case of squamous cell carcinoma arising in long-standing necrobiosis lipoidica in a type 1 female diabetic patient. The tumour and the skin lesion were successfully excised and repaired with full thickness skin graft.

The development of squamous cell carcinoma in association with this skin disorder is rare (only four cases reported in literature since 1966), but should be considered in chronic, non-healing and recalcitrant ulcers developing within areas of necrobiosis lipoidica.


Necrobiosis lipoidica diabeticorum treated with chloroquine.

Nguyen K, Washenik K, Shupack J.

Department of Dermatology, The University of Texas-Houston Medical School, USA

J Am Acad Dermatol 2002 Feb;46(2 Suppl Case Reports):S34-6 Abstract quote

Necrobiosis lipoidica diabeticorum (NLD) is an idiopathic granulomatous skin disorder. We review previously described therapies from the recent literature and report the first case of successful treatment of NLD with oral chloroquine.


Persistent ulcerated necrobiosis lipoidica responding to treatment with cyclosporin.

Darvay A, Acland KM, Russell-Jones R.

Department of Dermatology, Ealing Hospital, Uxbridge Road, Southall, Middlesex UB1 3HW, UK.

Br J Dermatol 1999 Oct;141(4):725-7 Abstract quote

We report two patients with severe ulcerated necrobiosis lipoidica (NL) who responded to cyclosporin.

One patient had suffered persistent ulceration for a period of 7 years and the other had NL of recent onset. In both cases, ulceration healed completely after 4 months of therapy, and both patients have remained free of ulceration since discontinuing therapy.

The possible mode of action of cyclosporin in the context of this debilitating disease is discussed.


Healing of chronic leg ulcers in diabetic necrobiosis lipoidica with local granulocyte-macrophage colony stimulating factor treatment.

Remes K, Ronnemaa T.

Turku University Central Hospital, Department of Medicine, Finland.

J Diabetes Complications 1999 Mar-Apr;13(2):115-8 Abstract quote

Two young insulin-dependent diabetic patients suffering from chronic nonhealing leg ulcers of necrobiosis lipoidica diabeticorum were treated by applying topically recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) on the ulcer repetitively during 10 weeks.

Evaluation of ulcer size was assessed with clinical examinations at 1-week or 2-week intervals. Topical GM-CSF healed the ulcers of both patients in 10 weeks. Decrease in the size of the ulcers was already evident after the first topical applications. During follow-up, the ulcers have remained healed for more than 3 years.

This excellent treatment result suggests that topically applied GM-CSF may be a valuable drug for chronic, nonhealing ulcers in patients with diabetes.


Necrobiosis lipoidica: treatment by hyperbaric oxygen and local corticosteroids.

Bouhanick B, Verret JL, Gouello JP, Berrut G, Marre M.

Service de Medecine B, CHU, Angers, France.

Diabetes Metab 1998 Apr;24(2):156-9 Abstract quote

Necrobiosis lipoidica (NL) is closely associated with diabetes mellitus. Two-thirds to three-fourths of patients with NL have diabetes, although NL occurs in only 0.3% of diabetic patients. Typical lesions are found on pretibial skin, usually in young female diabetic patients whose disease is inadequately controlled. The cause of this dermopathy remains unknown. Multiple treatments have been described but have not led to consistent results.

We report the case of a 28-year-old insulin-dependent diabetic woman with a disease duration of 23 years who spontaneously developed ulcerated NL on pretibial skin. NL progressively improved during 113 sessions of hyperbaric oxygen therapy and local corticosteroids.


Necrobiosis lipoidica diabeticorum treated with the pulsed dye laser.

Moreno-Arias GA, Camps-Fresneda A.

Department of Dermatology, General Hospital of Catalonia, Sant Cugat del Valles, Barcelona, Spain.

J Cosmet Laser Ther 2001 Sep;3(3):143-6 Abstract quote

BACKGROUND AND OBJECTIVE: Different treatment modalities have been advocated for necrobiosis lipoidica diabeticorum but clinical response is unpredictable. The purpose of this study was to evaluate the usefulness of pulsed dye laser (Candela SPTL, Irvine, MA, USA) in the treatment of an area of necrobiosis lipoidica of 4 cm in diameter on the anterior aspect of the leg in a non-diabetic patient.

MATERIALS AND METHODS: A spot test was made at 6.0, 6.5 and 7.0 J/cm(2) energy fluences and the best energy fluence was selected after a 2-month postoperative evaluation. The patient received three treatment sessions with a fluence of 6.5 J/cm(2), 585-nm wavelength, 5-mm spot size, and 450 micro(s) pulse duration at 8-week intervals. The patient was given routine skin care advice with emollient cream and sunscreen (SPF 15) until the following session.

RESULTS: Overall cosmetic improvement was achieved, with a decrease of erythema and telangiectasis, and stabilization in terms of progression (size) in the left half of the lesion, with no modification of atrophy or pigmentary changes. The right upper quadrant of the lesion showed an erythematous peripheral halo with minimal reduction in the erythema and telangiectasia, and discrete size increase.

CONCLUSION: Pulsed dye laser may be a useful treatment for improving the telangiectasia and erythematous component of necrobiosis lipoidica.


Treatment of necrobiosis lipoidica with topical psoralen plus ultraviolet A.

De Rie MA, Sommer A, Hoekzema R, Neumann HA.

University of Amsterdam, Department of Dermatology, A0-222, Academic Medical Centre, PO Box 22660, the Netherlands.

Br J Dermatol 2002 Oct;147(4):743-7 Abstract quote

BACKGROUND: Necrobiosis lipoidica (NL) is a rare skin disease, mostly seen on the legs and often occurring in patients with diabetes mellitus. The disease belongs to the idiopathic cutaneous palisading granulomatous dermatitides associated with a degeneration of collagen, thus leading to skin atrophy. Application of topical corticosteroids is the most widely used treatment but the results are not always satisfactory and may worsen skin atrophy. Preliminary studies in patients with NL have shown a clinical response with psoralen plus ultraviolet (UV) A (PUVA). Objectives To study the effect of topical PUVA on NL in a multicentre prospective study.

METHODS: Thirty patients (27 women and three men) including 13 with insulin-dependent diabetes mellitus, with a diagnosis of NL proven by histopathology, were included. All patients had been unsuccessfully treated with topical and/or intralesional corticosteroids. Patients were treated twice weekly with an aqueous gel containing 0.005% psoralen followed by irradiation with UVA. Clinical photographs were taken for evaluation. In addition, 20-MHz high-frequency ultrasound analysis was performed in 10 patients to evaluate the thickness and density of the dermis during topical PUVA therapy.

RESULTS: Five patients (17%) showed complete clearing (healing of ulceration and disappearance of erythema) after a mean of 22 exposures (range 15-30). Eleven patients (37%) showed improvement, defined as healing of ulceration and/or reduction of erythema, after a mean of 23 exposures (range 11-42). Ten patients (33%) showed no effect and four patients (13%) worsened during topical PUVA therapy. The treatment results of the patients who suffered from diabetes mellitus were not different from those who did not have diabetes mellitus. No difference was seen in mean dermal thickness (1666 vs. 1706 micro m) and density (17 vs. 16 units) before and after topical PUVA therapy. Side-effects were seen in 10 patients: hyperpigmentation (n = 4), blistering (n = 4) and bacterial infection (n = 2).

CONCLUSIONS: Topical PUVA may be a useful treatment modality for NL in patients not responding to topical or intralesional corticosteroids.


Tissue-engineered dermal skin grafting in the treatment of ulcerated necrobiosis lipoidica.

Owen CM, Murphy H, Yates VM.

Department of Dermatology, Royal Lancaster Infirmary, UK.

Clin Exp Dermatol 2001 Mar;26(2):176-8 Abstract quote

Necrobiosis lipoidica is a well recognized but comparatively rare cutaneous complication of diabetes mellitus. The aetiology is probably multifactorial with microangiopathy, immune complex formation, abnormal collagen synthesis and breakdown, and altered haemostasis all thought to play a part. Necrobiosis lipoidica often proves very resistant to treatment.

We report a case of a 44-year-old woman with ulcerated necrobiosis lipoidica that healed following grafting with a tissue-engineered living dermal tissue.

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