Necrobiosis Lipoidica Lesions Research Articles

Necrobiosis lipoidica-associated cutaneous malignancy

To the Editor: Necrobiosis lipoidica (NL) is an idiopathic granulomatous disease associated with collagen degeneration. Rarely, NL can be associated with cutaneous squamous cell carcinoma (cSCC) within the diseased tissue. cSCC within NL lesions was initially reported to be associated with severe, unremitting ulcerating NL.1

The many faces of necrobiosis lipoidica: a report of three cases with histologic variations

Necrobiosis lipoidica (NL) is a granulomatous disease with unknown etiology and pathogenesis. Clinically, it is characterized by yellow-brown atrophic plaques with inflammatory rims on shins. Histologically, it shows diffused palisade and interstitial granulomatous dermatitis with focal connective tissue degeneration (necrobiosis). We described three non-diabetic NL cases with unusual histologic features. All patients presented erythematous to brownish plaque(s) on the shin(s). In Case 1, in addition to the characteristics of NL, the biopsy showed dense perineural infiltration, which may explain the pathogenesis of the anesthesia of NL lesions. In Case 2, well-formed tuberculoid granulomas were of special interest. In Case 3, there was conspicuous lobular panniculitis. These histologic features present difficulties in the diagnosis and represent the broad spectrum of NL lesions, histologically.

Does pancreas transplant in diabetic patients affect the evolution of necrobiosis lipoidica?

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. Retrospective chart review of diabetic patients with NL who underwent transplant. 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. 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.

Venous insufficiency in patients with necrobiosis lipoidica

The pretibial area is the most frequently affected site in necrobiosis lipoidica (NL), but proposed mechanisms of NL cannot fully explain this high frequency. Although a few case reports indicate NL patients are complicated with venous insufficiency, no accurate assessment of the relationship between these two conditions has been performed. By using color Doppler ultrasonographic screening of four NL patients for venous insufficiency, we detected venous insufficiency in at least one leg of each patient. NL lesions were observed on all legs with venous insufficiency, and laboratory examination findings revealed that all the patients had hypercholesterolemia. The skin lesions did not respond satisfactorily to 6-month use of anticholesterolemic medication and elastic stockings. However, these results indicate that both hyperlipidemia and venous reflux, in addition to other pathogenic factors, can trigger tissue damage in the lower legs and lead to the onset of NL.

Healing of chronic necrobiosis lipoidica lesions in a Type 1 diabetic patient after pancreas-kidney transplantation: A case report

Necrobiosis lipoidica (NL) is a degenerative disease of dermal connective tissue of unknown etiology characterized by erythematous plaques preferentially localized to distal extremities. Skin lesions show a chronic relapsing nature. NL is often associated with diabetes mellitus and satisfactory treatment options are lacking. We describe the spontaneous healing of NL lesions after pancreas and kidney transplantation in a Type 1 diabetic patient with chronic NL recalcitrant to a variety of standard treatments. The 31-yr-old male patient had experienced NL lesions for more than 15 yr; despite various systemic and topical treatments, the skin lesions had pregressively enlarged. Because of end-stage renal disease, a simultaneous pancreas and kidney transplantation was performed and immunosuppressive therapy with tacrolimus (TAC), mycophenolate mofetil (MMF), and prednisone was started. Pancreatic transplantation maintained satisfactory metabolic control with no need of exogenous insulin. After transplantation, skin lesions slowly healed without any specific treatment, leaving residual areas of fibrotic scars. A skin biopsy confirmed the absence of typical NL lymphocytic and histiocytic inflammatory response. Clinical remission of NL lesions may probably be explained by the concomitant effect of multiple-drug regimen for immunosuppression (TAC, MMF, and prednisone) and improved skin microcirculation secondary to the good metabolic control provided by pancreas transplantation.

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

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: Ultrastructural and Biochemical Demonstration of a Collagen Defect

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 and Granuloma Annulare

Necrobiosis lipoidica (NL) and granuloma annulare (GA) occurred simultaneously in a patient with diabetes. Staining with colloidal iron showed deposition of acid mucopolysaccharides in the GA lesions and the absence of acid mucopolysaccharides in the NL lesions. If the two diseases have a common cause, that being the necrobiotic process, then one would expect to encounter their simultaneous occurrence much more frequently.