Ulcerating necrobiosis lipoidica effectively treated with pentoxifylline

A 30-year-old man had suffered from persistent ulceration within an area of necrobiosis lipoidica diabeticorum for 13 months. The ulcerating necrobiosis lipoidica was resistant to topical therapy and oral therapy with acetylsa-licylic acid. However, the ulcers healed completely within 8 weeks of administration of 400 mg pentoxifylline twice daily.     

Superficial ulcerating rheumatoid necrobiosis: a perforating rheumatoid nodule

We report a case of superficial ulcerating rheumatoid necrobiosis (SURN), which is a recently described cutaneous manifestation of severe rheumatoid arthritis. As with classic rheumatoid nodule, there is evidence that this lesion may result from a vasculitis. SURN appears to represent a form of "perforating" rheumatoid nodule, and completes a triad of major necrobiotic processes (granuloma annulare, necrobiosis lipoidica, rheumatoid nodule) that have been reported to show epidermal perforation.     

Persistent ulcerated necrobiosis lipoidica responding to treatment with cyclosporin

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.     

Ulcerative necrobiosis lipoidica responsive to colchicine

Necrobiosis lipoidica is an uncommon granulomatous disease of unknown aetiology. Few treatments have emerged with consistent efficacy and the ulcerated form of necrobiosis lipoidica can be particularly difficult to treat. A 56‐year‐old non‐diabetic woman with chronic ulcerative necrobiosis lipoidica unresponsive to other therapies was commenced on colchicine treatment. Complete resolution of the ulcers was observed after 2 months therapy with colchicine 500 µg twice daily.     

Coexistence of sarcoidosis and necrobiosis lipoidica of the legs—A report of two cases

Two patients are reported with systemic sarcoidosis and necrobiosis lipoidica on the legs. There are no previous reports of this association. In view of the relative rarity of these two diseases, there is a clear suggestion of a pathogenetic link between sarcoidosis and necrobiosis lipoidica. Therefore, in patients with necrobiosis lipoidica the possibility of systemic sarcoidosis should be borne in mind and appropriate investigations should always be carried out.     

Necrobiosis lipoidica and sarcoidosis

We report the case of a female patient with necrobiosis lipoidica of the lower legs and coexistent systemic and cutaneous sarcoidosis. We review the six previously reported patients with coexisting necrobiosis lipoidica and sarcoidosis. The associations between the granulomatous disorders of the skin, especially necrobiosis lipoidica, sarcoidosis and granuloma annulare, are discussed. The common pathogenetic features of these disorders are reviewed.     

Necrobiosis lipoidica diabeticorum: a clinicopathologic study

Necrobiosis lipoidica diabeticorum is an unusual dermatologic condition with a characteristic clinical appearance and a clear association with diabetes mellitus. There is currently no treatment that reverses the atrophic changes associated with this lesion. We have carried out a clinicopathologic study on 15 subjects and, in addition, have reviewed 10 further biopsy specimens of necrobiosis lipoidica diabeticorum. We found a frequent association of necrobiosis lipoidica diabeticorum with other chronic complications of diabetes mellitus, including limited joint mobility. It is possible that nonenzymatic glucosylation or other changes in collagen may be important in the etiology of necrobiosis lipoidica diabeticorum and the limited joint mobility. We confirmed that cutaneous anesthesia is usually present in the necrobiosis lipoidica diabeticorum lesions. With the use of an antibody to S100 protein and an immunohistochemical method, there was an apparent decreased number of nerves in the skin lesions. We suggest that sensory loss results from local destruction of cutaneous nerves by the inflammatory process. Finally, in six elliptical biopsies extending into clinically normal skin, we demonstrated that the inflammatory infiltrate of necrobiosis lipoidica diabeticorum extended from the lesion into apparently normal skin surrounding clinically active lesions. Thus, intradermal steroids might be administered to perilesional areas surrounding active lesions in the hope of halting progression.     

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

BACKGROUND: 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. METHOD: 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. RESULTS: Histopathological findings revealed a well-differentiated squamous cell carcinoma overlying an area of necrobiosis lipoidica. Treatment was by excision and split-thickness skin graft. CONCLUSION: Clinicians should be aware of malignant transformation within a plaque of necrobiosis lipoidica. Early detection will allow conservative treatment.     

Simultaneous occurrence of ulcerated necrobiosis lipoidica and granuloma annulare in a patient: case report

Simultaneous occurrence of granuloma annulare and necrobiosis lipoidica is quite rare. There are seven reported cases in the literature, but only one presenting ulcerated necrobiosis lipoidica. We report a 39-year-old male with histopathologically confirmed granuloma annulare and ulcerated necrobiosis lipoidica, without diabetes mellitus.     

Dramatic response of chronic ulcerating necrobiosis lipoidica to ultraviolet A1 phototherapy

We report on a 52-year-old female patient with chronic, ulcerating necrobiosis lipoidica (NL) who dramatically responded to ultraviolet A1 (UVA1) phototherapy. The patient had NL on her right shin for more than 30 years without evidence of diabetes mellitus. Treatment with a variety of local and systemic agents failed to prevent progression into ulceration, which necessitated repeated surgical interventions in the past. When the patient presented again with torpid ulcers at the periphery of previously grafted skin, high-dose UVA1 phototherapy was initiated. Improvement occurred rapidly and after 22 irradiations and a total exposure dose of 1480 J/cm2, the ulcers had healed completely. During a follow-up period of 6 years,two minor recurrences were successfully retreated with UVA1 phototherapy.     

Links Between Granuloma Annulare,Necrobiosis Lipoidica Diabeticorum and Childhood Diabetes: A Matter of Time?

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

Ulceration in necrobiosis lipoidica—a case report and study

A case of aggressive ulceration of necrobiosis lipoidica was successfully treated with oral prednisolone. A retrospective study of 23 cases of necrobiosis lipoidica revealed a 13% incidence of ulceration. The pathogenesis, clinieal features and treatment of ulceration in necrohiosis lipoidica are discussed.     

Serum alpha 2 globulin levels in granuloma annulare and necrobiosis lipoidica

Alpha 2-macroglobulin, caeruloplasmin and haptoglobin were measured in the sera of patients with necrobiosis lipoidica, granuloma annulare and diabetes. Alpha 2 Macroglobulin and caeruloplasmin were significantly raised in diabetes, and caeruloplasmin was raised in necrobiosis lipoidica without diabetes. The ratio of alpha 2-globulin to serum albumin was significantly high for all three proteins in diabetes, and for haptoglobin and caeruloplasmin in necrobiosis lipoidica. None of these proteins was abnormally raised in non-diabetic patients with granuloma annulare. There is good evidence that the plasma protein changes in diabetes contribute to the development of microangiopathy by their influence on blood viscosity. The altered plasma protein profile in necrobiosis lipoidica may therefore be of relevance to the development of the vascular lesions in this disorder.     

Transcutaneous measurement of oxygen and carbon dioxide pressure in necrobiosis lipoidica

Transcutaneous measurement of oxygen pressure (PcO2) and carbon dioxide pressure (PcCO2) was performed in nine patients with histologically confirmed necrobiosis lipoidica. None of the patients had diabetes mellitus. All measurements were taken at the lower leg. In each case, the atrophic center, the inflamed border, and the surrounding clinically normal skin of necrobiosis lipoidica were examined at 44 degrees C sensor temperature (maximal vasodilatation). Statistically significant hypoxia was found in the area of necrobiosis lipoidica, which was even more pronounced in the inflamed border. Inhalation of 100% oxygen provoked a marked increase in the PcO2 in the lesion, but the values were still significantly lower than in the normal skin. At the edge of the lesions the PcCO2 was significantly elevated. These findings support a vascular origin of necrobiosis lipoidica, involving reduced vascular perfusion combined with diffusion block.     

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

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.     

SQUAMOUS CARCINOMAS DEVELOPING IN BILATERAL LESIONS OF NECROBIOSIS LIPOIDICA

Squamous cell carcinomas developed in bilateral pretibial lesions of necrobiosis lipoidica in a 39 year old non-diabetic male. The tumours and areas of necrobiosis were successfully excised and repaired with full thickness skin grafts. Despite the chronic scarring and at times ulcerative nature of necrobiosis lipoidica, complicating squamous cell carcinomas have infrequently been reported.     

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

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.     

Epidermal dendritic S100 positive cells in necrobiosis lipoidica and granuloma annulare

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.     

Necrobiosis lipoidica: treatment with systemic corticosteroids

In an attempt to find an effective therapy for necrobiosis lipoidica, we have treated six patients with this disease with a 5-week course of systemic corticosteroids. This treatment resulted in complete cessation of disease activity in all patients and no recurrence in a mean follow-up period of 7 months; however, restitution of atrophic skin lesions could not be achieved. The therapy was well tolerated and did not pose problems, even in diabetic patients. These results strongly suggest that short-course therapy of necrobiosis lipoidica with corticosteroids is of lasting benefit to these patients and should probably be considered early in the course of their skin disease.     

Necrobiosis lipoidica and Koebner phenomenon

Our report describes a 52-year-old female patient with bilateral foci of necrobiosis lipoidica in pretibial scars. The skin changes appeared 6 months after internal fixation of a tibial fracture in each case.